Topic	Subtopic	Note
AIDS		AIDS CNS- d/t HIV, Opportunistic infections, Neoplasm In HIV pt the most common brain lesions- toxo, B cell NHL, pyogenic abcess, syphylis, PML, mets Tx of toxo- pyrimethamine and sulfadiazine are of initial benefit in up to 90% of patients. most adult in US have ab indicative of prior exposure. Cerebral involvement is thought to represent reactivation of a late primary infection. AIDS dementia- subcortical, PM slow, impaired concentration, reading and forgetfulness
Alcoholism		DT Chronic alcoholic hallucinosis is characterized by auditory hallucinations with a clear sensorium. DT 3-21 days DT 3 days-3 weeks some believe if happen after 5 days it is not DT according to Dr. Ross DT is dx of exclusion why pt stopped drinking if no money they also may have SDH, MI, meningitis, pancreatitis, bowel obstruction, .... mortality 20-30% s tx DT can go on for 1-2 days string sign pt can not identify color of string also happens in other delirious states In Wernicke-Korsakoff syndrome, lesions are located in the periventricular gray matter, periaqueductal gray matter, mamillary bodies, and floor of the fourth ventricle. cerebellum purkinjee cells, mamillary body, dorsomedial thalamus, dorsolat prefrontal, periaquductal gray matter Wernicke- ataxia, nystagmus, ophthalmoplegia or ocular dyskinesia, lethargy inattentiveness Korsakoff- antegrade amnesia and patchy longterm memory, confabulation, opposite TGA not stressed about their amnesia Korsakoff amnestic synd: -impairment in verbal learning antgrade amnesia - forgetting recent events retrograde amnesia - motor and semantic memory(word meaning) as well as digit span are normal. Antegrade/recent memory impaired immediate/remote memory intact remote recent immediate antegrade memory Methanol intoxication results in severe metabolic acidosis due to oxidation of methanol to formic acid. Dilated, unreactive pupils and reduced vision are typical, due to destruction of retinal ganglion cells. Bicarbonate is the keystone of treatment of methanol poisoning. Concomitant administration of ethanol, a competitive substrate of alcohol dehydrogenase, may have some benefit. A loading dose (0.6 g/kg) should be administered as soon as the diagnosis of methanol poisoning is made. Fetal alcohol synd. ASD, Microcephaly, growth retardation
Behavioral neurology		Alien Hand Syndrome: 2 form Dysparetic: intramanual conflict, mirror movement, interference etc in Corticobasal ganglionic degeneration associated with parietal/frontal lobe degeneration and has cortical sensory loss, regidity/myoclonus and alien hand synd. and speech gait apraxia Frontal lobe reflexes: groping, grasping with inability to release, misutilization etc associated with ACA stroke A comm anurysm corpus callusom lesion tumor Marchiafava Bignami
Behavioral neurology		Antipsychotic tx for tx effectiveness 65% D2 blockade Prolactin elevation 75% EPS to occure >80% D2 blockage needed. 3D of psychosis Dementia, Delirium, Depression tx of agitation in pt c dementia - trazodone 50-250 mg/d -haloperidole 1-5 mg/d esp for aggression not agitation - behavior manageement techniques BMT - atypical antipsychotics clozapone risperidone low DM revelation, inc stroke risk 3 times olanzapine Zyprexa inc mortality inc DM quitipone low DM, low EPS ziprasodone aripiprazole 10 mg/day they have - no or low EPS, TD - no sustained inc in prolactin - reduce neg symptoms (typical reduce positive symptoms)
Behavioral neurology		Callosal apraxia results from a lesion in the genu of the corpus callosum. This results in a left limb kinetic apraxia. Tactile and auditory input cross the corpus callosum posteriorly and are therefore unaffected by a genu lesion. Alexia without agraphia results from a left occipital splenium of the corpus callosum lesion. Witzelsucht (inappropriate jocularity) is seen in patients with orbitofrontal cortex lesions. Lesions in the orbitofrontal cortex also include disinhibited and antisocial behavior.
Behavioral neurology		Catatonia statue synd - immobility/waxy flexibility/posture - mutism/analgesia - mannerism/rituals - grimacing/shoulder shrug - psychosocial withdrawal/stupor Catatonia is a syndrome manifested by a number of motor and neuro behavioral features. It may have a "retarded-stuporous" form or an "excited-delirious" form. It may be seen in over 10% of inpatient psychiatric patients. Catatonia is more prevalent in mood disorders than in schizophrenia. The most common mood disorder in which it is seen is bipolar. Catalepsy, waxy flexibility, echophenomena, and negativism including mutism are common. Many neurological and systemic illnesses may also present as catatonia. Treatments include benzodiazepines, barbiturates, and ECT. Dopamine antagonists (neuroleptics) as well as baclofen may worsen the condition. Reference: Taylor MA, Fink M. Catatonia in psychiatric classification: a home of its own. Am J Psychiatry 2003;160:1233-1241.
Behavioral neurology		Frontal lobe syndromes - medial: akinetic mutism, UI, bil leg weakness - orbitofrontal: disinhibition, Witzelsucht (compulsion to say jokes funny only for the pt)or Witzelsucht (inappropriate jocularity) - convexity: apathy, perseveration, poor sequencing Reduplicative paramnesia- person believes is in two place at once, in bilat frontal and R parietal lobe lesion
Behavioral neurology		Ganser syndrome is sometimes known as the "syndrome of approximate answers," or "pseudostupidity." Most often seen in psychiatic disorders, it has also been reported following neurologic conditions such as head trauma and neurosyphilis. The presentation of disinhibited, poorly monitored verbal output that is socially unacceptable has been termed verbal dysdecorum and is seen most frequently following damage to the right frontal convexity. frontal lobe syndromes - medial: apathy, akinetic mutism, UI, bil leg weakness - orbitofrontal: disinhibition - convexity: apathy
Behavioral neurology		Geriatric neurology special neurology issues in the elderly, common aging changes and impact on fx GerNeur is pt disability based. fx and psychosocial issues. Elderly- context/task specific, chronological, physical/functional, historical/societal (65yo),political Geriatric synd c neurologic presentation: - Altered MS, Delirium - UI - Gait instability/falls Geriatric assessment: H & P- MS, hearing,vision Detailed med including OTC Mood assessment Nutrition/Skin status Fx status continence,gait,finance Socioeconomic status Advance directive/discharge plan driving and elderly- if you concern can send a report to dept of public safety. It is not mandatory in OK. mandatory in CA, PA.
Behavioral neurology		Lewy body dementia dementia, parkinsonism, visual hallucinations, sensitivity to neuroleptics tx- Exelon is drug of choice, can use Serequel up to 100 mg qhs
Behavioral neurology		Neurodegeneeative disorders location- cortex dementia BG movement disorder cerebellum ataxia motor neuron weakness Etio- Prion, toxin MPTP, Triplet repeat, oxidation Cytoplasmic inclusions structural pr stress pr neurofilament Ubiquitin Tau Crystalline Synuclein Heat Shock pr Neurodegenerative c dementia 1- Alz neurofilament tangles 2- Taupathies FTD, Pick, CBG, PSP 3- Synucleinopathies LBD, PD, MSA(OPCD, SND, SDrager,Parkinsonism-Amyotrophy)
Behavioral neurology		Occipital lobe syndromes *Anton synd- cortical blindness. pt deny blindness bil O lesion calcarine * Bonnet synd-formed stereotyped visual hallucinations * (Disorder of visuospatial processing) Balint- impair visual scanning, inability to visually guide limb movement, in bilat OP junction lesions. components: 1- Simultan agnosia-visual disorientation 2- Optic ataxia-deficit of visual reaching (inability to visually guide limb movement) 3- Ocular apraxia- deficit of visual scanning (Disorder of object recognition) * Achromatopsia- loss of color vision in OT junction lesion (lingula-fusiform gyrus,nondominant) * Color anomia- recognize the color can not name it * Prosop agnosia- unable to recognize faces, bil inf visual association cortex(bil OT junction) * Word blindness- Alexia s agraphia, L occiptal lesion near splenium of CC, associated c achromatopsia/color anomia and R hhemianopsia in L PCA stroke (emboli) alexia c agraphia in angular gyrus of parietal lobe Balint can be seen in Alz. Prosopagnosia (inability to identify faces visually) is most often seen after bilateral inferior occipito-temporal lesions affecting both fusiform gyri. Similar bilateral lesions (or a nondominant lesion) of the fusiform and lingual gyri account for cerebral achromatopsia. Palinopsia (recurrence of a visual image after diverting gaze or when the stimulus object is withdrawn) occurs with occipito-temporal disease, often epileptogenic.
Behavioral neurology		Parietal lobe syndromes - dominant: Gerstmann(finger agnosia, LR Confusion, acalculia, agraphia, +- alexia, more in inf parietal lesions) - non dominant: neglect(autotopagnosia, apractagnosia), dressing apraxia, anosognosia, tactile allesthesia, receptive aprosodia
Behavioral neurology		Prosopagnosia (inability to identify faces visually) is most often seen after bilateral inferior occipito-temporal lesions affecting both fusiform gyri. Similar bilateral lesions (or a nondominant lesion) of the fusiform and lingual gyri account for cerebral achromatopsia. Palinopsia (recurrence of a visual image after diverting gaze or when the stimulus object is withdrawn) occurs with occipito-temporal disease, often epileptogenic. Alexia without agraphia (inability to read but with preserved writing ability) occurs with combined lesions of the dominant occipital lobe and the inferior splenium of the corpus callosum or with a single lesion of the dominant occipito-temporal paraventricular white matter behind, beneath, and beside the occipital horn of the lateral ventricle. Alexia with agraphia (central alexia) is usually due to an angular gyrus (parietal lobe) lesion. Bilateral lesions of the amygdala result in the Kluver-Bucy syndrome. This syndrome is seen in herpes simplex encephalitis, Pick's disease, anoxic-ischemic lesions in the anterior medial temporal lobes, and after bilateral temporal lobectomy. It is rarely, if ever, seen as a manifestation of Creutzfeldt-Jakob, Alzheimer's or Huntington's disease. clinical features include- hyperorality, hypersexuality, blunt affect, hypermetamorphosis, visual agnosia Contusion of the orbitofrontal cortex is associated with social disinhibition. Apathy, depression and loss of task set is more commonly seen in dorsolateral prefrontal lesions. Akinetic mutism is more commonly associated with medial frontal lesions. Anosognosia (unawareness of deficit or illness) is usually seen associated with non-dominant parietal lobe lesions. Achromatopsia is found after lesions of the inferior lip of the occipital lobe. Limb kinetic apraxia is seen after lesions of the anterior corpus callosum. Expressive aprosodia is seen after right frontal lesions. Semantic aphasia is seen after dominant hemisphere lesions.
Behavioral neurology		Psychogenic amnesia loss of remote memory (autobiography loss) plus no problem c new learning TGA d/t tia, sz, migraine, trauma ddx wernicke, intoxication, dissociative states repeat same question, stressed about situation opposite to Korsakof intact cognition, language profound antegrade amnesia and retrograde amnesia for preceding several hours or days chance of recurrence eg 25% of pt Tx ASA MRI c Sz protocol or stroke w/u EEG
Behavioral neurology		Rapidly progressive dementia w/u -EEG for PLED EKG changes - MRI/MRA - Cerebral angio - Viral studies IgG IgM for HSV, CMV, EBV , Rubella, Rubeola, HHV, HIV, - ESR, ANA - ANCA, APL, Whipple - SPEP, IFE, Amyloidosis - Hepatitis profile, cryglobulin - CSF cytology for malignancy - CSF VDRL, FTA Ab, RPR - Tick panel - B12, FA, TSH, FT4 - Homocysteine Etio above causes - Hashimoto encephalitis, check antithyroglobulins and anti thyroperoxidase - FTD - Lewy BD - Postviral encephalitis - SSPE - Paraneoplastic - Anoxic brain injury - CJD sporadic vs varient, associated with myoclonus, cerebellar ataxia, psychiatric symptoms, cortical blindness, akinetic mutism etc, MRI may show ribbon like high signal in cerebral cortex (or high signal in striatum) in DWI or high T2 signals in post thalamus pulvinar, inc pr 14-3-3, PLEDs on EEG, travel to UK Sylvia Frazier E002184265
Behavioral neurology	Language	Aphasia is a disorder of language, to be distinguished from disorders of speech (dysarthria, dysphonia) and disorders of thought (e.g., dementia, confabulation, perseveration, agnosia). Aphasic utterances can involve nonexistent word forms called neologisms. The characteristic feature of conduction aphasia is a striking deficit of repetition, with relative sparing of speech comprehension and output, though literal paraphasic errors may be present. Decreased repetition is noted in all the presylvian aphasias, including Broca's, Wernicke's, conduction, and global aphasia. Repetition is generally spared in the transcortical aphasias. Alexia without agraphia is often seen with lesions of the left occipital cortex that frequently are seen to extend into the splenium of the ipsilateral corpus callosum. Because of the occipital cortical involvement and splenial involvement, there may be associated color anomia and right homonomous hemianopia. Aphemia writing is preserved, in Broca, TCMotorAphasia and MixedTCAphasia writing is impaired. Borderzone stroke cause transcortical expressive and receptive aphasia. repetition is intact d/t sparing of perisylvian area. SMA is pacemaker for verbal output.
Behavioral neurology	Memory	Alz gene early onset AD - APP gene on ch 21 - presenilin 1 on ch 14 - presenilin 2 on ch 1 late onset AD - APOE4 on ch 19 - a2M gene on ch 12 anxiety, depression, Capgras synd common in Alz. depression also common in PD,Wilson,Huntington,MS Intellectual fx- language, memory, visualspatial skills, emotion or personality, and cognition (abstraction, calculation, judgment, etc) Dementia- acquired persistant impairment of at least 2 or 3 of the above spheres of mental activity.
Behavioral neurology	Memory	Digit span, which involves attentional processes, immediate recall and ability to sequence bits of information, may be reduced following lesions of dorsolateral frontal cortex. Lesions of the fornix, mammillary bodies and medial dorsal nucleus of the thalamus, on the other hand, cause amnesia (impaired secondary memory) without a reduction of digit span. Galantamine is a therapeutic agent for Alzheimer's disease that acts by both inhibiting AChE and allosterically modulating nicotinic ACh receptors. Rivastigmine acts by inhibiting AChE and butyrylcholinesterase. Choline acetyltransferase is decreased in AD. Chromosomes 1, 14, 19, 21 and possibly 12 have been associated with the genetics of AD but not 3. Alpha secretase cleaves APP normally. Beta and gamma secretase have been implicated in the production of toxic beta amyloid. Human prion diseases include kuru, sporadic Creutzfeldt-Jakob disease, iatrogenic Creutzfeldt-Jakob disease, new variant Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, and fatal familial insomnia. The loss of remote memory including autobiographical memory in the face of intact new learning ability is consistent with psychogenic amnesia. I One of the most striking characteristics of a patient with Pick's disease is a tendency to make the same statements repetitively (gramophone syndrome). Although memory impairment has been attributed to frontal lobe dysfunction, true amnesia is uncommon with frontal lobe lesions. Inattention, distractibility, poor motivation, and impaired strategy formation lead to the forgetfulness associated with frontal lobe lesions. Lesions of the temporal lobe have been associated with pure amnesia and lesions of the occipital and parietal lobes or cerebellum do not produce forgetfulness. The combination of early visual hallucinations, markedly fluctuating mental status, sensitivity to neuroleptics and lack of response to levodopa are characteristic of dementia with Lewy bodies.
Behavioral neurology	Memory	FTD Pick can be associated c Kluver-Bucy synd (hyperorality, hypersexuality, plasticity) in addition to personality changes and dec impulse control. placidity lack of normal aggresiveness. FTD linked to ch. 17 thumb sign sup temp gyrus usually very thick b/o auditory reciever, but in FTD or Alz they become prominent in MRI. types - picks - primary progressive aphasia/aprsodia - Corticobasal ganglion degeneration - post cortical atrophy (in parietal lobe) dementia progressive decline in intellectual function that include not only memory but also language, agnosia, executive functions, ... AntiCholinergics good for Lewy body dementia (visual allocination, delusions)opposite to other dementias. Neuroleptics in dementia haldol 0.5-2 mg/d zyprexa 2.5-7.5 /d enhance cholinergic transmission seroquel low EPs effects vit e Memantin NMDA antagonist
Behavioral neurology	Treatment	donpezil can be used in AD, Vascular dementia and mixed, MS, PD, ADHD, Closed head injury
Brain death		Vegetative state - present sleep awake cycle - present cn reflexes - present autonomic hypothalamiçfunction - unaware of self and environ - no language understanding - no purposeful voluntry movement etio: diffuse axonal injury or post hypoxic ischemic encepaholopathy with laminar necrosis thalamus or thalamo cortical fibers severely involved prognosis nontraumatic very poor more than 3 m traumatic very poor more than 12 month ethic committee to decide MCS - some definite behavioral evidence of self or environmental awareness can do simple commands, smile or cry, some verbalization tx: neurorehabm, levodopa, dopamine agonists, SSRI, stimulant, Ambien experiment: DBS in intralaminar nuclei
Brain death	Brain death	AAN PREREQUISITES cessation ofall brain fx proximate cause is known (no hypothermia or drug overdosage) condition irreversible CARDINAL FEATURES - coma - absent brain stem reflex pupill light, corneal, nasal, OCephalic, OVestibular, gag - Apnea test (no spontaneous respiration after 10 min or with PCO2 >60 -caution in using PCO2 for COPD pt) pt are ventilated for 10-30 min c 100% O2 (maintain baseline PCO2) and then disconnected from the ventilator while 100% O2 is given at >= 6 Lit/min. ABG is measured before the ventilator disconnected and 5-10 min after disconnecting the ventilator. CONFIRMATORY - eeg (some activity may persist in first 24 h after cessation of CBF) - PET SPECT for CBFlow or Angio (earliest and most definitive proof of brain death) - TCDoppler study PVS persistant vegetative state wakefulness s cognition after recovery from coma keep sleep-awake cycle and veggie fx etio- HIE, Metabolic, Encephalitis, head trauma AAN - All medical tx including nutrition, hydration MAY be ethically discontinued if it is clear the pt didn't want to be maintained on this AND family agree. Children who remain in PVS for 3 months do not regain FUNCTIONAL skill. order EEG at least 6 h after CP arrest as there may be a transient suppression following anoxic insult. A repeat EEG after 24 h may be helpful but flat EEG is not necessary for dx of brain death. Prognostication is best evaluated 3-7 days after brain injury.
Clinical trials		PQRI inpt stroke care neuroimaging/rehab screening for future fall risk advance care plan medication reconcilation if 3 or more measure reported 80 percent of time eligible 1.5 percent bonus payment.
Clinical trials	No Value	Clinical trials in neurology 1- surgery for carotid disease NASCET ACAS 2- Aspirin dose for stroke prevention 81-325 3- WARRS trial- warfatin in non cardiogenic noncarotodogenic stroke has no advantage over ASA even in subgroup of pt with pfo, apl ab synd. or large/small stroke 4- HOPE PROGRESS trial- ace i is good for stroke even in normotensives 5- STATIN AS CARE LIPID trial- statins are good for stroke 6- MATCH CURE trial plavix has added benefit with ASA 7- EVIDENCE study Rebif 44 mcg Sc tiw c/t 30mcg Avonex im qweek had less relapse (18%)or MRI lesions 8- PRISM PRISM4 Rebif 44 ug 3/week had less burden of disease or relapse c/t 22ug or placebo Avonex dose comparison study no diff in 22 vs 66 but ug 22x3 qweek had better response less relapse so frequency of admin more important than higher dose. - class I randomized clinical trial - II prospective case control study nonrandomized - IIIa case series - IIIb case report - IIIc just personal opinion CEA - symptomatic >70% - symptomatic 50-69% make decision case by case - asymptomatic >60% if pt 40-75, risk<3%, life expectancy>5 year stent if lesion not surgically accssible, medically high risk, post radiation stenosis cardioembolic stroke wait 2-3 days repeat ct if no bleed start warfarin po no need for heparinoverlap. Sq heparin is ok for dvt prophaxis basilar artery stutering my benefir from ia tpa or clot retrieval if pt on ap no contra to tPA if pt on AC if inr less than 1.7 may do tPA ace arb statin are good in stroke pt even if normotensiv, keep ldl low
EEG		EEG 2 - FIRDA seen in metabolic encephalopathy - OIRDA is seen in kids as primary generalized epilepsy - JME generalized multiform spikes= polyspikes and waves, fragmented, shifting laterality - MTS TIRDA temporal intermittent rythmic delta activity - In LGSynd interictal EEG also shows slow spike/slow activity that doesn't mean pt is in SE.
EEG		EEG 3 Video EEG Monitoring indications- sz dx, sztype, presurgicl evaluation nonepiletic- panic, depression/anxiety, psychosis, don't call pseudosz, not malingering because they have seroius psych problem. Syncope, Movement disorders, red flags- persistant normal eeg, paradixical response or many allergies to AEDs, psychosocial issues. dystonic movement contralat, aphasia dominant hemisphere origin, noserubbing seen in ipsilateral temporal origin, coughing shows right temporal lateralization. SISCOM- SPECT difference superimposed on MRI.
EEG		EEG in encephalopathy common causes- hepatic, renal, drugs, sepsis - diffuse slowing - if eeg shows reactivity, Claps the hand if any eeg change better prognosis - ddx of nonconvulsive SE - triphasic waves, bidynchronous, initial neg largest pos component, etio in HF, RF, Hypoxia post arrest, can be initiated by painful stimuli - Drug toxicity, fastactivity eg barb, bnzd, also can present occ as bisynchronous sharp complexes, alpha coma, spindle coma, burst suppression, ECS - bisynchronous sharp complexes or PLEDs can be seen in CJD, Hypoxia, Herpes, Baclofen, Li, Levodopa, EEG looks like EKG - Hypoxia can cause alpha, theta,spindle coma, BSP, ECT - Alpha coma, alpha everywhere and nonreactive to pt stimulation, it is a thalamic spontaneous rhythm and seen in subtentorial lesions, midbrain and down. - Spindle coma in propofol, versed and infratentorial lesion after trauma, see spindle with k complex - burst suppression only open or close eyes in ICU or post op after anesthesia - Myoclonus status or myoclonic status epilepticus, Subtle status. almost dead, mudcle artifact inc the amp of myoclonus, if mucle paralyzing given amp decrease - NCSE, more then 30 min change in MS with ictal EEG. in 2 condition Ambulatory eg CPSz status or Abscence status versus Obtubded/Comatose pt may beNCSE or Electropheragic sz, EEG atterns- PLEDs, BIPLEDs, Tripasic Waves most EEG expert don't believe PLEDs need tx. NCSE Tx- lorazepam, DPH, Pentobarbital some use Versed, Propofol NCSE should be differentiated from prolonged postictal, scan negative
EEG		EEG Peds The illustration shows typical centrotemporal spikes, often associated with benign rolandic epilepsy of childhood, which is manifested by clonic movements of the face and hand that often progress to a more generalized seizure. Sylvian or Rolandic epilepsy start age 6 to teens associated c focal jerking or tingling of face or hand c progression to GTC Sz The combination of fast activity (12-14 Hz activity) and delta slowing is most often seen as an anesthetic effect or drug overdose. Vertex or V-waves are high voltage sharp contoured waveforms that can occur with phase reversals on a bipolar montage over the central areas. wicket spikes, constitute a benign pattern of uncertain clinical significance, occurring predominantly in the EEG of older adults during light sleep. The breach rhythm consists of EEG activity that is increased in amplitude and prominence recorded over the area of a skull defect. The breach rhythm is most prominent when seen over the central and temporal regions. Normal EEG changes in neontes - trace alternant discontinuous rhythm in quiet sllep - vertex sharp waves not seen until 2-3 months - Delta brushes pattern of prematurity but can be seen in normal neonate - rhythmic ant slow waves can be seen during sleep
EEG		Intracranial EEG Periodic spikes under 2 hz before fast rhythmic activity point to sz localization in intracranial eeg perodic spikes last 15 sec or 3 min herald sz. you don't see them in interictal or nonelectrical activities. the other pattern could be mixed theta and beta. you see these in neocortex sz. periodic spike is seen more in MTS. Low voltage fast activity is the most common neocortical sz activity in intracranial monitoring. Pediatric intracranial - suspect dual pathology eg bil MTS or MTS plus neocortex - extratemporal>>temporal - substrare for epilepsy tumor cerebral dysgenesis TS hypothalamic hamartoma
EEG	No Value	EEG 1 Different waves Calibration square wave biologic At least 20 min in adults, 1 hour in kids for base line and then response to hvt photos and in epileptic pt during sleep ARTIFACTS muscle Movement artifacts sweat artifact 60 hz artifact eye movements Extracerebral- pulse, electrode pop up, ekg, outside powerline Photostimulation abnormal asymmetric occipital driving photmyoclonic or photomyogenic response is normal noncerebral response characterized by brief repetitive muscle spikes in the frontal head regions photoparoxysmal symetrical occipital driving is normal HYPERVENTILATION general slowing if prolonged more than1 1/2 or 2 minute is abnormal avoid hvt in COPD,Asthma, CVA, Myomoya EEG in infants infantile spasm hypsarrhythmia or burst suppression myoclonic epilepsy 3 >3 cps polyspike and wave LGSynd 2-2.5 polyspike and wave Spike 20-70 ms Sharp 70-200 ms they are associated with slowing afterward, stand out from background, stereotype, activated by sleep Normal spike & sharp - vertex sharp waves - BETS - POSTS - 6 Hz phantom, - 6 and 14 Hz positive spikes - Occipital lambda - Wicket spikes Focal slowing- focal structural lesion Diffuse slowing- toxic metabolic encephalopathy, neurodegenerative process eg dementia, multifocal CVA, Headtrauma Fast beta activity- BNZD sedation use chloral hydrate pre EEG 25-50 mg/kg po or pr, doesn't affect EEG Focal spike or sharp- partial sz or CPSz Diffuse spike or sharp- generalized Sz, can not r/o secondary generalization, primary focus may not be clear Inc EEG yeild by, sleep deprived esp for TLE, HV, PS, Repeat study or prolnged EEG, >30 min Yeild dec by tx c barb, bnzd, vpa or other AEDs - Partial sz present as spike/sharp or focal slowing - disruption in the background ddx epi from normal varients, normal varients are also bilateral. (Wicket spikes = rhytmic midtemporal theta of drowsiness) - Lambda waves like POSTs in occipital when pt scanning environment and will disappear when pt close the eye
EMG/NCS
EMG/NCS		CLINICAL QUESTIONS - Muscle disease - NMJ disorder - Peripheral neuropathy axonal vs demyelination conduction block - CTS - Brachial plexopathy - Cervical radiculopathy - ALS FINDINGS - prolonged latency - prolonged F wave - H reflex - myotonic discharges
EMG/NCS		Electrode placement For motor everywhere 7 cm x post tibial 8 cm, Radial motor is 9 cm above wrist For sensory 14 cm for Sural nerve 10 cm Dr. Merkey office everywhere 8 post tibial 10
EMG/NCS		In normal subjects, the maximum difference between right and left median nerve motor distal latencies (stimulating at the wrist) is 0.7 msec. The maximum difference for median sensory distal latencies is 0.5 msec. When the differences between right and left are greater than these values, one can confidently diagnose median mononeuropathy at the wrist (carpal tunnel syndrome) on the side with the longer latencies. The difference between right and left is not helpful in assessing bilateral compression. Conduction velocity between elbow and wrist is not affected in this condition. The Martin-Gruber anastomosis produces a characteristic nerve conduction pattern of a larger median motor amplitude with proximal stimulation (compared with distal stimulation) and a significantly smaller ulnar motor amplitude with proximal stimulation (when compared with distal stimulation).
EMG/NCS		Normal values LATENCY tarsal post tibial motor 4.5 ms median ulnar motor 3.8 median sensory 3.5 measuements above these values abnormal. CTS esp >5 distal latency, or can check NCV across wrist and if less than 35 m/s is in favor of CTS AMPLITUDE Amp motor upper ext 5 or 4 mv lower ext 4 or 2 mv Amp sensory below 10 microvolt abnormal Amp sensory below 9 microvolt in sural abnormal F WAVE LATENCY abn in UE >32 in LE >58 side to side diff abn if > 3-4 msec H REFLEX abn if >35 msec or if side to side diff > 3 msec CONDUCTION VELOCITY in UE >50 m/s in LE > 40 m/s
EMG/NCS		Radiculopathy fibrilliations, PSW are the most reliable EMG parameters for dx of radiculopathy. another evidence of chronic denervation or HALD MUPs. fas or inc polyphasic MUPs, For H late response not good parameter. PSWs develops 1 week earlier than fibrilliations. needle EMG should be done 3-4 weeks after disc herniation. Sensory nerve conduction study is the cardinal rule for differentiation plexopathy from radiculopathy. paraspinal muscles innervated by post primary rami, limb muscles by ant primary rami. paraspinal muscles develop fib PSWs 1 week earlier c/t distal muscle. above c normal sensory NCS absolute evidence of lesion prox to DRG namely nerve root or ant horn cell. Illiac crest L3-L4 level. 2.5 cm from midline, 2.5 cm deep. exam part uppermost in cer lumbar, downward in thorasic (DM). fib PSWs can be tested, MUPs can not be tested because paraspinal relaxation is almost impossible. Negative EMG in radiculopathy - acute phase - root compression caused more demyelination than axonal loss - sensory root compression instead of root compression, pt has more pain and paresthesia, SomatoSensory EP may be useful in such situation although has it is own caveat (overlaping dermatome) - paraspinal muscles are normal d/t sampling errors or fasicular sparing of fibers from dorsal rami
EMG/NCS		Time course of neuropathic lesions Acute phase- reduced recruitment in clinicaly weak muscles 1-2 w- + fib in proximal muscles, normal MUAP morphology 3-4 w- + fib in distal muscles, normal MUAP morphology 5-6 w- +fib in all muscles Reinnervation phase- larege (amp,dur) polyphasic MUAP started from proximal to distal muscles
EMG/NCS	No Value	EMG in myopathy brief small amp polyphasic potentials BSAPP, in neuropahty denervation potentials fibrillation, fasiculation, sharp waves and large prolonged polyphasic motor unit potentials. In demyelinating neuropathy greater slowing of CV C/T greater dec of CMAP in axonal neuropathy Repetitive nerve stimulation for NMJ disorder (presents with fatiguability, fluctuation, prox weakness, dysphagia, dysartheria, ocular palsy)mainly for MG, LEMS, Botulism in MG ab against ach receptor in LEMS ab against presynaptic Ca channel Blink reflex afferent v efferent vii 2 response R1 main sensory nucleus v in pons ipsilateral fascial R2 to spinal nucleus of v then both fascial nucleus 4 nucleus of v- main light touch higher in midbrain mesoenvephalic for proprioception lower spinal tract for pp temp then median and anterior motor nucleus fascial nerve also carry proprioception of face that is why pt with Bell's palsy state numbness in face although light touch is normal. A progressive increase in latency, duration, amplitude and area of motor and sensory nerve action potentials accompanies a physiologic decline in temperature. This is reversed by warming. Motor conduction block, abnormal temporal dispersion, slowed conduction velocities, and prolonged late responses are the electrodiagnostic features of demyelination. The Martin-Gruber anastomosis occurs in 15-30% of the population. It consists of a communicating branch from the median nerve to the ulnar nerve in the forearm to supply the first dorsal interosseous, adductor pollicis, and abductor digiti minimi. The most sensitive test for myasthenia gravis is single fiber EMG of the frontalis muscle. Electrodiagnostic characteristics of neuropathy include decreased motor unit action potential (MUAP) recruitment, increased MUAP amplitude, and fibrillation potentials with a distal to proximal gradient.
Epilepsy		AEDs Incidence about 1 percent half of the cases are idiopathic DDX syncope TIA movement disorders myoclonus startle sleep disorder complicated migaine jitteriness,shuddering breath holding spells sel stimulting beaviour GI disorders pschiatri disorders brainsem,diencephalic disorders Surgery for epilepsy VNS Corpus Callosotomy Ant Temp lobectomy rate of success is about 70% AEDs Keppra 10 20 % behavioral probledepression Topomax cognitive SEs dificulty c memory word findings, 1.5 % kidney stone Zonergn not first line lss cognitive SEs Zonergan stored in Erythrocytes Lamictal no effect on cognition , doesn't affect sonolence but actually may be stimulant. Stevens Jonson incidence is about 0.02 % among Lamictal users. rash producing drugs: DPH, CBZ, LAM, PB use Keppra in this situation. Lamictal is good choice for pregnancy and elderly.strtingLamictal low dse c/t cbz, dph and vpa didn't have significant difference in s control or sz free frequency. Lamictal good for neuropathy and maybe migraine. rash is more common when start initial dose more than 25 or rapid titration or when added to vpa or in younger pt or previous hx of atopy Trileptal SEs dizziness, start slowly, hyponatremia more common than tegretol Gabitril 2 percent psychosis another unusual side effect is hypotonia switch vpa to lam 1- inc lam to 200 mg/day 2- once at 200 mg/d gradually dec vpa to 500 m/d by 500 mg decrement weekly hold this dose for 1 week 3- dec vpa 250 mg/d and inc lam to 300 mg/d , keep on this dose for 1 week 4- dicontinue vpa and if needed clinically inc lamictal if pt on vpa start at 12.5 mg and do 12.5 mg increment weekly or every 2 weeks. VNS success- in 40% dec sz by 50% TL success- 70% complete control, 20% better control, 10% failure DC of AEDs- in 1 year stop one, in 3 year dc second one and after 5 years will decide stopping all AEDs
Epilepsy		Both auditory and visual hallucinations, persecutory delusions, and ideas of reference are seen in both temporal lobe epilepsy (TLE) and schizophrenia. A positive family history of schizophrenia, schizoid personality, or schizotypal personality is often present in schizophrenia but usually not in TLE. Affect is better preserved in TLE than in schizophrenia.
Epilepsy		Depression Anxiety very common in sz pt tx - avoid pb - use activating AEDs eg lamictal, CBZ - Buspar also for anxiety/depression didn't affect sz - Clorazepate also good for anxiety not habituating TCA in 50% makes sz better, in 30% no change, in 10% increase sz frequency
Epilepsy		diference between absence and cpsz - postictal - automatism simple in abs, complex in cpsz - duration 5-10 if more than 15 cpsz - frequency abs many, cpsz 3-4/day
Epilepsy		Dizziness check for hypoglycemia, SVT, Anemia neurological causes-
Epilepsy		Geschwind synd personality changes in some pt CPSz that include: hypergraphia circumstamtiality intense emotion or cognition altered sexual state more hypo,dec libido sickness
Epilepsy		JME - Familial 50%, respond well to VPA - life long c good cognition - start at puberty 11-18 max around 15 - myoclonus or twitching upon awakening following sleep deprivation etoh consumption - EEG 4-6 Hz polyspikes predominantly frontal - ddx with hypnagogic myoclonus - Tx VPA 85% response Top, Keppra Avoid DPH, CBZ Avoid sleep deprivation, etoh, photosensitive lights, night shifts, driving restriction, working at heights or with heavy mashinery, supervised swimming, pregnancy counseling, FA supplement. - VNS in refractory cases Absence sz 1/3 get better 1/3 JME 1/3 GTC Sz
Epilepsy		MRI findings - lesion in temp - MTS either smaller hippo (normally L hippo 15% smaller) or inc density in hippo softer signs enlargement of temporal horn or whole temporal lobe is smaller look at cochlea for symetricity SPECT Interictal dec perfusion Postictal inc perfusion in 1/3 of pt this pattern is reversed.
Epilepsy		New issues in epilepsy prolactin need to be measured in 15 min after sz, in status it may decrease afterward. all AEDs cause bone loss x neurontin, keppra mechanism- inc metabolism of 1,25 dihydroxy D3 in inducing agents, inc PTH, dec GI absorption in aeds such as VPA. Bone tx Prevention- ca 1000-1500 mg/d + vit D 400-2000 IU Osteopenia/Osteoporosis- ca plus 2000-4000 vit D Osteomalacia- Ca plus 5000-15000 vit D only for four weeks only then back to preventive dose Measure BMD Advised pt about long term consequences and document that. In severe cases use Bifosfonates but NOT IN CHILDREN. When can u give a loading dose of LTG in neonate up to one month, 15 mg/kg
Epilepsy		Pseudoseizure better called non-epileptic sz or nonelectrical spells about 1/3 of pt with psz have also real sz DSM IV TR 300.XX conscious production +present in malingering - absent in factitious unconscious production + conversion -absent in somatization (or somatiform milder) psychiatry disorder c psz- major dep panic substance abuse histrionic/borderline/antisocial personality Munchasen Munchasen by proxy make adult or kid dependent on them sick Ganser's synd miss everything by one psz about 20%, 80% female, 90% report childhood abuse or first memory after 7 or amnestic intervals presentation to pt- good news u don't have sz. there is brain and mind these come from your mind not brain. 3 reason it is not sz - sz last 1-2 minutes at most as it is self limiting process unless status - pattern either partial onset then march generalization or primary GTC - post ictal slowing confusion The clinical and EEG findings in supplementary motor seizures are distinctive, with tonic posturing, focal symptoms in the legs, not hands, and usually preserved consciousness. The seizures are often misdiagnosed as psychogenic seizures and the EEG findings are often subtle or absent.
Epilepsy		Sz and women estrogens epileptogenic progestrone protective - Cataminial sz d/t inc est few days before start of bleeding or drop in progest few days after start of bleeding true dx need pt record 6 months hx of sz and menses tx- extra dose of AED during vulnerable period, progestrone use Provera, depoprovera IM q 3 month, acetazolamide for 10 days (250-1000 mg/day) Katamenios-greek word means monthly Contraceptives and AEDs inc metabolism, inc failure, Gaba, vigabatrin, lamictal, keppra no effect VPA inhibitor at least take 50 ug estradiol should be in OCP
Epilepsy		Sz in elderly less aura and automatism more prolonged postictal frontal lobe common, more during in sleep, behavioral changes for tx start low and go slow depakote, neurontin cause weight gain topomax, zonesemide cause weight loss after surgery or infection acute phase reactants may inc free level of AEDs dec and they mag get Sz. AEDs cause osteopenia osteoporesis in elderly
Epilepsy		Sz syndrome - LG MR, EEG slow spike wave, underlying genetic, structural, metabolic problem, diffuse brain hypoxia, CNS infection, atonic attack, myoclonus, GTC Tx- VPA, LTG, TPM, ZNS, VNS, Ketogenic diet, avoiding sedating drug and polypharmacy, helmet, metabolic w/u Infantile spasm usuall first 2 year 3-9 month cluster of spasm c hypsarrythmia - ACTH cause remission in 60-75% - etio malformation eg lissencephaly, cns infection, perinatal hypoxia, cryptogenic West synd treatable cause- b6 sz, biotin serum, folinic acid in serum, glucose transport defect (CSF glucose low, tx with ketogenic diet) surgical tx for focal brain malformation, tuber lesion, perinatal stroke ischemic change or developmental tumor eg gangliocytoma that can be remived by surgery. esp if EEG shows focality.
Epilepsy		why not tx sz - idiosyncratic reaction - cognitive se - birth defect - osteoporesis - drug interaction - economic implication is this sz or epilepsy - previous history maynot be recognized - hx ofepisodic aberrant behavior - metabolic causes glu, lytes, ca, sepsis, rf, lf, res failure, b6 - genetic predisposition evaluation of first sz VS Trauma Oral/fascial injury UI Floppy infant Stiff adults NE (confusion, craniofascial asymmetry, hemiatrophy) EEG, CT Scan MRI Whom to tx - known Etio - partial - FHx - abn NE, EEG, MRI
Epilepsy	therapy pearls	Uremia uremia inc unbound fraction of phenytoin, also pt tend to have low serum alb. Target level for 5-10 mg/dl corr dph= dph reported/ (0.1 alb+0.1) only 2-4% of dph removed by hemodialysis so no supplemental dose is necessary. dph is 90% alb bound reported level is bound and free. It should be adjusted when alb is low corr dph= dph reported/ (0.2 alb+0.1) Equation to inc subthera level 0.7 x IBW x (15-current level) measure dph level 2h and 2days after loading Diamox sequels 500 mg bid or 750 bid everyday is good for cataminal epilepsy. Sequels is long acting slow release formulation. Extra dose of keppra at qhs to help sleep. Take vit d and ca with all aeds esp pb dph and tegretol. Also take mv qd. - Taper dph by 100 mg q2week to stop on 4/16/04 - stop driving when dose gets down to 200 mg qd - may resume driving on 6/1/04 if no sz (after 2 months off the aed if sz free)
Epilepsy	Treatment	Drugs that can raise carbamazepine levels include isoniazid, erythromycin, cimetidine, calcium channel blockers (such as verapamil), and propoxyphene. Carbamazepine levels are lowered by phenobarbital, phenytoin, and primidone. Warfarin, chlorpromazine, digoxin, and gabapentin have no significant effect on carbamazepine levels. Fetal vitamin K deficiency with hemorrhagic complications occurs in 10% of neonates born from mothers receiving antiepileptic drugs that induce liver metabolism of vitamin K, including phenobarbital and phenytoin. Women taking enzyme-inducing antiepileptic drugs should be treated with vitamin K1, 10-20 mg daily during the last month of pregnancy. Infants should receive 1 mg intramuscularly at birth and, if needed, fresh frozen plasma. Reference: Foldvary N. Treatment issues for women with epilepsy. Neurol Clin 2001;19:409-425. for CPSz tegretol unless eeg shows a generalized pattern start at dose 10 mg/kg/day inc at weekly interval to a dosage of 15-20 mg/kg/day. potential ADR and Sz first aid, Sz precaution discussed. in 3-4 week CBC, CMP Na LFTs and Tegretol level should be checked. A majority of epileptics experience significant depression at some time during the course of the disease. The suicide rate is over five times higher in epileptics than in the population as a whole. Topiramate and zonisamide are weak inhibitors of the carbonic anhydrase, and therefore may increase urinary pH and decrease urinary citrate excretion. Both effects may predispose to kidney stones. In addition, both drugs have been associated with impaired concentration and memory, and could potentially affect school performance. Idiosyncratic toxic reactions to valproic acid include thrombocytopenia, hepatotoxicity and pancreatitis.
Epilepsy	Treatment	Efficacy stat measurement of sz reduction Effectiveness- clinical reduction of sz and toxicity, tolerability and so on. Oxacarbamezine is not enz inducer x in 3A4 isoenz that cause failure of OCP while on this drug. Enz inducer dph, pb, cbz, oxa non inducer top, lam, gab, kep enz inhib vpa weight + 0 - vpa,cbz,gab lam,kep,dph top,zon,fel AEDs my inc vit D met, dec Ca abs, inc bone turnover Bone density measurement rec for pt c chronic AEDs malformation happen in 2-3% of general population twice in epileptic populations choice in pregnancy lamictal, cbz choice in elderly lamictal, neurontin if quick load dph, vpa lam agitation edgy gab somnolence top memory problem pb sedation or hyperactivity tachyphylaxis most seen c keprra less c lam zonisomide Levetiracetam does not have a clinically significant effect on liver enzymes and is inactivated to a a small extent by the liver. It is mostly eliminated unchanged by the kidneys. Valproate inhibits the metabolism of other anticonvulsants, including lamotrigine and the epoxide metabolite of carbamazepine. Tiagabine has been reported to produce non-convulsive status epilepticus and absence seizures. Hyponatremia, ranging from asymptomatic to hyponatremic coma, may occur during oxcarbazepine use, particularly in the elderly. Urinary tract calculi may occur in patients while taking zonisamide (4%) or topiramate (1.5%). Weight loss with or without diminished appetite is more likely to occur with felbamate or topiramate.
Falls in elderly		Falls in the elderly 1 Acute- Stroke,TIA, Syncope, Sz Chronic- OH (autonomic neuropathy), Meds, Visual problem (inf quadroanopsia esp.), Gait/postural instability in parki, Ataxia, Vertigo, Gait apraxia in bil strokes/dementia, Hydrocephalus (magnetic gait, urinary incontinence, dementia), Poor proprioception B12 def, muscoloskeletal, fixed cardiac output synd (vasodilation in muscles) or pt with emphysema, anemia, otherwise it is idiopathic fall of elderly Falls are the leading cause of both nonfatal injuries and unintentional injury deaths among older people in the United States. More than half of people age 65 or older fall each year, and 10% of these falls result in serious injury. Injuries from falls include hip fracture, other fractures, subdural hematoma, and other head injury. Factors that increase the risk of falling: • Depression • Confusion • Alzheimer's disease, or other dementia • Impaired vision • Impaired hearing • Arthritis • Weakness • Neuropathy • Parkinson's disease • Impaired balance and gait • Acute illness • Recent hospitalization • Multiple medications • Specific medications Falling is one of the most common problems associated with medications. Some medications are particularly likely to increase the risk of falling: • Antidepressants (especially tricyclics and serotonin-reuptake inhibitors) • Anxiolytics (especially benzodiazepines) • Antipsychotics (especially haloperidol and phenothiazines) • Antihypertensives • Antiarrythmics • Anticonvulsants Many elderly people have multiple medical problems for which they are receiving medications. The risk of falling and confusion increases with increasing number of medications, independent of the types of medications. At least on a yearly basis, medical care providers should ask elderly patients about any falls or difficulty with balance and gait. They should also observe their patients while rising from a chair, while standing, and while walking.
Falls in elderly	Treatment	Falls in the elderly 2 Any elderly patients who have observed difficulty with getting around should be considered for professionally supervised balance, gait, and muscle-strengthening programs. Such programs, coordinated by physical, occupational, or kinesio-therapists, can decrease the risk of falls by 10%. For any patients who are falling, providers should also • Review all medications (including over-the-counter medications) • Eliminate problematic medications (if possible) • Decrease the total number of medications to 4 or fewer (if possible) • Assess for orthostatic hypotension • Assess vision, hearing, heart, lungs, joints, muscles, and sensory function • Obtain appropriate blood tests (including complete blood count, serum electrolytes, blood urea nitrogen, creatinine, glucose, vitamin B12 level, and thyroid stimulating hormone level). • Obtain neuroimaging if there is a head injury, if there are new focal findings, or if there is a suspected central nervous system process based on history or examination. • Consider tests for osteoporosis, particularly in postmenopausal women or those at increased risk of osteoporosis for other reasons (eg, steroids, cigarette smoking) • Refer to physical therapy for comprehensive evaluation and rehabilitation • Refer to occupational therapy for an inhome safety evaluation • Recommend hip protectors, which decrease the risk of hip fracture by more than 50% (Lauritzen et al 1993; Ekman et al 1997). Elimination of home hazards can result in a 20% decrease in risk of falling. Some of the changes that can decrease falling include: • Removal of rugs • Change to safer footwear (eg, soft, flat-soled shoes) • Use of nonslip bathmats • Improvement of lighting (including use of a night light) • Addition of stair, bathtub, and toilet rails • Removal of low chairs • Repair of pavement irregularities
Headache Migraine		1 Headache Migraine Cluster HA Whitdrawal/Rebound HA HA and pregnancy Psuedotumot cerebri Convergence Hypothesis: Migraine is a neurological process and a headache is just one symptoms that evolves from that process. A variety of different clinical presentation of ha may emerge from the migraine process including: Prodrome, Aura, Mild HA, Moderate to severe HA and actual migraine. Tension can evolve to migraine and migraine resolve into tension. Triggers: Internal Hormonal changes, Stress, Sleep habit changes External Weather chnages, Etoh, Glare/flickering light Prodrome: mood disruption, sensory disruption, constititutional chnages, cognitive changes, food craving, muscle tension, nasal stuffiness/drainage, yawning may precede migraine by 1-2 days Aura: Focal and reversible neurological symptoms, typically visual but maybe sensory, generally less than 90 mi, usually preceded ha but may occut with or during ha, does not invariably led to ha (acephalgic migraine), primary mechanism is (spreading) cortical depression Mild/Mod HA:d/t trigeminal system inhibition: generally begins with qualities of tension type ha (dull, nonthrobbing, poorly localized,+/- muscle tenderness) last min to hours and has highest efficacy for treatment Mod/Severe HA=Migrainous: disinhibition spread from trigeminal to central level (cortical sentization) and migraine became allodynic pain state and abortive treatment difficult. Tx should start before central sensitization occurs IHS criteria for dx of migraine: duration 4 to 72 hours Pain (2 of 4): Unilat, throbbing, mod to severe, aggravated with activity Plus (1 of 2): NV, P/P No evidence of organic disease
Headache Migraine		2 Why convergence hypothesis is important? It explains clinical vaiability of ha pattern, inc our dx sensitivity to migraine, permits optimal tx Prodrome, Aura-Acephalgic=Electrical, Tesnsion(siunus, trigeminal disinhibition, Mild/Mod ha), Migrainous(mod/sev ha, neurovascular inflammation), IHS migraine, Intractable HA (central desensitization) muscle+vascular= migraine w/ tension features sinus+vascular= migraine w/ sinus features Migraine tx: Education Abortive Preventive Selfcare Abortive tx: Antiemetics: Dopamine receptor blocker NSAIDs: PGE1 blocker and raise sensory threshold of trigeminal afferent Opioids: inc central threshold for pain reception Ergot: eg DHE serotonin agonist Misc.: Midrin 2cap at onset can repeat 1 cap qh max 5 cap/12h Triptans: Selective 5-HT 1B agonist (prevent vasodilation) 1D agonist activity (prevent inflammatory peptide release peripherally from trigeminal nerve, inhibition of central pain transmission by the trigeminal nucleus caudalis) Sumatriptan has shot Oral: 25, 50, 100 mg Nasal: 5, 20 mg Autoinjector: 6 mg Rizatriptan highest efficacy Oral: 5, 10 mg ODT (oral disintegrating tablet) 5, 10 mg Zolmitriptan Oral: 2.5 5 mg ODT 2.5 5 mg Naratriptan Oral 1, 2.5 mg Frovatriptan long acting especially good for cataminal migraine mesntruall associated migraine Oral 2.5 mg, faster acting Triptans in practice: - Oral meds do work at any time but they work better earlier in the migraine process - ODTs are convenient in some settings but they are absorbed in the GI system - Nasal spray can help children and patients with nausea but taste can be a limitation - Injection is highly effective but usually reserved for rapid onset ha and for rescue if oral tx fails - We have to try 3 different triptans (after an adequate trial) before we call it triptan resistant - Use can use another oral tablet after 2 hours with max of 2 times in a day and not to use it everyday - Give pt 3 d
Headache Migraine		3 - Efficacy can be augmented by combination with another agent (with a different mechanism) Triptan + NSAIDs or Triptan + Antidopmainergics - Recurrence of ha (same ha returning before 24 hours) can be reduced by achieving pain-free response. Rescue therapy for severe intractable migraine (d/t central sensitization): - SQ Sumatriptan 6 mg - DHE IM/IV 0.5 or 1 mg or Raskin protocol - Phenothiazines eg procholperazine 10 mg IV/IM or 25 mg PR - Valproate Na IV Depacon 500 mg over 5 minutes - Narcotics eg Demerol - Mg IV 1000 mg in Normal Saline iv slowly minimum should take 30 min - Occipital nerve blocks Post HA treatment: - Make sure we have right preventive treatment - Treat similar to prodrome: Rest, Fluids, NSAIDs
Headache Migraine		4 which triptan Ergot extract of rye fongus trigeminalnerve 5HT1D on nerve ending 5HT1B on vascular artery pain sensation inartery goes trigeminalnerve and then to trigeminal nucleus caudalis,sensory relay center and then cortex. dopamine accelerator serotonin brake for migraine. most triptans similar structure to seretonin. triptan D antagonist B agonist on vascular wall, causing vasoconstriction that's why they get CAD, contraindicated in CAD, over 40 get EKG, some may have esophageal spasm or dysphagia or neck pain Fastest RT, ST ZT ET Less Recurrence NT FT ET sumatriptan may not be used in Sulfa allergy triptan c SSRI may cause serotonin syndromes.
Headache Migraine		Cataminial migraine metoprolol 50 mg bid 5 days before last day of period naprosyn 500 mg po bid prn HA compazine 5 mg po tid prn NV drop in estrogen cause Migraine Estradiol 0.05 mg qd or Estroderm TTS 50 mcg to change twice a week Should take one day before HA onset (usually 3-4 days before mense ) up to 3 days after start of bleeding. Frova 2.5 qd or bid for 6 days transcutaneus estradiol 100 to 150 ug qod for 6 days naratriptan 1 mg bid for 6 days with supplemental 2.5 mg for breakthrough pain
Headache Migraine		Chronic daily headache CDH >15 days and >4 hours/day untreated prevalence about 4% 4 forms- transformed migraine, chronic tension ha, new daily persistant ha, hemicrania continua often associated with analgesic abuse. simple analgesic, ergotamine compounds, opioids, triptans
Headache Migraine		Cluster HA Abortive tx High efficacy - O2 7-10 lit/min for 15 minutes - Imitrex SQ 6 mg - IV/IM/SQ dihydroergotamine mesylate 0.5-1 mg Limited efficacy - Zolmitriptan 5-10 mg PO - Ergotamine 1-2 mg PO or PRectal - intranasal lidocaine - Triptans eg Imitrex, Zomig, Ergots, migranal - Lidocaine intranasal - Capsaicine - Stetoids/lidocaine blockade of greater occipital nerve - Radiofrequency or glycerol rhizotomy - Gamma knife of Gaserian ganglion - Microvascular decompression
Headache Migraine		Cluster HA why many cluster HA patients have Homers syndrome. It may be d/t some cavernous carotid arterial changes with compression of sympathetic fibers. Alternatively, since the generator for cluster HA may be in the hypothalamus, the lesion in the sympathetic system may be at the first order neuron. How you treat this patient? Cluster HA should be treated as an emergency since the pain is so severe as to lead some patients to suicide. Prednisone 60-80 mg daily for several days with tapering over the next week is a very effective treatment. As HAs may return after lowering the prednisone dosage, many will add a prophylactic meds such as verapamil or lithium until the HA cycle is clearly at an end. Acute treatment of cluster HAs is difficult because since absorption of analgesic medication is often too slow. Oxygen inhalation with a facemask at approximately 8 liters/mm is often dramatically effective. Injectable sumatriptan can be very effective as well. - cluster can be 6-8 w - eaely morning REM sleep trigger CHA, 1-3 epiosode/day, last 1-3 h, onset vey quick and stops suddenly diff from migraine, they have to move, more supraorbital, temporal - suicide HA, it is spontaneous or triggered by etoh, stress, hypoxia - autonomic activation, sympathic horner, parasympathic causing lacrimation, rhinorhea etc Tx- - O2 up to 8 lit/min 15 min Horton HA - Steroids Solumedrol iv and then 60 mg taper - CaCB verapamil 240 mg sustained release qd can go up to 900 mg/day - Ergotamine, DHE 1 mg bid contra in CAD, CVA, HTN, Ergotism (constant vasospasm ssp in limbs) - Li carbonate esp for chronic form of cluster HA, 300 mg/d titrate weekly up to 900 mg po qd, monitor level very potential for side effects, tremor, sz, dysrhytmia, hypothyroidism - VPA 250 mg bid can titrate up 250 q3days up to 500 mg bid - Topomax 50-150 mg/day max 200 bid - Neurontin 900 mg/day - Naratriptan like Frova is long acting can be used for prophylaxis in this case.
Headache Migraine		DDx of short lasting HA Or Trigeminal-Autonomic Cephalgias - cluster ha 15-180 min - paroxysmal hemicrania 2-45 min (can change to hemicrania continua) - hypnic ha 15-30 min - SUNCT 5-240 seconds - idiopathic stabbing ha <30 sec - trigeminal neuralgia <1 sec - cluster ha orbital - paroxysmal hemicrania orbital - hypnic ha generalized - SUNCT orbital - idiopathic stabbing ha anywhere - trigeminal neuralgia v2-v3 every type of ha more common in f x cluster, SUNCT and hypnic HA Triggers - cluster ha etoh, nitrates - paroxysmal hemicrania etoh, nitrates - hypnic ha sleep in elderly - SUNCT cutaneous - idiopathic stabbing ha none - trigeminal neuralgia cotaneous tx - cluster ha o2-verapamil - paroxysmal hemicrania indocin - hypnic ha Li200-600 qhs, Verapamil 160 mg qhs, indocin - SUNCT can try everything triptans, tegretol, baclofen, verapamil, steroids, Li, Elavil etc x indocin, lamictal, neurontin and topomax recently were efficacious. - idiopathic stabbing ha indocin - trigeminal neuralgia <1 sec DDx- trigeminal neuralgia vs idiopathic stabbing ha DDx- ha with autonomic activation- Cluster ha, Paroxysmal hemicrania ,SUNCT
Headache Migraine		Hydrocephalus Types: - Obstructive or non communicating in Foramen of Monro, Third V, Aqueduct of Sylvius, 4th v, Foramina of Luschka and Formen of Magendie - Commuinicating HCP - NPH - HCP ex Vacuo Etio: - Head trauma or birth trauma - SAH - Meningoncephalitis, esp basilar meningitis syphilis, TB, Sarcoidosis - Occult brain tumors - Genetic x linked or sec to Dady Walker, ACM, Congenital abscence of archnoid villi (difficult to confirm) - Mass lesion archnoid cyst of post fossa or any SOL in cereberum or cerebellum Commuinicating HCP specific etiologies - Oversecretion chroid plexus papilloma CSF>1cc/min normal is about 1/3 cc/min or 500 cc/day - Impaired venus return lat sinus thrombosis in Otitic HCP - Impaired absorption: Congenital abscence of archnoid villi, CSF hyperviscosity Pr>500 mg/dl (Polyneurtis or spinal cord tumors) S & S: - in kids skull enlargement, imapaired upward or lat gaze, exophthalmus, sluggish pupillary reaction, abcense of visual fixation or response to visual threat, Sz - in adults HA, Papilledema, 4 or 6th palsy, Lethargy Ataxia or weakness, Sz less common - in Olds dementia, magnetic gait or retropulsed posture, urinary incontinence Dx: - US, CT, MRI (inc perivent signal in T2) - MRI with cineflow also good for ACMalformation - or Cisternogram or Post LP improvement in walking memory in NPH (eg check opening closing pressure, large volume tap 30 cc at least) danger- if acute HCP check ICP monitor before doing LP while on ICP monitor need to be on Ancep 1 gram q 8h and max of 5 days can be with ICP monitor or EVD. (Pseudotumor cause small ventricles or slit like ventricles) Can be arrested HCP in Kids 15% risk of Mental retardation and Sz Tx; Shunt (Ventriculoperitoneal or pleural) (risk of infection especially first few weeks of Shunt placements or shunt failure, disconection or Sz)
Headache Migraine		low CSF pressure HA and intracranial hypotension etio - spontanous leak, dura tear - post LP, dx, anesthesia - postoperative craniotomy or spinal surgery - postraumatic csf rhinorrhea, dural tear, nerve root avulsion, occult pitutary tumor - systemic illness eg dehydration, dm coma, hyperpnea, uremia, sepsis dx - dec opening pressure (<7 cm) - csf pleocytosis, mild inc pr - meningial enhancement in MRI - less common enlarged sella, slit ventricles, tight basilar cisterns, engorged venus sinuses, crowding of post fossa, descent of cerebellar tonsils mimicking ACMalformation (sagging brain) - Radioisotope nuclear scan, cisternogram Tx - bed rest, abdominal binders - caffeine, theophylline - ACTH, CSs - Epidural interventions (blood patch, NaCl, Dextran patch, Fibrin glue, morphine sulfate) - Surgical repair of leak
Headache Migraine		migraine and epilepsy linked b/o - both familial, paroxysmal and associated c transient neuro disturbances - incidence of epilepsy inc in migraine sufferers and vice versa - ha can be sz manifestation - abn EEG common in both like basilar migraine and benign occipital epilepsy both have ha, sz epileptiform discharge
Headache Migraine		Post LP HA positional, but if CSF pressure very low they may HA all the time. - Lumbar blood patch - MRI of cervical spine c cineflow - Caffeine benzoate 500 mg/1 lit NS TRO 6h not later after 6 pm - strong coffee not later after 6 pm - lay flat to minimize symptoms
Headache Migraine		Pseudotumor cerebri 1 idiopathic intracranial HTN worsen during pregnancy but healthy baby usually develop after 14 w disappear after 1-3 months, obese or gain weight during pregnancy - check VF, VA, BSpot - check MRV and if abn Angio eg L transvers sinus thrombosis then pt need 3-6 m AC and repeat studies. - if CSF>35 is severe - moderation in diet to prevent weight gain - if vision loss prednisone or dexa x 2 weeks - 4-6 LP can be done sometimes weekly before considering optic nerve fenestration or lumboperitoneal shunt - Acetazolomide 250 mg qd or bid start and inc by 250 mg qw to max 500 bid , should start after20w gestation - Lortab or Tylenol3 - pain control during delivery to dec acute rise in CSF pressure - pt c pseudotumor frequently have migraine but can diff it, that's my pressure HA, the other my episodic migraine HA Causes - obesity - ID eg OM, Mastoiditis, sinusitis, varicella - head trauma - inc vit A, or other fat soluable vitamins - Cystic fbrosis - poisoning eg herbicides, insectisides - dec PTH - dural venus thrombosis (chicken or egg story) - R heart failure - APL synd, SLE, Sarcoidosis - HTN - DRUGS abx tetr, mino, genta, pcn, nalidixic acid, ofloxacin, nitrofurantoin, SMX OCP oral, implant CSs use or withdrawal triamcinolone Thyroid hormones AEDs DPH, VPA IS eg cyclosporin NSAIDs ketoprofen, Indocin Others Amiodarone, Li, NTG, Sinemet, Bromide, Fentanyl, Halothane, rGH, Provera rest LP csf>25 cm h2o DDx - meningoencephalitis - venus sinus thrombosiscerebral abcess or SOL - Optic neuritis - Lyme disease - SAH - migraine
Headache Migraine		pseudotumor cerebri 2 Tx - check VF, VA, enlarged BSpot if abn ophthalmology consult - check MRV and if abn Angio eg L transvers sinus thrombosis then pt need 3-6 m AC and repeat studies. - if CSF>35 is severe - moderation in diet to prevent weight gain, promote weight loss - if vision loss prednisone or dexa x 2 weeks pred A 40-60mg/d C1-2mg/kg/d qd dexa A 4mg po q6h C 0.25-0.5 mg/kg/d in 2-4 divided dose - 4-6 LP can be done sometimes weekly before considering optic nerve fenestration or lumboperitoneal shunt - Acetazolomide 250 mg qd or bid start and inc by 250 mg qw to max 500 bid , should start after20w gestation A 250-1500/d C 10mg/kg/d - Topomax, Depakote - Lasix A 20-80 mg/d C 1mg/kg/d - Manitol 1-2 g/kg/ IV over10-20 minutes then 0.25 g/kg q6-8h - Lortab or Tylenol3 - pain control during delivery to dec acute rise in CSF pressure - pt c pseudotumor frequently have migraine but can diff it, that's my pressure HA, the other my episodic migraine HA
Headache Migraine		Status migrianosous severe migraine with total disability lasting > 3 days migraine could be intermittent, chronic, status migranosous tx - Raskin - IV Depacon 250 over 5 min or 500 over half hour max 750-1000/day - Droperidol 1 mg IV - Thorazine 25-50 mg IV watch hypotension Intravenous fluids and electrolyte replacement as indicated Sumatriptan 6 mg SC Intractable migraine may respond to metoclopromide 10 mg IV and DHE 0.5 mg to 1.0 mg (depending upon response) IV every 8 hours for 2 to 3 days as indicated. DHE and triptans should not be used within 24 hours of each other. Prochlorperazine 5 to 10 mg IV Ketorolac 30 to 60 mg IM Corticosteroids (single or rapidly tapering dose of prednisone starting at 80 mg a day or dexamethasone 6 mg PO or IV) Parenteral narcotics such as meperidine with promethazine Valproate sodium 500 mg diluted in 50 ml of saline administered IV over 5 to 10 minutes: can be repeated every 8 hours for 2 days Droperidol (2.5 mg IM or IV) Magnesium sulfate 1 g IV over 15 minutes
Headache Migraine		Trigeminal neuroalgia DDx cluster HA, SUNCT, paroxysmal hemicrania, MS, dolichoectasia of BA, tumors NCS impaired blink reflex Etio mostly primary idiopathic secondary- MS, Vascular compression, tumors(shwanoma,ependymoma), trauma, dental procedures, infectious Zooster W/U MRI of brain c 5th nerve focus LP if suspect MS ORL/Dental consult NCS Blink reflex Tx *carbamazepine titrate slowly b/o autoinduction 400-1200 mg/d check for cbc na lfts SE ataxia, diplopia, NV, sedation *Oxcarbazepine second line in intractable causes more hyponatremia and OCP failure *Baclofen 10-30 tid taper b/o risk of sz *Gabapentin *phenytoin variable efficacy *Lamictal promising *Lidocaine patch *Botox *Surgery- risk corneal ulcer anesthesia, anesthesia delarosa, jaw weakness -Etoh, glycerin injection, -TENS, -microvascular decomp Jannetta procedure displace artery by Teflon cushion or glue to somewhere else complication contralateral paresis cerebellar injury, chemical meningitis, 5 or 7 paresis same side (pre op BAER). -Gamma knife 60-70% good result in 5 years Glossopharyngeal neuralgia- lancinating throat pain that radiate to tongue, tx c CBZ,DPH, microvascular decompression or nerve root section
Infection		Amebic infections - Acanthamoeba fresh water, granulomatous encephalitis in immunodef - Entamoeba hep brain abscess in immunocom - Negleria fresh water in swimmer fulminant mencephalitis - Plasmodium and Trypanosoma produce me s abscess
Infection		Aseptic meningitis - d/t meds NSAIDs, AEDs, Sulfa - d/t CVD eg SLE - mild viral meningitis
Infection		CSF The CSF findings of pressure elevation, hypoglycorrhachia, mildly elevated protein, and mononuclear pleocytosis are most consistent with chronic meningitis due to fungi or mycobacteria. The reduced glucose is especially helpful in distinguishing viral infections such as herpes encephalitis and progressive multifocal leukoencephalopathy from chronic fungal or tuberculous meningitis. high pr no cell- GBS, Froyn synd Spinal block, DM, recovering stage of GBS, very old age >100 pr not old age high pr and cells in polio, HIV Oligoclonal band- SSPE, Sarcoidosis, neurodyphilis, MS, ADEM
Infection		Encephalitis - Check for Herpes PCR (if first lp neg second week repeat lp) - Serum IgM, Ig G for Herpes, CMV, EBV - West nile virus - HIV, Enterovirus, Echo, Coxsacki, arbovirus - California, St. Luis, Western/Eastern equine virus - Rubella, Rubeola - Tick panel (Borrelia, Ricketsia, Ehrlichia) - Syphilis - Leptospirosis
Infection		NeuroSyphilis neurosyphilis 4 forms meningovascular general paresis of insane tabes dorsalis cranial neuropathy, basilar meningitis RPR reactive FTA reactive titer VDRL and RPR with tx decrease or even s tx become negative eventually. RPR been used to check response to treatment. MHA and FTA remain high even after treatment. CSF VDRL positive worthy neg does not r/o it, esp if pt have high pr and lymphocytosis CSF FTA neg worthy may became false positive upon blood contamination Tx PCN G 4 million unit q4h for 3-5 weeks False positive RPR - CVD, Pregnancy, old ages, drug addiction, pt vaccinated against hep B or influenza or other numerous nonsyphilitic infectious inflammatory states
Infection		Prion disease 80-90% sporadic, familial, iatrogenic, vCJD Prion syndromes - Kuru Guaina - GGS familial ataxia, <55, late dementia, amyloid plaque - FFI familial fatal insomnia, gliosis, <55 - CJD transplant - vCJD from BSE not activated by formalin so neuropath specimen or surfaces should be cleaned by 1-2 N NaOH or high degree autoclav CJD defenite probable- pro dementia<2, myoclonus, ataxia, pyramidal/extrapyramidal/psychiatric/painful sensory symptoms AND EEG change . sl (60% sensitivity), Pr 14-3-3 in CSF possible- abscence of EEG changes
Infection	Infection	Tuberculosis CNS even 1-5 bacteria deposited in alveoli can cause infection. primary infection asymptomatic or nonspecific pneumonitis then become dormant and then reactivated somewhere in body including CNS. Miliary is hematogenous spread that all lesions same age synchronously. CNS TB case fatality rate 15-40% - Meningitis - Tuberculoma - Archnoiditis in spinal cord HIV inc the risk 3 times one in 3 HIV pt may have mycobacterial infection Radiology - cerebral edema, periventricular edema in PD - Tuberculoma - Basilar meningial enhancement - Cold abcess epidural abcess with destruction of bones - HCP is very common complication Dx PPD, AFB Smear not very sensitive PCR, ELISA , Adenosin deaminase Serial LP QD for 3 days and send for Zeil-Nilson stain, if lymphocytosis and clinical suspicious start tx Tx 6 months regimn 4 months IREP 2 months IR - Steroids dec inflammatory response, dec ICP Dexamethasone for inc ICP
Infection	Y	Cysti cercosis eating undercooked pork cause tapeworm infection which is diferent from neurocysticercosis caused by eating ova. 82% paranchymal 15% meningial 3% ventricular causing HA, HCP, Sz Tx - Albendazole 15 mg/kg/d for 14 days - Dexa (for multiple cyst) 8.4 mg/day in 4 divided dose for 7 days - Dilantin for sz for 2 years or cysts gone - Repeat neuroimaging in 2 years Tx of meningial or ventricular forms - CSF shunt for HCP - Albendazole and Steroids for years - Cyst removal of cysts if possible Prevention - Avoid eating ova ( through raw veg, fruits, handshake) risk for occ visitors maybe low - Stool ova and parasite should be checked in entire family if tapeworm found Praziquantol 20 mg/kg once for all family member - Cook or freeze (-20 degree) all pork to prevent tapeworm infection - As high as 15% of mexican worker or farmer may have tapeworm infection.
Movement disorders		Basal Ganglia Disorders gp i and gp e although close to each fx different. BG outflow is GPi SNc everywhere gaba x STN glutamate that cause hemibalismus. glutamate is bad for body b/o neurodamage in PD direct circuit underactive indirect hyperactive GPi destruction for tremor dyskinesia or high frequency DBS (inc refractory peroid ofneurons) then better option would be DBS in STN STN better than GPi for DBS MPP + inhibit on complex I of mitochondria Rotenone organic pesticide obtained from tree can act similar dementia puligistica and post encephalitis pd and psp don't have lewy body only tangles lewybody in pd (x pd d/t parkin gene)and lewy body dementia. The subthalamic nucleus modulates (suppresses) ispilateral basal ganglionic activity, which in turn modulates cortical motor outflow to the contralateral effector muscles. In general, basal ganglionic lesions have contralateral motoric effects. In the case of the subthalamic nucleus, contralateral hemiballismus – high amplitude flinging appendicular movements – ensues. A right subthalamic infarct leads to left sided hemiballismus. STN of luys infarct usually d/t stroke methanol cause bil hemorrhagic necrosis of lat. putamen and claustrum. CO cause bil hemorrhagic necrosis of GP.
Movement disorders		Botox injection Each bottle has 100 unit to mix with 1.1 cc solvent NaCl 0.9% Torticolis ipsilateral splenius capitus 40-60 U contralat SCM 50-60 U inject higher up, lower injection cause dysphagia Levator scapulae 15 u Trapezius 15 u Scalene Belpharospasm 5-5-5 in 3 lateral around eye 1.25 in lat. upper lid Hemifascial spasm - upper lid med and lat 2.5 - lower lid lat 2.5 - canthus 2.5 - zygomatic 2.5 adduc shoulder pec 25 25 elbow flex brachialis not biceps since it is also secondary supinator brachioradialis wrist flex fcu fcr fdp fds thumb in oppenens Gebauer ethyl chloride Teca Sapphire 2 flex toes flexor mid sole 50 u flexor halu longus 50 gm solus gas pass the knee soleus does not extensor hall for hitch hiker toe few cm above maleus in front and middle writer cramp 5 10 u eip opp fcr fdp fds rectus abdominis spine retus 200 paraspinal 100 each side parotid 20-30 u 1 cm below targus and ear atropin scopolamine patch glycopyrolaate subligual usee if atropin benzotropin trihexiphenidyl each myobloc 50 equal 1 unit Botox ambu needle are better for skin preparation
Movement disorders		Botox Sialorrhea parotid 20-30 u 1 cm below targus and ear atropin scopolamine patch glycopyrolaate subligual usee if atropin benzotropin trihexiphenidyl radiation and surgical removal you have to inject both parotid gland secretion more with food submandibular at rest parotid 5-75 SM 5-30 u 1000 250 myobloc pt 2500 myobloc each parotid 250 each SM depth of gland 5.2- 5.3 mm not more than 8 mm deep parotid 12.5 SM 12.5 each side parotid 2 injections SM 1 injec half way between corner of mouth to targus toward ear 2 injections SM half way between mentalis and mandible angle 1 cm inside Myobloc has more selectivity for parasympathic innervation myobloc for drooling pd pt who need bont treatment parotid secretion thicker SM serous
Movement disorders		Chorea - Gravidarum - SLE, APL - Drugs eg Neuroleptics - Huntington - Inc FT4 - Polycytemia - Acanthocytosis - Stroke - MS - Sydenham chorea most common cause of chorea in kids d/t group A beta hem streptococcus ss chorea, emotional liability, dysartheria, hypotonia, OCD dx by inc antistreptolysin O titer Tx dopamine depleter klonopin neuroleptics
Movement disorders		Huntington CAG repeat auto dominant +FHx Genetic test Haldol Inderal good for impulsive behavior but inc risk of depression Zoloft for depression Bladder problems fre urgency Detrol or Ditropan
Movement disorders		Myoclonus 1 cortical, subcortical, reticular (gillian mallort triangle), spinal etiologic classification - physiologic hypnic (sleep jerk), hiccup - c sz no encephalopathy eg epilepsy synd (Epilepsia partialis continua, JME, Lennox Gastaut, infantile spasm, photosensitive myoclonus, myoclonus absence, idiopathic) - c static or progressive encephalopathy eg dementia (alz, cbgd, cjd), metabolic (hepatic, uremia, hyperthyroidism etc), post hypoxic/ischemic encephalopathy (lance adams) - subcortical BD disorders, Storage disorders - spinal cord injury, myelopathy, ataxia-telengectasia, friedrich ataxia - idiopathic essential - meds eg serotonin synd, TCA, DPH, PCN, Demerol/morphin, Li, L dopa Metabolic- RF,HF astrexis Posthypoxic/ischemic after MI arrest Paraneoplastic ovar opsoclonus myoclonus Spinal myoclonus eg AIDS Myoclonus/cervical dystonia Myoclonic epilepsy w/u - EEG - CMP, LFT, NH4 - TSH, FT4 - MRI of brain Tx clonazepam 0.25-0.5-1 mg tid Valium drip Valproic acid Piracetam Primidone Keppra
Movement disorders		Myoclonus 2 palatal myoclonus- lesion in Guillian Mollaret triangle (central tegmental tract-red nucleus, inf olivary nucleus, contralat dentate nucleus), also cause rubral tremor - posthypoxic (Lance Adams synd) - essential or idiopathic - epileptic - d/t meds eg serotonin synd, TCA,DPH, PCN, Demerol/morphin, Li, L dopa - multiorgan failure - Dementia Alz, CJD - BG disorders, CGBD - Spinal myoclonus after any spinal lesion eg SCI etc. Tx - remove drug or etiology - klonopin 1 mg/day or more - depakote for epileptic, essential, posthypoxic or myoclonus associated c Huntington - 5 OH Tryptophan start 100 mg increment of 200 mg q3days up to 1000 mg or more 4000 mg, carbidopa 75-150 mg/day can be given to prevent extracerebral conversion of 5-OH Tryptophan to serotonin. this regimen esp good for posthypoxic or epileptic myoclonus - anecdotally eg etoh, estrogens, tetrabenazine, artane, benztropine, botox for oculopalatal myoclonus
Movement disorders		Parkinson plus *PSP *Lewy body dementia- visual hallucination, fluctuating MS, sensitivity to neuroleptic, resistant to L Dopa * * * *
Movement disorders		PD hallucination/psychosis - Serequel 25 mg qhs - dc or minimize sedatives/narcotics ativan vistril demerol.... - make sure not d/t organic causes, check cbc cmp ua dc foley - enforce day/night cycles, during the day window open and keep pt active during dar, recreational therapy, during nights no nursing interruption For tardive dyskinesia- can use tetrbenezin 25 mg bid up to 50 mg bid. may cause depression, is dopamin depleter. Tardive dyskinesia complex repetitive neck or buccolingual movement in 25 per of pt on antipsychotic or tf per who discontinue them (emergent tardive dyskinesia) Combo tx tetrabenzaine 100-150 plus 100-200 clozapine plus 6 clonazepam
Movement disorders		PSP - vertical gaze palsy downward>upward - regidity axial>exteremity - more postural instability - less dementia, mild
Movement disorders		RLS Pergolide start at 0.05 up to 0.25-0.75 be careful about cardiac valvular fibrosis Mirapex better choice Sinemet causing daytime rebound, earlier appearance of symptoms in afternoon referred to as augmentation and tolerance Oxycodone addictive, but very effective last resort not related to analgesic effect BNZD daytime somnolence, addictive Gabapentin maybe helpful Secondary RLS - IDA check ferritin if low supplement (low CNS iron storage dec CSF ferritin inc transferin) esp if serum ferritin <50 and iron sat <16 iron not efficasious if no IDA iron is cofactor for tyrosine hydroxylase for dopamine synthesis - RF - Pregnancy 3 trimester - Neuropathy low back syndrome - Meds TCA, SSRI questionable, DA receptor blockers antihistamins contrindicated in RLS Assessment of RLS - serum ferritin level - Cr, Glu, B12, FA, MCV - EMG/NCS if neuropathy suspected - PSG sleep study - 40 60 percent familial DDx - PLMD pt is not aware unlike RLS which pt is aware and give good hx commonly in sleep with regular interval - PN do w/u - Akathisia generalized inner restlessness - Muscle cramp quinin localized cramp - Arthritis
Movement disorders		Serotonin syndrome consists of a combination of mental and behavioral changes, motor hyperactivity, and autonomic lability, that occurs following use of potent serotomimetic agents alone or in combination with non-specific monoamine oxidase inhibitors (MAOIs). This syndrome can occur in patients taking various combinations of drugs, including serotonin precursors (e.g. tryptophan), serotonin reuptake inhibitors (e.g. fluoxetine, sertraline, clomipramine, imipramine, nortriptyline, trazodone), MAOIs (clorgyline, phenelzine, tranylcypromine, iproniazid). Reference: Bodner RA, Lynch T, Lewis L, et al. Serotonin syndrome. Neurology 1995;45:219-223. The serotonin syndrome displays myoclonus, fever, confusion, ataxia, movement problems, sweating, and shivering. Prominent myoclonus helps differentiate it from the neuroleptic malignant syndrome. The onset of orofacial dyskinesias with lingual and oral dystonia in a 30-year-old patient is characteristic of neuroacanthocytosis which may also be associated with chorea and peripheral polyneuropathy. ddx c whipple Causes - L tryptophan for sleep - Amphetamines - MAOI - SSRI, TCA, Ectasy - LSD, Li direct receptor stimulator - ECT can inc S in body or S synd - Triptans serotonin agonists but less likely to cause S syndrome. Triad - autonomic - motor eg myoclonus, inc reflexes - cognitive/behavioral eg hallucinations - r/o infectious metabolic causes, neuroleptics should not be on board or the dose not inc recently Labs- inc CPK, WBC, LFTs DDx- - NMS (slower in onset, temp>38, S synd sudden onset in 24h after new drug introduction plus myoclonus) - Overdosage sympathomimetics, anticholinergics - DT - Herpes infectious encephalitis - Akathisia Tx - DC drug - IVF - Klonopin - Inderal - Cyproheptadine 4 mg q2-4h up to 0.5 mg/kg/day - Benadryl 50 mg IM
Movement disorders		those persists at nights fascial hemispasm palatal myoclonus severe general dystonia paroxysmal nocturnal dystonia acute onset x hemibalimus, destractable x tic, suppressible
Movement disorders		TIC motor, vocal or sensory tic eg itching Etio: - Physiologic mannerisim in MR or Autism - Idiopathis Hereditary - Head trauma, encephalitis - Drug induced antipsychotics, Stimulants eg Amphethamines - Huntington - CO or Mn poisoning - Tourette syndrome (both motor and vocal tic present > 1year, onset before 18) associated with OCD, ADHD Treatment - Behavioral therapy - 1 alpha agonists eg clonidine, guanfacine ADHD subtype clonidine+/- methylphenidate quarter tab for 1week, half tab for 1week then quarter in am half tab in pm - 2 Atypical AS risperidone, olanzapine - 3 traditional Neuroleptics Haldol, pimozide - Other eg dopamine depleters, Klonopin, Botox, SSRIs for OCD
Movement disorders		Wilson’s disease is an autosomal recessive trait associated with mutations of the copper-transporting ATPase gene on chromosome 13q14.3. Clinical features are neurological (40%), hepatic(40%), and psychiatric (15%). Patients present in the second or third decade of life. Neurologic features include an akinetic-rigid syndrome resembling parkinsonism, generalized dystonia, or postural tremor with ataxia. Dysarthria and clumsiness of the hands are common presenting features. Kayser-Fleischer rings are present in virtually all patients with neurological features. Symptoms of liver disease include a history of prior or concurrent liver disease. The pathologic abnormalities are primarily in the basal ganglia, with cavitary necrosis of the putamen and caudate, in addition to cortical atrophy. The liver develops a nodular cirrhosis.In most cases Wilson’s disease can be diagnosed by measurement of the serum concentration of the copper protein, ceruloplasmin, which is often low (<20mg/dl). Serum total copper is low in many patients and urinary copper excretion is always raised. Definitive investigation is a liver biopsy with measurement of copper concentration.D-penicillamine with pyridoxine is the gold standard of treatment. Alternative therapies include trientene, zinc, tetrathiomolybdate, dimercapol, and liver transplantation. Symptomatic treatment with antiparkinsonism drugs may be of benefit. Reference: Bradley WG, Daroff RB. Fenichel GM, et al, editors. Neurology in clinical practice. 3rd ed. Boston: Butterworth-Heinemann, 2000.
Movement disorders	ET	Essential Tremor Most common adult-onset movement disorder more common than PD Partly genetic AD or Ch 2p and 3q Hand tremor (difficulty writing, eating, drinking), Head bobbing, voice changes (vocal tremor) and rarely legs Suppression by Etoh DDx: - Meds: Lithim, valproic acid, B2 agonists, theophylin, cyclosporin - Hyperthyroidism - Parkinsonism: Absence of rigidity, bradykinesia or postural instability Hand writing large macrogrphia, in parki micrographia Head nodding, in parki movements of jaw/lip/tongue - Cerebellar intention tremor: Absence of dysmetria, dysdiadochokinesia and exaggeration of tremor with intention - Physiologic tremor in mild cases - Post CVA tremor - Wilson (tremor c fascial dystonia, always below age 55, mri t2 signal changes in BG and dentate nucleus), Huntington disease - Serotoninergic syndrome/reaction like SSRI myoclonic jerks - Head tremor mostly d/t cervical dystonia, hyperthyroidism, cerebellar disorders Treatment: - B blocker e.g. Inderal up to 240 mg/day - primidone up to 750 mg/day (not very effective in fast metabolizer b/o fast metabolization to pb, its effect d/t to p metabolite) - pramipexole (Mirapex) 0.125 mg po bid or tid - clonazepam (Klonopin) 0.25 or 0.5 mg po bid - clozapine - methazolamide - glutethimide - Topomax good for essential tremor 50-200 mg - Gabapentine - Botox injection - In severe cases stereotactic thalamotomy to reduce tremor in contralateral limbs. or VIM ventrointermediate nucleus of thalamus stimulation or ablation orthostatic tremor can be part of ET, tx neurontin, klonopin
Movement disorders	Parkinsonism	DBS although called stimulator they put axon and neurons in refractory period. - in VL thalamus only for tremor - in GPi for dyskinesia - in subthalamic for regidity, hypokinesia, best option, best efficacy Poor candidate - minimal response to levodopa - dementia - untreated depression or other psych problem - uncontrolled htn or bleeding diathesis - need for MRI can not have it afterward - uncooperative during surgery or programming visits - atypical parkinsonism DBS not good for midline symptoms eg speech, dysphagia, postural instability DBS good for off time and reduce dyskinesia as well DBS reduce the need for meds by 33 percent
Movement disorders	Parkinsonism	drug induced parkinsonism - anti psychotics haldol thorazine perphenazin trifluoperazine fluphenazine thiothixene thioridazine mellaril loxapine risperidone risperidal olanzepine zyprexa - antidepressant/antipsychotic combinations perphenazine/amitriptyline - anti emetics reglan compazine - anti histamine promethazine phenergan - dopamine depletors reserpine tetrabenezine - other Li depakote buspar methyldopa Ca CB flunarizine, cinnarizine vincristine, 5 fluorouracil meperidine prozac amphotericin B procaine Tx- Amantadine is choice because it is AC, NMDA antagonist and also cause dopamine release. 100 mg bid, if debilitatd or taking other parkinson med start 100 mg qd then inc by 100 mg qw usual dose 100 bid max 400/day Sinemet doesn't work and Mirapex either because drugs eg haldol are D2 receptor blocker and Mirapex D2 agonist.
Movement disorders	Parkinsonism	PD Management Dopaminergic drugs for young pt because it may neuroprotect in elderly c MCI Ldopa mirapex better for pt with tremor, requip better for pt c cognitive impairment you should try up to 3 mg tid to call it requip failure. requip and mirapex less retroperitoneal fibrosis, bromocriptin and permax ergot compound and risk of retroperitoneal fibrosis. also reported cardiac valve fibrosis. for OH flurocortizone or midodrine for REM behavior sleep disorder Klonopin for depression/insomnia trazodone for hallucination/psychosis - Serequel 25 mg qhs to max 25 tid max dose 200-300/day for drooling trihexiphenydil but caution anticholinergics in elderly b/o risk of confusuion, glucoma, constipation, boo (b o obstruction) tx for wearing off in advanced PD - inc freq of L dopa - change standard L dopa to CR Sinemet - add entacapone - add dopamine agonist - add amantadine - add selegeline tx for dyskinesia - add amantadine - add dopamine agonist reduce dose of L dopa - eliminate selegeline - eliminate entacapone - change CR Sinemet to standard L dopa tx of psychosis reduce or eliminate - amantadine - selegeline - anticholinergics - dopamine agonists Consider adding - Serequoel 25 mg qhs - Clozapine tx can be started c AC, or amantadine for mild SS in young <50 pts for mod young pts c DAgonists for severe elderly c L dopa new neuroprotective agents for PD tx- vit E, Coenzyme Q10, Rasageline (1-2 mg/day) or selegeline selegeline for fatigue sleepiness Anticholinergic for tremor Amantadine for tremor good anticholinergic, dopamin agonist and NMDA Agonist Sinemet for elderly pt and c cognitive deficits, if used in young people cause dyskinesia the younger you are the worse you can get DA no interaction with dietry pr, longer half life, less risk of dyskinesia, possible neuroprotective effect, risk for sleepiness one step before narcolepsy, use sleep screening or use Provigil. DBS
Movement disorders	Parkinsonism	PD Sleep problems - insomnia RLS BNZ,dopa, opioid, depression TCA, med SE, dyskinesia (reduce dopminergic drug or add hypnotic) - hypersomnia ask about their night sleep, switch dopa agonist, or reduce the dose slightly. - excessive nocturnal motor activity - hallucinations/behavioral problems EDSleepiness in PD ask about their night sleep, switch dopa agonist, or reduce the dose slightly. can use caffeine, bupropion Wellbutrin, modafinil 100-200/day. REM Behavior Disorder tx - safety measurement - clonazepam 0.25-0.5 mg - melatonin 3-12 mg - neuroleptics (Serequel) - gabapentin works for everything x epilepsy RBD vs Sundowning less than 30 min >30 mostly in bed mostly wandering appears sleepy dreaming vs awake/confused PSG REM sleep s atonia vs awake rhythm c excessive slow activity most RBD have Lewy body dementia or MSA not PD PLMSleep - c RLS - c Narcolepsy,OSA, MSA, LBD, PD, RBD RLS is subcategory of PLMS MSA they can have paradoxical movement of vocal cord and have sudden death at sleep.
Movement disorders	Parkinsonism	PD genetic-alpha synuclein, parkin, tau pr ,uch-lh park 1to 8 gene parkin gene produce ubiquitin ligase and malfunction and accumulation of alpha synuclein PD is a synucleopathy dementia puligistica don't have Lewy body like MPP+ induced parkinsonism. in dementia puligistica they have tangles like ALZ. MPP+ cause parki through inhibition of complex I. same as Rotenone brain stimulator use high frequency and actually destruct STN GPi good for tremor dyskinesia, VL Thalamus stimulation good for tremor only (board q) Pallidotomy Fetal cell transplant Eye movement ocular bubing in icu pt bad prognosis in thalamic lesions in pvegstate pt can have pursuit occipital movement saccadic eye movement in frontal eye feild optokinetic nystagmus with strip drum they should have downward saccad in PSP they loose it Opsuclonus myoclonus of eye new agents fo PD tx- vit E, Coenzyme Q10, Rasageline GPi outflow teact in BG circuitary
MS		ADEM postinfectious demyelination can happen with or after viral illnesses and persumed to be immune mediated. RFs- viral illnesses (measles), bacterial infection, vaccination (MMR, Rabies), inc incidence in immunocompromised pt on CT or HIV positive Demyelination eg GBS Brachial or Lumbar plexopathy transverse myelitis acute cerebellar ataxia optic neuritis ADEM Bell's palsy SS lethargy, weakness, HA, NV FND, Sz, Coma at the other end of spectrum Mortality highest in first week CSF- inc Pr, Lymph pleocytosis MRI wm changes r/o ADLeukodystrophy in boys ddx c MS, polysymptomatic MS monosymptomatic, preceding illness, AEDM involve more basal ganglia thalamus as well as optic nerves, MRI lesions all enhaced c GAD same time and in MS CSF Pr close to normal. W/U- May need to get MRI of spine repeat LP if not get better and if severe sec ICP, tx of infection, check for herpes PCR, EBV, bartonella Tx- CS or plasmapheresis MP 400mg/m2 for 3 days (IV over 8 hours) then 7 days of Prednisone 2 mg/kg/day then taper over 3-4 weeks per pt condition If suspect infection use IVIG 1gr/kg qd for 2 days Some may have recurrent ADEM, if >6 months then it would be MS. Prognosis- 50-70% recovery, 10% may develop MS, Devic etc. Postimmunization encephalopathy 3 vac type - live attenuated (MMR, Varicella, oral polio) - killed organism (pertusis sz, influenza, rabies EM or polyneuropathy, inactivated polio) - toxoids (diphteria, tetanus GBS, Brachial plexitis)
MS		MRI - Lupus - Sarcoid has meningial enhancement too - B12 def - Lymphoma corpus callosum lesion in GBM, Lymphoma, MS, Marchiava bignami - migrain, ischemic, CADASIL depends of cut 3 mm ideal is better than usual 10 mm GAD should be 5-10 min time before scan MS also involve U fibers mainly in frontal problem memory problem d/t lesions in frontal or thalamic for MS PD>T2>FLAIR sequences is better brain parancymal fraction= BPV/BV most accurate c disability and cognitive decline mri criteria 3 of 4 one gad or more than 9 lesion one infratentorial or spinal cord one juxtacortical more than 3 T2 lesions time criteria 3 months or 30 days or anytime new T2 lesions if more than 3 T2 lesion there is more than 80 percent chance to develop MS in 7 or 10 years
MS		MS DDx Lyme CSF picture Lyme MS WBC: Inc, L Pleocytosis Normal Lyme Ab: +++ + in 24% IgG index: Normal Inc MBP: Absent Present Oligo Band: + + Lyme CSF in 38 patients: WBC 166 (15-700) Lymph93% (40-100) Glu 49 (33-61) Pr 79 (8-400) IgG index 0.18 (0.44-0.9) Oligoclonal Band Present MBP Absent VDRL Absent
MS		MS DDx VASCULAR - Vasculitis eg PAN, SLE, Primary CNS Angitis, IVDA - HTN PVWM changes - CADASIL, MELAS INFECTIONS - HIV, PML, HTLV1 test ab - Lyme ab titer - Meningovascular syphilis RPR METABOLIC - B12 def. eg. subacute combined degeneration - Leukodystrophy check VLCFatty acid - Mithochondrial disorder eg Leber optic atrophy check serum CSF lactic acid, muscle biopsy, mitochon DNA analysis, MELAS, Leigh disease (subacute necrotizing encephalomyelopathy) AUTOIMMUNE - SLE, APL synd check ANA, dsDNA ab or anti SM ab, Lupus anticogulant - Sjogren LO, RI ab - Behcet synd - Sarcoidosis (progressive optic atrophy, Bell palsy, myelopathy)check serum CSF ACE - CIDP TUMOR/MASS - CNS lymphoma - Arnold Chiaty malformation - Spinal tumors - Syringomyelia - Post fossa mass MS-RELATED - ADEM (less Dawson finger, less single lesion, more BG and thalamus - Optic neuritis - Transverse myelitis - Devic disease (normal brain MRI, CSF cell>50, no brainstem cerebellar or cognitive dysfunction, only spinal cord plus optic nerve, devic Ab in Mayo clinic ) - Schilder disease PVWM changes also involve the U fibers - Marburg disease is acute MS with involvement of brain stem cause death in 1 year - Balo disease, varint of MS c concentric rings of demyelination ANA APL ANCA LYME B12, CBC, MCV ESR, CRP ENA Reichlin SSa SSb Sarcoidosis ACE RPR HTLV1 CADSIL VLFA Leber optic neuropathy Novantrone if fail immunomodulation check EF through MUGA scan (nuclear ventriculogram by nuclear medicine) if EF>50% then Novantrone 12 mg/m2 IV q3months MS progression monitoring - Clinical relapse - MRI enhancing MRI lesion, no of lesion, volume of lesions - EDSS Scale During pregnancy stop all inf, copaxone, most MS pt get better during pregnancy if they get worse after delivery use IVIG or put them back on inf they should not breast feed. Apl ddx from ms in ms mri changes more corpus callusum involvement more periventricular more confluent lesion in cadasil more temporal pole involvement
MS		MS Masqurades inf make vasculitis sarcoidosis devic psychosis worse vasculitis more peripheral lesions dissemination in time space no better explanation DIS DIT NBE mri left atrial myxoma instantenous symptom onset. Red flag normal mri normal csf no eye findings no bladder symptom DDx Lyme SLE VASCULITIS SJOGREN SARCOIDOSIS Actual DDx Cadsil SCA ADLeukoDystrophy Leber optic neuropathy 100 conditions can mimic MS Psychiatric Normal Vascular,migraine,tia neuropathy spondylosis paresthesia 1866MSTREAT MD-info@nmss.org
MS	Diagnosis	CSF oligoclonal bands are seen in nearly all patients with subacute sclerosing panencephalitis and 83-94 percent of patients with definite multiple sclerosis. They are also seen in 25-50 percent of patients with neuroborreliosis, cryptococcal meningitis, Guillain-Barre syndrome, and other conditions. Many patients with neuromyelitis optica fail to have oligoclonal bands in CSF. Numerous studies of the cognitive disturbance in multiple sclerosis demonstrate the absence of classic cortical (e.g., language, cognition, visuospatial, memory) impairments but clearly show a slowing of information processing. Postinfectious disorders - GBS - Brachial plexus neuritis - Optic neuritis - ADEM - Post infectious Cerebellitis Brachial plexus neuritis- Parsonage Turner synd, develops suddenly, may last for weeks, shoulder pain inc c shoulder arm movement but not c neck movement or Valsalva In neuromyelitis optica, women are affected up to four times more often than men and the clinical course of the disease is frequently rapidly progressive. Devic disease is much more common in Asia, with up to 8% of multiple sclerosis cases in Japan being of the Devic type. Oligoclonal bands are absent from the CSF in most cases. The presence of necrosis in spinal cord virtually defines the entity. Significant keys to pathogenesis in multiple sclerosis may be associated with the topographic features of demyelinative plaques. Older plaques tend to be sharply, not poorly, demarcated from surrounding brain. In two thirds of cases, spinal cord, cerebrum, and optic nerves are equally involved, with sparing of one or another of these regions in less than 15% of autopsied patients. Gray matter, including cerebral cortex, is not spared even though the largest or most grossly visible plaques are in deep white matter. Plaques extend along veins, not arteries, in finger-like projections called Dawson's fingers. Subpial plaques are classically wedge-shaped, with a broad base near CSF pathways.
MS	Diagnosis	INO or MLF Syndrome MLF carries fibers from vestibular nuclei to CN III, IV, VI synd c/o - medial rectus paresis on attempted lateral gaze - intact convergence diagnostically important - mono ocular horizontal nystagmus in the abducting eye Etio- MS, Stroke, other demyelinating lesions ADEM, tumors, infection
MS	Treatment	Complications tx FATIGUE amantadine 100 mg bid modafinil (helps concentration, energy, no withdrawal can take it whenever needed, Kick in in 1-2 hours), Modafinil 100 or 200 mg tab start at 50 mg qam increase by 50 mg qweek to max 600 mg/day SEs sleep disturbances, HA, jitteriness 4 aminopyridinr acts on K channels prolong action potential also helps memory and heat tolerance for weakness and fatiguibility may cause sz start 5 mg qd, increase by 5 mg qweek up to 10 mg tid SEs perioral numbness acts centrally 3,4 aminopyridine acts peripherally good for LEMS SSRI- prozac, lexapro SPASTICITY Dantrolene also act sarcoplasmic reticulum cause weakness Diazepam drowsiness Baclofen tid better because bid causes more drowsiness increment qweek 10 mg Zanaflex tizanidine tid better increment 2 mg qw or even 2week also helps bladder so you can try it before detrol-LA (causes constipation) Botox for local spasticity PAIN neurontin 600 mg tid AEDs tegretol, trileptal, lamictal BLADDER DYSYNERGIA- flomax, cardura, massage over bladder, or small batery charged massager PREGNANCY while on INF no pregnancy (risk of misscariage)no Breast Feeding (INF secretion) copaxone cautious to use estriol natural immunosuppressive that is why baby not immunogenic there is 25-30% increase risk of MS exacerbation postpartum Can use CSs prophylactic for postpartum period until restart of INF pulsetherapy one day Solumedrol 1000 mg IV q1-2 months per degree of severity sometimes can use combination therapy pulse steroids + INF
MS	Treatment	Immunomodulatory best for MS Relapse Solumedrol 1000 mg iv for 5 days or 1000 g iv 3 days then 60-50-40-30-20-10 mg taper CSs shorten/or dec severity of attack not long term disability significant relapse - dec vision>20/60 - motor relapse - cerebellar relapse - gait relapses MS present c - optic neuritis - spasticity/gait problem - ataxia - motor weakness plasmapheresis for those that don't response to corticosteroids or DMD. immunomodulatory reduce relapse 33% and secondary outcome dec of t2 mri lesions. they have to be one drung long enough and committed. if fail immunomodulatory im plus azathioprin, mycophenolate, methotrexate, cytoxan rescue therapy mitoxanthrone clinically isolated synd. if high T2 burden, gad enhancing, black hole if patient fail change im to copaxone or vice versa add DMAgent aza, myco, metho or add mitoxanthrone for secondary progressive methotroxate or cytoxan pulse therapy knly for <40 years. Mitoxantrone 12 mg/m2 monthly x 3 then q3month for 8 dose at least 1 year of immunomodulatory tx should be tried before adding DMDrugs if mitoxantrone completed then add CSs and/or Imuran to INF Rebif 33% Avonex37% reduction in disability, Betaseron 29% Copaxone 12% Rebif vs Betaserone more effective less side effect flu like symptoms more in first 8-12 week, can use NSAIDs or small dose prednisone 5-10 mg one dose at time of shot also Can start Avonex 1/4 or 1/2 usual dose and increase by 1/4 dose check CBC, CMP, LFTs, TFTs , B12 Testosterone for decrease libido use cream or shot IVIG used postpartum when can not tolerate pulse therapy or they have major steroids side effects or they failed IV steroids or if pt have very high IgG index INF failure monthly solumedrol use imuran cellcept next use monthly cytoxan (in woman who does not want to become pregnant) next use IVIG Plasmapheresis mitoxantrone no use too cardiotoxic
MS	Treatment	Mito
MS	Treatment	MS Types RRMS Primary progressive MS (tend to male, older, different MS) Sec progressive MS progressive relapsing MS AAN Guideline on MS Tx GC- short term pulse benefit no benefit of longterm tx regular pulse tx may be useful INF B- reduce attack rate by third also dec T2 MRI lesions as well as disability progression (most important) dose-response relationship or more accurately frequencyof adm c response, NAb probably less c inf b a avonex c/t betaseron SQ may cause more NAb Cyclophosphamide- possible benefit only in younger pt c progressive MS Methotrexate- possible benefit in pt c progressiveMS Azathioprine- reduce therelapse rate Cladribine- reduce Gd enhancement but no change in attack rate or disease progression Cyclosporine- not rec b/o nephrotoxicity Mitoxantrone- reduce attack rate and disease progression, 5-12 mg/m2 usuall dose, q3months check cardiac EF while on drug IVIG- no benefit PExchange no value in tx but may be useful in severe attack of demyelination Sulfasalazine- no benefit Betaserone esp. good forMS pt c spinal involvement IV Steroids is must in optic neuritis as well as transverse myelitis or acute cerebellar ataxia, not very useful for sensory attacks, po steroid for optic neuritis worse than giving nothing and may be sued. for spinal cord injury must give 1000 mg first hour and then 1000 mg over next 23 hours it is must will reduce ASIA class demylination can happen with copper def. either cerebral demylination or like subacute combined degeneration in spinal cord Tx copper 2 mg po qd
MS	Treatment	MS chlamydia or HLA DR2 may play role in pathogenesis monosymptomatic disease then relapsing remitting then secondary progressive MRI lesions >4 mm PV or juxtacortical MS is demylinating but later on have axonal loss EVIDENCE study Rebif 44 mcg Sc tiw c/t 30mcg Avonex im qweek had less relapse (18%)or MRI lesions MS half common in aferican american associated with hla dr2 b cell autoantibody esp against mog is importnt in addition to main t cell response. PRISM PRISM4 Rebif 44 ug 3/week had less burden of disease or relapse c/t 22ug or placebo Avonex dose comparison study no diff in 22 vs 66 but ug 22x3 qweek had better response less relapse so frequency of admin more important than higher dose. SE of inf- flu like give ibuprofen naprosyn, depression, impaired LFTs , dec WBC check lft and cbc q3months NAb less in Avonex but not necessary do poorly but if they develop in high titer they may get worse. Then you can give drug holiday or switch them to Copaxone Women c MS we didn't see breast cancer some issues in MS Primary prophylaxis in high risk ind when gets pregnant shold stop inf give Copaxone DMAgents such as CS IV 5days q 4months, Neuroprotection- c NGF or glioprotective agents or dec nitric oxide or glutamate damage to CNS nitrous oxide used in dentists or NASCAR cars can block B12 and they develop subacute combined degeneration or sensory ataxia Atrophy in brain volume is more correlated with MS disability c/t no.of MRI lesions. What time do u measure Nab- when they have 2-3 relapses or severe relapses How to manage- give higher dose inf if they were on low dose, or switch to Copaxone Rebif maybe better more natural molecule, less Nab c/t Betaseron, tiw c/t qod of Betaseron Threshold for starting MS maybe >4 lesions in MRI or if they develop 2nd episode MS Types RRMS Primary progressive MS Sec progressive MS progressive relapsing MS
MS	Treatment	Tx initiation and f/u - assess disease hx and baseline relapses - rate of progression EDSS - MRI - review tx option - vit D 1200 u/day - Ca - pt make sure compliance c medications - schedule visit q 3m first y then annually - Get details of relapses affected part to have accurate est of disease progression - f/u MRI annually to monitor disease progression or show the pt improvement. MRI doesn't correlate c disease activity. new Gd, new T2 lesion, number of black holes T1 hypotense lesions, and brain atrophy will be seen in MRI. if not sure about dx f/u MRI in 3 (MDonald)-6 (practice for insurance)months advisable if MRI normal after a year less likely. if patient relapse on INF first check NAb if neg relapse within 1 year reasonable or you can increase INF dose, but if titer high change to copaxone alone or copaxone c pulse tx q month. If pt male or new lesion in spinal cord treat more aggresively. add DMD like Imuran start 25-50 mg/day titer up to max hematological criteria MCV, Lymphoid ratio. INF therapy practical points: 1- Dose escalation 25% first week, 50% 2nd, 75% of dose 3rd week then full dose 2- Inject early evening so person is sleeping when inf peaks in 8-10 hours 3- Use NSAIDs or Tylenol 1 hour or with injection or 10-20 mg prednisone weekly with Avonex 4- How to inject, Sites and Rotate sites 5- CBC c Diff, LFTs every 3 months in first year then twice a year. 6- Check TSH once a year
Neoplasms		Drop mets seeding through CSF can happen in - medulloblastoma - ependymoma - anaplastic glioma - germinoma - chroid plexus tumors
Neoplasms		Meningitis Carcinomatosis HA treatment- Steroids and external beam radiation Polyradiculopathy- Multiple cranial neuropathies
Neoplasms		Neurofibroma type I pathology neurofibroma in spinal cord and nerves, plexiform neurofibroma in plxus esp. brachial also associated with optic glioma type II path schwanoma
Neoplasms		Pituitary tumors mass effect (infarction)vs endocrine effect (mostly d/t PR, GH, ACTH, rest of them cause less endocrine effect) Prolactinoma - Brmocriptine 2.5-5 mg po tid - Cabergoline 0.5-1 mg twice a week less nausea less hypotension Acromegaly - mainly surgical tx - Somatostatin or GH or dopamine agonists for GH evaluation should measure somatomedian or IGF-1 the endproduct secreted from liver. monitoring tumor response to somatostatin analoge check GH (less reliable), IGF-1, Tumor size in MRI normalizing IGF-1 normalize lifeexpectancy of pts. GH Agonist- Pegvisomant recently approved for acromegaly cross link GH receptors Cushing's disease the pt presented c hip fx w/u - 24 h urine for cortisol - ACTH - Poor suppressibility of ACTH Cortisol by Dexamethasone - DHES level main adrenal androgen - Petroseal venous sampling, more reliabe c CRH stimulation, co firm pituitary source of ACTH - GAMMA KNIFE, PROTON beam, radiaion if surgery not possible Pituitary destruction hormonal def. most important abundant ACTH then TSH, then less important GH, PR, LH, FSH causes- trauma, infarction, infiltrative disease, hypophysitis preop evaluation- cortisol am TSH, FT4 PR IGF-1 Gonadal hormones, LH, FSH CMP, urine SG for ADH def. postoperatively you should check the same hormones after 2-3 weeks Suspect hypothalamic disease when: DI or inc prolactin but less than 200 ng/ml postoperatively check again for visual field defect. pitutary enlargement in MRI check for deficiency if there is replace and watch them for a while, if they have excess more in favor of tumors but enlargement could happen c pregnancy, hypophysitis or infiltrative disease eg sarcoidosis.
Neoplasms	Brain tumors	- Intraventricular tumors Chroid plexus papilloma Colloid cyst Ependymoma SEGA subepengiantcell astro Meningioma Neurocytoma central -Corpus callosum lesions Agenesis Demylination MS Marchiafava Bignami Butterfly lesions (GBM, Lymphoma, PML) Lipoma Common Sellar Masses Pituitary adenoma apoplxy hemorrhage lymphocytic hypophsitis Empty sella syndrome Aneurysm Mets breast Rathke's cyst Craniopharyngioma Optic glioma or hypothalamic glioma Meningioma MRI DDx of dural based mass meningioma and its mimics: Meningioma Hemangiopericytoma Solitary fibrous tumor Rosai-Dorfmann disease Granulocytr sarcoma (chloroma) Solitary dural mets DDx of a solitary mass in lumbar cistern: meningioma, schwanoma, paragaglioma of the filum, ependymoma myxopapillary Common tumors that rarely mets to brain- prostate, cervix, sarcoma in general, scc of skin Multiple Tumors in MRI- Mets Multifocal- GBM, Primary CNS Lymphoma ddx c abcess, demyelination (open ring sign to cortex) Genetic predisposition-Neurofibromatosis:neurofibroma,schwanoma,meningioma Tuberous sclerosis: sega Von Hippel-Lindau:hemaangioblastoma, renal cell carcinoma multiple masses are not always neoplastic
Neoplasms	Brain tumors	Acoustic neuroma exact name vestibular schwanoma no sex or side bias, unilateral x in NF2 which is bilateral, common in 4-5th decade S & S gradual sensorineural hearing loss esp to high frequency, unilateral tinitus, disequilibrium hypoesthesia of face d/t CN5 earliest dec corneal reflex fascial palsy may occur esp in large tumors but more present as fascial twitching CN 9-10-11 dysfx long tract signs cerebellar tonsil herniation hydrocephalus Rinne ac>bc Weber lat to normal size W/U Audiometry Brainstem-evoked response audiometry MRI c GAD can detect >1mm tumor DDx SAME, cholesteatoma, aneurysm, hemangioma, lipoma, arachnoid cyst, mets Tx observation- 6 or 12 months MRI f/u esp if no neurological deficit or compression on brainstem Surgery RT for tumor >2-3 cm
Neoplasms	Brain tumors	Brain tumors Medulloblastoma is especially prone to widespread leptomeningeal metastases. Occasionally, this can be seen with glioblastoma and ependymoma. Hemorrhagic mets lung ca small cell renal cell ca choriocarcinoma melanoma GBM may be but not multifocal nor discrete lesion has butterfly appearance Schwannoma arise from vestibular nerve but vertigo seen only in 20% of pt. most common unilat progressive hearing loss. unilat tinnitus. ifadvanced compression of facial trigeminal paresis also seen. Up to 50% of patients with dysplastic gangliocytoma of the cerebellum have the stigmata of Cowden syndrome (multiple hamartoma syndrome), which include oral mucosa fibromas, multiple trichilemmomas, hamartomatous colon polyps, thyroid neoplasms, and breast cancer. About 5% of patients with Gorlin syndrome (nevoid basal cell carcinoma syndrome) develop cerebellar medulloblastoma, particularly the desmoplastic subtype. Type 2 neurofibromatosis patients are prone to develop spinal cord ependymomas, whereas subependymal giant cell astrocytomas are characteristic of tuberous sclerosis.
Neoplasms	Brain tumors	Brain tumors: - Mets - Glial ast, oligo, ependymoma - Neurons - Menings and Chroid plexus difference between chroid and epyn epy no basement membrane chroid plexus tumors have bm. -Tumor of uncertain origin: gc, astroblastoma, chroid glioma of 3rd ventricle, cerebellar liponeurocytoma Neuronal supportive cells- emb-neuroblastoma mature-gn then gf PNS TUMORS: schwanoma, neurofibroma, perineurocytoma Glial: 1- Astrocytoma: PURE diffuse,anaplastic,gbm C SPECIFIC FEATURES pilo,pxa, dia, sega pilocytic ast, pleomorphic xantho ast, desmoplastic ifantile ast, subependymal giant cell ast 2- Oligo: oligodenroglioma, anaplastic oligodenroglioma 3- Ependymoma: Ependymoma, Subependymoma, Ana Ependymoma, Ependymoblastoma Neuronal: Neurocytoma Gangliocytoma Dysplastic gangliocytoma of cerebellum Lhermitte-Duclos Paraganglioma Mixed glial and neuronal- Ganglio glioma Desmoplastic Ganglio glioma Dysembryoplastic neuroepithelial tumor DNET Common features: infant children, mostly benign, hamartomatous features, well demarcated, Sz Markers for germ cell tumors germinoma-placental alk phos PLAP Yolk sac tumors AFP Choriocarcinoma HCG
Neoplasms	Brain tumors	Post fossa tumors in children: 1- cystic astrocytoma in cerebellar hemisphere appendicular ataxia 2- medulloblastoma in midline typically vermis causing truncal ataxia and obstructive hgdrocephalhs 3- ependymoma obs hcp 4- brain stem glioma cn dysfx in adults also consider mets
Neoplasms	Peripheral nerves	Malignant peripheral nerve sheath tumors most commonly arise in a neurofibroma, often of the plexiform type. They may also arise de novo in a normal nerve. Malignant transformation of a schwannoma or ganglioneuroma is rare. It is extremely rare to find these malignant peripheral nerve sheath tumors involving or arising from cranial nerves or cranial nerve neurofibromas.
Neoplasms	Spinal cord tumors	Spinal cord masses: Intramedullary- Myelopathy Astrocytoma, Ependymoma, Oligodendroglioma Extramedullary(intradural)- Myelopathy,Radicular pain Schwanoma, Neurofibroma, Meningioma Epidural(extradural)- Myelopathy,Radicular pain, Localized pain Meta, Myeloma/Lymphoma, Lipoma Abscess, Herniated disk 50-60% mets(prostate,lung,breast, kidney) 10-20% myeloma/lymphoma lipoma or lipomatosis complicating endogenous or iatrogenic CS excess prostate mets to vertebral body. or pedicle, pseudonormalization pattern.
Neuroanatomy		8th nerve cochlear nuclei- sup olivary nucleus-lat lemniscus- inf colliculi-med geniculatr-sup. transverse gyrus of temporal lobe
Neuroanatomy		Based on the history obtained and the deficits found on examination, develop a differential diagnosis employing the "VITAMIN DEC" mnemonic: 1. Vascular 2. Infection 3. Trauma 4. Autoimmune/Inflammatory 5. Metabolic/Toxic 6. Iatrogenic 7. Neoplastic 8. Degenerative 9. Electrical 10. Congenital/Familial
Neuroanatomy		Brain hemispheres Taste sensibility is represented in the parietal operculum (area 43) and adjacent parainsular cortex. The insular cortex receives visceral nociceptive input via the ventromedial posterior (VMPO) thalamic nucleus.
Neuroanatomy		Circumventricular organs periventricular areas s BBB that sample blood or monitor CSF and modulated by seretonin from dorsal raphe nuclei 6 center around 3rd vent & diancephalon 1- Pineal gland 2- Median eminence, infundibulum and neurohypophysis 3- Subfornical organ 4- Organum vasculosum of lamina terminalis 5- Subcommisural organ (vestigial remnant in human, x b/o has BBB) 6- Area of postrema (x b/o is paired, reason why L dopa cause NV, dopamin can not pass BBB and through here it affects CTZone)
Neuroanatomy		Embryology Neural crest derivatives - sympathetic chain need NGF - dorsal ganglia(capsule cell)need NGF - chromaffin cells - schwan cell - melanocyte axoplasmic flow bidirectional, retrograde displayed by ...., colchicine inhibit it. Microglia from mesoderm Glia Oligo Schwann Ependymal Tanycytes and neurons from ectoderm
Neuroanatomy		Herniation - subfalcine paraparesis babinski - uncal pca hemiparesis - tonsilar res depression - central everything drops in midline - upward cerebellar herniation pontine sign
Neuroanatomy		Papez circuit plars a critical role in the transfer of information from short term memory to long term memory and its emotional component. ento rhinal cortex- dentate gyrus- CA3-CA1- Subiculum-fornix-mamillar body- ant. thalamus-cingular gyrus- hippocampus damage to - basal forebrain (septum, nucleus basalis, orbitofrontal gyrus) cause Alz - dorsomedial thalamus Korsakoff - bil limbic Herpes, hypoxic encephalopathy, vascular lesion - bil amygdal Kluver-Bucy
Neuroanatomy		sympthic origin fromparaventricular nucleus of hypothalamus. most vulnerable part ofspinal cord to ischemia is T4-T6
Neuroanatomy		The anterior choroidal artery arises from the internal carotid artery distal to the origin of the posterior communicating artery. It has a long subarachnoid course, enters the inferior horn of the lateral ventricle through the choroidal fissure, and supplies the amygdaloid complex, hippocampal formation, globus pallidus, and the ventrolateral portion of the posterior limb and the entire retrolenticular portion of the internal capsule. The inferior cerebellar peduncle connects the medulla to the cerebellum and contains the dorsal spinocerebellar tract, cuneocerebellar tract, olivocerebellar tract, and the vestibulocerebellar tract. The trigeminocerebellar tract lies within the superior cerebellar peduncle and would be spared in a lesion confined to the inferior cerebellar peduncle. Unlike the relay and association nuclei of the thalamus (dorsal thalamus), the reticular nucleus (ventral thalamus) does not project to the cerebral cortex. It receives inputs from the cortex and projects to the other thalamic nuclei, and is critical for thalamocortical synchronization, particularly generation of sleep spindles. The anterior choroidal artery supplies the lateral part of the medial segment of the globus pallidus, the target of pallidotomy in patients with Parkinson's disease. The posterior communicating artery supplies the medial part of the medial segment. The chemoreceptor trigger zone is located in the area postrema. , Alexia without agraphia follows combined damage to the dominant medial occipital region and the inferior fibers of the splenium of the corpus callosum. This is in the distribution of the posterior cerebral artery. post choroid a. arises from PCA supply pineal gland, tectum, chroid plexus of third and lat ventricles. ant. choroid artery arise from MCA supply hippocampus, amygdale. recurrent artery of Hubner from ACA.
Neuroanatomy	Cranial nerves	All fascial muscles supplied by 7, x master, temporalis, med lat pterygoid, tensor veli palati, tensor tympani, ant belly of the digasteric, myelohyoid
Neuroanatomy	Cranial nerves	Facial nerve palsy - upper stroke - in Pons Millard Gubler, Foville, Brissaud - in subarachnoid or in internal auditory meatus with CN 8 palsy - before geniculate ganglion ear canal pain, dec lacrimation - before stapedius hyperacusis - before chorda tympani f weakness,loss of taste, dec salivation - in fascial canal or ouside stylomastoid only fascial weakness branch to occipitofrontalis causes weakness in raising eyebrow forms- - Bell(if complete Prednisone 1mg/kg/day for 10 days then tapered over 5 days, if incomplete Prednisone 1mg/kg/day for 5 days then tapered over 5 days, can combine Acyclovir 800 mg po five times a day if suspect Herpes), - Belpharospasm(Meige if loer face involved, Tx Botox), - Hemifascial spasm(exacerbated by alkalosis, ddx c focal sz, etio aberrant vascular loop in subarachnoid, Tx decompression, CBZ, Botox), - Fascial myokyma (benign or in MS, , Brain stem glioma,Stroke)
Neuroanatomy	Cranial nerves	The foramen ovale transmits the mandibular division of the trigeminal (V) nerve. The foramen rotundum transmits the maxillary division of the trigeminal (V) nerve. The nucleus of the tractus solitarius (NTS) contains the first central neuron for the baroreceptor afferents. Lesions involving the NTS produce fluctuating hypertension mimicking a pheochromocytoma. The following structures travel through the various foramina: foramen rotundum -maxillary nerve; foramen ovale -mandibular nerve; foramen spinosum -middle meningeal artery; foramen lacerum -internal carotid artery; jugular foramen -glossopharyngeal nerve, vagal nerve, spinal accessory nerve. The internal carotid artery would be affected by a fracture through the foramen lacerum. Derivatives of the alar plate include the cerebellum, inferior olivary complex, quadrigeminal plate and the red nucleus. Derivatives of the basal plate include motor nuclei of cranial nerves in the nucleus ambiguus that provides motor neurons to the striated muscles of the larynx and pharynx via the vagal, glosspharyngeal and accessory nerves. The rubrospinal tract is concerned with control of tone in flexor muscles. This tract arises from the red nucleus, crosses in the ventral tegmental decussation, and lies anterior to the corticospinal tract in the lateral funiculus. Nucleus Solitarious is the neuron for baroreceptors. lesion can cause fluctuating BP like pheochromocytoma
Neuroexam		DDx in neurology VITAMINS C D Vascular Infection Trauma Autoimmune Metabolic Iatrogenic Neoplastic Seizure Congenital Degenerative
Neuroexam		Jandressic maneuver increase GABA efferent discharge to muscle spindle. to enhance reflex
Neuroexam		Nystagmus defined by direction of fast component horizontal, vertical, rotational, diagonal 2 type jerk vs pendular (oscilliations of equal velocity) localization- vestibular system including end organs and vestibular nerve, brainstem, cerebellum flocculus (peripheral causes can be suppressed by fixation ) causes drugs eg AEDs, barbiturates, tranquilizers, etoh, phenotiazines, Li or OP toxicity vascular, neoplastic and demyelinating lesion of brainstem floccunodular lesion of cerebellum congenital nys gaze evoked nys usually drugs, upbeat nys usually pontine lesions downbeat nys when look down and lat usually in cervicomedullar junction lesion eg Arnold Chiari, basilar invagination, paget, foramen magnum meningioma see-saw nys one eye rising one eye falling parasellar mass esp interstitial nucleus of cajal convergence-retraction nys midbrain post commisure eg pineal tumors, parinaud's synd Tx congenital- prism, surgery, contact lens Baclofen for periodic alternating nystagmus (90 sec one direction 90 sec another direction, in cervicomedullary junction, brainstem, cerebellum) trihexyphenidyl for MS pendular nys gabapentin for MS pendular nys Botulinum toxin A Ocular oscillation differ from nys because no distinct slow or fast component. subtypes ocular bobbing downward jerks ocular dipping ping pong oscillations oculopalatal myoclonus flurries of REM ocular flutter(purely horizontal) vs opsuclonus (multidirectional) sup oblique myokyma spasm nutans
Neuroexam		papapa/bababa tatata/lalala kakaka/gagaga respectively show lip(p) tongue(t) palate(gag) weakness Encephalopathy definition- 3 of these change in LOC change in cognition or personality Sz respiration bil hemisphere or anywhere down decending pathways to upper pons cause Cheyne-Stokes (it can also produced by any encephalopathic states as well as severe CHF) ventral to aqueduct or 4th ventricle cause central neurogenic hyperventilation (it may be associated with neurogenic pulmonary edema and often resolves with correction of metabolic abnormalities) respiratory centers in pons medulla cause either of these apneustic (pontine level)/ataxic(medulla level )/ Ondine's curse (failure of automatic respiration during sleep) pupillary light reflex preserved in met (x mydriatic in one eye or breathing tx)abn in structural lesion hypothalmus horner midbrain midposition fixed pupills pons pinpoint medulla horner Lhermitte sign MS, B12 def, radiation mgelopathy seen in demyelination of post column Amaurosis fugax in diseases of ICA not MCA
Neuromuscular
Neuromuscular		Acute autonomic neuropathy small fiber sympathic or parasympathic insufficiency, relative sparing of somatic nerves so less paresthesia problem c OH, NVD, Constipation, urinary retention, impotence, pupillay dilation, dry eye or mouth Etio- autoimmune (preceding viral infection, inc CSF Pr), paraneoplastic LEMS (dry eye, mouth, proximal weakness), DM, Entric neuropathy (acute abdomen, watery diarrhea), Botulism (pickle, honey, acute cholinergic neuropathy, diplopia, blurred vision, diarrhea/constipation), Porphyria (abdominal pain, diarrhea), Antineoplastic vincristin, taxol, cisplastin, amiodarone, heavy metal, organic solvents (hexane), Dx- Supine/Standing noreepinephrine, sweat test (absence of sweating with alizarin), QSART quantitative sudanomotor axon reflex test (identify posganglionic sympathtic neuropathy) Tx- -Prednisone 50 mg qd for 2 weeks then taper -IVIG 2 gram/kg over 5 days - Plasma exchanfe
Neuromuscular		Acute weakness Myasthenia gravis; Myoglobinuria Myosin loss myopathy; Carnitine dec Periodic paralysis: X-Episodic Xp22 Hypo K+: CACNA1S; SCN4A; KCNE3 Hyper K+: SCN4A; KCNE3 Andersen: KCNJ2 Electrolyte disorders: K+ é inc or ê dec; Mg é; PO4 ê; Barium Rule out: Neuropathy; Spinal cord
Neuromuscular		ANA FN - 2-5% untreated SLE - 10-15% Systemic Sclerosis - Common in Sjogren, PM, Sleroderma FP - in 75% of elderly - in 20% pt c rheumatic disease - in 2% of normal nonelderly titer >= 1/160 significant Patterns - homogenous SLE RA - speckled SLE Scleroderma Sjogren MCTD - peripheral SLE - nucleolar Sleroderma Anti ds DNA or Anti sm ab are specific for active SLE and lupus nephritis
Neuromuscular		Antibodies + Myopathy MG: Anti-AChR Binding & Modulating MG + Thymoma: Anti-striational vs. Titin; Actinin; Ryanodine R LEMS: P-type Ca++ channel Polymyositis: t-RNA synthetase (Jo-1): Lung; Raynaud's; Arthritis Signal recognition Particle: Acute Mi-2: Dermatomyositis; Nail D PM-Scl: PM + Scleroderma Decorin: M-protein; Myopathy
Neuromuscular		Bariatric surgery, Neurologic complications of nutritinal def. - mineral iron, ca, mg, po4, copper - vitami def. B1 B2 B6 B12 D E, Niacin - Lactic acidosis - Rapid fat metabolim or loss of carnitine Encephalopathy B1 B6 def induced Sz Neuropathy Myelopathy B12, copper Ataxia vit E Plexupathy Myopathy Vitamin B1-
Neuromuscular		Brachial plexupathy Formed by ant rami of C5 T1 Etio- most common injury(hematoma or in coagulation abn),then tumor infiltration (Pan coast), radiation(5 months after, incontrast to tumor infiltration upper or entire plexus affected, pain is less common, lymphedema is frequent), infection Upper trunk C5C6- ErbDuchenne lat aspect of arm forearm numbness proximal weakness Lower trunk- Klumpke C8T1-medial aspect of arm forearm, hand weakness intrinsic, finger flexor extensors, maybe d/t Pancoast tumor Postinfectious disorders - GBS - Brachial plexus neuritis - Optic neuritis - ADEM - Post infectious Cerebellitis Brachial plexus neuritis- Parsonage Turner synd, develops suddenly, may last for weeks, shoulder pain inc c shoulder arm movement but not c neck movement or Valsalva, 1/3 bilat following inf or vac, Px good but need PT/OT ROM Exerciss to prevent weakness atrophy dx c NCS/EMG, Steroids or IVIG may help radiation cause more upper plexopathy because less surronding tissue radiation vs neoplastic infiltration- radiation more upper plexus radiation NCS no change radiation EMG myokyma
Neuromuscular		Bulbar dysfunction MG; Thyroid; Cranial nerve D Oculopharyngeal MD Distal myopathy (MPD2) Polymyositis: IBM; Scleroderma Motor neuron D: ALS Pseudobulbar palsy; Fazio-Londe Brown-Vialetto-van Laere; BSMA
Neuromuscular		Camptocormia Bent spine syndrome abnormal posture of the trunk thoracolumbar spine which increase during walking and abates with recumbent positions. Etiology -NMD eg ALS, IBM, Nemaline myopathy, focal paravertebral myopathy, MG -Parkinsonism PD, MSA, Postencephalitic parkinsonism -Dystonia primary dystonia or secondary dystonia due to PD or structural lesion of brain or spinal cord - Stroke - Spine deformity - Idiopathic or psychogenic - Misc drug, graves, paraneoplastic, Tourette Some patients respond to Botox injection into rectus abdominis muscles if clinical evidence of contraction of the muscle like 300-600 u for both side.
Neuromuscular		Cardiac disorders Dystrophy: DMD/Becker; Myotonic; McLeod; Emery-Dreifuss; Barth; Scapuloperoneal; Desmin Polymyositis; Nemaline rod Acid Maltase; Debrancher Carnitine ê; Desmin é Mitochondrial; Amyloid Drugs: Metronidazole; Emetine; Chloroquine; Clofibrate; Colchicine Cardiomyopathy + cores Periodic paralyses
Neuromuscular		CNS + Myopathy Congenital MD: Santavuori (POMGnT1; 1p32); Merosin (6q22); Fukuyama (Fukutin; 9q31) Integrin-a7 (12q13) Dystrophy: DMD; McLeod Myotonic; PROMM; HIBM (9p13) Metabolic: Thyroid; Mitochondrial Acid Maltase: Aneurysms Phosphoglycerate Kinase Myosin-loss Necrotizing Encephalopathy; Pipestem capillaries Hearing loss: FSH; Scapuloperoneal
Neuromuscular		Complex regional pain syndrome type I= RSD type II =Causalgia demonstrable peripheral nerve injury progressive neurovascular pain characterized by -pain, burning hyperesthetic pain -edema -vasomotor instability color temp of skin (hyperhydrosis,hypertrichosis) -trophic changes dystrophic skin nail happen after traumatic or nontraumaticdamage to soft tissues or bone evev after MI Immersion test- immerse exteremity in warm water absence of wrinkling in fingers toes is suggestive of a lesion in the central or the peripheral sympathetic pathway also seen in DM neuropathy procedure xray may show soft tissue swelling or patchy osteopenia bone scan inc activity around joints sweat test ddx ms, neurologic or vascular problems, neoplasia eg bone should not be missed Tx Tylenol NSAIDs such as ibuprofen acetaminophen with codeine or with oxycodone Vioxx in adults ketorolac iv or im meperidine morphin TCA AEDs tegretol, neurontin, dilantin clonidine lidocaine patch or ELMA cream capsaicin steroids medrol dosepack or iv solumedrol antispasmodic baclofen Zanaflex vitamin c after fx bisphosphonates osteoclast inhibition PT Extremity elevation distal to proximal massage Local heat or cold compress Sympathetic nerve block Spinal cord stimulation
Neuromuscular		Contractures Arthrogryposis Bethlem Myopathy Congenital MD Dermatomyositis Dystrophinopathies Emery-Dreifuss IM drug injections Rigid spine syndrome SMA: 5q; X-linked Tel Hashomer Williams-Beuren
Neuromuscular		CPK - Increased rhabdomyolysis, hyperthermia, myoglobinemia, etoh, hypothyroidism, idiopathic essential, myopathy/myositis, mitochondrial disorders, Glycogen storage disease, McArdle, muscular dystrophy, mild dystrophies, cramp myalgia syndrome, last third trimester of pregnancy, substance abuse, snake bite, check CPK, Aldolase, LA, Pyruvate, Anti GAD for stiffman synd, EMG, Muscle bx CK: High > 1,000 Dystrophy X-linked: DMD/Becker Recessive: 2A-2I Dominant: 1C; Ankle contractures Distal myopathy: Miyoshi Polymyositis Acid maltase Acute damage: Injection Rhabdomyolysis; Trauma Thyroid: Hypo- - Decreased hyperthyroidism, hereditary spherocytosis, CVD, malnutrition, lab error, 8-20 weeks pregnancy
Neuromuscular		Cramp, stiffness, exercise intolerance *d/t abn muscle activity - Neuromyotonia(Issac synd,ab to K channel, myokyma, multiplets discharge on spontaneous EMG), - Schwartz-Jampel synd(short stature, bony deformity), - Stiff person synd(truncal spasm hyperlordosis, triggered by startle or emotional upset, ab against glutamic acid decarboxylase, pancreatic islet cell, DM, tx diazepa, baclofen), - Myotonia congenita or fluctuans, - Systemic eg dec T4, dec cortisol, uremia, dec Ca (hyperparathyroidism), Mg, Strechnine poisoning (rat poison oderless, glycine antagonist) - Cramp myalgia syndome - ALS - MMN c CB - Cervical or Lumbar spondylosis - Metabolic myopathies, McArdle, CPT def. Tx- Ultram, Baclofen, Ca 1500 mg/day, Mirapex 0.25 mg qhs-bid, if fails above may purse muscle bx to look for metabolic myopathies or mitochondrial disorders esp if CPK is high. * Dec muscle energy carb(myophosphorylase McArdle), LCFA or VLCFA (carnitine palmitoyl transferase 2 def, VLC Acyl Co A dehydrogenase def.), Mitochondrial myopathies * Myopathies eg Cramp/Tubular aggregates, Familial X linked Myalgia/Cramp, Malignant hyperthermia, NMS, Rigid Spine Synd, Rippling Muscle disease Cramps Normal: Single Muscles Post-contraction; Sleep Electrolyte: Dehydration Na, Mg, Ca, Glucose Thyroid; Adrenal Drugs; Pregnancy; Spinal stenosis Cramp-fasciculation; Familial Myopathy: Becker Motor neuron: ALS Electrically silent: phosphorylase Rippling muscle; Brody's Cramp treatment avoid dehyration check thyroid adrenal low sodium pregnancy check diet pills stimulant myopathic drugs quinine 200 qd or bid or tonic water ca 500-1000 mg/day mg gluconate 500 mg a day vit E riboflavin 200 qd or bid Ginko biloba Japanese quince
Neuromuscular		Critical care neurology electrodx Causes- MUSCLES meds undx nm disorder spinal cord damage critical illness polyneuropathy loss of muscle mass electtolyte disorders systemic illness SIRS or SEPSIS diff weaning off the respirator premorbid disease sirs neuromuscular agents and steroids can impair muscle nerve microcirculation Critical illness polyneuropathy usually after sirs and septic encephalopathy polyneropathy dec ref abs babinski red in cmap with minor changes in latency dec snap amp fibril and sharp waves may not appear til 3 weeks can happen after burn and organ transplantation acute motor neuropathy after curar agents used other possibles gbs oraxonal gbs or cidp, vasculitis, drugs metronidazole, nitrofurantoin, amiodarone, antineoplastic, antiretroviral, cmv, dm, heavy metal, hepatic failure neuropathy ICU MYOPATHY thick filament myopathy dt steroids and nm blocking agents cachectic myopathy type ii atrophy acute necrotizing myopathy dt infection or chemicals ICU NMJ DISORDERS Neuroasthenia either of feeling of exhaustion after
Neuromuscular		Critical illness neuropathy skeletal-muscle wasting RFs- sepsis, meds eg neuromuscular blocking agents, corticosteroids and aminoglycosides Tx- intensive insulin therapy with drip to keep glu between 80 to 110 (130) dec mortality from 8% to 4.6%, dec polyneuropathy by 44%, infections by 46%, ARF by 41%, transfusion need by 50%, less prolonged mechanical ventilation NEJM 345;19:1359-1365 Nov 2001
Neuromuscular		CTS wrist,2&3 flexion and thenar n are spared since these nerves branch befor carpal tunnel tinel phalen flick (shaking of hands to relieve paresthesia) DDx CARPAL TUN EMG/NCS prolonged distal latency Tx - Wrist splint - NSAIDs - Medrol dosepack - local steroid injection 25 gauge needle to inject 1 ml of 1 percent lidocaine just to ulnar side of the palmaris longus tendon, proximal to wrist crease. Aim needle at 30 degree angle. if no paresthesia on injection of a small amonut of lidocaine, the rest of lidocaine injected followed by depot CS. Limit injection to 3 in a year. Complications- tendon rupture, nerve irritation. Surgery- when pt has s & s suggestive of axonal loss- constant numbness, symptoms more than one year, loss of sensibility, thenar atrophy
Neuromuscular		CVD, Autoimmune disorders SLE-sz (in 30-54%),sensory neuropathy, sychiatric symptoms, stroke in 15% of pt mainly d/t coagulopathy, cardiac valve abn rather than CNS vasculitis. BECHET- aseptic meningitis 10-50% or dural thrombosis SJOGREN- dorsal ganglionopathy less motor RA- no direct involvement but indirectly through cervical spine abn myelopathy
Neuromuscular		Dermatomyositis PM - prox muscle weakness esp shoulder abd, hip flex causing difficulty climbing stairs, combing hairs, rising from chair. - inc cpk, aldolase, ab myosin specific ab anti jo1 - emg low amp polyphasia, spont fibrilliations - muscle bx in DM IC deposition perifasicular inflammation vs PM Tcell attack directly on muscle fibers - in case of DM heliotrope rash and over finger knuckles w/u if adult do paraneoplastic w/u inc CT of chest/abd/pelvis CA 125 Transvaginal US UA Colonoscopy tx steroids azathioprin metothroxate cellcept sever
Neuromuscular		Diabetic Amyotrophy DM lumbosacral plexopathy d/t inflammatory vasculitis of LS plexus - asymmetric onset - pain in proximal thigh - affecting femoral, obturator, sciatica peroneal in order - weight loss 10-40 pound - minimal back pain or mri changes - more common in elderly in noninsulin dependent DM - may be associated with foot drop or co existing distal symmetrical polyneuropathy - pathophysiology like parsonage turner is axonal loss w/u - r/o paraneoplastic causes CT of chest abdomen pelvis with attention to plexus, - LP to rule out carcinomatose meningitis cytology - routine PN w/u including SPEP, IFE - Lyme screen - MRI of L spine or LS plexus tx Lyrica 100 mg tid Cymbalta Narcotics fentanyl oxycontin IVIG 0.4 g/kg in 5 days measure Ig A before PT OT ASA or Plavix prognosis 60% recovery in 1-2 year DM thoracoabdominal neuropathy ddx lyme, shingles, sle, autoimmune
Neuromuscular		Distal & Proximal weakness Dystrophy: Myotonic; FSH Scapuloperoneal Myopathy: Congenital; Distal Glygogenoses: Debrancher Phosphorylase b kinase Neuropathy + Myopathy: Paraneoplastic; Sarcoid; Mitochondria; HIV; Drugs (Amiodarone; Doxorubicin Colchicine; Chloroquine)
Neuromuscular		DM Neuropathy - axonal pp temp - demyelinating pos vib - autonomic erection con/dia dysrrhythmia OHypotension - amyotrophic - diabetic CIDP they can have AIDP on top of these Tx- plasmapheresis, or IVIG after plasmapheresis, check c Peter Dyck's neurologic disability scale (NDS) should be dec after plasmapheresis.
Neuromuscular		Dysphgia neurologic causes - PD - ALS, PLS - Stroke, bulbar palsy - MG - Myopathy - MS causing more high dysphagia as cricopharyngeal spasm. Mechanical, tumor, scleroderma, achalasia, reflux stricture
Neuromuscular		Focal hand atrophy (Split hand phenomenon, Focal amyotrophy) atrophy of hypothenar or thenar DDx 1- ALS 2- MMN c CB 3- Neurogenic thorasic outlet syndrome, cervical rib 4- DADS neuropathy, distal acquired symetrical demyelinating polyneuropathy 5- Multilevel cervical myelopathy 6- Nerve root injury C7-T1 7- Hirayama disease Ant myelopathy due to slack dural canal in spinal canal and pressure from dural canal on vascular supply of ant horn cell or epidural venus congestion, usually asymetric hand atrophy dx confirmed by flexion MRI look for post dural enhancement and mass effect or phase-contrast MRA for epidural venus congestion. 8- SMA autosomal dominant distal spinal muscular atrophy, mild disease, lower limb predominance involvement 9- SCA 3, spinocerebellar ataxia type 3 Machado-Joseph disease, late onset 40-60 yo, purtogeause descend, slow progression, cerebellar ataxia, cramp, fasiculation, muscle atrophy, AD, CAG repeat 10- JMA juvenile spina muscular atrophy, focal amyotrophy, stabilization of disease, atrophy of C7-T1 innervated muscles, intrinsic motor neuron disease or results from mechanical distortion of C spine d/t neck flexion during growth
Neuromuscular		GBS ddx - cord compression b/b i can happen in 15% of GBS - transverse myelitis - botulism, tick paralysis, widow spider, lyme, campylobacter - heavy metal, lead, mercury, arsenic, thalium - porphyria esp if axonal feature on EMG - HIV, Rabies, CMV, , EBV, Polio - SLE - Paraneoplastic eg Lymphoma botulism and polio don't have sensory deficits GBS Forms AIDP, AMSAN(worse px), AMAN MF, Acute sensory Ataxia, Brachial form clinical monitoring BP, HR FVC <1.5 stepdown ICU (risk of infection, ARDS, iatrogenic) FVC<1 intubation intubation when VC <15ml/kg extubation when VC >25 ml/kg Choice of Tx PE IVIG AMAN or AMSAN can happen after C. jujeni (Ag mimickery with GM1, check anti-GM1) or H. Flu (Check anti-GM1); CMV infection (check anti-GM2); Mycoplasma infection (Check anti GalC ab) EMG/NCS - Inc DL, Late response > 130% ULN - Dec CV < 75% LLN - Asymmetry, CB >50% drop in CMAP amp, TD >15% inc in CMAP duration (ddx for aquired vs hereditary demyelinating polyneuropathy) - first abn inc F response b/o prox demyelination at root level (check in 2 or more nerves) - sural sparing b/o its thick myelin sheet make it more resistant to inflam changes (compare sural with 2 abnormal UE SNAPs median,ulnar and radial) - EMG demyelinating pattern no denervation, normal MUAP morphology, reduced recruitment in weak muscles - best predictor for prognosis, dital CMAP (0-20% LLN in 3-5 weeks) Protocol: 1- SNAP in median,ulnar, radial and sural for sural sparing pattern 2- Absent or prolonged F wave (and or absent H reflex?) in relatively normal distal CMAP of tibial and median or more nerve 3- CB, TD,focal slowing in 2 motor nerves 4- Repeat study in 3-5 weeks if distal CMAP is less than 20% of LLN bad prognosis 1 or 2 suggestive 1 and 2 highly suggestive 2 and 3 definite
Neuromuscular		Hereditary Myopathy Syndromes 1 Dystrophies: Limb-Girdle & Other Dominant: 1A (Myotilin; 5q31); 1B (Lamin A/C; 1q11); 1C (Caveolin-3; 3p25); 1D (7q); FSH (Deletion; 4q35); Cytoplasmic (2q24; 2q21); Emery-Dreifuss (Lamin A/C); Myotonic (DMPK CTG rpt; 19q13); Spheroid body; Bethlem (COL6A; 21q22 & 2q37); PROMM (ZNF9; 3q21) IBM3 (Myosin HC2; 17p13); MD + Cardiac (6q23); Oculopharyngeal (PABP2 GCG rpt; 14q11) Desmin (2q35); aB-crystallin (11q22); Paget (9p13) Diaphyseal (TGFB1; 19q13) dysplasia Epiphyseal (COL9A3; 20q13) dysplasia Recessive: Sarcoglycans- 2C (g; 13q12); 2D (a; 17q21); 2E (b; 4q12); 2F (d; 5q33); 2A: (Calpain-3; 15q15); 2B (Dysferlin; 2p12); 2G (Telethonin; 17q11); 2H (TRIM32; 9q31); 2I (FKRP; 19q13); 2J (Titin; 2q31); 4; Caveolin-3; CMD: Nl CNS (FKRP; 19q13); Rigid spine (SEPN1; 1p35) Respiratory failure (1q42); Ullrich (COL6A2; 21q22) X-linked: Barth (Tafazzin; Xp28); Autophagy (Xq28); Emery-Dreifuss (Emerin; Xq28); McLeod (XK; Xp21) Becker & Duchenne (Dystrophin; Xq21); Danon (LAMP-2; Xq24); Scapuloperoneal
Neuromuscular		Hereditary Myopathy Syndromes 2 Distal Myopathies Dominant: Welander (2p13): Late onset; Hands & Ant. Legs Finnish & Markesbery (Titin; 2q31): Late onset; Ant Tib Gowers-Laing (MPD1)(14q11): Early adult; Ant leg Dystrophy + rimmed vacuoles (19p13) IBM1: Quad weakness IBM +: Paget's (9p13); Respiratory failure (6q27) Oculopharyngodistal Vocal cord & Pharyngeal (MPD2) (5q31) Myofibrillar myopathy: Desmin; aB-crystallin; Other Recessive: Nonaka & IBM2 (GME; 9p12): Quad sparing Miyoshi & LGMD 2B (Dysferlin; 2p12-14) Early adult; Posterior leg LGMD 2G (Telethonin; 17q11): Teens; Ant leg & Prox
Neuromuscular		Hereditary Myopathy Syndromes 3 Other myopathies Barnes; Congenital; Lipid; Glycogen; Familial MG; Tubular Aggregates
Neuromuscular		Inflammatory myopathies Antibodies: Decorin; SRP; Mi-2; t-RNA synthetase (Jo-1 75%) Dermatomyositis: Mi-2 Ab; Adult vs Child Microvasculopathies: DM; SRP Granulomatous ± Sarcoid Idiopathic myositis: Poly-; Focal Inclusion body (IBM); Infectious Mitochondrial D in muscle Systemic disease: Drugs; Collagen vascular; GVHD; Malignancy; Toxic Hereditary: IBM; FSH
Neuromuscular		Issac synrome - continous or intermittent muscle twitching - cramp, myotonia, myokymia - increased sweating - slowed movement - age 15 60 max around 40 - severe cases bulbar symptoms etio - autoimmune disorder d/t ab against voltage gated k chnnels on peripheral nerves - exposure to toxins gold mercury - tumors lymphoma, thymoma, lung cancer - genetic dx - EMG - Ab against VG K channel - Ab against ganglionic nicotine AChR Tx - dph or cbz - immunosuppression meds - quinine, - ginko biloba Neuromuscular hyperexcitability syndromes - Issac syndrome or neuromyotonia - cramp myalgia synd - rippling muscle syndrome (wave of muscle cramp for 5 sec, myoedema by percussion, toe walking, muscle hypertrophy, muscle activity electrically silent, tx bnzd) - focal neuromuscular hyperexcitability
Neuromuscular		IVIG 6 approved label indications primary immunodeficiency, B cell CLL, ped HIV, BMTransplant, Kawasaki synd., Acute ITP IVIG in neurology in GBM, MMN, MG, MS, CIDP, PM/DM MS (for 5 days and then 0.4 g/kg every month), LEMS, Stiff person syndrome if fails other tx also maybe good for infilterity, pamphigus in pt with DM good prehydration and do it very slowly.
Neuromuscular		Large muscles Overusage: Myotonia; Exercise Neural Overactivity Partial denervation Endocrine: ê Thyroid; Acromegaly Dystrophy: DMD; LGMD; Lipo Infections: Cysticercosis; Trichinosis; Schistosomiasis Drugs: b2 adrenergic; Androgen Storage: Glycogen; Amyloid Fat; Gangliosides Short stature: Schwartz-Jampel; Myhre
Neuromuscular		Livedo reticularis - RA, SLE, APL Syndrome - DM/PM, occult malignancy - Hepatitis C, PAN - Beurger's disease - Amantadine, meds - Cholestrol emboli - Benign idiopathic, they have problem for the life
Neuromuscular		Lumbar plexupathy
Neuromuscular		Motor Neuron disease Tx - Riluzole (Rilutek) 50 mg po q12h (check for neutropenia, hepatotoxicity while on Rilutek) reduce neuroexcitotoxicity by diminishing glutamate release, increase few months to life expectency prognosis 5-10 years side effects may include NV Dizziness weight loss and inc LFTs Cox2 inhibitors neuroprotection Celebrex 100 mg po bid or Vioxx 12.5-25-50 mg po qd or Baxtera qd or bid Coenzyme Q 10 mg po bid Minocycline 100 qd or bid (watch for photosensitivity) Creatin Antioxident vitamins A, C Vitamin E 400 u po qd MV or B12 Possible neurontin topiramate creatine brain derived neurotrophic factor, glial derived neurotrophic factor for general discomfort can use NSAIDs Advil 800 mg po tid Naprosyn 500 mg po bid less gastric effect or Tramadol Ultram 25-50 mg po q6-8h for spasticity, stifffness and abnormal movements Baclofen (Lioresal) Tizanidine (Zanaflex) 2-4 mg po q6h-q12h Tx of psychiatric problems symptoms Depression Zoloft 25 or 50 or100 mg qhs Effexor PT/OT for stretching for contracture foot drop splints, Finger extension splints Discuss limits of care with patient Pt should have advance directive or living will for DNR or DNI orders Hospice care: may need respiratory support tracheostomy intubation or PEG tube for nutriotion and dysphagia
Neuromuscular		Motor Neuron disease DDx: Cervical meyelopathy (Monomelic amyotrophy, Hirayama disease= segmental spinal muscular atrophy secondary to slack dural canal that cause vascular compromise to ant horn cell causing AHC ischemia, usually assymetric confirm with flexion MRI of C spine, may call it ant myelopathy) Multifocal motor neuropathy with conduction block Motor neuropathy with paraproteinemia or cancer Motor predominant peripheral neuropathy Primary lateral sclerosis (upper motor neuron disease) Postpolio syndrome (asymetric weakness + areflexia+neutrophills in CSF and involvement of spine ant horn cell and brain stem motor neuron) Postinfectious echo coxsaki HTLV-1 and HTLV-2 Hereditary spinal muscular atrophy Lead or Aresenic exposure Guam dementia complex=ALS+Parkinson+Dementia Motor system atrophy=Joseph Machedo disease w/u MRI of C spine with gad CT of chest fo CA esp small cell lung ca 5-10% of ALS paraneoplastic like LEMS check serum or CSF Anti-Hu 24h urine for heavy metal Serum Pr Electrophoresis (SPEP), ImmunoFixation Electrophoresis (IFE) for monoclonal gammopathy CBC, CMP, CPK TSH, FT4 B12, FA, Megaloblastic profile (Homocysteine and Methylmalonic acid)
Neuromuscular		Muscle activity Brody's syndrome: ATP2A1 Cramps: Benign Myoedema Myotonia Congenita Dominant (Thomsen): CLCN1 (Cl-) Recessive (Becker): CLCN1 Acetazolamide responsive: SCNA4 Myotonic Dystrophy 1: DMPK, CTG rep Myotonic Dystrophy 2: ZNF9, CCTG rep Paramyotonia: Na+ channel (SCNA4) Periodic paralysis, Hyperkalemic Schwartz-Jampel: Perlecan Neural & Spinal activity
Neuromuscular		Muscle pain Myositis: + Connective tissue dis Polymyalgia; Rhabdomyolysis Infections: Trichinosis; Brucellosis Myoadenylate deaminase ê (< 2%) Myopathy +: Tubular aggregates; Focal ê mitochondria Drugs: Azathioprine; Steroid ê... Rule out: Small fiber neuropathy; Phlebitis Bone & joint pain; Muscle Ischemia
Neuromuscular		Myasthenic Syndromes Acquired MG: Immune ± Thyroid or Thymoma; Childhood; Drug-induced; Neonatal Transient Lambert-Eaton myasthenic syndrome (LEMS) Congenital & Familial: Presynaptic Familial infantile (ChAT; 10q11) ê Synaptic vesicles & Quantal release Congenital Lambert-Eaton-like Synaptic: AChE deficiency (ColQ; 3p25) Postsynaptic: AChR a b d e; Rapsyn; Plectin AChRs: Kinetic D & ê # @ NMJs Slow AChR channel; ê Channel open time AChRs: Kinetic D & Normal # @ NMJs é Conductance & Fast closure of AChRs ê ACh-affinity & Fast-channel AChRs: ê #s @ NMJs & Kinetic WNL Rapsyn (11p11): ê AChRs @ NMJs Plectin (8q24) Other syndromes: Familial limb-girdle; Benign congenital MG & Facial malform Congenital LEMS-like; Familial immune
Neuromuscular		Myoglobinuria Hereditary: Glycogenolysis; CPT II; Malignant Hyperthermia; Central core King-Denborough; DMD (Some) ê K+: Licorice; Li; Thiazide; Amphotericin; Laxative Infections; Mitochondrial; Trauma Muscle: Ischemia; Overactivity; PM Neuroleptic malignant syndrome Drugs: Heroin; Phencylidine; e-ACA Clofibrate + Renal failure; Cyclosporine A + Lovastatin Toxins: Venoms; IV drugs Oral: Haff; Mushrooms; EtOH
Neuromuscular		Neuropathy 1 Etio Axonal (idiopathic acute one such as porphria, lead, alcohol, amyloidosis, carcimatous sensory neuropathy, glue sniffing, they are axonal involving more PP Temp if severe enough may exhibit sec demyelination) vs Demyelination Position Vib impairment (GBS, CMTs, HSMLPP, Diptheria (toxin inhibit myelin synthesis), Paraprotein (either IgM gammopathy or secondary to solitary myeloma), Refsum, Tangier, Metachromatic leukodystrophy, CIDP, MMN c Conduction block ( a Varient of CIDP that respond to IVIG and IS but not CSs or plasma exchange) <in demyelination there is weakness s wasting, global areflexia c/t ankle areflexia in axonal> Acute vs Subacute vs Chronic Sensory(paresthesia spontatenous unpleasant sensation, dysesthesia unpleasant sensation d/t painful stimuli, allodynia painful sensation to unpainful stimulus) vs Motor (fasiculation, cramp, myokyma) vs Autonomic (impotence, anorgasmia, lack of vaginal lubrication, dyspareunia, heart dysrrythmia, GI early satiety,postprandial fullness, dia or constipation, urinary frequency) Small fiber (pa/te + auto in DM, Etoh, Amyloidosis, Paraprotein, vasculitis, 33% idiopa) vs Large fiber (position/vibration) (B12 def, Sensory neuronopathy in Sjoegren or paraneoplastic ganglionopathy
Neuromuscular		Neuropathy 2 W/U Most PN are CASSD PN chronic/axonal/symmetric/sensory/distal Demyelinating PN- AIDP, CIDP, MMNCB, MADSAM, DADS, Gammopathy, Diphteria, Toxic, CMT Motor PN- AIDP, Lead, Porphyria,CMT Acute PN- AIDP, Porphyria, Diphteria, Toxin/Drugs, Tick paralysis, Vasculitis, DM Proximal PN- AIDP, DM Amyotrophy (DM LS Plexupathy), Porphyria DRG Sensory Neuronopathy- Paraneoplastic, Sjogren, Syphilis, B6 intoxication, Friedreich ataxia Asymmetric- mononeuritis multiplex, asymmetric CIDP, superimposed neuropathy or entrapment neuropathy.
Neuromuscular		Neuropathy 3 W/U (Do the right things not everything) - CHECK Urine- Glu, Pro, BJ Pr - 3h OGTT pt gets 70 gram ofglucose, venus blood sample obtained, several scenarios (at 2h normal<140, 140-200 IGTT, >200 DM) GestationalDM 105, 1h 190, 2h 165, 3 h145 Impaired Fasting 110-126 >126 DM - CHECK Blood- CBC, CMP - B12 FA Megaloblastic profile (homocysteine, methylmalonic acid if B12 borderline value) - Check B1, B6, B12 or Vitamin E for sensory ataxic neuropathy esp after gastric intestinal bypass surgery - TSH, FT4 - ANA, ESR, RPR, - SPEP, IFE, UPEP, if M pr do bone survey and HemOnc consult for lymphoproliferative disodeers - Heavy metal screening - anti RO anti La for Sjogren (anti SS-A, anti SS-B, only 10-15% ab positive, need lip bx) - ANCA for Wegner - Hepatitis profile - CSF ace and electrophoresis - Serum ACE - LP (if suspect demyelinating or inflammatory/infectious PN) check for cell glu pr Oligoclonal band MBP IgG index - HIV, HTLV1, Lyme - Malignancy CXR, Anti Hu, anti Yo=Purkinje cell Ab, Anti Ri - CT of chest abdomen for carcinoma lymphoma or solitary myeloma (skeletal survey, pelvic US) - mamography, PET - Autoimmune antiGliadin tests for Sjogren (salivary flow rate, Schirmer's test Rose Bengal test, labial gland biopsy) - anti Sulfite or SGPG if senosry ataxic - anti MAG (varient of CIDP, associated c IgM gammopathy, in elderly c significant sensory ataxia, in NCS causing prolonged DL oyt of proportion to other abn); Anti GM1 in MMN c CB, Anti GQ1b in MF varient - CMT Panel for Hereditary- PMP22 duplication CMT1a MP0 for CMT1b (more severly affected, axonal form) PMP22 deletion HSNPP Connexin 22 for CMTx no male to male transfer Skin Bx- only for evaluation og small fiber neuropathy Sural nerve Bx- only if you suspect vasculitic neuropathy because most PN are chronic axonal and changes are not specific NCS/EMG
Neuromuscular		Neuropathy 4 Tx TX: Foot care Ankle care AFO ankle foot orthoses weight reduction sensible shoes, boots stick, crutches walking frame PT/OT for evaluation and equipment needs Pain management with Amitriptyline Gabapentin Carbamazepin or Trileptal Lamictal Ultram Opiod for short term severe pain or for disabling resistant chronic pain Oxycontin or Fentanyl patch about 25% up to one third of polyneuropathies especially chronic axonal sensory neuropathy is cryptogenic or idiopathic. and treated with symptomatic treatment. - Peripheral neuropathy acute aggressive treatment IVIG 0.4 mg/kg/day x 5 days or 1 gram/kg/day x 2 days Plasmapheresis for 5 days qod - If DM CIDP or DM demyelinating polyneuropathy IVIG - If bx showes autoimmune or inflammatory CS and IS Dr. Cheema compound cream Lidocaine 5% + Ketoprofen 5% or 10%+ Flexeril 5% disp=60 gm use topical bid Lidoderm patch
Neuromuscular		NM Antibodies - Anti MAG in distal ataxic NP - Anti GM1 in MMN c CB - Anti GQ1b in MF form of GBS - Anti GQ1d in GBS - Anti Hu(or ANNA-1) in paraneoplastic sensory neuropathy or dorsal ganglionopathy neuronopathy - Anti GAD (glutamic acid decarboxylase) in stiff person synd. - Anti purkinje or anti Yo cerebellar degeneration - Antivoltage gate Ca in LEMS - Anti-CAR antibodies stain the inner and outer segment layers and the outer nuclear layer of the retina. These antibodies react with the 23-kd calcium-binding protein recoverin, which functions in the light adaptation process associated with the phototransduction cascade and initiated by light activation of rhodopsin. Cancer-associated retinopathy (CAR) occurs in patients with small cell lung carcinoma, melanoma, breast carcinoma, and a variety of gynecological tumors. ABs in MG 1- AChR binding ab most common ab in 87% of generalized MG and in 71% ocular MG and in 81% of all MG pt in remission. its absence make dx of MG unlikely 2- AChR blocking ab in 40% of MG pt and correlate c disease activity. muscle relaxants cause false positive result 3- AChR modulating ab cause endocytosis of ACh receptor and inc degradation. with binding ab they present in 90% of pt. 1-2% of MG pt have only modulating ab 4- Striate muscle ab in 80-90% of MG c thymoma in 30% adult MG in 20-25% pt s clinical evidence of MG Ab can be against Na, K, Ca channels, ACh receptors and MuSK muscle specific kinase. MuSK is candidate for seronegative MG. MG 85% seropositive 7% MuSK positive 8% seronegative.
Neuromuscular		OH OH drop 10torr in DBP 20torr SBP reverse volume depletion,anemia, meds effect if no HR inc in favor autonomic insufficiency Tx- 2 liter fluid, 200 mg sodium, abstain from etoh, thigh high tedhose, small carb meal meds- Fludrocortizone 0.05-0.3 mg bid Midodrine a agonist 5-10 mg up to 40 mg/day (supine HTN, pruritus) Clonidine a2 agonist Propranolol
Neuromuscular		Pain - nociceptive vs neuropathic - source of stimulus inside nervous system vs outside - porportinate to stimulus vs out of proportion pain fibers- unmy c fiber (slow sustained pain), slightly myelinated A delta fiber (reflex withdraw)(Abeta mechanoreceptor Aalpha proprioception) Pain neurotransmitters- Glu mainly, sub P, calcitonin gene related pr TX - Balm - AEDs - TCA - Ultram - Neurontin work through GABA rec best - Lamictal Na CB - Keppra not well known best - Tegretol - Topomax NaCB - Gabatril GABA Agonist - Trileptal Na CB - Zonosemide
Neuromuscular		Paraneoplastic syndrome - cerebellar degeneration anti purkinje or anti Yo - anti Hu in dorsal ganglionopathy neuronopathy - antivoltage gate Ca in LEMS Paraneoplastic synd- Cerebellar degeneration LEMS Dorsal neuronopathy Limbic encephalitis cancer-associated retinopathy CAR Opsoclonus-myoclonus synd c neuroblastoma the most common extracranial solid tumor in kids Paraneoplastic syndromes predominantly affect the brainstem, cerebellum, dorsal root ganglia and medial temporal lobe. Paraneoplastic cancer-associated retinopathy (CAR) occurs in patients with small cell lung carcinoma, melanoma, breast carcinoma, and a variety of gynecological tumors. Anti-CAR antibodies stain the inner and outer segment layers and the outer nuclear layer of the retina. These antibodies react with the 23-kd calcium-binding protein recoverin, which functions in the light adaptation process associated with the phototransduction cascade and initiated by light activation of rhodopsin. Limbic encephalitis- dementia, sz, psychiatric symptoms associated with T2 signal changes in limbic area. affected pt are withdrawn occ agitated. one form could be associated with paraneoplastic chorea involving BGanglitis and they have collapsin related mediating protein 5 -CRMP5- positive Ab.
Neuromuscular		Periocular without EOM Weakness Dystrophies: Myotonic; FSH; Oculopharyngeal Myasthenia Gravis (MG) Congenital Myopathies Polymyositis Rule out: VII nerve lesion
Neuromuscular		Periodic paralysis Hyperkalemic periodic paralysis and paramyotonia congenita are associated with mutations in the gene coding for the alpha subunit of the skeletal muscle sodium channel. About 70-80% of patients with the clinical diagnosis of Charcot-Marie-Tooth disease type 1A have a region of DNA duplication on chromosome 17; deletion of this same region is associated with hereditary neuropathy with liability to pressure palsies.
Neuromuscular		Piriformis syndrome
Neuromuscular		Posterior column diseases B12 def, HIV (vascular myelopathy), TD, herpes Posterior and lateral columns are selectively damaged in vitamin B12 deficiency and HIV vascular myelopathy. Tabes dorsalis results in posterior column dysfunction. Nitrous oxide abuse interfere c vit B12 dependent conversion of homocysteine to methionine causing myeloneuropathy similar to B12 def.
Neuromuscular		Posterior neck weak Common: MG; PM; ALS Focal myopathy: Neck; Paraspinous Rare: FSH dyst; LMN synd; IBM; Rod; PROMM; Acid maltase; ê K+ Carnitine; Endocrine; Desmin
Neuromuscular		Posthereptic neuralgia acute vs chronic >3 months nocioceptive vs neuropathic dormant infection in DRG Prehereptic neuralgia- 7-21 days before rash dermatomal pain Zoster sine herepte- segmental/dermatomal pain like radiculopathy, can be associated c motor weakness, rash PHN- pain >3 months after initial rash, cause of pain nerve damage incidence inc with age tx- In first 1-3 days for vz infection acyclovir, valaciclovir, famciclovir For pain neurontin, tegretol, DPH, Ultram, Elavil Neuro manifestation of VZV Skin superinfection, Pneumonitis esp in pregnancy, - Aseptic M - Cerebellitis ataxia, Encephalitis - Transversemyelitis, GBS - Pediatric vasculopathy Stroke (post varicella angiopathy may account for third of peds stroke) - RHunt syndrome PCR pos in CSF for VZV role of IV acyclovir in above sever situations maybe appropriate.
Neuromuscular		Proximal arms weak Dystrophy: Scapuloperoneal; FSH Absent muscles; Shoulder joint D MG; Neuropathic: ALS; P-LMN; Brachial plexopathy Quadriceps weak Myopathy: Becker; Ring fiber Myositis: IBM; Mitochon; Focal Nerve: Femoral; LS plexopathy; Diabetic amyotrophy; L3-L4 root
Neuromuscular		Respiratory Failure Myasthenia gravis Myosin-loss myopathy Acid Maltase Amyloid; Desmin Polymyositis (Jo-1) Congenital Myopathy: Rod; Centronuclear Hydroxychloroquine Neural: Phrenic lesions Arnold-Chiari; Churg-Strauss Brachial plexopathy; ALS
Neuromuscular		Spastic paraparesis familial vs acquired DDx- familial spastic paraplegia SCA (Joseph Machado) MS Slow growing tumors of spinal cord Infectious myelopathy, HTLV1, Tropical spastic paraparesis Tethered cord disease Vitamin E defieiency Friedrich's Ataxia adrenomyeloneuropathy (adult onset form of adrenoleukodystrophy which is xlinked and d/t defective beta oxidation of VLCFA)
Neuromuscular		Statin myopathy some they have myalgia 10 percent prevalence other drugs toxic nefazodone gemfirozil cylosporin etoh exercise verapamil diltiazem grapefruit pomegranite juice Pravachol, Chinese red rice yeast 2 tab hs cause 17 percent reduction try lipitor or rosuva biw tonic water quinine, q10 pulse therapy with
Neuromuscular		Stiffman syndrome etio- autoimmune or paraneoplastic (breast cancer) anti GAD (+ in 60-70%), anti amphysin, geyhertin clinical- prox stiffness, hyperlordosis, DM, Autonomic instability, fear of open spaces, myoclonus some pt may have only one leg stiffness eg after R knee injury. EMG- continous spontaneous MUAP discharge esp in thoracolumbar paraspinal Labs- check for neoplasm CXR, Mamography, prostate Hb1c DDx- - spasticity from myelopathy, MS, brain stem tumor, motor neuron diseases - spondylosis - fibromyalgia - myotonia - proximal myopathies - dystonia Tx- pt diary for no of episodic spadm symptomatic vs immunologic - BNZD diazepam average dose 20-40 mg/day, clonazepam, alprazolam - AEDs VPA, vigabatrin, tiagabine up to 6 g/d, gabapentin 3600 mg/d - Botox, Myoblock - Baclophen pump - clonidine inhibit NE release Immunotherapy - CSs varying degree of improvement - Immuran, Cellcept, cyclophosphomide - Plasmapheresis less than 15% benefit - IVIG was effective in NIH study NEJM Dalakas 2000,345:1870 Prognosis- stabilize in several year they may need baclofen pump or IVIG. they have normal longevity like general dystonia Diazepam is the mainstay of treatment for the stiff-person syndrome, which occurs about as often in women as in men. Onset in adult life, proximal distribution of stiffness, development of lordosis, and precipitation by motion or emotion are typical. Diabetes and organ-specific autoimmune disorders are common. Seizures sometimes occur. Stiff-person synd has a plus varient called progressive encephalomyelitis with regidity PER GAD65 Antibody act against GAD rate limiting enz for GABA synthesis results in alpha motor neuron hyperactivity.
Neuromuscular		Wasting > Weakness Pathology: Type II atrophy Cachexia: Wt loss > 15% Disuse; Steroid myopathy; Paraneoplastic; Aging Weakness > Wasting Polymyositis; Myoglobinuria; Periodic Paralysis; Myasthenia gravis; Neuropathy with conduction block
Neuromuscular	CIDP 1	CIDP Varients of CIDP Temporal-SIDP, Relpsing GBS Regional-DADS, MADSM, Paraparetic CIDP, CNeuropathy Functional- motor, sensory, ataxic CIDP Dx 1) clinical course->8w, relapsing remiting 2) CSF pr>45 in DM CIDP>100 3) NCS/EMG sample 4 nerves (inc DL and F wave, dec CV, CB and temporal dispersion) 4) Nerve bx EMG Criteria - 4 nerve sample, 3 should be abnormal - CB TD in 1, f dl cv in 2 - f dl cv in 3 in abcense of cb td - f dl cv with positive bx cb drop 20% in p-p amp or area td 0.9 ms Etio - Idiopathic - Monolonal gammopathy, MGUS, POEMS, lymphoma - Autoimmune: SLE,RA,Sjogren,Sarcoidosis, thyroid, MG - Infection: HIV, HTLV 1,hep b c - transplantation, vaccination - malignncy - meds eg procainemide, inf alpha pt c DM CIDP - prominant prox or generalized weakness - progressive course over a few months - conduction block not in entrapment sites and other NCS findings - CSF Pr>100 - Response to therpeutic trial of IVIG or PE - DM LS radiculoplexopathy might share pathologic features of DM CIDP Lab w/u - CBC,CMP, ANA, ESR, OGTT, HbA1c - SPEP, IFE serum, urine - M pr 1.5 - 3 g/dl MGUS - M pr >3 g/dl malignant plasma cell disorder also check for cryoglobulins, B2 microglobulin, serum viscosity, bone scan, BM bx - Skeletal bone survey for osteosclerotic myeloma and POEMS esp if IgA, IgG or lambda light chain monclonal gammopathy. Sometimes CT of thorax and abd is necessary to rule out lymphoma - if suspecious ANCA, RF, ACE, anti SSA-SSB, Hep B and C, HTLV1, Lyme serology - if suspect or younger than 40, genetic study for CMT type 1A,1B and X, HNLPP - CSF pr >45, cell should be <10, fewer than 50 in HIV cases if CSF pleocytosis check for HIV, lyme, lymphomatous meningitis and sarcoidosis DDx - other immune mediated neuropathy - CMT HNPP - toxin meds, glue sniffing, aresnic poisoning, amidarone - IgM MGUS neuropathy or DADS distal, predominantly sensory, prolonged DLIndex, lack of response to CS, associated with anti-MAG or anti-GD1b - MADSAM - MMN c CB
Neuromuscular	CIDP 2	CIDP Tx Goals: reduce symptoms (weakness, sensory loss, ataxia, pain), improve functional status, long term remission - Use PT/OT cane, walker, AFO First line tx: CS,IVIG,PE If elderly with steroid complication use Steroid sparing agents (Imura, Cyclosporine A, Cellcept etc) - 1/3 not respond to conventional therapy and have axonal loss on EMG, use prednisone plus PE or IVIG monthly, if no improvement add cyclosporine or monthly IV cyclophosphamide CS 1to 1.5 mg/kg/d takes 2w to 2m to show effect taper by 5-10 mg q2or4 week or monthly pulse metylprednisolone or oral dexamethasone Steroid side effects Acute: mood lability, insomnia, fluid retention, steroid psychosis Chronic: check PPD, weight gain, DM,cataract, glucoma, gastritis, osteporosis, vertebral fx, aseptic necrosis of femoral or humeral head, steroid myopathy, impaired wound healing, increased infection (herpes zooster, cutaneous fungal infection, TB reactivation, recurrent pneumonia), hirsutism, cushingoid state, pseudotumor cerebri IVIG 0.4 gram/kg qd x 5 days or 1gram/kg qd x 2day over 4-6 hours infuse slower in pt with CHF, RF, vascular disease or elderly - check IgA, CMP, CBC before - For HA, Flu like pretreat with 60 mg Solumedrol IV and for fluid overload infuse slower esp in elderly PE - Contraindications hypotension, coagulopathy, thrombocytopenia - administer NS 1 lit several h before PE reduce risk of hypotension and vasovagal response - a single PE remove 3-5 lit of plasma and reduce IgG by 45% and 5 PE reduce igG by 90% - 5 PE 250ml/kg qod times 5 - PE complications CVC access pneumothorax, site infection, venous thrombosis Then dec BP, dysrrhythmia, vasovagal response, citrate toxicity with NV and carpopedal spasm (hypocalcemia), muscle cramp, paresthesia, allergy to infused plasma, anemia, bleeding, infection
Neuromuscular	CIDP 3	CIDP Tx2 IS when - pt not improved with above - improved but has frequent relapse - intolerable side effect to CS - takes 4-6 m to see effect Mycophenolate Mofetil (Cellcept) - inhibit purine nucletide synthesis, dec proliferation of B and T cells - IS c/t Azathioprine with less BM suppression - Dose 500 mg bid to increase by 500 mg q2w to 1000 mg bid, check CBC and CMP - SE include NV,HA, tremor, leukopenia, dec platelets, inc inf,potential for developing lymphoma and other malignancies Azathioprine (Imuran) 2-3 mg/kg/day - Start 50 mg qd first week and then inc by 50 mg qweek to max dose - Check CBC,LFTs qweek x 4 then monthlyx4 then q3months - Avoid in WBC<1000, Platelet<50000, with Allopurinol (dec dose by 1/2 or 1/3) and ACE I (inc risk of leukopenia) - Avoid pregnancy up to 6 months after discontinuation of drug - SE include inf, neoplasia, inc LFTs, rassh, alopecia, arthralgia, pancreatitis Cyclosporine A -5mg/kg/day PO in 2 divided dose bid - Keep trough level 100-200 ng/ml - Adjust the dose by 1mg/kg/day if Cr inc by 50% or above 2, SBP>150 or DBP>90, Higher trough level, dose adjustment should not occure more frequently than q4w and nore tan 1mg/kg/day -SE include RF, HTN, Hirsuism Cyclophosphamide -PO or monthly IV - PO 2mg/kg/day - IV 1 gram/m2 monthly - SE NV (give zofran) BM supression, Alopecia, Hemorragic cystitis (check UA and CBC every 2 weeks), teratogenic effect, infertility - Give drug holiday for 3-6 months if they are taking PO for 12 months or IV for 6 months Interferons INF alpha2a 3 million IU SQ tiw INF Beta1a 3-10 million IU SQ tiw INF Beta1a 30 ug IM qweek
Neuromuscular	EP	Evoked potentials normal values Visual BAER Median somatosensory EPs
Neuromuscular	EP	Median somatosensory evoked potentials in cervical spondylosis may show diminished amplitude of N13. Arnold-Chiari malformation is associated with normal amplitude of N13 and increased N13-N20 interpeak latency. In amyotrophic lateral sclerosis, median SEP's are typically normal. In BAEP's, absence of wave I with intact wave V is most commonly due to peripheral hearing loss. wave V impaired in inf colliculus. Reference: Chiappa KH. Evoked potentials in clinical medicine. 3rd ed. New York: Raven Press, 1997. A unilateral P100 abnormality indicates an ipsilateral lesion of the visual pathway anterior to the optic chiasm such as a unilateral demyelinating process or optic nerve glioma. A tumor of the occipital lobe or a thalamic hemorrhage would cause a bilateral abnormality or little or no effect on the P100 latency. The N13 potential is generated at the cervical cord level, and an absent response would suggest a lesion involving the cervical cord. Somatosensory evoked potentials can be elicited in the absence of a recordable peripheral sensory nerve action potential because the CNS can amplify the incoming responses.
Neuromuscular	Limb-Girdle dystrophy	Limb-Girdle dystrophy - AR or AD - difficulty reaching high objects or climbing stairs - scapula winging - ddx from fasciscapulahumeral FSH dystrophy, they have scapula winging, can have foot drop. - cbc, cmp, la, cpk, aldolase, esr, ana, tsh, ft4 - emg - genetic test Aethena athenadiagnostics.com genetic consult - check heart echo - muscle biopsy - pt/ot for walking - check for other myopathies eg mitochondrial, metabolic, inflammatory, congenital, meds induced myopathies
Neuromuscular	Myasthenia	MG Abs 1- AChR binding ab most common ab in 87%of generalized MG and in 71% ocular MG and in 81% of all MG pt in remission. its absence make dx of MG unlikely 2- AChR blocking ab in 40% of MG pt and correlate c disease activity. muscle relaxants cause false positive result 3- AChR modulating ab cause endocytosis of ACh receptor and inc degradation. with binding ab they present in 90% of pt. 1-2% of MG pt have only modulating ab 4- Striate muscle ab in 80-90% of MG c thymoma in 30% adult MG in 20-25% pt s clinical evidence of MG
Neuromuscular	Myasthenia	MG DDx *LEMS in lems more autonomic sx eg dry mouth impotence,more prox muscle weakness hip shoulder girdle, less ocular sx ptosis diplopia loose reflexes earlier than MG LEMS can be associated c cerebellar ataxia d/t Ca ch. IgG against purkinje cells. *Myotonia fluctuans- EOM Myotonia as well trunk, limbs fluctuating daily, warming up usually relieves symptoms. EMG shows myotonia, muscle biopsy normal, DNA analysis shows mutatio in Na channel. Tx acetazolamide, mexilitine to relieve stiffness. * Neuromyotonia, cramp/fasiculation syndrome associated c K ch. ab implicated c Limbic encephalitis, Morvan disease and peripheral nerve hyperexcitibility If can not get knee reflexes do knee ext and b/o facilitation phenomenon u can get knee reflex, no facilitation in MG increment response from 2 Hz 50 Hz stimulation b/o facilitation - cerebellar degeneration anti purkinje or anti Yo - anti Hu in dorsal ganglionopathy neuronopathy - antivoltage gate Ca in LEMS Paraneoplastic synd- Cerebellar degeneration LEMS Dorsal neuronopathy Limbic encephalitis (K ch. ab implicated c Limbic encephalitis, Morvan disease and peripheral nerve hyperexcitibility) Paraneoplastic syndromes predominantly affect the brainstem, cerebellum, dorsal root ganglia and medial temporal lobe. usually we treat LEMS same as MG ab evalution- ca ch. blocker achr blocking ab (most important correlate disease activity), smooth muscle ab , achr binding ab (most common), achr modulating ab, striated muscle ab, 3,4-diaminopyridine (3,4,-DAP) blocks a K+ channel and increases acetylcholine release. It has been used for treatment of Lambert-Eaton myasthenic syndrome. dose 0.5-3.5 mg/kg/day po in 2-4 divided dose. may be wrong dose usuall dose 5-10 mg tid Also use varient 4-aminopyridine for MS 5 mg tid for fatigue.
Neuromuscular	Myasthenia	MG DX don't get knee ext or toe flexor Dx - Abs- most important Achr abs 10-15% abs neg but in these pt MUSK muscle specific kinase ab is positive. (in general pt population 70% is positive) - Tensilon if pt has ptosis - RS repetitive stimulation decremental or very minimal incremental response c/t LEMS which has significant incremental response. - SF EMG single fiber EMG in ocular MG or when ab neg Dx double vision on lat gaze or ptosison upwrad gaze happen in less than 60 sec arm stretching at 90 degree drop in less than 4 min swalling impaired as well as fascial weakness 10% of MG are are associated with autoimmune disorders such as SLE, Thymoma, Hyper/Hypothyroidism, Pernicious anemia, DM. So need to check for these at time of dx. Jitter on single fiber EMG can be seen with diseases of neuromuscular transmission such as myasthenia gravis as well as a denervating neuropathy such as amyotrophic lateral sclerosis. The congenital myasthenic syndromes are not related to an immune process, but are caused by genetic defects affecting the neuromuscular junction. These include defects in acetylcholine synthesis and packaging (familial infantile MG), end-plate deficiency of acetylcholinesterase, acetylcholine receptor deficiency, and the slow channel syndrome. The most sensitive test for myasthenia gravis is single fiber EMG of the frontalis muscle.
Neuromuscular	Myasthenia	MG TX IVIG 2mg/kg Plasmaheresis in ICU setting IS Azathioprine (Imuran) less prednisone dose requirement but it takes about 18 months to start working, cyclosporin takes 2-4 months to start working, mycophenolate (Cellcept) may take 2 months to start working (check for skin TB Test before starting CS or IS, also check for DM before CS) Thymectomy for sure, emphesize on radical surgery as much as possible. higher remission rate for thymectomy pt 2 times rate. Not useful in pt c MUSK positive pts and pt over 60 age group b/o risk of surgery in presence of class II trials not advisable to do surgery. Prednisone may get worse in 1-2 weeks of intiation of therapy Mestinon symptomatic tx with Robinul (glycopyrrolate 1 mg prn 1/2 1 h before mestinon dose) to dec NVD associated c mestinon. or use long acting Mestinon completeremission no ss without tx after 1 year pharmacologicremission when no ss on meds for 1 year Drugs safe in MG Bromocriptine, chloramphenicol, prozac, gabapentin, ACE I Drugs cotraindicated CaCB, Beta B eg inderal Aminglycosides, polymyxins, procainamide, quinidine, chlopromazine Li, thyroid hormones
Neuromuscular	Myoadenyalte Deaminase	MAD deficiency Myoadenylate deminase deficiency - Seen in 5% of population - Can cause Statin hypersensitivity - Can be diagnosed with enzyme assay (muscle biopasy and enzyme staining by histochemistry) or IFET or genetic test for AMPD1 gene mutation, common form is C34T Ischemic Forearm Exercise Test (IFET) - Can dx glycogen storage disease, mitochondrial disorders and MAD deficiency - Pt should be fasting , 30 min rest, lay supine - Draw blood from the antecubital vein of the ipsilateral exercising arm - Before and 10 min after sustained ischemic hand grip - Inflate BP cuff 30 mmhg above SBP and ask pt to do forceful forearm and hand grip excercise (can use hand grip dynamometer from Jamar Inc, Bolingbrook, IL) - Check for lactate and ammonia, lactate should inc and - Complications: forearm compartment syndrome or rhabdomyolysis Mechanism: if you can't metabolize glucose you go to the anerobics and Pr breakdown pathways MAD in Pr breakdown causing ammonia production Glycogen storage/Glycolytic disease: decreased lactate rise, Normal to inc Ammonia rise MAD Def: Normal lactate rise, Decreased Ammonia rise Mitochondrial disorders: Inc lactate and ammonia at baseline fasting,
Neuromuscular	Myopathy	Deuchenne Biopsy abscence of dystrophin inc utrophin (in nm junction) dec sacroglycan (immunostaining also performed for merosin def, dysferelin for LGMD) geneic test 70% deletion rest of them point mutation Tx - PT/OT AFO - weight control, speech therapy, assistance c learning difficulties - Pulmonary care, annual flu shot, overnight sleep study for nocturnal hypoventilation esp when VC reach <60%, cough assistance for mucocilliary clearance - at age 10-12 Cardiology evaluation - Orthopedics >25%-35% scoliosis - Supportgroups - MV - Calcium supplement - Steroids prednisone 0.75mg/kg/day check k(def eat banana) cbc cmp TB Skin test, CXR (as baseline as well as TB), - warn about behavioral side effects as well as obesity, DM, PU may improve muscle weakness a little bit Oraped (prednisolone oral syrup)15 mg/5ml better tolerated - check BP after 2 weeks - check for indigestion pu if anyproblem reported start Zantac (steroids may work for Becker) Deflazacort (0.9-1.2 mg/kg/day)has less SE available in Canada or Mexico but Cataract more common vs prednisone Creatine monohydrate 5-10 gram/day may improve strngth inc muscle supply of phophocreatine inc ATP resynthesis NSAIDs or COX2 inhibitor may work. DMD by definition ss start before age 5 Becker by definition still ambulatory at age 16 in DMD they can have smooth muscle involvement eg gastric bladder dilation, mild dec IQ, hypertrophic cardiomyopathy cor pulmonale pseudohypertrophy can also be seen in vastus lat, deltoid in FSH in contrast to LGMD, deltoid is always spared. Dx hp, incCK, myopathic EMG, Bx immunestaining (dystrophin ab staining) DMD <3% dystrophin BMD >20% dystrophin female can also get DMD, b/o x random inactivation, XO Turner synd Future tx gene (micro mini gene) therapy stem cell therapy up regulation Utrophin myoblast implantation more effective meds
Neuromuscular	Myopathy	Extraocular muscles weak Myasthenia Gravis (MG) Thyroid; Botulism Mitochondrial: KS; PEO; MNGIE Centronuclear; Multicore Oculopharyngeal MD; IBM + Contracture Oculopharyngodistal myopathy Congenital ophthalmoplegias
Neuromuscular	Myopathy	Inclusion body myositis produces a characteristic pattern of weakness involving finger flexor and quadriceps muscles most severely. Muscle enzymes are normal or minimally increased, and EMG studies typically reveal an inflammatory myopathy. The muscle biopsy finding most typical of inclusion body myositis is vacuole formation surrounded by a basophilic rim. Critical care myopathy is an under-recognized disorder characterized by selective loss of myosin from myofibers. Also known as myosin losing myopathy, this disorder is most commonly seen in critically ill patients treated with corticosteroids and neuromuscular blockers. Drug-induced muscle disorders include myalgia, myotonia, type 2 atrophy (e.g., prednisone,MG), and focal (e.g., oxycodone), necrotizing, inflammatory (e.g., L-tryptophan), mitochondrial (e.g., zidovudine) or autophagic (e.g., amiodarone) myopathies. Reference: Mastaglia FL, Laing NG. Investigation of muscle disorders. J Neurol Neurosur Psych 1996;60:256-274. Which myopathy can cause ptosis- mitochondrial myopathy in old ages ocilopharyngeal muscular dystrophy myotonic dystrophy stiner disease Deuchenne tx prednisone 0.75mg/kg/day check k cbc cmp TB Skin test, CXR, warn about behavioral side effects may improve muscle weakness a little bit Hypothyroid myopathy is commonly associated with painful cramps and impressive elevations in serum CK levels. Muscle percussion commonly results in a slow, prolonged, electrically silent local mounding called myoedema. Polymyositis is not typically accompanied by painful cramps. Paramyotonia congenita ch 17q23.1 muscle Na voltage gated channel defect. major symptom orbicularis oculi myotonia on exposure to cold.
Neuromuscular	Myopathy	Muscle biopsy findings reflect the underlying biochemical abnormalities. In carnitine deficiency, there is a defect of transport of fatty acids into the mitochondria, and lipid therefore accumulates in the muscle. Myophosphorylase deficiency impairs carbohydrate utilization leading to accumulation of glycogen. In mitochondrial myopathies, subsarcolemmal accumulations of numerous malformed mitochondria are seen as red accumulations on the modified Gomori trichrome stain ("ragged red fibers"). Inclusion body myositis is an indolent myositis of late adult life characterized by rimmed vacuoles in muscle fibers best seen on cryostat sections. Ultrastructurally, filamentous whorls are seen within the rimmed vacuoles. abn Z band in nemaline myopathy
Neuromuscular	Myopathy	Myotonic dystrophy AD Ch. 19, c variable penetrance anticipation, triplet repeat SS- frontal balding, temporal /master wasting, elongated faces(sad face)(hatchet face, fish mouth appearance), thin neck (SCM Atrophy) distal weakness c/t prox weakness in other myopathies, myotonia in hands (grip myotonia)or tongue, percussion myotonia over thenar eminence that dimples and stay dimpled for several seconds, or when shaking hands difficult letting it go. Cataract Endocrinopathies, dec T4, testicular atrophy, inc Insulin, DM, dec GH, adrenal atrophy Cardiomyopathy check EKG, Echo Inc Aldolase, CPK minimal inc TG, Cholestrol Dysphagia speech Dyspnea PFT Procainamide EMG myotonia waxing waning MUP, myopathic potentials, involvement of large fiber motor/sensory fibers Aethena myotonic dystrophy panel Tx PT/OT mexilitine, procainamide (250 mg qid), DPH (Na CB), CBZ for myotonia, quinine or tocainamide also suggested but maybe more toxic - if K sensitivity is demonstrated acetazolamide may be used AFO Wrist splint for foot/wrist drop
Neuromuscular	Neuropathy	Dorsal root ganglia/sensory neuronopathy/ganglionopathy *Infectious/Postinfectious Chronic active hepatitis HIV Rickettsia conorii infection *Nutritional Vit B6 or E def *Paraneoplastic (anti Hu ab) *Sjogren (ANA,RF,SSA or anti Ro,SSB or anti La) *Idiopathic *Toxic Abx related (4-12 days after Abx) Cisplatin Pyridoxine Thalidomide (when used in tx of skin diseases or leprosy)
Neuromuscular	Peripheral nerves	CMT Hereditary Neuropathies CMT I demyelinating, CV around 20 m/s CMT II axonal (dec CMAP, CV around 30s)more leg involvement, inverted champagne leg MPO mutation CMT X no male to male transmission HNLPP PMP22 deletion PMP22 duplication CMT1a MP0 for CMT1b (more severly affected, axonal form) PMP22 deletion HSNPP Connexin 22 for CMTx no male to male transfer
Neuromuscular	Peripheral nerves	heavy metal poisoning A heavy metal screen tests for chronic heavy metal poisoning and exposure, and the test is almost always done on urine. Blood screening for heavy metals, such as arsenic, is done only for the uncommon situation where acute poisoning is suspected. Since arsenic is rapidly removed from blood, blood is not the specimen of choice to rule out chronic arsenic exposure. The heavy metal screen will almost always include tests for lead, arsenic, and inorganic mercury, but toluene and methanol are not heavy metals and must be analyzed by separate methods. Organic mercury poisoning is a unique situation where tests need to be done on whole blood since this form of mercury is mainly located in erythrocytes.
Neuromuscular	Radiculopathy	LOWER EXT NEUROPATHIES: femoral vs L3-L4 radiculopathy (also involves obturator neuropathy=thigh adduction w medial thigh n) happens inpelvic injuries/surgeries or retropritoneal hematoma or pelvic mass c hip flex knee ext weakness, loss of knee reflex and ant thigh numbness L3-L4= femoral + obturator sciatic neuropathy (post tibialis + common proneal) ddx stroke in foot area of motor cortex, radicuolopathy causes-muscular or bony pressure on sciatic, post hip dislocation, acetabular fx,im injection all foot ankle w plus knee flex w plus loss of achilles reflex and foot lateral leg n proneal palsy- ddx c L5 radiculopathy(distinguish from L5 radiculopathy-hip abduction <gluteus medius> should be spared in pure peroneal, distinguish from sciatic neuropathy- ankle inversion <tibialis post> and hamstrings should be spared, in other words sciatic neuropathy also involves foot inversion w as it carries out by post tibialis) ss foot drop, foot dorsiflexion eversion weakness no inversion weakness, lat leg n causes: stretch injury by forcible foot inversion, compression by tight stocking cast crossed leg or trauma L5= common proneal + post tibial Meralgia paresthetica- lat femoral cut nerve- lat thigh n no ref or motor w causes- obesity, pregnancy, weight loss, or heavy equipment belt wihch cause compression of nerve under femoral ligament ddx c L2 L3 radicucause motor w or knee areflexia Morton metatarsalgia- tight shoes compress toes nerves esp 3 and 4 one causing patchy paresthesia donpezil can be used in AD, Vascular dementia and mixed, MS, PD, ADHD, Closed head injury
Neuromuscular	Radiculopathy	Patients with spinal stenosis may have leg pain on exertion, which is relieved by rest (neurogenic claudication). This pain is worse with back hyperextension, relieved by leaning forward when walking (e.g. when using a shopping cart), and often not present when riding a bicycle. Absent peripheral arterial pulses suggests vascular claudication rather than neurogenic claudication. Erb-Duchenne upper plexus paralysis occurs secondary to damage to the fifth and sixth cervical roots or upper trunk of the brachial plexus. It is a common deficit and is usually due to traumatic separation of the head and shoulder but may also be due to pressure on the shoulder, birth injuries, or idiopathic plexitis. A femoral neuropathy causes quadriceps weakness with sparing of the adductors and iliopsoas muscles, absent or decreased ankle jerk, and loss of sensation of the anteromedial thigh and medial lower leg. Neck-Tongue synd. pain/paresthesia in half of the tongue following neck movement. sometimes c neck/occipital pain, trapezius discomfort, ipsilat hand paresthesia. getC spine MRI, cervical collar.
Neuromuscular	Radiculopathy	Radiculopathies Changes in dermatome myotome or reflex changes but could be overlaping and usually dense numbness is more indicative of a peripheral nerve lesion Etiology- * structural- Musculoskeletal (disk, spondylolisthesis, spondylosis eg lig flavum hypertrophy, facet syndrome), epidural abscess, mets * microscopic s evidence of mass lesion- (pt has normal mri but true radiculopathy) 1) infiltration by tumor carcinomatous or lymphamtous meningitis, 2) infiltration by granulamatous tissue eg sarcoid, or 3) infection eg Lyme, herpes zooster, cmv, herpes simplex 4) inflammation eg AIDP GBS 5) infarction eg vasculitis or dm causing nerve root infarction CT is the best imaging study for bone deformity combine with myelogram for soft tissue CT good for >350 and pacemaker MRI for soft tissue, MRI c s contrast useful to delinate scar from recurrent disease CT good for >350 and pacemaker MRI for soft tissue, MRI c s contrast useful to delinate scar from recurrent disease If bone deformity or hardware steel ct c myelo prefered titanium hardware you can get open mri mri for previous surgery or tumor infection bone scan for fx otherwise not visible like pars interarticularis facet artheropathy Discography only in discogenic pain may help localize orexclude a motion segment Brachial plexus - post cord ARTS - medial cord ulnar medial head of median - lat musculocutaneous lat head of median radiculopathy intact Motor Sens NCV paraspinal involvement nerve root avulsion intact S only NCS brachial plexopathy impair M S NCS mononeuropathy impair M S NCS
Neuromuscular	Radiculopathy	Upper ext nerve injuries- radiculopathy nerve root avulsion brachial plexopathy mononeuropathy * radi associated with radicular pain and abscence reflexes * plexupathy 2 type: upper trunk erb duchenne palsy waiter tip in traction of neonate shoulder or motorcycle accidents causes c5 c6 s s with deltoid biceps infraspinatus wrist ext weakness hand finger spared similar to c5 c6 radiculopathy or root avulsions Tx- immobilization PT/OT for range of motion exercise ortho consult EMG/NCS in3-4 months or 6 weeks Ortho operation in 5 moths lower trunk klumpke - grabbing something when falling from tree or thorasic outlet or pancoast tumors c8 t1 ss mainly hand finger ext weakness and ulnar neuropathy ss ddx c ulnar neuropathy t1 numbness occ horner and involvement of LOAF muscles c5 vs axillary mononeuropathy- in dislocation or fx of prox humerus c deltoid w and shoulder n c5 also cause biceps weakness Radial neuropathy- sat night palsy, crutch palsy or after humerous fx-w of all ext of arm/hand/finger wrist drop loss of triceps reflex radial distribution n subgroup trauma or pressure on post interosseous below elbow or tight wrist band or handcuff causing only numbness on back of hand (cheralgia paresthica) Median- honeymoon palsy, fx of humerous or distal radious, preacher (orator) hand subgroup- pronator synd as nerve passes through pronator tres muscle w of pronation cts- wrist,2&3 flexion and thenar n are spared since these nerves branch befor carpal tunnel tinel phalen flick (shaking of hands to relieve paresthesia) different hands- wrist drop radial palsy preacher (orator) hand-median palsy claw hand- ulnar palsy simian monkey paw hand- median and ulnar palsy ulnar palsy- fx of medial epicondyle, restin elbow on table, leaning while cycling compresssion of ulnar nerve over hamate bone in Guyon canal of wrist or cubital tunnel synd radiculopathy intact Motor Sens NCV nerve root avulsion intact S only NCS brachial plexopathy impair M S NCS mononeuropathy
Neuromuscular	Tensilon test	Tensilon test should be double blind edrophonium cl is rapidly acting anticholinestrase that improve ptosis and oculomotor paresis. rare pt supersensitive b/o depolarization of motor endplates or abn vagal response so code tray and intubation devices should be ready at the time. doses- in newborns SQ 0.15 mg/kg in infants IV 0.2 mg/kg reverse weakness within 1 minute
Neuroophthalmology		A lesion of the third nerve nucleus produces weakness of muscles innervated by that third nerve, but also bilateral weakness of the superior rectus, levator palpebrae, and pupillary constrictor muscles. A lesion of the third nerve itself does not affect any contralateral muscles. Thus, ptosis of the left eyelid could result from lesions of the left third nerve or either left or right third nerve nucleus. Cortical lesions have also been reported to cause either contralateral or bilateral ptosis on occasion. The optic nerve is part of the central nervous system and, hence, its myelin is derived from oligodendroglia as opposed to Schwann cells that provide myelin to the other cranial and peripheral nerves. Transient episodes of monocular or bilateral visual loss lasting seconds are characteristic of increased intracranial pressure and may be precipitated by changes in posture. Anton's syndrome, the denial of blindness, is typically associated with bilateral posterior cerebral artery territory infarction producing "cortical" blindness plus memory impairment.
Neuroophthalmology		Adie's tonic pupils dilated pupils nonreactive to light/accomodation respond to very diluted 0.125% pilocarpine and dec from 7-8 mm to 3-4 mm after 30 minutes parasympathtic denervation hypersensitivity areflexia, common in women 20-40 yo etiology- postviral, no pathology in CNS
Neuroophthalmology		CRANIAL NERVE III PALSY MANAGEMENT In complicated third nerve palsies where other neural structures are involved, have the patient undergo an MRI. In isolated third nerve palsies with no pupillary involvement where the patient is over 50, MRI scanning, an ischemic vascular evaluation, and daily pupil evaluation is indicated. If the patient is under 50 and has a non-pupillary involved isolated third nerve palsy, intracranial angiography is indicated since ischemic vasculopathy is less likely to occur in this age group than is aneurysm. If the adult patient of any age presents with a complete or incomplete isolated third nerve palsy with pupillary involvement, consider this to be a medical emergency and have the patient undergo intracranial angiography immediately. In these cases, the cause is likely subarachnoid aneurysm and the patient may die if the aneurysm ruptures. Children under the age of 14 rarely have aneurysms; the majority of third nerve palsies in this age group are traumatic or congenital. CLINICAL PEARLS * Isolated third nerve palsy due to ischemic vasculopathy will spontaneously resolve and recover over a period of three to six months. If the palsy fails to resolve in this time frame, repeat the MRI to search for the true etiology. * Myasthenia gravis has the ability to mimic virtually any cranial neuropathy, including isolated third nerve palsies. Myasthenia gravis must remain a possible diagnosis when encountering a third nerve palsy, especially when the course is variable or atypical.
Neuroophthalmology		CRANIAL NERVE III PALSY PATHOPHYSIOLOGY Third nerve palsy results from damage to the oculomotor nerve anywhere in its course from the nucleus in the dorsal mesencephalon, its fascicles in the brainstem parenchyma, the nerve root in subarachnoid space, or in the cavernous sinus or posterior orbit. Damage to the third nerve nucleus results in an ipsilateral third nerve palsy with contralateral superior rectus under action and bilateral ptosis. Damage to the third nerve fascicles results in an ipsilateral third nerve palsy with contralateral hemiparesis (Weber's syndrome), contralateral intention tremor (Benedikt's syndrome), or ipsilateral cerebellar ataxia (Nothnagel's syndrome). Vascular infarct, metastatic disease and demyelinization are the common causes of brainstem involvement. Damage to the third nerve within the subarachnoid space produces an isolated third nerve palsy. The main causes are compression of the nerve by an expanding aneurysm of the posterior communicating artery or the basilar artery, and ischemic vasculopathy. There will always be pain in aneurysmal compression and pupillary involvement is typical, though there have been infrequent cases of aneurysmal compression that did not initially affect pupillary function. In ischemic vascular nerve third palsies, pain is frequent and the pupil is typically normal and reactive. Damage to the third nerve in the cavernous sinus, superior orbital fissure, or posterior orbit is unlikely to present as third nerve palsy due to the confluence of other structures in these areas. Cavernous sinus involvement may also include pareses of cranial nerves IV, VI and V-1, and an ipsilateral Horner's syndrome. The most common causes of damage in these areas include metastatic disease, inflammation, herpes zoster, carotid artery aneurysm, pituitary adenoma and apoplexy, and sphenoid wing meningioma.
Neuroophthalmology		CRANIAL NERVE III PALSY SIGNS AND SYMPTOMS The patient will usually present with sudden onset unilateral ptosis (or rarely, a bilateral ptosis if the damage occurs to the third nerve nucleus), which is frequently accompanied by significant eye or head pain. The patient rarely complains of double vision because the ptosis obscures the vision in the affected eye; however, if the lid is manually elevated, the patient will experience diplopia. Acuity is typically unaffected unless damage occurs in the superior orbital fissure and cranial nerve II is also involved. The affected eye positions in a non-comitant exotropic, hypotropic position (down and out). There will be limitation of elevation, depression and adduction. There is an underaction of the superior, inferior, and medial recti muscles and inferior oblique muscle, which may be total or partial. The pupil may be dilated and minimally reactive to light (pupillary involvement), totally reactive and normal (pupillary non-involvement), or may be sluggishly responsive (partial pupillary involvement). The patient is frequently elderly and often has concurrent diabetes and/or hypertension. PATHOPHYSIOLOGY Third nerve palsy results from damage to the oculomotor nerve anywhere in its course from the nucleus in the dorsal mesencephalon, its fascicles in the brainstem parenchyma, the nerve root in subarachnoid space, or in the cavernous sinus or posterior orbit. Damage to the third nerve nucleus results in an ipsilateral third nerve palsy with contralateral superior rectus under action and bilateral ptosis. Damage to the third nerve fascicles results in an ipsilateral third nerve palsy with contralateral hemiparesis (Weber's syndrome), contralateral intention tremor (Benedikt's syndrome), or ipsilateral cerebellar ataxia (Nothnagel's syndrome). Vascular infarct, metastatic disease and demyelinization are the common causes of brainstem involvement.
Neuroophthalmology		CRANIAL NERVE IV PALSY 1 SIGNS AND SYMPTOMS The patient will present with complaints of vertical diplopia, which is especially manifest as the patient tries to read. There may be an inability to look down and in. There may also be horizontal diplopia, as a lateral phoria occurs due to the vertical dissociation. The patient often has a head tilt contralateral to the affected superior oblique muscle. The chin is often tucked downwards as well. There is frequently concurrent hypertension and/or diabetes. The patient will present with a hyperphoric or hypertropic eye on primary gaze. On alternate cover test, the hyper-deviation will increase in contralateral gaze, reduce in ipsilateral gaze, increase on ipsilateral head tilt, and decrease on contralateral head tilt. Visual acuity is unaffected and there is very rarely pain. In bilateral cranial nerve IV palsy, the patient will manifest a hyper-deviation which reverses in opposite gaze.
Neuroophthalmology		CRANIAL NERVE IV PALSY 2 PATHOPHYSIOLOGY The fourth cranial nerve nucleus is located in the dorsal mesencephalon. From here, the nerve fibers then decussate and exit the brain stem dorsally into the subarachnoid space. The nerve then courses around the brain to enter the cavernous sinus, superior orbital fissure, orbit, and innervate the superior oblique muscle. Damage to the fourth nerve nucleus or its fascicles within the brain stem will give a contralateral fourth nerve palsy, along with the associated signs of light-near dissociated pupils, retraction nystagmus, up-gaze palsy, Horner's syndrome, and/or internuclear ophthalmoplegia. Bilateral fourth nerve palsies are possible as well. The main causes of damage to the fourth nerve in this area are hemorrhage, infarction, trauma, hydrocephalus and demyelinization. The fourth nerve is especially prone to trauma as it exits the brain stem and courses through the subarachnoid space. In contrast to third nerve palsies within subarachnoid space, fourth nerve palsies are rarely due to aneurysm. The most common causes of damage to the fourth nerve in this region are trauma and ischemic vasculopathy. The most likely result from damage within subarachnoid space is an isolated fourth nerve palsy. Due to the large number of other neural structures that accompany the fourth nerve as it travels through the cavernous sinus and superior orbital fissure, it is unlikely that the patient will exhibit an isolated fourth nerve palsy due to damage within these areas. More likely, there will be an associated palsy of cranial nerves III and VI. Common causes of damage to the fourth nerve in these areas are herpes zoster, inflammation of the cavernous sinus or posterior orbit, meningioma, metastatic disease, pituitary adenoma, and carotid cavernous fistula. Trauma to the head or orbit can cause damage to the trochlea, resulting in superior oblique muscle dysfunction.
Neuroophthalmology		CRANIAL NERVE IV PALSY 3 MANAGEMENT A CN4 palsy often presents suddenly, but may additionally result from decompensation of a longstanding palsy. In order to differentiate these two types of palsies, examine old photographs of the patient. A patient with a decompensated longstanding palsy will present with a compensatory head tilt in old photos. Further, patients with decompensated longstanding fourth nerve palsies will have an exaggerated vertical fusional ability. Longstanding CN4 palsies typically are benign and no further management is necessary. In the case of complicated CN4 palsies, (i.e., those that present with other concurrent neurological dysfunction), the patient should undergo neuroradiological studies dictated by the accompanying signs and symptoms. In the case of isolated CN4 palsies caused by recent trauma, the patient should undergo an MRI or CT scan of the head to dismiss the possibility of a concurrent subarachnoid hemorrhage. If the CN4 palsy is not associated with recent trauma, investigate for a history of past trauma. If the CN4 palsy is due to previous trauma and has recently decompensated, you can manage the diplopia with vertical prisms. If the patient is elderly and has a CN4 palsy of recent origin, perform ischemic vascular evaluation to search for diabetes and hypertension. If the palsy is caused by vascular infarct, it will spontaneously resolve over a period of 3-6 months, periodic observation and either temporary occlusion or press-on prism therapy. CLINICAL PEARLS * Consider cases of true vertical diplopia to be a CN4 palsy until proven otherwise. In children, nearly all cases of isolated CN4 palsy are either congenital or traumatic. In adults, 40% of all isolated CN4 palsies are traumatic, 30% idiopathic, 20% due to vascular infarct, only 10% due to tumor or aneurysm. * Majority of CN4 palsies are benign. for sudden-onset isolated CN4 , delay permanent prisms for 3 months to allow autorecovery.
Neuroophthalmology		Horner syndrome 1 ptosis (muller muscle weakness in upper lid), miosis, Enophthalmus (pseudo b/o ptosis) and ipsilateral anhydrosis of the face (if external carotid invo. Other findings: - Iris blue or heterochronmia if lesion happened before age 2 - Loss of ciliospinal reflex (pinching back of neck C2-C3 afferent cause pupillary dilation) - Raeder para-trigeminal syndrome= orbital or periorbital pain, miosis and ptosis is considered varient of migraine, if associated with CN 3to6 palsy is due to middle cranial fossa mass There is a 3-neuron pathway to the 3 end organs (Muller muscle, External carotid branches, Iris dilator) involved. 1sr order sympathetic fibers arise from the hypothalamus, descend uncrossed through the mid brain and pons, and terminate in the intermediolateral cell column of the spinal cord in the C8-T2 segments. 2nd order preganglionic fibers exit the spinal cord at the level of T1, enter the cervical sympathetic chain, ascend and synapse in the superior cervical ganglion at the level of the bifurcation of the common carotid artery. Postganglionic fibers then travel along the ICA. Sudomotor fibers branch off, and travel along the ECA to innervate the blood vessels and sweat glands of the face. The pupillomotor fibers enter the cavernous sinus, then enter the orbit through the superior orbital fissure along with the ophthalmic branch of the trigeminal nerve (Vi) via the long ciliary nerves. Then, the long ciliary nerves innervate the iris dilator and Muller muscle (which elevates the eyelid along with the levator palpebrae - a cranial nerve Ill innervated muscle).
Neuroophthalmology		Horner syndrome 2 Causes - idiopathic most common - congenital, hereditary (auto dom) usually associated with iris heterochromia/albinism (blue eyes) as iris pigmentation is under sympathic control before age 2 - central lesions in hypothalamus, medulla wallenberg, upper cervical cord syrongomyelia, demyelination, trauma Horner in coma rare but can occur in large cerebral hemorrhage that affected thalamus and hypothalamus. Ipsilateral horner c laryngeal palsy suggest medullary lesion. Horner in SCI means lesion above T2. - Peripheral causes Pancoast tumor, trauma, carotid artery dissection or trauma or TB Sarcoidosis in upper cervical lymph nodes. Horner c cranial neuropathy of 9-12 can be associated c carotid artery blow out a fatal complication of lateral laryngeal space infection.
Neuroophthalmology		Horner syndrome 3 Dx and DDX Determination of Horners synd and localization of the defect in the sympathetic system can be achieved c cocaine (2-4%) and hydroxyamphetamine (1%) eye drops: cocaine inhibits the re-uptake of norepinephrine. Dx of Horner: Cocaine instilled in an eye c intact sympathetic innervation will produce dilation of the pupil. A sympathetically denervated pupil dilates poorly to cocaine, regardless of the level of the sympathetic system lesion. Read eye dilation 30 min after Cocaine drop DDx of preganglionic vs postganglionic lesions Hydroxyamphetamine stimulates the release of NE from presynaptic postgang nerve terminals. Hydroxyamphetamine instilled into an eye with Homer synd with intact postgang fibers (i.e., first- or second-order neuron lesions) dilates the pupil. An eye c damaged postganglionic fibers (3rd-order neuron lesions) doesnt dilate. 24 h wait between 2 drops 1 or 2 can not differentiated from each other. W/U - Chest CT or CXR - MRI and MRA or CTA - Document lesion is old or long standing,check old photos or driver license, if one eye is blue lesion happened before age 2 - DDx with Adies or Argyll Robertson eyes, Miotic drugs or Senile miosis or physiologic anisocoria
Neuroophthalmology		The vestibulo-ocular reflex is mediated by the semicircular canals. Optokinetic nystagmus requires foveal fixation and smooth pursuit. Both have saccadic eye movements as a component.
Neuroophthalmology	No Value	Extraocular muscle movement Botulism Diabetes Miller-Fisher Diphtheria Rule out: MG; Myopathy Eye movement ocular bubing in icu pt bad prognosis in thalamic lesions in pvegstate pt can have pursuit occipital movement saccadic eye movement in frontal eye feild optokinetic nystagmus with strip drum they should have downward saccad in PSP they loose it Opsuclonus myoclonus of eye The triad of optic ataxia, ocular apraxia, and simultanagnosia (Balint's syndrome) is usually the result of bilateral occipitoparietal junction lesions. The combination of dysconjugate, highly variable nystagmus, head nodding and head tilt without ophthalmologic abnormalities, and with normal neuroimaging, is diagnostic of spasmus nutans. Latent nystagmus is a jerk nystagmus that is evoked or enhanced by covering one eye. Congenital nystagmus is usually conjugate and suppressed by convergence (in contrast to spasmus nutans, that is typically increased by convergence). Opsoclonus describes chaotic, conjugate saccades, seen classically in the paraneoplastic syndrome associated with neuroblastoma. Whipple's disease produces a convergence-divergence nystagmus with associated movements of the muscles of the head and neck (oculomasticatory myorhythmia). Prosopagnosia (in which visual perception is intact but there is an impaired ability to recognize the identity of the perceived figure by vision alone) is nearly always associated with bilateral lesions involving the occipitotemporal junctional area. The optic nerve provides inputs to the superior colliculus (for reflex saccades), lateral geniculate nucleus (relay of the visual pathway), pretectal nucleus (relay of the light reflex) and the suprachiasmatic nucleus (the circadian pacemaker). The medial preoptic nuclei would be spared by enucleation of the eye. The pupils react normally in Horner's syndrome, while lesions of the parasympathetic pathway are associated with poor or absent reaction of the pupil to light.
NeuroOtology		Vertigo d/t ear disease 1) BPPV: secs in duration, positional, no ear symptoms, 25%trauma, 25%URI, paroxysmal, 50%balance problems, Dix-Hallpike: geotropic (nystagmus to down affected SC canal), latency, then crescendo decrescendo, then habituation, audio NL, tx: Epley (CRM). 2) Meniere's: hours in duration, not positional,+HL/tinnitus, sensation of ear fullness or pain, rare precipitating factors, recurrent, NL balance, DH: acute, Audio: low freq HL, tx: low salt/caffeine, diuretics, vasodilation, surgery (non destructive v. destructive: intratympanic gentamycin, labyrinthectomy, vestibular n. resection). 3) Vestibular Neuronitis: days in duration, not positional, occ. mild HL/tinnitus, post URI, not recurrent,+balance problems, DH: early nystagmus, audio: nl,tx: vest. rehab.
NeuroOtology	Smell	Smell Dysosmia parosmia triggered by another odor or phantosmia spontaneous etio: -trauma head and nasal - sinusitis - toxin chemiacal exposure meds - post viral URT infections - idiopathic wu stop new med or possible med cbc cmp b12 tsh ana esr spep zinc mri of brain and base of skull CT 5 mm cut through ethmoid, cribriform plate, temporal bone EEG tx Saline nasal drops 10 cc in each nostril in head down position tid or qid GBP up to 900 mg/day or Zonergan 200 mg/day Amitriptyline 50-150 qhs
NeuroOtology	Taste	Taste Dysgeusia etio: -meds in last 3 months discontinue may takes 3 m to heal eg lunesta, cardizem, topamax, ct, antirheumatologic etc -poor oral dental hygiene -DM - impair saliva production - hypothyroidism - low B12 or Zinc - viral men/encephalitis, herpes - Lupus Sjogren etc - idiopathic wu stop new med or possible med cbc cmp b12 tsh ana esr spep zinc mri of brain and base of skull CT 5 mm cut through ethmoid, cribriform plate, temporal bone tx food prepration: chew slowly, add spice, marinate, use orange lemon, add small amount of MSG, serve hot amd steamy rdevere@austin.rr.com zinc gluconate 40 mg tid no matter def or nor zinc has 2 fx taste cell generation improve salivary fx Cepacol lozenges with benzocain prn Xylocaine mouth gel 0.5 to 1 percent bid or tid GBP up to 900 mg/day or Zonergan 200 mg/day Amitriptyline 50-150 qhs Burning mouth disorder after dental tx nasal sinus infection fungal infection of mouth tongue abx therapy DM vit B or Iron def. Kidney disease BP meds eg ACE Inhib tx klonopin 0.5 to 2 mg/d GBP 1200/d Baclofen 30 - 60 mg/d Lamictal 200/day or combination of above
Neuropathology		Astrocytosis - Alz type II in hyperamonia, no cytoplasm like nonreactive astrocyte - Creutzfeldt in demyelinating - Bergmann in cerebellar ischemia - atypical bizzare astro in PML - Chaslin in subpial gliosis normal
Neuropathology		Down synd box brain for frontal lobe shape cortical thining arhinoencephaly- abcense of olfactory nerve and bulb Agenesis of CC can be associated c Aicardi (retinal calcification, coboloma, sz), dandy walker, tourette synd, chromosomal abn eg triosomy(dysmorphic face) associated c prox bundle
Neuropathology		Hippocampus purkinje cells begin to die after 4 min of total anoxia and ischemia, total brain limit of viability 10 minute.
Neuropathology		Inclusions Intracytoplasmic inclusions in oligodendroglia, termed glial cytoplasmic inclusions (GCIs), are found in multiple system atrophy (MSA). GCIs are immunopositive for alpha-synuclein and MSA is considered by some to be a "synucleinopathy." Neuronal intranuclear inclusions are found in Huntington's disease and other CAG-polyglutamine expansion diseases. Intranuclear "ground glass" inclusions in oligodendrocytes are characteristic of progressive multifocal leukoencephalopathy (JC virus infection). The characteristic inclusion body seen in rabies encephalitis is the Negri body, which is found in the cytoplasm of large neurons. Intranuclear -Cowdry A solitary large in herpes family, PML, SSPE -Cowdry B in Polio acute multiple small inclusions Intracytoplasmic
Neuropathology		Polymicrogyria results from failure of early neuronal migration or later postmigrational cortical destrucion. Seen in - IU hypoxia or hypoperfusion - TORCH esp CMV - peroxisomal disorders eg Zellweger, neonatal adrenoleukodystrophy - Fukuyama congenital muscular dystrophy Pachgyria thickening of cortex Lissencephaly smooth brain actual defect is pachgyria. associated with genetic defect LIS1 and REELIN gene defect.
Neuropathology		The cell shown contains a neurofibrillary tangle -an intraneuronal intracytoplasmic inclusion composed of paired helical filaments. The section has been stained with a silver stain. Neurofibrillary tangles can be seen in a variety of conditions including Alzheimer disease, Pick disease, progressive supranuclear palsy, Down syndrome, Parkinson-dementia complex of Guam, and post-encephalitic Parkinsonism.
Neuropathology		Triplet diseases Myotonic dystrophy Huntington Fragile X Friedrich ataxia SCA spinocerebellar ataxia
Neuropathology	Brain tumors	Angioinvasive branching fungal hyphae are characteristic of aspergillosis and mucormycisis. In contrast, in blastomycosis, coccidioidomycosis, cryptococcosis, and histoplasmosis rounded yeast forms are seen. Candidiosis has both fprm hyphae and yeast. The photograph shows a biphasic cellular population consisting of small reactive lymphocytes and large neoplastic germ cells, which is characteristic of germinoma -the most common pineal region tumor. Pineocytomas, in contrast, are composed of small mature pineocytes that form large rosettes with fibrillary cores. Pineoblastomas are densely cellular primitive neuroectodermal tumors that often form Homer Wright (neuroblastoma-type) rosettes and occasionally fluerettes. Pineal astrocytomas show prominent eosinophilic cytoplasmic processes. Regarding terminology, the designation "pinealoma" is an inaccurate, arcane and imprecise historical relic that should not be used; it dates to a time before a distinction was made between germinoma and pineoblastoma. St Anne/Mayo classification of astrocytoma grade I none II pleomorphism III pleomorphism + mitotic figure IV + neovascularization or necrosis
Neuropathology	Infection	4 forms of CNS TB- basilar meningitis, tuberculoma, abcsess, malacia or paranchymal form AIDS CNS- d/t HIV, Opportunistic infections, Neoplasm The astrocyte illustrated in the photomicrograph is a Creutzfeldt astrocyte. These reactive astrocytes are characterized by multiple small nuclei (micronuclei) and abundant eosinophilic cytoplasm. Although not pathognomonic, they are typically seen in demyelinating diseases and serve as a red flag to alert the pathologist to consider demyelinating disorders in the differential diagnosis. There are a number of other types of astrocytes with distinctive morphology. The Bergmann astrocytes of the cerebellar cortex send long cytoplasmic processes from the Purkinje cell layer to the pial surface and show striking proliferation in response to ischemic insult. Alzheimer type II astrocytes can be seen in many types of liver failure that result in hyperammonemia. They differ from all other reactive astrocytes in lacking discernible cytoplasm; rather, the nuclei are enlarged, pale, with only a thin marginal rim of chromatin, and are often irregular in shape. Superficial reactive astrocytosis occurring in the normally very hypocellular molecular layer is referred to as Chaslin’s subpial gliosis. Finally, highly atypical, bizarre reactive astrocytes can be seen in progressive multifocal leukoencephalopathy (caused by infection with the JC virus).
Neuropharmacology		Cocaine, like amphetamine, binds to the presynaptic dopamine transporter (DAT) inhibiting dopamine reuptake and increasing dopamine concentrations in the nucleus accumbens. This mechanism underlies the acute reinforcing effects of these drugs of addiction. The hypocretin/orexin system of the lateral hypothalamus has been implicated in the mechanisms of narcolepsy. These neurons project to cholinergic and monoaminergic cell groups involved in regulation of REM sleep. Reduced CSF levels of hypocretin and reduced numbers of hypocretin cells have been found in patients with narcolepsy. NMS d/t insufficient stimulation of dopamine receptor participated by neuroleptics tx c bromocriptine. Statin myopathy d/t inhibition of mevalonic acid synthesis, precursor of several essential metabolites including Coenzyme Q10 (ubiquinone) This toxic action potentiate by clofibrate, gemfibrozil, nicotinic acid, cyclosporine.
Neuropharmacology		Fish/Shellfish poisoning Saxitoxin in NE NW USA Ciguatoxin in FL HA brevotoxin in gulf of Mexico & Caribbean Domic acid (glutamic agonist)in eastern Canada Tetro dotoxin in Japan by puffer fish
Neuropharmacology		neurologic ADR Bactrim chemical meningitis Vancomycin ototoxic Ethambutol optic neuropathy Zalcitabine for HIV sensory neuropathy Acyclovir tremor CT Agents methotrexate intrathecal transverse myelopathy Cisplatin sensory polyneuropathy 5FU cerebellar dysfunction Vincristine peripheral neuropathy/Sz BCNU necrotizing encephalopathy
Neuropharmacology		Neurotransmitter metabolism After presynaptic reuptake, neurotransmitters are metabolized by specific enzymes. Some of the metabolites can be measured in the cerebrospinal fluid as an indirect index of activity of the corresponding neurons. GABA is metabolized by GABA-transaminase to succinic semialdehyde, which serves as a precursor in the Krebs cycle. Monoamines are metabolized by monoamine-oxidases and methyltransferases. The final metabolite of dopamine is homovainillic acid; of norepinephrine is 3-methoxy-4-hydroxy-phenylglycol (MHPG), of serotonin 5hydroxyindoleacetic acid (5-HIAA), and off histamine methyl-imidazolacetic acid (MIAA)
Neuropharmacology		Pain po takes 1 hour im,sc 30 min iv 6-15 min takes to reach Cmax or kick in It needs about 3-5 half life to reach steady state. PO narcotis usually half 4-5 halflife, parenteral 3 hours. for normal takes one day to adjust the dose, for XR c halflife of 8-12 h dose adjustment should be 2-4 d, for methadone dose adjustment qweek. not recommended Demerol noremeperidine longer hl than demerol and they get build up. Propoxyphene or Darvocet useless Dependence vs Addiction if dose reduction required reduce by 25-50% q 3-4 days. How to cope c beureau of narcotics: - notify in writing about practice change - document phy-pt relationship - chart every prescription - schedule III drug tylenol3, lortab can be called in and you may be cheated
Neuropharmacology		Ptosis (upper lid reach or cover pupils) -mitochondrial myopathy -in old ages ocilopharyngeal muscular dystrophy - myotonic dystrophy stiner disease - MG (in ALS no ptosis ladt muscle to get involved) - LEMS - GBS papapa/bababa tatata/lalala kakaka/gagaga respectively show lip tongue palate weakness AC nuc meissner, pedunculopontine NE LC labeled by tyrosine hydroxylase S MRN D SN GABA CerebellumGPi SNpars reticulata label GADecarboxylase Glutamic acid subthalamic nuclei label by glutaminase Glycine Spinal cord Histamine hypothalamus tuberomamillary nucleus Glutamic activation of NMDA receptor requires presence of glycine
Neurophysiology		Vitamin deficiencies Pyridoxine deficiency results from dietary deficiency of pyridoxine, and has occurred in infants given formulas in which the sterilization process has destroyed pyridoxine, or in milk from unusual sources that is intrinsically deficient in pyridoxine (such as goat's milk). It should be distinguished from pyridoxine dependency, an autosomal recessive disorder in which mutations producing conformational changes in glutamic acid decarboxylase cause early onset seizures that are controlled by pharmacologic doses of pyridoxine.Cobalamin (vitamin B12) deficiency may follow inadequate dietary intake (as in some vegetarian diets), or malabsorption with or without intrinsic factor deficiency. Patients typically have a slowly evolving syndrome of loss of posterior column function, with parethesias, loss of vibration, proprioception and two point discrimination, and eventually spasticity and cognitive impairment.Thiamine deficiency most often occurs because of inadequate diet, as in alcoholics. Individuals with marginal diets may develop overt symptoms of thiamine deficiency if their remaining reserves are depleted by glucose loading. Acute thiamine deficiency causes Wernicke's encephalopathy, characterized by ataxia, confusion and abnormalities of eye movements.
Neurophysiology	Evoked Potentials	VEP - Check size to be 30-40 formaximal visual stimulation - Make sure pt look at the center of the screen - Indications MS, Pseudotumor, Optic nerve trauma, Postsurgical cahnges, Neoplasm BAEP - Acoustic neuroma interpeak latency I-V - Cochlea patholgy - MS pattern good I and II but IV and V distorted because MS is intraparanchymal pathology in brain stem - BAEP not sensitive to drug but sensitive to hypothermia - Interoperative monitoring - Hearing loss in infants and neonates SSEP - Spinal cord pathology Transverse Myelitis - MS - Intraoperative monitoring Motor EP or
Neuroradiology		ADC acute infarct has dec ADC in contrast to T2 shine through if lesion truly an acute infarct it should remain bright on adc map MS lesion have high ADC
Neuroradiology		BG changes - GP CO poisoning - Putamen methanol Putamen, Thalamus Wilson - Leighs disease - BG cacification Fahr's disease - BG iron deposit Hallverdon Spatz pnk gene panthokinase def - Caudate trophy Huntington - Caudate hypertrophy Sydenham chorea - Kernicterus unconjugated bilirubin passes into selected nuclei, especially globus pallidus, subthalamus and Ammon's horn in term infants. late onset neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz syndrome. In the globus pallidus can be observed the “eye-of-the-tiger” sign, described originally in this disorder and later found also in cortico-basal-ganglionic degeneration and in progressive supranuclear palsy.
Neuroradiology		Depressed fx compound when skin laceration penetrating when dura is torn Epidural more arterial lens shaped and more with lucid interval c/t SDH. if fresh SDH maybe isodense and be missed on CT.
Neuroradiology		fMRI, PWI, MRSpectroscopy Perfusion-weighted MR imaging (PWI) allows an assessment of perfusion of the brain microvasculature. PWI requires intravenous gadolinium contrast that causes a paramagnetic susceptibility effect. MRI signal declines as gadolinium transits the microvasculature. One of the uses of PWI is to complement the information obtained by diffusion-weighted MRI (DWI) in acute stroke patients. A variety of perfusion properties of the contrast bolus can be calculated, such as cerebral blood volume, cerebral blood flow, mean transit time, time-to-peak, and time of arrival. Flow-related enhancement is used in MR angiography. Changes in venous oxygenation are used in functional MRI. Magnetization transfer pulses, such as those used in MR angiography, measure magnetization transfer effects. MR spectroscopy measures brain metabolites such as choline in parts per million (ppm). Normal brain myelination is a dynamic process that begins during fetal life and continues after birth in a predictable manner. The progress of the myelination is seen as changes in white matter signal on the MRI image. In the term infant, myelination is best assessed on the T1-weighted image where it is seen as high signal. Normal adult patterns are seen by 18 months of age. Some areas, such as the white matter dorsal and superior to the ventricular trigone, have persistent high signal on T2-weighted images, which should be considered normal. These association fibers often become myelinated by the second or third decade of life. In proton magnetic resonance spectroscopy, the N-acetyl aspartate peak is an index of neuronal integrity; lactate acid of anaerobic glycolysis, phosphocreatine of energy metabolism, and choline of membrane synthesis and degradation.
Neuroradiology		Inc signal in T1 - hemorrhage, fat, melanoma(melanin, pr rich tissues), contrast, mucin, ca(hydrated) keratin hypodense in T1 Hyperintensity on T1-weighted image results from shortening of T1 relaxation time. This is seen in a variety of tissues on noncontrast images, most commonly, blood, fat, calcium, and protein-rich tissue. Toxic leukoencephalopathy is associated with exposure to therapeutic agents (particularly antineoplastic drugs), drugs of abuse and environmental toxins. Hyperintensity of white matter on T-2 weighted sequences is characteristic, and the diagnosis should not be made in the absence of such changes. Methotrexate and carmustine are the anticancer drugs most commonly implicated in toxic leukoencephalopathy. Carbon monoxide poisoning typically produces demyelination that begins days to weeks after exposure. Alcoholism produces a number of changes, including an excessive number of white matter hyperintensities, loss of total white matter volume and preferential involvement of the frontal white matter that correlates with observed neuropsychological deficits. Elongated lesion demonstrating hyperintensity on T2 -weighted images is most consistent with multiple sclerosis (MS) and represents focal demyelination. Degenerative myelomalacia may have these signal characteristics and ill-defined margins, but there is no adjacent spurring or other degenerative bony disease to have caused this problem. Ependymoma would be seen as a more focal mass with cord enlargement. Syrinx has well defined cavity margins, though would be of similar signal intensity as the lesion pictured. The lesion is too dorsal for motor neuron disease. MS cord lesions are usually one to two segments in length, or less. Both images demonstrate the missing vermis thus the 4th ventricle connects with the cisterna magna, the hallmark of Dandy-Walker malformation. The posterior fossa is enlarged.
Neuroradiology		Ring enhancing lesion tumor abcess cysticercosis cyst resolving hematoma less likely mass
Neuroradiology		Schmorl node Vertical disk herniation may cause LBP esp in teenagers active in sport activities. May not be detected in plain x ray films If it cause inflammatory response in bone marrow eg low intensity on T1 and high intensity on T2 around the node need to be treated or will be symptomatic. Common in mid and lower spine, common in teenagers, may cause radicular pain if there is signal changes in MRI Causes- trauma young athlets, (rare causes hyperpara, osteoporesis, osteomalacia, infection, tumor) Tx- NSAIDs, rest, prevention of axial pressure on spine
Neuroradiology		White matter changes - leukodystrophies MLD ant sparing u fiber ALD occi parietal sparing u fiber Canavan diffuse involves u fiber Krabbes associated with brain atrophy - gliomatosis cerebri - post leukoencephalopathy in htn mtx toxicity, eclampsia - Vasculitis ANA ESR APL ANCA CRYO - Binswanger's disease in HTN, pseudobulbar affect - CADASIL blood genetic test - Cocaine Heroine abuse - HIV HTLV1 - B 12 def myeloencephalopathy - glue or spray sniffing as a form of recreational drug use. Toluene exposure over time causes cognitive deficits and white matter abnormalities in cerebral white matter. Toluene toxicity is often the result of "recreational" abuse by sniffing and inhaling fumes from spray paint cans. Patients who chronically inhale toluene vapors develop dementia (clinically consistent with subcortical dementia), cerebellar ataxia and long tract findings, and in some cases cranial nerve palsies. It is not uncommon for these patients to also manifest a paranoid psychosis. MRI demonstrates a diffuse leukoencephalopathy, cerebral atrophy, and T2 hypointense lesions of the thalamus and/or the basal ganglia. front alexander MLD post adrenoleukodystrophy sparing u fiber multifocal adem Vanishing white matter disease
No Value	eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee	Steroid Equivalency Cortisone 25 qd eg hydrocortisone Cortisol 20 Prednisone 5 Prednisolone 4 eg methylpredniso Dexamethasone 0.5 mg
Ped Neurology		ADHD Pemoline and methylphenidate have both been of some benefit in the treatment of attention deficit disorder in children. Clonidine, a central agonist of the alpha-2 adrenoreceptors, is helpful to decrease hyperactivity and impulsivity in these patients. ADHD and obsessive-compulsive symptoms are often associated with Tourette's syndrome. Boys are more often affected than girls. An increase in seizures is not seen. Coprolalia is not necessary for the diagnosis. Tic can be seen in ADHD, OCD Tourette can get worse by psychostimulant such as methylphenidate. Tx c haloperidol, pimozide, clonidine
Ped Neurology		Board oral exam - localization - diff - dx - management - family counseling 3 yo c NV weakness intact reflexes, salivation- GBS, MF, organophosphate poison, porphyria, infections, rabies, rhomboencephalitis listeria unpasteurized milk, amebia negleria swimming in water, tick bite, bickerstaff encephalitis, tx ABx, IVIG,
Ped Neurology		Chromosomal disorder Down trisomy 21 Turner XO Prader-Willi & Angelman syndromes DNA Deletion in ch 15q (all PWS pt inherit a deleted ch 15 from father, all AS pt inherit defective ch 15 from mother) PWS defective hypothalamus-dec GH short stature, hypogonadism, hyperphagia obesity, thermoinstability. AS pt happy puppets c flat head, jerky movement, protruding tongue, bouts of laughter
Ped Neurology		Dandy Walker - agenesis of cerebellar vermis - cystic dilation of post fossa - hydrocephalus could be associated c - CCAgenesis - AS aqueductal stenosis - Heterotopia SS compression of post fossa lead to - apneic spell - nystagmus - truncal stenosis - CN palsies - hyperreflexia
Ped Neurology		Developmental delay progressive vs static (CP) progressive- WM vs GM GM- sz, cognitive deficits, personality changes, blindness WM- corticospinal tract, FND, hyperreflexia, ataxia, gait difficulty DDx - infections - metabolic - toxins - child abuse - ALTE, acute life threatening event - vascular, stroke metabolic - lysosome storage disease progressive - fatty acid oxidation when they get sick or starved they try to metabolize FA and it goes to faulty metabolism and cause neurological deficits. tx at acute stages is giving pt high glucose. Don't let them fast. screening for long chain, medium chain FA tests- LA, PA, CPK serum Aminoacids Urine organic acids the clue is get the test when they get sick, hand them list of the tests need to be done when they come to ER. self mutilation- Lecsh Nyhan, any hereditory sensory autonomic neuropathy, amyloidosis, Fabry LN purine metabolism, high uric acid, chorea BG bil- methanol, co, mercury, organic aciduria, Farr's disease deposit of iron ca, wilson, hyparthyroidism, HIencephalopathy, mitochondrial disease, leukodystrophy Stepwise worsening of pt in response to infections/fever - mithochondrial disorders - AA, OAciduria eg glutaric aciduria - Leukodystrophy - FA oxidation metabolic disorders serum VLCFA perioxisomal disorders, Carnithin profile level for deficiency that can also be seen with VPA tx (give carnithin 400 mg tid or 1-3 g/day) - Urea cycle disorders - lysosome storage disease eg gaucher Opistothunus - toxic antipschotis phenothisins - tetanus - BG disorders mithochondrial, Hallovorden Spatz, Wilson - Gaucher - Sandhoff - OAciduria - malignant hyperthermia
Ped Neurology		Glycogen storage diseases Pompe's disease is a lysosomal glycogen storage disease that affects practically all tissues and results from a defect of 1,4-glucosidase (acid maltase). Hypotonia, failure to thrive, and decreased reflexes develop during the first few months of life. Cardiomegaly is prominent in infantile forms, which more commonly present with pulmonary insufficiency. Unlike other glycogeneses, the liver is normal in size or only slightly enlarged and there are no abnormalities of glucose homeostasis. PAS-positive glycogen is seen in membrane-bound vacuoles in muscle, hepatocytes, and Schwann cells, but no abnormalities are seen in myelin sheaths.
Ped Neurology		Infantile botulism usually presents between 3 and 18 weeks of age. The disease is caused by the C. botulinum toxin which blocks acetylcholine release. Clinical features include constipation, hypotonia, areflexia, poor suck, impaired pupillary response to light and ophthalmoplegia. The infants are often breast-fed. Diagnosis is made by EMG with repetitive nerve stimulation, causing an incremental response and isolation of C. botulinum toxin in the stool. Children who develop infantile botulism typically are normal at birth and develop normally until the second to fifth month of life. Hypotonia then develops, accompanied by constipation. On examination the patient is quite weak and areflexic. Compound muscle action potential recording in response to 50 Hertz stimulation produces a diagnostic incrementing response.
Ped Neurology		Menke disease primary defect in intestinal transport of copper. dec copper and ceruloplasmin in serum kinky hair eyebrow, cheek fullness micrognathia, high arch plate, sz (myoclonic), lethargy hypotonicity, w/u radiography of long bone for ostegenesis imperfecta, hair analysis, genetic test for ch Xq13 mutation Tx- copper supplementation c copper histinate
Ped Neurology		Metabolic & Storage diseases Lipidoses - GM1 Gangliosidoses ß Galactosidase - GM2 Gangliosidoses Hexosaminidase - Fabry disease á Galactosidase - Gucher ß Glucosidase - Nieman Pick Sphingomyelinase - Faber disease Acid ceramidase - Wolman disease Acid lipase - Refsum disease Phytanic acid ãhydroxylase - Cerebrotendinous xanthomatosis - Neuronal lipofuscinoses (Batten) CLN1-5 gene products Leukodystrophies - Metachromatic Leukodystrophy - Krabbe Leukodystrophy Mucopolysaccharidoses - Hurler synd - Hunter synd - Sanfilippo synd - Morquio synd - Maroteaux-Lamy synd Mucolipidoses - Sialidoses - Salla disease - Fucosidosis - Mucolipidosis II III IV Peroxismal disease - Zellweger (cerebrohepatorenal synd) - Adrenoleukodystrophy - Refsum disease Cherry-red spot - Tay Sachs - Sialidosis usually - 50% of Niemann Pick - 50% of GM1 Gangliosidosis - Farber disease(inconstant) - Metachromatic leukodystrophy Conjunctival telangiectasia - Ataxia telangiectasia - Fabry disease (glycolipids accumulation in cerebral blood vessle stroke, glomeruli, PN pain c autonomic manifestation, typical rash in lower half of body)
Ped Neurology		Migraine in children - no gender difference - quicker onset - shorter duration - variants benign paroxysmal vertigo paroxysmal torticollis cyclic vomiting hemiplegic/basilar migraine confusional migraine
Ped Neurology		Neurocutaneous ds causing sz in infancy - Incontinentia Pigmenti - Linear Nevus Sebaceous Synd. - Neurofibromatosis (I c optic glioma II c acoustic schwanoma) - SWeber synd - TScelrosis c SEGA Tumors associated with Neurocutaneous ds - Neurofibromatosis (I c optic glioma II c acoustic schwanoma) most tumors esp neurofibroma/schwanomas - TScelrosis c SEGA - von Hippel Lindau c cerebellar hemangioblastoma - bathing trunk nevus c skin or CNS Melanoma
Ped Neurology		Neurodegenerative disorder WM- loss of motor skills, spasticity, ataxia GM- loss of intellectual skills (dementia), Sz, blindness
Ped Neurology		Newborn child with Apnea ddx Sz Meabolic disorders
Ped Neurology		Non epileptic spells in pediatrics divide to c LOC and s LOC c LOC 1) Syncope - Pallide infantile syncope frightened or cold blow to face - Cyanotic infantile spasm, older, temper tendrum, breath holding spells 2) Cardiac dysrhythmia (prolonged QT syndrome) 3) Migraine (basilar artery migraine) ophthalmoplegic, hemiplegic, vertigo, NV not much HA, ca channel mutation, ATPase mutation 4) Psychogenic mutation 5) ADHD 6) GERD, first 1-2 months with apnea, syncope, sandifer syndrome (arching) 7) HVT with dizziness, syncope 8) Sleep disorders -Parasomnias: night terros(+FHx), Somnambulism, Somniloquoy -Sleep myoclonus - Narcolepsy/Cataplexy - OSA (big tonsils) s LOC Movement disorders in general eg chorea, Tics, GERD (sandifer), shrudding attack (shaking attack), Paroxysmal kinosiogenic dyskinesia, Hyperekplexia (Jumping frenchman of Maine, New Orleans, Quebec, Stimulus myoclonus from Glycine receptor gene) Most Sz inPeds are cryptogenic (perhaps more genetic related) <3 months infants have RAM onset sleep especially after feeding. Almost all neonatal sz are partial <3-6months.
Ped Neurology		Normal milestones
Ped Neurology		Rett syndrome DDx- autism, CP, nonspecific developmental delay normal up to 6-18 months then regression with problem with expressive language, loss of purposefull hand movement, stereotype hand movement washing, wringing, tapping, clapping, unsteady gait, stiff leg/toe walking May have Sz, bruxism Mutation in MECP2 gene on X chromosome Tx- sowing of motor disability, PT/OT, and or elbow splint for reducing hand movement, intermittent weighted mobilization, music and hydrotherapy, speech therapy for communication skills, scoliosis management by ortho, prevention of bone loss ca, agitation tx less stimulating environment, laxatives for constipation
Ped Neurology		Storage diseases Seizures, blindness, psychomotor retardation are cardinal features of Tay-Sachs disease. Tay-Sachs disease is an autosomal recessive disorder in which hexosaminidase A is deficient and hexosaminidase B is increased. The disorder is panethnic, but is more frequent in Ashkenazy Jews. Prenatal diagnosis is now available. Hepatosplenomegaly is not a feature of Tay-Sachs disease, but does occur in Sandhoff disease (deficiency of hexosaminidase A and B). Macrocephaly is frequent in GM2 gangliosidoses. Zellweger's cerebro-hepato-renal syndrome presents with hypotonia and cranio-facial dysmorphic features and the brain shows widespread neuronal migration defects, especially pachygyria and cerebellar abnormalities. Wolman's disease, due to acid lipase deficiency, presents with diarrhea, vomiting, failure to thrive, hepatosplenomegaly and adrenal calcification, but minimal CNS abnormalities. Farber's disease is characterized by painful swelling of the joints and subcutaneous nodules; neurons show stored material but widespread migrational abnormalities are rarely found in the brain. Pompe's disease is primarily a disorder of muscle and presents with hypotonia, and while neurons and astrocytes may show increased storage of glycogen, there are no associated migrational disorders in the brain. Krabbe's leukodystrophy demonstrates no migrational disorders in the brain. Fabry's disease is an X-linked defect in the alpha-galactosidase. It is characterized by painful peripheral neuropathy with autonomic manifestations, a typical rash in the lower half of the body, and accumulation of glycolipids in the endothelium of cerebral vessels and glomerular arterioles. Current therapy for Bassen-Kornzweig disease includes high dose vitamin E; for Hartnup disease, nicotinic acid; for Refsum's disease, dietary restriction of phytanic acid; and for multiple carboxylase deficiency, biotin.
Ped Neurology		Sturge-Weber disease is characterized by a meningeal vascular malformation and calcification in the second and third layers of the underlying cortex. can be associated c port wine nevus on the face maybe progressive do ophthalmology consult for glucoma may have HA cause NV sz control c pb check MRI q6m or annual hemiatrophy skull x ray for ram track EEG SWeber clinic check for hemiparesis pb syrup alcohol based some kids don't like it can use tab 30 mg half bid take c only little water or formula Von Hippel Lindau hemangioblastoma in cerebellum renal cell carcinoma, pheochromocytoma parynchymal cyst PCKidney liver Osler Weber Randau hemorrhagic Telangectasia leptomeningial GI hemorrhage
Ped Neurology		Tegretol 100 chewable tablets no generic substituation 100 bid for 5 days 100 tid for 5 days 150-100-150 continue Dilantin 5 mg/kg/day orally for 2 weeks then taper to dc over 2 weeks check cbc cmp teg level in 3-4 weeks at pcp office - baseline lfts if not done - neuro f/u in 2 months - MRI
Ped Neurology	Ataxia	Ataxia DDx Acute recurrent ataxia 1- Drug tox (psychoactive drugs, AEDs, antihistamines esp in setting of OM) 2- brain stem encephalitis or post infectious eg ADEM, Miller Fisher, MS, Myoclonic encephalopathy and neuroblastoma 3- Genetic Episodic ataxia like PParalysis Hartnup, Maple, Pyruvate DH def. 4- Migraine basilar or BPVertigo 5- Epilepsy pseudoataxia 6- Trauma hematoma postconcussion VB dissection 7- Vascular cerebellar stroke hemo, Kawasaki disease 8- Conversion 9- Hydrocephalus magnetic gait Chronic static or progressive ataxia 1- Congenital malformation cerebellar degeneration, AC or DW malformations, basilar impression (odontoid pressure on spinal cord) 2- Brain tumor eg cerebellar astrocytoma, hemangioblastoma VHL disease, ependymoma, medulloblastoma 3- Herditary AD SCA spinocerebellar ataxia triplet disease AR Metabolic hartnup, maple syrup, GM2 gangliosidosis, pyruvate def, ramsy hunt synd, refsum (HSMN IV, deafness) Most common Friedreich ataxia Ataxia Telangectasia (recurrent sinopulmonary infection, oculomotor apraxia, ataxia telan(malar, conjunctival which develop before nystagmus & ataxia),choreoathetoid movement, inc risk of B cell neoplasia eg lymphoma, Hodgkin or ALL) X Linked ADLDystrophy(white matter, spasticity, behavioral changes ddx in adult c adrenalmyelinoneuropathy) Leber optic atrophy The syndrome of spinocerebellar degeneration is most characteristic of prolonged chronic vitamin E deficiency. hereditory ataxia Friedrich ataxia Adult ataxia-SCA Machado Joseph disease OPCAtrophy DentoRubropallidoal atropy Ataxia Telenctgasia
Ped Neurology	Ataxia	Friedreich Ataxia Lesions associated with Friedreich ataxia include degeneration of the posterior columns, corticospinal tracts, spinocerebellar tracts and dorsal roots. Anterior motor neurons are not affected. ataxia more truncal than appendicular, dec position vibration in LEs, ddx with severe combined degeneration of B12. triplet GAA Frataxin Ch. 9 mithochondrial inner membrane iron deposit w/u - spinocerebellar degeneration panel CAG triplet repeat, ataxia panel - EKG ECHO more cardiomyopathic hypertrophy than dysrrhytmia c dyspnea on exertion chest pain(the more triplet repeat more cardiac involvement, Ibedonide) - NCS/EMG more dec amp in sensory normal motor - PT/OT - SPEP Vit E (def) - GTT 10% develop DM - Ortho consult for scoliosis >35% - MRI of brain for cerebellar degeneration, AC or DW malformations, cerebellar astrocytoma, hemangioblastoma, ependymoma, medulloblastoma - MRI of spine for cord atrophy - Tx vit E, coenzyme Q, mithochondrial cocktail carnitine, NIH Study drug name for prevention of hypertrophic cardiomyopathy. The syndrome of spinocerebellar degeneration is most characteristic of prolonged chronic vitamin E deficiency. 5 hydroxytryptophan new treatment for FA
Ped Neurology	Hypertonicity	Hypertonicity respiratory distress pain tonic sz dt birth asphyxia, meningoencephalitis or metabolic abnormality - check for metabolic problems lactic pyruvic acid, aminoacids organic acid - ammonia level neonatal drug withdrawal neonatal tetanus sandifer gerd hyperplexia neuromuscular pathology
Ped Neurology	Hypotonicity	Hypotonicity1 - ammonia level - check for metabolic problems lactic pyruvic acid, aminoacids organic acid, CPK - TSH, FT4 - Chromosomal study Causes- Dysgenetic syndromes eg Down Prader-Willi synd, Zellweger, Riley-Day (familial dysautonomia) synd. toxins eg fetal exposure to heroin, dilantin, etoh or tridione can also cause dysmorphism and hypotonia Perinatal insults to brain spinal cord eg birth asphyxia, hypoxic/ischemic brain injury, ich, bacterial/viral infections, metabolic disturbances, extereme prematurity - spinal cord injury following iu malpositioning or traumatic birth (sphincter dysfx and loss of sensation below midchest) NM disorders- - SMA Most common a recessice disorder Werdnig-Hoffman-limb weakness areflexia tongue fasciculation - Poliomyelitis - Infantile neuropathies eg metachromatic leukodystrophy, adrenaloleukodystrophy, giant axonal neuropathy, petoneal muscular atrophy - infectious diphteria, GBS, tick paralysis, infantile butulism - Myasthenia congenital nonimmunologic vs neonatal - Myopathies congenital (central core, nemaline, myotubular), metabolic(Pompe, mitochondrial, cytochrome-C oxidase def.), myotonic dystrophy Connectiv tissue disorders- congenital ligament laxity, Ehlers-Danlos, Marfan Metabolic- - congenital hypoglycemia/hypothyroidism (have hypothermia) - aminoaciduria, organic acidemia, ca disorders, renal tubular acidosis, metabolic cerebral degenerations (leukodystrophies, lipid storage diseases, peroxisomal diseases, mucopolysaccharidosis , aminoacidurias, Leigh synd.) Focal neonatal hypotonia flaccid arm imply brachial plexus injury BPI upper bpi maybe with ipsilateral diaphragm paralysis, loer bpi with ipsilateral Horner dx by emg, spinal evoked potential or mri may show nerve root avulsion Leg hypotonia/weakness- spinal dysraphism, caudal regression synd., arthrogrypotic leg seformity or gross maldevelopment of the leg associated c sacralagenesis (seen in 15% of dm mothers)
Ped Neurology	Hypotonicity	Hypotonicity2 frog leg position head drop more then 45 traction if central they have dec MS, hyperreflexia Central causes of hypotonicity acute- HIE [multiorgan failure and encephalopathy/sz/low APGAR score alone is not enough, not 1-5 min but 10 minute APGAR is relevent] /Trauma, infection, metabolic aquired eg T4 vs inborn errors AA OAciduria chronic- brain malformation, chromosomal abn (21, cri du chat, pradder willi) Ant horn cells- SMA 123, Autosomal recessive 25% chance in other kids, dec movements in uterine, dx by DNA test blood cells or skin fibroblast, life expectency less than 6-18 months, need feeding tube, res failure intubation like locked in syndrome. Congenital polyneuropathy NMJ congenital myasthenia about 6 transient mother MG Congenital myopathies most prominent present at birth is myotonic dystrophy and congenital myopathies eg nemaline ..., mitochondrial
Ped Neurology	Mitochondrial disorders	Mitochondrial disorders - KSS or CPEO - Leber optic atrophy - Leigh dz - MERRF - MELAS (mitochondrial tRNA leu, MRI shows post cerebrum j farct and almost always BG hypodensity and calcification) - NARP Kearns-Sayre synd or congenital progressive ext opgthalmoplegia - mitochondrial DNA analysis - skin fibroblast for cytochrome c oxidase MELAS -mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes is one of several mitochondrial encephalopathies. In cases where a clear maternal inheritance has been established, there is a mutation in the mitochondrial tRNA leu. Cranial CT and MR scans in patients with MELAs reveal infarct-like areas bilaterally in the posterior cerebrum and almost always hypodensities or calcifications in the basal ganglia region. TX - for myoclonus klonopin or lamictal - mitochondrial cocktail: co enz q10 30 mg qd nicotinamide 500 mg bid riboflavin 500 mg bid vit c 1000 mg qd succinate 25 mg qd Carnitin - avoiding condition that incbody energy demand (fasting, overexertion, infection/fever, hot temp) - avoiding meds that inhibit respiratory chain eg DPH, Barbiturates - avoid meds that inhibit mitochondrial pr synthesis eg tetracycline, chloramphenicol
Ped Neurology	Stroke	Stroke in neonate -mri -if high cpk check for mithochondrial disease if continue to be high muscle biopsy mitochondrial genetic tests - check for metabolic problem LA, PA, AA and OA acids - apolipoprotein -apl abs, lupus anticoagulant - ana, esr, rpr - homocysteine Hemorrhage- - check for coagulation abn - hypercoagulabe test for venus sinus thrombosis stroke and hemorhagic transformation - underlying tumor - vascular malformations, AVM - head trauma Lobar hemorrhage: HTN AA Trauma GBM/Oligodandroglioma Hemorrhagic mets-renal,melanoma,choriocarcinoma, thyroid A study of 160 children from 36 weeks gestation to 18 years of age with radiographic confirmation of cerebral sinovenous thrombosis found that 58 percent of children had seizures, 76 percent had diffuse neurologic signs, and 42 percent had focal neurologic signs. 43 percent of patients were neonates, and 54 percent were under one year of age. Risk factors were present in 98 percent of cases, and included acute systemic illness, head and neck disorders and abnormal tests for prothrombotic disorders (in 38 percent). Seizures at presentation and the presence of venous infarcts predicted adverse neurologic outcomes. Reference: DeVeber G, Andrew M, Adams C, et al. Cerebral sinovenous thrombosis in children. N Engl J Med 2001;345:417-423. IVH in low birth weight premature <1500 Dx by US indicated in neonate <32 week of gestational age should be repeates by 2 weeks of age and garding based on maximum hemorrhage seen I hemorrhage in germinal matrix only II IVH s ventriculomegaly III IVH c ventriculomegaly (30-40% chance of motor/cognitive deficit) IV IVH c ventriculomegaly c periventricular hemorrhage (60-80% chance of motor/cognitive deficit) there is also risk of hydrocephalus in IVH. pt should have frequent f/u c pediatrician Tx- maintaine acid-base balance, avoid fluctuation in BP, indomethacin for prevention of severe hemorrhage 0.1 mg/kg/dose IV Q24 hr x three doses, initiated at 6-12 hr of age.
Ped Neurology	Stroke	Strokes in kids - MoyaMoya - Kawazaki (IgE fluctuation, conjunctivitis, rash, erythema, edema) - Venus infract, d/t NVD - CADASIL cerebral AD areteriopathy c subcortical infarct and leukoencephalopathy Notch 3 gene on ch 19, media is replaced c eosin PAS positive congo red neg material, systemic vasculopathy, dx by skin nerve biopsy.
Ped Neurology	Sz	DDx of sz in <2yo *Apnea >15 sec or if c bradicardia lesser 2 type- cyanotic(breath holding spell )vs pallid syncope cyanotic provoked by anger,fear, frustration pallid by pain like bump on head both brainstem release phenomenon flat EEG then get normal, in cyanotic anger, fear -crying-cyanosis-apnea-loc in pallid pain-white pale-limp-loc tx- piracetam 40mg/kg/day or keppra effective in 92% picking up the child will prolong spell, hold the child c head in dependent position also get ECG to r/o prolonged QT synd. other DDx * dystonia transient paroxysmal dystonia of infancy glutaric aciduria * migraine benign paroxysmal vertigo paroxysmal torticollis cyclic vomiting, confusional state * steretypies finger tapping, hair curling *sandifer GERD * Sz febrile(complex if focal, >15 min, + FHx, + FND), nonfebrile, myoclonic Neurocutaneous ds causing sz in infancy - Incontinentia Pigmenti - Linear Nevus Sebaceous Synd. - Neurofibromatosis (I c optic glioma II c acoustic schwanoma) - SWeber synd - TScelrosis DDX of sz in >2 - hyperventilation synd. - narcolepsy-cataplexy sleep paralysis (generalized hypotonia on awakening), hypna gogic hallucinations (vivid visual auditory hallucination on awakening) - night terrors - startle disease - paroxysmal dyskinesia kinesigenic vs nonkinesigenic choreathetoid sec to min dystonic min to hours - syncope - migraine - sz
Ped Neurology	Sz	Infantile Spasm onset after 2 m peak 4-6 m etio- one third cryptogenic, 2/3 b/o CNS malformation (lisencephaly, holoproencephaly, double cortex, abscence of CC), acquired brain injury, TS, IEM (organic, aminoaciduria), chromosomal abn 13,17,18 poor px TX- ACTH(gel 20-40 U/24 hr IM QD x 6 weeks or 150 U /m2/24 hr : BID for 2 weeks then gradual taper)(pt should be in hospital for at least 2 days check bp q8h, guaic stool, parents learn to give injection), VPA, Clonazepam (0.5 mg bid to tid), LAM, TOP(30mg bid up to 9 mg/kg/day), Zonisemide, ketogenic diet(pt in the hospital for 2days starvation then use high fat no sugar diet watch for hypoglycemia many loose too much weight loss), surgery SE of TX such as risk of infection, lyte abn, htn, gi hemorrhage dw parents
Ped Neurology	Sz	Neonatal sz tonic, myoclonic, clonic or subtle (blink, chew, bicycling, apnea) b/o immature CNS. etio- HIE 35-42%, ICH 15-20%, CNS infection 12-17%, CNS malformations 5%, metabolic (dec glu, ca, B6, toxins)3-5%, IEM 5-20% W/U 1) search for acute causes-glu, ca, na, mg, suds, sepsis w/u (LP, CT, EEG) 2) IF abov Sz wu -EEG -if febrile pancx, lp c herpes pcr -mri c sz protocol - check for metabolic problem lactic pyruvic acid, aminoacids organic acid - ammonia level high level in favor of urea cycle disorder need HD as well as scavenger tx c Na pheylacetic and Na benzoate also send sample to Pittsburgh for AA OAcids - post traumatic or postsurgical - TX pb 15 mg/kg loading dose 5 mg/kg maintenance dose start after 12hours check level before that use dilantin keppra m dose 45mg/kg topomax 12.5 mg bid vpa sprinkle Jitteriness in neonates metabolic disorder addicted mother perinatal asphyxsia (multiorgan failure, 5 min apgar less than 3) any episode of hypoxia sufficiently severe to cause brain damage also causes derangements in other organs. mild HIE irregular HR, pass meconium. Severe HIE lactic acidosis, inc LFTs, entrocolitis, RF, MI DDx of neonatal sz by peak time of onset 24 hours infections- sepsis, meningitis, IU infections IVH at term, SAH, HI encephalopathy Laceration of tentorium or falx Direct drug effect, B6 def 24-72 hours all of the above plus hypocalcemia (Ca<7 mg/dl d/t low birth weight, asphyxia, maternal DM, transient neonatal hypoPTH, maternal hyperPTH, DiGeorge syndrome, after 72 hours in maternal hyperPTH, DiGeorge syndrome as well as feeding by cow milk or improper formula)dec PTH, AA OA met disorder, Urea cycle disorder, TS Incontinentia pigmenti 72 hours-1 week all of the above familial neonatal sz cerebral dysgenesis kernicterus 1 week-4 week all of the above adrenoleukodystrophy herpes encephalitis Drug withdrawal- marijuana, etoh do not cause drug dependence in the fetus, ot happens c heroin, methadone, codeine, propoxyphene
Ped Neurology	Sz	Neonatal sz tonic, myoclonic, clonic or subtle (blink, chew, bicycling, apnea) b/o immature CNS. etio- HIE 35-42%, ICH 15-20%, CNS infection 12-17%, CNS malformations 5%, metabolic (dec glu, ca, B6, toxins)3-5%, IEM 5-20% W/U 1) search for acute causes-glu, ca, na, mg, suds, sepsis w/u (LP, CT, EEG) 2) IF above normal, evidence of encephalopathy or IEM or recurrent sz then plasma AA, CSF AA,CSF Imino acids, CSF Pyruvate urine OA, urine sulfites serum PA, LA, ammonia, PH, very long chain FA (VLCFA), Neurotransmitters Infantile Spasm onset after 2 m peak 4-6 m etio- one third cryptogenic, 2/3 b/o CNS malformation, acquired brain injury, TS, IEM poor px TX- ACTH(gel 20-40 U/24 hr IM QD x 6 weeks or 150 U /m2/24 hr : BID for 2 weeks then gradual taper)(pt should be in hospital for at least 2 days check bp q8h, guaic stool, parents learn to give injection), VPA, Clonazepam (0.5 mg bid to tid), LAM, TOP(30mg bid up to 9 mg/kg/day), Zonisemide, ketogenic diet, surgery The cerebrospinal fluid in preterm newborn infants without bacterial meningitis and without other disease can have a protein of 65-150 mg/dl and the white blood cell count can have a range of 0-29 cells/cu mm with a mean of nine.
Pregnancy		2- Headache most common form tension HA No association c hormonal changes 80% of migrainour imrove 15% some, 5% get worse DDx- - HTN - Pre/E ususally after 20 w - Pseudotumor - Sagital ST usually after 16-18 w get MRV - inc in pituitary adenoma size - AVM become symptomatic hypoglycemia, dehydration can make HA worse MRI indications first worst HA of life, thunder clap HA, FND, systemic dz, meningismus CT c abdominal sheild Tx for mild tylenol, tylenol3, percocet, vicodin (apap+hydrocodon) for severe HA, amitrip /doxepin questionable C cat 10 mg qhs safest, nortrip, zoloft, prozac Caffeine can be used <300mg/d Mg oxide 400 to 800 mg/day B2 200mg bid behavioral therapy, moist heat, ice packs acute- - APAP, - ASA, NSAIDs B in 1, D in 2-3 trimester - Opiates eg MS, Demerol 50-100 mf iv prn - antiemetics promethazine, dimenhydrinate, meclizine, compazine, reglan C, phenerga - Mg 1 g IV over 30 min - Triptans contraindicated, only if other tx fails, registry, Ergot x A cocktail- IV Compazine+ IV Narcotics+ IV dexamethsone for acute attack- demerol 50-100 mg po max dose 1-1.8 mg/kg up to 150 mg PO/SC/IM/IV q3-4h for menstrual migraine/sz can get OCP, Acetazolomode 250 mg bid preventive- Inderal, metoprolol xl (lowest effective dose, cat C in 1-2, D in 3 trimester), Calan Cyproheptadine B 2mg bid for 3 days then 4 mg bid for 3 days then 4 mg tid until 2-3 weeks before pregnancy as it may cause neonatal hypoglycemia, Elavil questionable, Neurontin Short course steroid Prednisone better than dexameth which crosses the placenta more readily
Pregnancy		4- Stroke
Pregnancy		MS steroid 2 3 rd trimester ok IVIG postpartum interferone not in pregnancy and breast feeding ms and oc no contrdiction if positive ana and apl should not use oc
Pregnancy		Obstetric Neurology and Pregnancy Preexisting disease - Epilepsy - Migraine/HA - MS - MG - Movement didorders, Parkinson, RLS - Stroke - SCI - ALS/MN Diseases Pregnancy complications - Stroke/CVA - Neuropathy
Pregnancy		Postpartum angiopathy part of hypertensive angiopathy, causing (sever thunderclap) HA, SZ, FND, visual deficits associated c HTN, Pregnancy, eclampsia, migraine, vasoactive drugs, uremia, methtroxate two imaging pattern- PLS post leukoencephalopathy associated with small vessele disease endothelial dysfx and breakdown of BBB, vasogenic edema, loss of autoregulation RCV reversible cerebral vasoconstriction involving medium large arteries with segemental narrowing Management - r/o vasculitis, ESR, ANA, RPR, SUDS - r/o sinus thrombosis by MRV - Can check for Fibrin split products etc, peripheral blood smear - tx of HTN - MRA, CT Angio, 4V Angio, TCDoppler - Usually resolves in 10-20 days
Pregnancy		Pseudotumor cerebri idiopathic intracranial HTN worsen during pregnancy but healthy baby usually develop after 14 w disappear after 1-3 months, obese or gain weight during pregnancy - check VF, VA, BSpot - if CSF>35 is severe - moderation indiet to prevent weight gain - if vision loss prednisone or dexa x 2 weeks - 4-6 LP can be done sometimes weekly before considering optic nerve fenestration or lumboperitoneal shunt - Acetazolomide 250 mg qd or bid start and inc by 250 mg qw to max 500 bid , should start after20w gestation - Lortab or Tylenol3 - pain control during delivery to dec acute rise in CSF pressure - pt c pseudotumor frequently have migraine but can diff it, that's my pressure HA, the other my episodic migraine HA
Pregnancy		1- Eiplepsy Fetal vitamin K deficiency with hemorrhagic complications occurs in 10% of neonates born from mothers receiving antiepileptic drugs that induce liver metabolism of vitamin K, including phenobarbital and phenytoin. Women taking enzyme-inducing antiepileptic drugs should be treated with vitamin K1, 10-20 mg daily PO during the last month of pregnancy. Infants should receive 1 mg intramuscularly at birth and, if needed, fresh frozen plasma. Reference: Foldvary N. Treatment issues for women with epilepsy. Neurol Clin 2001;19:409-425. Safest AEDs all of them have risk esp VPA for neural tube defect, need to be on 1-4 mg FA daily at least 3 months before pregnancy less risky Lamictal, CBZ - Cataminial sz d/t inc est few days before start of bleeding or drop in progest few days after start of bleeding true dx need pt record 6 months hx of sz and menses tx- extra dose of AED during vulnerable period, progestrone use Provera, acetazolamide for 10 days AEDs withdrawal should be contemplated 6 months before planned pregnancy. For neural tube defect- check afeto pr at 14 and 16 week, level 2 ultrasound at 20 week, if any abnormality check amniosynthesis fluid for a feto pt and ACholine estrase. WWEpilepsy have more - anovulatory cycle - hypogonadotropic hypogomadism - PCO - hyperprolactinoma folic acid 4mg a day aeds level decreased during pregnancy esp lamictal by more than 65 percent check level q month
Pregnancy		3- Neuropathy LOWER EXT NEUROPATHIES: - most of them involve femoral n. at inguinal ligament - L5L4 lumbosacral trunk plexopathy at pelvic brim when cushion effect of psoas muscle finish it is compressed by baby head in women c short stature, big baby, prolonged or arrested labor, forceps use SS- w of ankle dorsifle ion toe dorsiflex as well as eversion inversion no w in plantar flexion S1 or ankle reflex was normal EMG/NCS- no block over fibular head,no paraspinal involvement x rarely b/o epidural anesthesia, dec proneal CMAP, dec MUAP L5 predominant path demyelination traction injury usually resolve in 3-4 months if axonal may takes up to one year DDx of radiculopathy root vs plexus - paraspinal involved in root - sensory CNAP or SNAP involved in plexopathy (lesion distal or at dorsal root ganglia) femoral vs L3-L4 radiculopathy (also involves obturator neuropathy=thigh adduction w medial thigh n) happens in pelvic injur/sur lithotomy or retropritoneal hematoma or pelvic mass c hip flex knee ext weakness, loss of knee reflex and ant thigh numbness sciatic neuropathy (post tibialis + common proneal) ddx stroke in foot area of motor cortex, radicuolopathy causes-muscular or bony pressure on sciatic, post hip dislocation, acetabular fx,im injection all foot ankle w plus knee flex w plus loss of achilles reflex and foot lateral leg n proneal palsy- ddx c L5 radiculopathy(also involves foot inversion w as it carries out by post tibialis) ss foot drop, foot dorsiflexion eversion w no inversion weakness, lat leg n causes: stretch injury by forcible foot inversion, compression by tight stocking cast crossed leg or trauma Meralgia paresthetica- lat femoral cut nerve- lat thigh n no ref or motor w causes- obesity, pregnancy, weight loss, or heavy equipment belt wihch cause compression of nerve under femoral ligament ddx c L2 L3 radicucause motor w or knee areflexia Morton metatarsalgia- tight shoes compress toes nerves esp 3 and 4 one causing patchy paresthesia
Psychiatry		Agitation Haldol Atypical antipsychotic - Zyprexa 2.5 mg qhs, neutral - Seroquel less EPS, sedative - Geodon activating side effects of antipsychotics EPS,acute dystonia, akathisia (acute), tardive dyskinesia (chronic rabbit synd.), inc Prolactin, weight gain, hyperlipidemia, obesity - olanzapine Zyprexa is drug of choice - fast acting tolerated better than Haldol - can be given IM or oral disintegrating tablet or mixed c water juice or nancarbonated beverage for fast acting
Psychiatry		Antipsychotics - clozapine most effective least EPS, agranulocytosis - olanzapine weight gain DM hyperlipidemia - quetiapine OH Catarct, least EPS, worst weight gain - respiridone fast acting depot form available - Geodone prolonged QT, penultimate best in no weight gain - Abilify some dopamin agonist, best no weight gain, lowest agranulocytosis
Psychiatry		Chronic fatigue syndrome Approach to pt with persistent fatigue: Hx - record the medical and psychosocial circumstances at onset of symptoms - Assess previous physical and pschological health - Seek clues to an underlying medical disorder (eg fever, weight loss, dyspnea) - Assess the impact of the symp on the pt life style Characteristic symptoms of chronic fatigue synd include fatigue, myalgia, arthralgia, impaired memory and concentration and unrefreshing sleep PE check for hypothyroidism, chronic hepatitis, chronic anemia, Neuromuscular disease, sleep apnea syndrome, occult malignancy PE in CFS is normal Mental examination - Past or family history of psychiatric disorder, notably depression, anxiety - Past hx of frequent episodes of medically uneplained symptoms - Past hx of alcohol or substance abuse - Current symptoms: depression, anxiety, self destructive thoughts, and use of OTC meds - Current signs of psychomotor retardation - Evaluate psychosocial support system CFS pts have depressive symptoms but not guilt sucidal ideation or observable psychomotor slowing Labs investigations CBC, CMP, ESR, ANA, RPR, Hepatitis profile, Ca PO4 Random blood glucose and Thyroid function tests CFS: 1- unexplained persistent or relapsing chronic fatigue lasting 6 or more consecutive months that is of new or definite onset; is not the result of ongoing exertion; in not substantially relieved by rest; and results in substantial reduction in previous levels of occupational educational social or personal activities; and 2- Four more of the following symptoms occuring concurrently: 10 impairment of shortterm memory or concentration 20 sore throat 30 tender cervical or axillary LNs 40 muscle pain or multijoint pain 50 HA 6) unrefreshing sleep and 7) postexertional malaise TX see comprehensive physhiatry kaplan saddock
Psychiatry		Conversion exam MS- loss of childhood memory low monotone speech, poor historian and not contributing to hx and exam CN- unable to see but respond to visual threat or do visual fixation or follow you in the room - split of vibration over forehead - cornea nasal reflex SENSORY- c/o sensory problems but higher cortical sensory intact REFLEX- no reflex changes or atrophy MOTOR- give away weakness - + Hoover sign - the whole limb moves en bloc no distal drop - contraction in hamstring when you hold leg up like if to push it down
Psychiatry		Mania speech-rapid, circumstantiality thought-flight of ideas mood-elation mania in child can be confused with ADHD. Mania in adults can be associated with substance abuse. FDA approved drugs- Li, VPA, Olanzepine Tegretol also very good
Psychiatry		mental status exam inverse pyramid (no lobe approach) executive fx visuospatial orientation memory language attention attn - arousal - basic attention eg digital span normal is 7- + 2 around 5 - concentration eg spelling word backward, months of the year language - answering questions appropriately - aphasia, paraphasia, anomia memory - registration, recent working memory test by 3 words, remote (has no localization stored all over places) visuospatial - 3d cube - copy pentagon - dividing line to 2 equal part - mimicking hands like you executive functions - drawing clock 10 after 11, 3 step commands - judgememt - calculation
Psychiatry		Panic Attack (even in pregnancy) - Paxil CR 25 mg qd - trazodone 50-100 mg qhs - Avoid Xanax cat D - Check for TSH FT4 MVP EKG Depression due to medical condition Lexapro 5 mg qd can increase to 10 mg qd after few days lowest sideeffects Depression during pregnancy Trazodone C 50-100 mg qhs DDx manic-depression c borderline personality shortest manic episode is 4-7 days personality is few hours Anxiety during pregnancy Buspar Category B Bipolar treatment Lamictal also has good antidepressant effect Li CBZ VPA Atypial Antipsychotic In refractory case of Li or VPA treatment, can add lamictal or atypical antipsychitic Antidepressant is not recommended in tx of bipol ar because they increase mania phase of their illness Aggression behavior/psychosis Haldol 5 mg + 1-2 mg Ativan or 50 mg Benadryl outpt Olanzapine 2.5-10 mg/day Antipsychotics - clozapine most effective least EPS, agranulocytosis - olanzapine weight gain DM hyperlipidemia - quetiapine OH Catarct, least EPS
Psychiatry		PTSD > 1 month flashbacks reminiscences of stress persistant inc arousal state such as exaggerated startle response
Psychiatry		The pathophysiology of schizophrenia as associated with pathological changes in the dorsomedial thalamus and the dorsolateral prefrontal cortex thereby affecting the pathway between the two sites. Any role of pedunculopontine, nigrostriatal, hippocampal-fornical-mamillary, and amygdala-orbitofrontal pathways is not clearly established in schizophrenia if in fact there is a role in these pathways. Brains at autopsy taken from schizophrenic patients show an increase, not decrease, in ventricular size, especially of the temporal horns of the ventricles due to loss of cortical gray matter in medial temporal lobes. Both auditory and visual hallucinations, persecutory delusions, and ideas of reference are seen in both temporal lobe epilepsy (TLE) and schizophrenia. A positive family history of schizophrenia, schizoid personality, or schizotypal personality is often present in schizophrenia but usually not in TLE. Affect is better preserved in TLE than in schizophrenia. ADHD and obsessive-compulsive symptoms are often associated with Tourette's syndrome. Boys are more often affected than girls. An increase in seizures is not seen. Coprolalia is not necessary for the diagnosis. dissociative state- fugues, psychogenic amnesia, hypnosis. material is available in the preconscious but selectively ignored.
Sleep disorders		Excessive daytime sleepiness EDS DDx - OSA - Insufficient sleep - PLMD periodic limb movement dis. - Stimulant withdrawal - Sedatives - Circadian rhythm disorders - Psychiatric disorders - Malingering - Idiopathic Drugs for tx of EDS Dextroamphetamine 5-60 mg Methamphetamine 5-60 mg Methylphenidate 10-60 mg Mazindol 0.5-6 mg Modafinil 100-400 mg Pemoline 20-115 mg Drugs for tx of cataplexy Protriptyline 5-60 mg Imipramine 10-100 mg Desipramine 25-100 mg Clomipramine 10-150 mg Fluoxetine 20-60 mg Venlafaxine 75-225 mg Reboxetine 2-10 mg Sodium oxybate 4.5-9 gram
Sleep disorders		Sleep 1 NREM and REM sleep alternate, with each cycle lasting for approximately 90-100 minutes. Four to six such cycles are noted during a normal sleep period. the first one third of a normal sleep episode is dominated by slow-wave sleep (SWS) and the last third is dominated by REM sleep. The first REM sleep episode is noted 60-90 minutes after the onset of sleep. REM sleep accounts for 20-25% of sleep time. Arousal is a shift in EEG frequency shifts lasting for 3-14 seconds and includes alpha, beta, or theta activities but not spindles or delta waves. The subject must be asleep for 10 consecutive seconds before an arousal can be scored. In REM sleep arousals are scored only when accompanied by a concurrent increase in submental electromyographic (EMG) amplitude. Unless accompanied by EEG frequency shifts, K complexes, delta waves, artifacts, and increased submental EMG activities are not counted as arousals. An arousal index is defined as the number of arousals per hour of sleep and up to 10 can be considered as a normal arousal index. The usual arousals signifying sleep fragmentation. The newborn infant spends approximately 50% of the time in REM sleep, but by 6 years of age this time is decreased to the normal adult pattern of 25%. On falling asleep, a newborn baby goes immediately into REM sleep or active sleep, which is accompanied by restless movements of the arms, legs, and facial muscles. In premature babies, it is often difficult to differentiate REM sleep from wakefulness. By 3 months of age, the NREM-REM cyclic pattern of adult sleep is established. However, the REM-NREM cycle duration is shorter in infants, lasting for approximately 45-50 minutes and increasing to 60-70 minutes by 5-10 years, and the normal adult cyclic pattern of 90-100 minutes by the age of 10 years. Sleep spindles begin to appear at approximately 3 months and K complexes are seen by approximately 6 months of age.
Sleep disorders		Sleep 2 A characteristic feature of sleep in old age is marked attenuation of the amplitude of delta waves and, therefore, during scoring of delta sleep, which depends not only on the rate but also on the amplitude of delta waves, the percentage of delta waves decreases. The other characteristic feature during old age is the repeated awakenings throughout the night, including early morning awakenings. Depending on the sleep habit, two groups of individuals are recognized: evening types (Owels) and morning types (Larks). Morning and evening types are most likely determined by genetic factors. An average adult's sleep requirement is approximately 7.5-8.0 hours, regardless of environmental or cultural differences. Kripke and co-workers found that chances of death from coronary arterial disease, cancer, or stroke are greater for those who sleep less than 4 hours or more than 10 hours compared with those who sleep an average of 7.5-8.0 hours. Approximately 80% of dreams occur during REM sleep and 20% occur during NREM sleep. REM sleep dreams appear to be more highly emotionally charged, complex, and bizarre, whereas NREM dreams are characterized by more realistic and rational facts. The significance of dreams remains unknown. Some suggestions include activation of the neural networks in the brain, restructuring and reinterpretation of data stored in memory, and removal of the unnecessary and useless information from the brain during dreams. Sleep-promoting neurons are thought to reside in the preoptic area of the anterior hypothalamus and wake-promoting neurons in the posterior area. Sleep results from both passive and active processes. The active hypnogenic neurons for NREM sleep are located primarily in the preoptic area of the anterior hypothalamus and the basal forebrain area as well as in the neurons in the regions of the nucleus tractus solitarius in the medulla.
Sleep disorders		Sleep 3 The sleep-promoting role of the anterior hypothalamus depends on inhibition of the posterior hypothalamic histaminergic awakening neurons. The pons is, therefore, sufficient and necessary to generate all the signs of REM sleep. Neurons in the pedunculopontine tegmental (PPT) and the laterodorsal tegmental (LDT) nuclei in the pontomesencephalic region are cholinergic and are the REM-on cells, which are responsible for REM sleep, showing increased firing rates at this stage. The REM-off cells are located in the locus ceruleus and raphe nucleus; these cells are aminergic neurons and are inactive during REM sleep. Histaminergic neurons can also be considered REM-off cells. A reciprocal interaction between the cholinergic REM-on and aminergic REM-off neurons in the brainstem is thought to be responsible for REM generation and maintenance. The systems responsible for arousal include ARAS in the upper brainstem and its projections to the thalamus and posterior hypothalamic regions, the recently described hypocretin (orexin) system in the lateral hypothalamus with its widespread ascending and descending projections (de Lecea et al. 1998; Sakurai et al. 1998), and the system responsible for cognition resides in the cerebral cortex and its subcortical connections. The term circadian rhythm originated from the Latin circa meaning about and dian meaning a day. Human circadian rhythm generally has a cycle length of about 25 rather than 24 hours (range of 24.7 to 25.2 hours), although this has been challenged recently. The human body also has an internal biological clock. The paired suprachiasmatic nuclei (SCN) of the hypothalamus above the optic chiasma are the sites of the biological clock. The master circadian clock in the SCN receives photic information from the retinohypothalamic tract, which sends signals to multiple synaptic pathways in other parts of the hypothalamus, the superior cervical ganglion, and the pineal gland where melatonin is released. The SC
Sleep disorders		Sleep 4 The SCN contain melatonin receptors and there is a feedback loop from the pineal gland to the SCN. Melatonin is secreted maximally during the night and is an important modulator of human circadian rhythm for entrainment by the light-dark cycle. The melatonin level rises fairly abruptly in the evening and then reaches its maximum level between 3:00 am and 5:00 am after which it decreases to low levels during the daytime. Biological functions of sleep Body and brain tissue restoration (enhanced synthesis of macromolecules during sleep) Energy conservation Adaptation Memory reinforcement and consolidation (take place during REM) Synaptic neuronal network integrity (REM sleep maintains motor circuits, whereas NREM sleep maintains nonmotor activities) Most of the autonomic changes involve respiration, circulation, thermoregulation, and the pupils (e.g., pupilloconstriction during sleep). During NREM sleep, there is an overall tonic increase in parasympathetic activity, which increases further during tonic REM sleep. In addition, during phasic REM sleep, sympathetic activity decreases. Sympathetic activity during REM sleep, however, increases intermittently, which results in swings of blood pressure and heart rhythm, causing bradytachyarrhythmias. Thermoregulation
Sleep disorders		The hypocretin/orexin system of the lateral hypothalamus has been implicated in the mechanisms of narcolepsy. These neurons project to cholinergic and monoaminergic cell groups involved in regulation of REM sleep. Reduced CSF levels of hypocretin and reduced numbers of hypocretin cells have been found in patients with narcolepsy. Somn ambulism in stage 3-4 of NREM sleep PNT, hypotonia and PGO spikes in REM sleep
Spinal cord		Ant Syndrome Clinical features: Sensory loss: Pain & temperature Weakness: Legs ± arms Related lesion: Ant spinal artery D Disk; Osteophyte
Spinal cord		Autonomic dysreflexia major splanchnic sympathetic outflow from T5-L2 is not inhibited by supraspinal centers and any bladder problem, catherterization, bowel retention constipation may cause sweating, tachcardia, hypertension and ... tx is clonidine and relief of triggering factor.
Spinal cord		Cauda equina Syndrome Clinical features: Onset: Progressive; Asymmet Pain: Severe; Radicular Fatigue; Fasciculations Sensory: All modalities; Lumbar > sacral Weakness: Lumbar > Sacral Reflex loss: Knee > Ankle ± Bladder involvement Related lesion: Compression Tumor Arachnoiditis
Spinal cord		Central Cord Clinical features: Sensory loss: Pain & temperature Sacral sparing Weakness: Arms > legs Related lesion: Trauma Syringomyelia Cervical arthritis Spondylosis Neoplasm: Glial; Metastatic Lymphoma
Spinal cord		Epidural abcess back pain with fever RFs- IVDA, pelvic infection, UTI, Endocarditis, OsteoMyelitis, HIV Labs- inc CBC, MRI of whole spine check UA Tx- - Emergency surgical drainage send surgical swab and tissue for Cx & Sensitivity - Vancomycin check peak and trough around 3rd dose - Cardiac echo for endocarditis - Bone scan with Tc for OM
Spinal cord		FAMILIAL MYELOPATHIES 1 (Spastic Paraplegias) Dominant (Strumpell) SPG3 (FSP1): Atlastin; 14q SPG4 (FSP2): Spastin; 2p22 SPG6 (FSP3): 15q11.1 SPG8: 8q23 SPG9: 10q23 SPG10: KIF5A; 12q13 SPG12: 19q13 SPG13: HSPD1; 2q24 SPG17: 11q12 SPG19: 9q33 Multiple exostoses Recessive SPG5A: 8q SPG5B: ? SPG7 (5C): Paraplegin; 16q24 SPG11: 15q13 SPG14: 3q27-q28 SPG15: 14q22-q24 SPG20 (Troyer): Spartin; 13q12.3 Sjögren-Larsson: FALDH; 17p11 DRPLA: 12p13 Homozygotes Intermediate # repeats Spastic paraplegia +: Dementia & Extrapyramidal D Retinal degeneration Evans syndrome Leukodystrophies: Late-onset MLD & Krabbé X-linked SPG1: L1CAM; Xq28 SPG2: Proteolipid protein; Xq21 SPG16: Xq11 AMN: ALDP protein; Xq28 Adult onset: 5q31 Retardation, psychosis, macroorchidism Woods-Black-Norbury
Spinal cord		FAMILIAL MYELOPATHIES 2 (Other syndromes) Syringomyelia + Arnold-Chiari & Scoliosis Cleidocranial dysplasia Acromesomelic dysplasia Spine Disorders & Myelopathy Coffin-Lowry Syndrome: Ribosomal Protein S6 kinase Morquio's Syndromes: A: Galactosamine sulfatase B: b-galactosidase Achondroplasia: FGF Receptor-3 Type II Collagenopathies Spine dysplasias; Spina bifida Trisomy 21 Ankylosing spondylitis Lumbar Stenosis Hypophosphatemia: Vitamin D resistant rickets Other familial syndromes Arnold-Chiari Malformation Spastic Ataxias: DRPLA Charlevoix-Saguenay Paroxysmal Choreoathetosis/Spasticity Hereditary Motor Syndromes Spastic dystonia syndromes: DOPA-responsive dystonias: GTP cyclohydrolase I; Tyrosine hydroxylase; Mitochondrial & Leber's optic atrophy Infections: HTLV-1 Mass lesion: Meningioma von Hippel-Lindau Hemangioblastoma Neurofibroma
Spinal cord		FOCAL LESIONS AVM Fluctuating signs Slow progression Radiation Partial Brown-Séquard Epidural abscess: Pain Parasagittal lesion: Leg Spine: Disk; Stenosis Spondyolsis Mass: Neoplasm; Hematoma; Cyst é spinal root or vessel Arachnoiditis: Sarcoid; Mpl surgery; Infection Trauma Toxic: Contrast agents; Chymopapain; Methotrexate; Cytosine arabinoside ----------------------------------------------------------- 1° CNS DISEASE Multiple sclerosis ALS: Pure motor Syringomyelia Transverse myelitis: Parainfectious; Vaccine; Immune
Spinal cord		Hemicord (Brown-Séquard) Syndrome Clinical features: Ipsilateral loss: Position sense; Motor Contralateral loss: Pain & temperature Related lesion: Trauma: Penetrating Radiation Decompression Tumor: Dumbbell Facet; Luschka joint
Spinal cord		Inf (Conus) Syndrome Clinical features: Onset: Rapid; Symmetric Pain: ± Perineum & thighs Sensory: Saddle; Pain, Temp Weakness: Sacral Reflex ê: Ankle > Knee Bladder D; Impotence Related lesion: Tumor Compression Ischemia
Spinal cord		Paraplegia/Paraparesis usually d/t spinal cord (sensory/motor level, b/b inc, umn in le, lmn at the level of injury, occ respiratory compromise in C4 above)or peripheral nerve (distal weakness or sensory loss, dec ref, atrophy)or brain (CP, ArChMal,MMCell) ETIOLOGY 1- Trauma (fx, hematoma, concussion, neonatal cervical cord trauma) 2- Cord compression (tumor, abcess, lipoma, TB, Diskitis) 3- Myelitis (devic, ADEM, CVD, lupus,HTLV1, Herpes Zoster, Idiopathic) 4- Tumor(epyndymoma, neuroblastoma, astrocytoma, ewing sarco a) 5- Congenital malformation (arachnoid cyst, avm, atlantoaxial dislocation < in RA, Down, Achondroplasia, Morquio mucopolysaccharidoses<check urine for keratan sulfate>, KlippelFail synd>, ArnoldChiariMal, Myelomeningocele, Tetherd cord syndrome ) 6- Familial spastic paralegia AD,AR,XL 7- Metabolic (Adrenomyeloleukodystrophy<inc VLCFA, can be mistaken c MS in young female>, Krabbe<globoid LD, Galactoceramidase def>, Argininemia<Urea cycle disorder, NV, Sz, Para or Quadriplegia>)
Spinal cord		Post Syndrome Clinical features: Sensory loss: Position sense Relative preservation: Motor Pain & temperature Related lesion: Post spinal artery changes dec collateral perfusion: Atherosclerosis Vitamin def: B12; E Lipoma; Lig flavum
Spinal cord		SCI ASIA: American Spinal Cord Injury Assoc. A: complete motor, complete sens B: complete sens, <3/5 motor C: complete sens, >3/5 motor D: Acute SCI: Methylprednisolone within 8hrs: 30mg/kg bolus (15min) <3hrs: 5.4mg/kg/h (45min after bolus) x 24h 3-8hrs: 5.4mg/kg/h (45min after bolus) x 48h - bowel costipation/bladder uti foley care - decubitus ulcer care - respiratory care - autonomic dysreflexia
Spinal cord		Spinal cord synd - Transverse cord lesion (sensory level d/t tumor, trauma, transverse myelitis, ms) - Hemicord Brown Sequard ipsilat weakness, pos vib, contralat pain temp d/t penetrating injury, ms, lat compression - Central cord synd cape distribution loss of pain temp intact crude touch c bigger lesion LMN at level UMN weakness below lesion d/t spinal cord contusion, syringomyelia, tumors (hemangioblastoma, ependymoma, astrocytoma) - Post cord synd truama, ms, B12 def, tabes dorsalis - Ant cord synd loss of pain temp, LMN weakness ant horn cell, UMN weakness lat corticospinal tracts d/t ant spinal rtery infarct, ms, trauma Cauda equina synd (neuro emergency) etio- djd(diskprotrusion, herniation, sequestration, spodylosis), neoplasm, hemo, inf, trauma ss- bil sciatica,saddle anesthesia, b/b inc, sexual function in conus more symetrical more saddle anesthesia, in quada more asymetric L4L5 most common Tx- neuro emergency steroids neurosurgery
Spinal cord		SPINAL DISORDERS: Points in differential diagnosis MNEMONIC Vascular Infectious B12 Deficiency Radiation ALS Tumor, Trauma & Toxic Epidural Abscess & Electricity Developmental & Hereditary Spondylosis & Spine Paraneoplastic & Parasagittal Arachnoiditis Syringomyelia Multiple Sclerosis & Myelitis Systemic Disorders
Spinal cord		SPINAL LEVELS Motor dec Sensory dec C3 - Post neck & ear C4 - Upper neck C5 Deltoid Shoulder C6 Pronator Thumb C7 Ticeps Middle finger C8 Intrinsic hand 5th finger L1 Hip flex Groin L2 Hip flex Ant-Med thigh L3 Knee ext Cent thigh L4 Knee ext Med leg L5 Ankle dorsiflex Large toe S1 Toe plantarflex Lateral foot
Spinal cord		SYSTEMIC CAUSES OF MYELOPATHY 1 Spinal Cord lesions Connective Tissue Disease Lupus Erythematosis Sjögren's Mixed Connective Tissue Systemic Sclerosis (PSS) Behçet's Embolism Decompression Sickness Ischemic Atherosclerosis Liver disease: Portosystemic shunt Aortic Aneurysm Anemia Hyperviscosity: Waldenström's Paraneoplastic Infectious HIV: Posterior columns HTLV 1: Spastic Syphilis Vitamin ê: E; B12 Toxic: Organophosphate N2O; Heroin Electricity Skeletal lesions Atlanto (C1)-Axial (C2) Arthritis: RA; Psoriasis Trisomy 21 Morquio A & B Skeletal dysplasias Klippel-Feil: Cervical vertebral fusion Ochronosis von Recklinghausen Ankylosing spondylitis Spinal canal stenosis Achondroplasia Coffin Lowry Stickler dysplasia Acrodysostosis (lumbar) Familial Lumbar Stenosis Hypophosphatemia, Vit D resistant rickets Spondyloarthropathy & chronic renal failure Other Epidural Masses: Gout; Xanthoma; Large nerves; Amyloid; Hematopoesis; Lipomatosis (Steroids) Acromegaly Myelomeningocoele Metastasis
Spinal cord	Transverse myelitis	Transverse myelitis Acute inflammation of spinal cord with dramatic presentation over hours or few days. - precedingviral ilness or vaccination esp in younger age - sensory level almost always midthorasic (20 % cervical causing arm weakness); monoapresis or paraparesis; B/B incontinence; back pain in half of them, spinal shock and then UMN signs with babinski later on - 1/3 mild, 1/3 moderate, 1/3 severe with B/Binc - Dx requires one of these clinical, CSF or MRI findings W/U - MRI of spinal cord c GAD urgent at minimum the sensory level and above and ideally total spine to r/o compression b/o disk, mass, epidural abscess sometime you don't see very much in MRI of spine and detailed repeat study with thin cut through or Somatosensory potentials EP are necessary. -MRI of brain c GAD to r/o ADEM, MS, and small stroke in corona radiata - LP and send it for PCR, viral ab (HIV,HTLV1, lyme , herpes family, CMV, WNV etc) and fungal Ag Also do IgG index, MBP, SPEP on CSF usually shows mild elevation of Pr or modest lymphocytic pleocytosis - B12, FA, ESR, ANA, ENA, RPR, HIV, HTLV1, p and cANCA, hepatitis profile - 25% will progress toward MS like ADEM, usually they have WM changes in brain MRI and need to be started on inf as delayes progression to MS by 1 year DDx of acute loss of spinal cord function - Idiopathic autoimmune transverse myelitis as above - Spinal cordcompression (disk, spondylosis, tumor eg lymphoma, abscess) - ADEM, MS - Viral myelitis including HIV - Spinal cord infarction, AAA, vasculitis - Spinal cord tumors - Paraneoplastic myelopathy eg meningitis carcinomatosis - Syphilis and Lyme Tx Solumedrol 1gram/day IV for 3-5 days often followed with oral taper dec inflammation and proteolytic enzymes, stabilize BBB, enhance NCV - May not offer better prognosis, no trial has been done - Spinal cord care and team management in severe case - Put pt on ASA and or Plavix - Use Neurontin for neuropathic pain or hypesthesia
Stroke		Cerebral vasculitis possible causes - Wegner cANCA (anti proteinase 3) - PAN, microscopic Polyangitis pANCA (antimyeloperoxidase) - Hairy cell leukemia blood smear - d/t Ca check AFP, CEA, PSA, CT C/A/Pelvis - Intravascular lymphomatosis type of NHL - APL synd.= arterial/venus thrombosis, abortion, LA or ACardiolipins - Giant cell arteritis 3% normal ESR, above 40 is significant, check also CRP if high specifity with high ESR is 97% they can have high APL; LA, AC, ANCA and antithrombin as epiphenomenon as exposure of phopholipis after endothelial damage. TABx should be done after US exam to make sure TA is not collateral artery to brain. involvement is patch so a fairly long specimen required. immune reaction to elastin. can cause pulseless disease like Takayasu but it is in young women and involve intima autoimmune reaction. in TA only large intracranial arteries get affected. - -
Stroke		Drug induced CNS vasculitis- DICV tx - Immunosuppression steroids, cyclophosphamide not indicated can be harmful, - DC Drugs - Referral to substance abuse clinic - CaCB like Isradipine may reverse cerebral hypoperfusion - ASA - Lamictal, Gabapentin DDx- moyamoya vasospasm APL Syndrome TTP Sickle cell disease Cholestrol or cardiac myxoma emboli radiation vasculopathy Hepatitis/HIV vasculitis CADASIL Fibromuscular dysplasia W/U - CBC, CMP, UDS - LP, ESR, ANA, Reichlin biopsy, HIV, Hepatitis - CT 65% sensitive - MRI, MRA 87% sensitive - Angio 100% sensitive
Stroke		Heparin anticoagulation Mnemonic HEPARIN D - hypercoagulable states - embolic stroke carotidogenic/cardiogenic - pregnancy - anemia of sickle cell - recurrent TIA - increasing TIA - dissection
Stroke		tPA The current guidelines recommend treating ischemic stroke patients who present within 3 hours of symptom onset with recombinant tissue plasminogen activator (rt-PA) at a dose of 0.9 mg/kg (maximum dose 90 mg) within 3 hours of symptom onset with 10% of the dose given as bolus followed by infusion lasting 60 minutes. Exclusion criteria include prior intracranial hemorrhage; history of intracranial neoplasm, aneurysm or anteriovenous malformation; stroke or head trauma within the previous three months; gastrointestinal or urinary bleeding within the previous 21 days; major surgery or biopsy of a parenchymal organ within preceding 14 days; recent myocardial infarction; seizure at onset of stroke; history of known heriditary of acquired abnormal hemostasis; current use of oral anticoagulants with prothrobin time>15 seconds, use of heparin in previous 48 hours with prolonged partial thromboplastin time; platelet count <100,000/mm3, and evidence on CT of major hypodensity or sulcal effacement (>1/3 of middle cerebral artery territory), and systolic blood pressure>185 mmHg or diastolic blood pressure >110mmHg, and blood glucose <50 mg/dl or >400 mg/dl.
Stroke		Vasculitis 1 Primary- small, medium, large artery Secondary - CVD:SLR,Behcet, Sjogren, RA - Infection: VZV (zoster ophthalmicus), Syphilis, TB, Lyme, infectiveendocarditis, crytococus - Meds: DPH, Hydralazin - Tumor: T cell lymphoma - Serum sickness Clinical manifestation - General: encephalopathy, HA - Focal: multifocal flactuating neurological deficits, myelopathy, sz, sensory neuropathy, sychiatry or sychosis W/U - ESR, CRP, RF - ANA, SS A SS B, P/C ANCA Anti sm and Anti dsNA Anti Jo1 SCL-70 -C3 and C4 - Cryoglobulins - Chronic Hepatitis Panel - SPEP, IFE - CBC,CMP - HIV, Lyme - LP may show inc cell and Pr - For primary CNS vassculitis MRA and then Angio beading Tx - CS and bolus MP - Cyclophosphamide oral and monthly bolus 600 mg/m2 q 4-6 month - Azathioprine - IVIG
Stroke		Vasculitis 2 Large- giant cell, Takayasu, primary CNS vasculitis Medium c or s Small- PAN, WG,Kawasaki, Chrug Strauss Small- systemic rheumatic diseases, cancer, microscopic polyarteritis, urticarial vasculitis, Leukocytoclastic vasculitis (Henoch Schonlein purpura, cryoglobolinemia, or infection) Any size(pseudovasculitis)- APL synd, Embolic phenomenon (eg those associated c myxoma), Endocarditis (bacterial or marantic), cholestrol embolism, drugs (eg amphetamines) In all of the above check for complement C3 C4, most of them normal x low in urticarial vasculitis and variable in PAN, Leukocytoclastic, Systemic rheumatic disease, Endocarditis Type of cryoglobulinemia - Monoclonal Ig eg Waldenstrom, myeloma, lymphoma - Monoclonal Ig M & polyclonal Ig G eg Hep C B, EBV, Bacterial/Parasitic infection - Polyclonal Ig G and Ig M eg SLE, Hep C, Lymphoma
Stroke	Cerebral Veins Thrombosis	Cerebral Veins And Sinuses Thrombosis - in youngs after NV dehydration - in females after OC start or obstetrics ward after sz esp 3rd trimester or peripartum - In hypercoagulable states - Head injury, Jugular cath, NES, After LP - Infections mastoiditis, sinusitis, meningitis - Systemic diseases eg SLE, Wegner, APL syndrome, Nephrotic synrome, Leukemia, Polycythemia - Severe HA, Sz, W or Numbness, Eye signs, Deep sinus thrombosis causes bil thalamic lesions manifest as delirium, amnesia, mutism Dx - CT hemorrhagic infarct in multiple arterial territory, Hyperintense signal in sinus or cortical vein (Cord sign); CT angio or venmogram, MRI/MRV, Cerebral angiography (Tortuous or Corkscrew veins) Tx -
Stroke	Hemorhage	Lobar hemorrhage: HTN AA Trauma GBM/Oligodandroglioma Hemorrhagic mets-renal,melanoma,choriocarcinoma,thyroid The pathognomonic feature of high intracranial pressure and transtentorial herniation is a wedge of pressure necrosis in one or both parahippocampal gyri. Hemorrhagic infarction due to entrapment of the posterior cerebral artery, and entrapment of the third cranial nerves also frequently occur. Secondary brainstem hemorrhages and infarctions are maximal in the midbrain and pons, and rarely extend to the medulla(Durret hemorrhage). Sturge-Weber disease is characterized by a meningeal vascular malformation and calcification in the second and third layers of the underlying cortex. pt can have hemangioma of chroid of the eye. - Berry Saccular aneurysm causes AD Polycystic kidney Marfan Ehlers Danlos Neurofibromatosis type I Coarctation of Aorta Fibromuscular dysplasia Most around A1 M1 Pcomm -Vascular malformation AVM nonfunctional brain tissue can besafely removed Cavernous angioma no nervous tissue no feedind artery no shunting in cerebellum pons and subcortical Venous angioma functional paranchyma within Capillary telengectesia in pons and rarely hemorrhage Foix Ala jouan ine disease = venus angioma of spinal cord causing myelomalacia mostly lumbosacral cord and slowly progressive fnd l
Stroke	Stroke	Hypercoagulable states: - Pr C S def functional - Antithrombin III - Factor V Leiden mutation - Prothrombin gene mutation G20210A - Dysfibrinogenemia, FSProducts - Homocysteine >15 - APL Anticardiolipins Lupus AC next stage tests - P-ANCA C-ANCA - Plasminogen activator inhibitors - UA and fibrinopeptide A assay to evaluate renal source for thrombus - FSProducts and D dimer to evaluate the stage at which clotting abn occured. - Peripheral blood smear - Hepatitis profile to evaluate intrinsic liver disease. Spontaneous or traumatic dissections occur most frequently in the carotid artery at the neck. Vertebral artery dissections may occur after chiropractic manipulations of the neck. or any neck injury Karate, Roller-Coaster Alexia without agraphia follows combined damage to the dominant medial occipital region and the inferior fibers of the splenium of the corpus callosum. This is in the distribution of the posterior cerebral artery. This non-contrast CT reveals a hyperdense tubular region in the proximal segment of the left middle cerebral artery (MCA), consistent with acute thrombosis (arrow). Also noted are subtle left cerebral sulcal effacement, hypodensity of the left basal ganglia, frontal, anterior parietal, and superior temporal lobes. These findings are consistent with an acute MCA infarction. This so-called dense MCA sign or hyperdense MCA sign has been correlated angiographically with embolic or atherothrombotic MCA occlusion. The hyperdensity is most likely due to either calcific or hemorrhagic components of the acute plaque. The hyperdense MCA sign is nonspecific when present in isolation. False positive hyperdense MCAs have been noted in asymptomatic patients with high hematocrit or calcific atherosclerotic disease; these are usually bilateral.
Syndromes		Kennedy- spinal/bulbar muscular atrophy, LMN ss esp in cranial nerves plus dec libido, testicular atrophy, dec FSH,LH, gynecomastia, F asymptomatic, dx by DNA, CAG repeat Miller-Dieker synd type I lissencephaly ch 7 del type II c congenital muscular dystrophy auto recessive pattern. Claude synd-dorsal midbrain tegmentum injury with involvement of 3rd nucleus, red nucleus, brachium conjunctivum SCP
Trauma		Depressed fx compound when skin laceration penetrating when dura is torn Epidural more arterial lens shaped and more with lucid interval c/t SDH. if fresh SDH maybe isodense and be missed on CT. Contrecoup contusions occur in the brain away from the point of impact and do not directly underlie the site of skull fractures. Orbital surfaces of the frontal lobe are the most common location and contrecoup contusions at this site usually occur following a fall on the occiput with the sudden deceleration of the head. Parasagittal contusions, also called gliding contusions, occur in association with diffuse brain damage and diffuse axonal injury. dec ICP Midazolam Versed is the best b/o less hypotension shorter sedation Pentobarbital Propofol more hypotension dec CBF Fentanyl Morphin worst blunt head trauma>carotid cavernous fistula> prptosis, chemosis, ophthalmoplegia
Trauma		ICP Monitor/Treatment if GCS>7 if GCS <7 ICP Monitor and can use hypertonic saline 2 or 3%, intermittent boluses of 250-300 cc to keep Na between 145-155 first tier for management of ICP - tx hyperthermia >37.5 - sz prophylaxis for one week - head elevation 15-30 degree - avoidance of juglar venus outflow obstruction: head midline s improperly fitting cervical collar - sedation/analgesia + pharmacological paralysis regimn - adequate xygenation, hb, airway, mech vent, O2 - venus resuccitation avoid hypovulomeia - CSF drainage ventricular catheters - hyperventilation to obtain PaCO2 30-35 mmHg - Manitol 1 g/kg serum osmolality 320 Manitol 1 g/kg IV over 10 min then 0.25 g/kg IV Q6H - possibility of surgical mass considered repeat CT SECOND TIER - hyperventilation to PaCO2 26-30 mmHg - hyperdynamic therapy high euvolemia c induced htn to support CPP>60 mmHg - repeat manitol - barbiturates pentobarbital coma - craniatomy HTN control labetolol 0.5mg/min drip titrate to max of 2 mg/min to keep SBP 150-170
Treatment		CSF Analysis routine 1- pr, glu, vdrl 2- cells, cytology 3- Ag, Crypto Ag, GS, Cx viral, bacterial, fungal, TB 4- save for future studies MS Screen
Treatment		Dementia 60 alz, vascular, lewy body, FTD and the rest about 10 percent above age 85, 50 percent demented. FTD frontal behavior dysexecutive or temporal primary progressive aphasia common side effects NV, Cramp, rhinorhea, bradicardia avoid in pt with sicksinus synd or bradydysrhythmia Vivid dreams when given at night to reduce NV no Benadryl no OTC sleep aid Avoid Elavil Oxybutinin CEinhibitors Fish oil omeg 3 acid Zocor Dimebon new drug Most not all go to AD. Vit E not used anymore bo cardiotoxicity Donezepil, behavioral therapy and compensation may help. halucination paranoid irritability CEI not proven effective - clonopin ativan xanax - SSRI Celexa Lexapro Zoloft - Seroquel 12.5 to 25 mg bid less eps confusion fall ct Resperadal and zyprexa. Go slowly - trazodone 25 or 50 mg qhs for sleep check for uti, enviromental trigers, sleep awake cycle, change one medications at a time phosphatydyl serine not sure
Treatment		Dementia CholinEstrase inhib Donepezil start 5mg then after 2 weeks 10 mg Exelon Galantamine vit e NSAIDs COX2 inhib Memantin NMDA antagonist Neuroleptics for agitation, delusion, hallucination haldol 0.5-2 mg/d qhs or bid zyprexa 2.5-7.5 /d enhance cholinergic transmission seroquel low EPs effects Insomnia diphenhydramin 25-50 qhs Ambien 5-10 qhs Anxiety ativan 0.5-1 mg up to tid Xanax 0.025-0.5 mg qd or bid Depression Zoloft 50-100 mg qd if slow Prozac 20 mg qd if anxiety Paxil with heart disease Lexapro
Treatment		LBP - Amitriptyline 50 mg qhs - Flexeril 10 mg tid - Neurontin 800 mg tid - get PT/OT - Flexion Extension Xrays of back to evaluate function and mobilty - MRI of back
Treatment		Mental status changes localization- bil cerebral hemisphere or RAS Pathophysiology- structural- dementia, vascular dementia, stroke, SDH neoplastic/paraneoplastic- met/toxic- HE, ResF, RenalF, hypothyroidism, alcohol, wernicke infec- electrical- subclinical sz, triphasic waves of HE Meds- anticholinergic, BNZD, narcotics Trauma Recom MRI c dementia protocol EEG LP CSF vdrl, herpes pcr Minimize sedation/narcotics Correction of met/toxic/inf per primary team check TSH, FT4, RPR, ANA, ESR, B12, FA, homocysteine for dementia
Treatment		Migraine1 can not tolerate vasoconstrictors triptans or risk for rebound with opioid analgesic do this - Mg SO4 IV 1 gram over 1-2 h or - Depacon 500 mg IV over 15 min can repeat after 1h - Vit B2 400 mg po qd response may take 3 months rule of 4-6 week to try new preventive med and at least continue it for 4-6 months if effective before change to another preventive med AEDs good for complicated or basilar migraine eg lamictal, depakote in children or complicated migraine. Abortive tx - apap=tylenol - asa - NSAIDs ketorolac IV vs Cox2 inhib - Triptan - Ergots cafe ergot or DHE - Depacon 500 mg over 15-30 min - MgSO4 1 gram over 1 hour in for CAD or basilar migrain - Droperidol 2.5 mg iv Compazin 12.5 mg iv chlorpromazine 12.5 or 25 mg watch for orthostasis - Midrin - Supp/ cafeine 150 mg, apap 1000 mg, promethazin 25-50 mg combined - Narcotics - Lidocaine 4% 1/2 cc in each nostril same side of HA Raskin and Lenaerts Suppository: 1) Acetaminophen 1500mg or Naproxen 750mg 2) Caffeine 150mg 3) Metoclopromide 10mg or Phenergan 50mg mix into suppository (Innovative Pharmacy Solutions) Raskin Protocol: EKG 1) Reglan 10mg IV over 60 sec. 2) Wait 5 min. 3) Dihydroergotamine mesylate (DHE) 0.5mg IV over 60secs. 4) Wait 5 min. 5) DHE 0.5mg IV over 60secs. -Repeat q8hrs x3, then q8hrs PRN. -Give Doxepin 50mg PO q4hrs PRN. 6) Doxepin 50mg PO qhs Status migrainousus DHE or IMITREX or DEPACON In pregnancy use mg, opiates (max 2 days/week, 20 no refill)or antiemetics (compazine) if fail may use triptan but pt should be in registry prevention inderal, cyproheptadin, elavil In menstrual migraine use Frova or continous estrogen or u can use 5 days of Relapex bid or Axert bid for 5-7 days Co enzyme Q and melatonin newer tx, melatonin in high doses vasoconstrictive. Botox injection works.
Treatment		Migraine2 Alternative therapy in migraine - B2 - B12 - Petadolex - Feverfew - Botox about 100 u spread bil q3months follow the pain or fixed points or combination of both - Biofeedback, relaxation, massage, physical therapy Status migranosous tx - Raskin - IV Depacon 250 over 5 min or 500 over half hour max 750-1000/day - Droperidol 1 mg IV - Thorazine 25-50 mg IV watch hypotension when they hit the floor amitrip or doxepin 50 mg q4h for 3 days and then for total dose of 200-300 mg/day. For withdrawal/rebound HA- if on butalbital use Phenobarb if on bnzd use clonazepam if on narcotics use methadon also put them on preventive tx and can also use medrol dosepack, compazine supp intractable HA usually drug induced use long acting agent Frova and stop offending agent and replace with long acting agent. Internet sources www.achenet.org www.headachecare.com www.headache.org
Treatment		MS Avonex 30 mcg IM QW c ancillary supplies 28 or 84 days Avonex can be used every 5 days
Treatment		Neuropathy 1 Anti-MAG polyneuropathy- chronic symmetric sensorimotor demyelinating polyneuropathy associated c paraproteinemia IVIG, PE, INF alpha, chlorambucil Rituximab: monoclonal ab against CD20 Ag on B lymphocytes ( used to treat B cell lymphoma and dec 90% of peripheral B Lym in 3 days) used qweek for 4 weeks dec anti-MAG titer by 52% (M & N 27:611-615, 2003)
Treatment		Parkinson diseas Sinemet for old pt Dop agonist for young pt, may have neuroprotective effects, Stalevo 50-100-150 based on levodopa dose Sinemet 25/... tid at least to have effective carbidopa effect Side effects: sudden sleep attack, NV Pramipexole- valvulopathy Mirapex drug of choice Requip
Treatment		RLS
Treatment		Seizure in children depakote 10 mg/kg/day after 2-3 days 15 mg/kg/day topomax 5-9 mg/kg/day dilantin/pb 20 mg/kg/day maintenance dose 5 mg/kg/day for pb can be given divided dose bid Minimum effective dose tpm 100 day Lam 150 Keppra 1000 mg a day tpm lam good for both partial generalized epilepsy lev zonesamide effective also for generalized sz. less interation gbp lev pgb oc interaction tpm cbz oxc reduce oc efficacy lmg become less effective with oc oc reduce lmg level by more than 50 lamictal no effet on oc less sedation and cognitive effect lmg weight tpm zonisamide depression cbz lmg oxc anxiety gpb lyrica vpa bipolar lam top oxc
Treatment		Syphilis
Treatment		Torticollis w/u - flexion extension x rays to rule out bony trauma or osteomyelitis or disk - MRI of brain for tumor thalamic lesion or MRI of c spine for disc - CT of neck to r/o retropharyngeal abscess Tx Botox type A bind to receptor on motor nerve terminal and inhibits release of AC Myobloc type B cleaves synaptobrevin which is the pr complex responsible for docking/fusion of synaptic vesicle to presynaptic membrane. Lorazepam, Klonopin, Valium Artane trihexiphenidyl 2,5 mg tab start half tab 1 mg increment 1 mg q3-5 days to max 2 mg tid SE- constipation, glucoma, GI obstruction, PU, BOObstruction it is centrally acting anticholinergic that diminish muscle spasms. there is acute form of torticollis called acute wryneck in young adults symptomatic tx c heat, massage, supportive cervical collar, muscle relaxants and analgesics.
Treatment	Neuralgia	Neuralgia Occipital neuralgia Marcaine (bupivacaine 0.25%) 12.5-25 mg or 5-10 ml Xylocaine ( lidocaine 1%) for infiltration and nerve block plus Dexamethasone 4mg/ml 30 ml in multiple dose vial 0.5 cc of 0.25% marcaine and 0.5 cc of decadron (4mg/cc) 2 mg injection with 3 cc syringe and 25 guage 1 1/2 inch needle
Treatment	Stroke	ICH and SAH - hyperventilation to obtain PaCO2 30-35 mmHg - Manitol 1 g/kg serum osmolality 320 Manitol 1 g/kg IV over 10 min then 0.25 g/kg IV Q6H - for HTN control drug of choice- Nicardipine (inc HR, Coronary vasodilation, no effect on cardiac output), Labtolol, Esmolol, Enalapril (takes longer to act), Nitroprusside (IC venodilation, inc ICP, cynide toxicity) labetolol 0.5mg/min drip titrate to max of 2 mg/min to keep SBP 150-170 Goal Below SBP180 DBP110 MAP130 SAH ICU Nimodipine Securing aneurysm surgical clipping titanium endovascular Tx of HCP 1/2 pts need EVD acutely or VPShunt later on (EVD should be removed before 2 weeks) Vasospasm (Nicardipine better for vasospasm but didn't improve outcome so Nimodipine may have neuroprotective effect) Laxatives Timing of aneurysm surgery better be in first 36h esp if they came wiyh highgrade of Hunt Hess Scale Importance of prognostication decision making based on individual, disease process and societal level CM Fisher classification of SAH I no blood in CT II blood layer<1mm III >1 mm IV intrcerebral intraventricular HHScale lethargy dec LOC grade 3 unruptured grade 0 overall mortality of SAH 20% Ogilvey Carter scale Is pt over 50 Is SA >1mm thick on CT Is aneurysm >10mm or giant >25mm in pcom Is pt comatose 1 point for each of above. Vasospasm most commonly present with dec LOC, first rule out pt is not hyponatremic, dec glu, dec O2, no evidence of HCP, no evidence of EVD infection or ventriculitis. inc risk in 4-14 days after SAH. tx of vasospasm 3H hemodilution, hypertensive, hypervolumia otherwise Nimodipine 60 mg q4h for 21 days. Hunt-Hess SAH grades I asymptom minimal ha or nuchal regidity II mod to severe ha, no FND x possible cn 3 palsy III drowsiness, confusion, FND IV Stupor, HParesis V Coma, veg decerebrate surgeryfor cerebellar more than 3 cm with brain stem compression or hcp lobar hemorrahge within 1 cm of surface
Treatment	Stroke	Stroke supportive care - Dysphagia solid-pureed diet fluid- honey, nectar and lastly thin liquid fluid - DVT scd, heparin sq, ted hose, lovenox study - GI prophylaxis pepcid - TF c free water - Perineal care cleaning 2 a day - Bowel care colace tid, dulcolax - Bladder care dc foley care, check pvr if > 300 ( normal people>150 cc) in out cath q6h - Cough chest PT and postural drainage - for HTN Enalapril 0.625 mg IV Q6H hold if SBP is less than 140