MIXED NUTS: Neurocrit Care Exam Notes




Adequate CPP = 70-90mm Hg


Abrupt coma with normal CT: differentials: seizure, encephalitis / meningitis, HSV?, intoxication, SAH, BS stroke (check for hyperdense basilar artery)




TIAABCD2 system: (age >60, BP >=140/>=90, clinical isol speech impairment, unilateral weakness, DM, duration 10-59mins, >=60mins), check 2day stroke risk


Crescendo TIA:  WASID Trial – anticoagulation (ASA vs Coumadin) in large-vessel intracranial stenosis (mortality 4.3% in ASA, 9.7% in Coumadin, p=0.02); SAMMPRIS trial – CAS vs aggressive med Mx (30d stroke risk 14.7% in stenting vs 5.8% on med Mx); unresponsive to med Mx – what next?; permissive HTN – controversial, WASID subgroup analysis – lower recurrent stroke with BP improvement


Cryptogenic Stroke:  2y risk of stroke = 2-5%;  PFO more prevalent, CLOSURE Study – no benefit of PFO closue; ASA mainstay of treatment;  no benefit of warfarin over ASA in the absence of hypercoagulable state


tPA:  window expanded to 4.5h based on ECASS Trial; excludes >80y, NIHSS>25, +DM, prior stroke;


Carotid Stenosis:  NASCET criteria (HG stenosis ~26% risk of stroke in 2 years); ASA+statin+revascularization (RRR 65% CEA, 20% ASA, 30-35% statisn); CAS=CEA, choose CAS if HR periop MI; CREST trial >70y/o less stroke with CEA, choose CEA; other factors: location of plaque, risk of CN palsies, cosmeting scarring


Carotid Dissection: anticoag and antiplatelet equally effective (single center series, 2008 Cochrane meta); surgical options – ligation when endovasc / medical Mx not possible; endovasc repair – failure e of initial med Mx or has intracranial extension; lacks prospective date for efficacy and safety,


Vertebral artery dissection:  Wallenberg syndrome from PICA involvement


Spinal cord infarction:  lumbar drain reduces intrathecal pressure, increases cord prefusion, do not lower MAPs; distal bypass during surgery to restore cord perfusion improves outcomes – check SSEPs during aortic repair, bypass when SSEPs show poor signal transmission




ICH:  EVD if GCS <8, does not worsen outcomes; Hemicraniectomy – HAMLET / DESTINY / DECIMAL = DHC vs medical Mx; 93 pts pooled, MRS <=4 (75% vs 24%, ARR 51%) <=3 (43% vs 21%, ARR 23%), survival (78% vs 29%, ARR 50%), NNT = 2 (survive MRS<=4), NNT=4 (survive MRS<=3), NNT=2 (survive, wev MRS); STICH trial – no benefit of surgical evacuation; Amyloid angio – surgery risks adjacent tissue heme; PROACT II Trial – IA thrombolysis poorly tolerated, worsen outcome; Prophylactic seizure does not improve outcome; early nutritional support improves outcomes


Infratentorial hemorrhages: urgent decompression; IV obst – rising ICP – MAP lowering risks cerebral hypoperfusion; EVD risks upward herniation unless in combi with SOC; angio after SOC


IVH:  few evidence-based therapies; induced hypothermia may halt perihematoma edema (single center trial), no evidence for high-dose steroids in ICH; FAST trial – rFVII reduced hematoma expansion, rebleed, no effect on perihematomal edema; IV tPA – reduces clot burden


Cerebral Venous Thrombosis:  requires high degree of suspicion; risk factors:  pregnant, hem/onc disease, autoimmune, TBI, intrathecal or spine procedures;  CT with contrast – dilated cortical veins, cortical subarach blood, dense sinuses; dense sinus sign / empty delta sign – in 1/3 of cases; treatment:  excellent response to heparin infusion, start even with small cortical bleeds; osmotherapy causes DHN, venous constriction, worsens thrombosis, (may use if other attempts to control ICP failed – LD, acetazolamide, optic n. fenestration); DHC last resort


Moyamoya disease:  no role of statins; ASA reasonable, but not long term; STA-MCA bypass or EC-IC bypass – effective, less risk of ischemia and heme; endovascular stenting C/I, rapid stenosis; STOP Trial – exchange transfusion in SCD, significant benefit; TCD to assess hyperviscosity requiring exchange transfusion; peds with SCD – routine TCD, ET if MCA velocity >200 cm/sec; no benefit of weekly CBCs


Carotid-cavernous fistula:  usually traumatic, may be spontaneous;  unexplained chemosis +/- ophthalmoplegia; treatment:  endovascular occlusion of fistula


Cal-Fleming Syndrome or RCVS:  thunderclap HA, AKA pseudovasculitis (angio mimics vasculitis); risk factors:  drugs, exertion, pregnancy, other HA types; no good evidence for treatment; self-limited, may be complicated by sz, cerebral ischemia



Hypertension:  JNC7 Guidelines; SCAST Trial – careful BP lowering no effect on outcome; COSSACS trial – continuing or stopping BP meds in hospitalized stroke patients no effect on outcome


Afib:  973 pts >75y warfarin vs ASA – ischemic strokes 2x more common (44 vs 21 events favoring warfarin), major bleeds equivalent (3 vs 4), RRR 52% with Coumadin with no increase in risk of major heme;  Active-A Trial – ASA+clopidogrel – no net benefit (modest improvement in ischemic stroke, but similar increase in bleeding risk)


Pupils:  Ptosis and miosis Horner’s syndrome, ptosis from sympathetic disruption subtle, lid lag only;  sympathetic innervations of pupil – dilate via dilator papillae (radial smooth  ms of iris), appears miotic in dark; constrict (sphincter papillae ms of iris) via parasympathetic – most active in light, pupils symmetric in full light; swinging flashlight – to detect RAPD; red lens – to isolate slight diplopia




Other SSx based on location of aneurysmPcomm – CN III Palsy; ptosis; involves pupil, papillary fibers lie on dorsomedial surface, vulnerable to compression; [cf ischemic causes which affect central fibers, spares pupil]; MCA – temporal lobe seizures / hemiparesis from mass effect; carotid artery (ophth segment) / Acomm / cav sinus aneurysms – VF cuts, bitemporal hemi, homonymous hemi, quadrantanopsia; ophthalmic a – inferior nasal VF cut due to pressure from overlying falciform ligament; cav segment of carotid – Horner’s due to compression of postganglionic sympathetic pathway; carotid cav fistula after aneurysm rupture – exophthalmus; post circulation – Weber’s syndrome / BS compression syndromes, CN III, VI, lower CN palsies; unruptured Acomm – dementia, abulia, pituitary dysfunction from mass effect; Terson syndrome: blindness due to vitreous hemorrhage


Diagnostics:  cerebral angio is gold standard, 1% Cx rate; TCD high sp for MCA, low Sn and NPV, 40% with DCI had velocities <120 cm/s; operator dependent; Lindegaard ratio: ratio bet MCA / EC ICA velocities; >6 = severe VSP; CTA overestimates VSP, less accurate for distal VSP, meta analysis 80%Sn 93% Sp;  CTP – CBF, MTT, CBV, late CTP 91% Sp 95% Sn cf DSA, early CTP helps predict, late CTP correlate with VSP and delayed ischemia; cEEG: alpha-delta ratio, changes seen 3d prior; detects NCS (20% of SAH); intracortical recording? – more accurate, less artifact;  lose faster frequencies when CBF 25-35 ml/g/min,  infarction threshold 10-23 mgl/g/min, silent / irreversible damage


Treatment:  BP goals:  AHA recommends esmolol, labetalol, nicardipine (superior, pure vasodilator), avoid nitroprusside (dilates intracerebral vessels, raises ICP, unreliable dose response, rebound HTN, CN toxicity); Nimodipine: only drug to reduce long-term poor outcome; exact mech unknown; blocks Ca-dep excitotoxicity, antiplatelet aggregation, dilates leptomeningeal or small dural collaterals; IV no benefit over PO; Statins: possible benefit? Reduced DCI / mortality?, reduces glutamate-mediated exitotoxicity, moderates inflammatory response; endothelin 1 antagonistCONSCIOUS 1 and 2 Trials – reduction in vasospasm with endothelin 1 antagonist, but not improved outcomes; Others: CSF drainage, endothelin 1 antagonists, IV Mg, nicardipine pellets intraop, intrathecal thrombolytics, calcium channel blockers


VSP: early day 3, max days 6-8, rare lasts day 15 and beyond; abulia and LE weakness if ACA affected; aphasia and UE/LE weakness if MCA affected, maybe just increased tone


Induced Hypertension:  Phenylephrine:  preferred drug, caution in patients with CAD, glaucoma, thyroid disease; alpha agonist, vasoconstricts, reflex bradycardia; immediate onset, effect lasts 20-40mins; Epinephrine: alpha and beta 1 agonist, tachycardia, use if with Cushing’s reflex or BP / CO needs augmentation; dopa / dobu – activates B1, tachycardia; prefer dobu if BP up and CO low, not strong vasopressor because B2 action vasodilates; Vasopressin:   vasoconstriction, caution – associated with VSP and cerebral edema in animal models




Negative CT:  CT detects 95% SAH within 24h, 98% within 12h; xanthochromia detected >4h after; if <4h, compare bottle 1 to 4, non SAH clears 70% with bottle 4 <500 RBCs, SAH clears 30% with 900 to 2M RBC in bottle 4


Perimesencephalic SAH:  ~10% of SAH; hypothesis:  venous anomaly, ruptured perf artery, capillary telangiectasia; definition:  bleed anterior to midbrain +/- extension to ambient cistern or basal part of Sylvian cistern, incomplete filling of the interhemispheric fissure; usually good clinical grade; VSP up to 16%; needs at least 1 6-vessel DSA; CTA or MRA not recommended; controversy with f/u angio


Rebleeding:  rerupture risk highest first 24 hours, esp first 6h; International Coop Aneurysm study – rebleed is 4%, likely higher; other studies 13% prehospitalization rate of rebleed; risk factors: >1cm, poor initial neuro presentation, seizure at onset; ?HTN; 2012 AHA recommends SBP <160, antifibrinolytic therapy to prevent;  ISUIA (International Study of Unruptured Intracranial Aneurysms) – published rupture risk of aneurysm, smaller and in anterior circulation lower rupture risk cf larger and in posterior circulation


Neurogenic myocardium:  inc ICP – hypothalamic injury – release of catechols à contraction band necrosis à LV dysfunction à rising troponin and BNP; troponin 100% Sn; EKG changes in clued ST up/down, QT prolong, peaked/inverted T, large U, peaked P, pathological Q


Neurogenic pulmo edema: overactive SNS – blast theory (BP surge shifts blood from systemic to pulmo circulation causing barotraumas) and permeability theory; seen within minutes, symptoms resolved after 24-48h, CXR shows bilateral infiltrates, more central, frothy sputum; treatment: supportive, mech vent, alpha antagonists (phentolamine) or B-stimulating catecholamines, ?dobu / dopa?, PEEP?; correlates with incidence of VSP, higher mortality rate


Hyponatremia: 30-50%, presents 3-14d after rupture; more frequently with blood in III ventricle, suprasellar cistern, Acomm rupture; DDx: thyroid, cardiac, meds, volume, CSW, SIADH;  SIADH vs CSW: both cause hypotonic hyponatremia, elevated UOsm>200, UNa >25 mOsm/Kg; fluid balance NEG in CSW, expanded volume in SIADH; treatment: fludrocortisones?, correct between 8-12 mmol/L in 24h


HCP:  early HCP: 20-30%, first 48h; delayed HCP: 25%, several weeks, risks: older, female, intraventricular blood; poor clinical grade best predicts HCP




EDH in TBI:  Indications for Sx:  volume >30cm3, >1.5cm thick, MLS >0.5cm, anisocoria; GCS>8 manage conservatively, but close monitoring


Post fossa bleeds:  uncommon, <3% of TBI, most common is EDH (<10% of EDHs); SDH 0(.5-2.5% of SDHs), ICH <1.7% of traumatic ICH; rapid deterioration


Skull fractures: open / depressed – needs surgery for wound cleansing, repair of bone / scalp; any dural laceration should be repaired (risk of meningitis); devitalized bone – discard; criteria for repair of closed depressed sklul fractures – fragment displacement greater than width of skull or cosmetic deformity; basilar skull fractures: prophylactic Abx does not decrease meningitis risk (5RCTs), 1/6 of skull fractures, rarely require surgery, suspect with pneumoceph on CT, raccoon’s eyes (perioribital ecchymosis) or Battle sign (postauricular ecchymosis);


CSF leak: common in TBI, 12-30% of basilar skull fractures; common with fracture of frontal or ethmoid sinus Fx, longitudinal temporal bone fractures; 60% present within 48h, 70% spontaneously resolve within 48h; delayed leaks after TBI is possible (months to years); meningitis in 7-30%, most common pathogen is S. pneumonia; meningitis occurs in between 7% and 30% of all patients who develop a posttraumatic CSF leak. Streptococcus pneurnoniae is the most frequent pathogen in patients developing meningitis after a posttraumatic CSF leak (8).


Blunt Cerebrovascular Injury:  2 criteria – Denver Criteria:  LeForte II or III Fx, cervical Fx or subluxation, basilar skull Fx with involvement of carotid canal, DAI with GCS <6, near hanging with anoxic brain injury;  Memphis Criteria: cervical Fx, LeForte II or III Fx, basilar skull fracture with involvement of carotid canal, Horner’s syn, neuro deficit unexplained by imaging, neck STI (seatbelt sign, hematoma, hangin); VA enters transverse foramen of C6 in 90%


DAI:  DWI sequence most sensitive, DTI highly sensitive, able to detect in hyperacute phase, high NPV, requires signif post-processing, not widely available; PET and Xenon CT metabolic studies, not useful in DAI


Hemorrhagic progression:  early heme in half of TBI with CT 2 hours post-injury; common, associated with ICP elevations; risk factors: male, >60y, early deterioration of GCS, elevated PTT,


Induced Hypothermia:  smaller studies demonstrate some benefit, large RCTs failed todemonstrate benefit on mortality in peds/adults; tendency toward better GOS; guidelines for severe TBI – prophylactic hypothermia is an option but not Class I or II intervention; also an option for TBI with refractory intracranial HTN after max medical therapy


Seizures: 4-25% adult TBI, 1/3 peds TBI; risk factors for late seizures:  SDH or ICH evacuation, GCS 3-8, early seizures (esp delayed early sz), depressed skull fractures not surgically elevated, dural penetration, 1 nonreactive pupil, parietal lesions on CT scan); 3 groups: immediate (<24h), early (<1week), late (>1week); prophylactic AEDs decrease risk of early seizures (Temkin study, phenytoin  decreased early sz from 14.2 to 6%) but treatment beyond 1 week did not decrease late seizures.


DHC: no evidence for routine use in severe TBI with refractory ICP elevation; may be justified in young <18y refractory to med treatment; DECRA Study (Australia), early bi-FTP DHC decreased ICP and LOS in ICU but associated with more unfavorable outcomes; complications of DHC:  infection in 2-6%, blossoming of contusion in 58%, subdural hygromas in 16-50%, HCP in 29%, expansion of contralateral mass lesion in 25%; Syndrome of the trephined:  delayed neuro deficits after DHC; may be mild deficit to severe hemispheric dysfunction, AMS; etio unknown, treatment:  cranioplasty


ICP monitor: severe TBI; 2 of 3 features: >40y, unilat or bilat motor posturing, SBP <90; trauma with abnormal head CT with no neuro exam due to prolonged anesthesia or extended use of paralytics;  ICP goals: guidelines – start ICP lowering treatments at ICP 20-25mm Hg (Level II), caveat that patients may herniated at ICPs <25, esp with mass lesions >20ccs in cerebellum or temporal lobe


Traumatic SCI:  ultra high-dose steroids does not improve outcomes (3 RCTs, NASCIS); NASCIS 3: megadose methylpred (30mg/kg bolus then 5.4mg/kg infusion x 24-48h) in acute nonpenet SCI, no improvement in outcome or motor scores, mortality from respiratory morbidity 6x higher in 48h group, 2-fold inc in severe PNA, 4-fold increase in severe sepsis in 48h group (not statistically signif); NASCIS 2: 2-fold inc in wound infections in steroid group;  NASCIS 1 – 4-fold increase in wound infection rates;




Ventriculitis: post EVD – ranges <1% to 45%, most report between 5-23% depending on criteria used; risk factors:  duration >7d, IVH; routine cath exchange does not decrease infection rate


Bleeding:  7% (4.5-9.4%) risk, clinically significant risk 0.8% (0.2%-1.4%); no difference in risk of hemorrhage with INR 1.2-1.6 vs <1.2;




Mannitol: primary mech – dec viscosity by alter RBC shape (rheol effect) – improves CBF esp microcirc – decreased ICP, occur within minutes; osmotic effects not apparent x 15-30 mins; also a free-rad scavenger




Status Epilepticus:  seizures >=5mins; 2 goals: stop all sz activity, determine cause; protocol:  BLS, labs for etiology, give thiamine 100mg IV, D50- 50mL; Columbia Univ Comprehensive Epilepsy Center SE Adult Tx protocol:  ativan 4mg IV x2 q5mins; if no IV access then diazepam 20mg PR or midazolam 10mg intranasal, buccal or IM; load fosphenytoin 20mg/Kg IV at 150mg/min, BP and EKG monitoring; if seizures persist, 4 options:  1.) midazolam gtt (load 0.2mg/kg, bolus 0.2-0.4mg/Kg q5mins to max load 2.9mg/Kg; drip 0.05-2.9mg/Kg/hr), 2.) propofol (load 1-2mg/kg, bolus 1-2mg/kg q5mins to max load 10 mg/Kg, drip 1-15mg/Kg/hr; 3.) Valproate IV 40mg/Kg over 10 minutes, 2nd dose 20mg/Kg over 5 minutes if seizures persist; 4.) Phenobarbital 20mg/Kg IV ( rate 50-100mg/min)




Absence SE:  irregular generalized spike and wave, or polyspike and wave activity at 3.0-3.5 Hz;  absence exacerbated by: phenytoin, CMZ, oxcarbazepine, tiagabine;  use: lorazepam / diazepam to break seizure, then load VPA


Spindle coma:  spindles are one of the hallmarks of St II sleep, spindle coma unarousable; seen in high mesencephalic lesions; also in post-TBI, post-encephalitis; harbinger of favorable prognosis for some meaningful recovery


Alpha coma:  diffuse alpha activity, but EEG not reactive to noxious or auditory stimuli; seen in patients with diffuse brain insults after CP arrest, BS lesions at or caudal to pontomesencephalic junction, toxic/metabolic abnormalities (barb overdose / HHS); grim prognosis in post- arrest


PLEDS:  q1-2seconds, spike or sharp wave followed by slow wave; acute stroke most common cause, any injury resulting in seizures also shows PLEDS;  consider HSV encephalitis if PLEDS in temporal lobes; marker of acute injury, transient and diminishes over days to weeks


GPEDS:  nonspecific;  post-anoxic coma after convulsive SE, metabolic, CKD, Hashimoto enceph, med toxicity (esp lithium; also baclofen, cefepime); less common with seziures


Triphasic waves: initial neg (up) component, subseq larger pos (down) deflection, and final negative component; frontal predominance; a type of generalized periodic dischargel; classically in hep enceph; seen also in any toxic/metabolic enceph, renal failure, hyperosmolar state, hypoglycemia, hyponatremia, hypercalcemia, hyperthyroidism;  repeats q1-2s, wax and wane in morph and persistence;


Breach rhythm:  skull defect resulting in increase in voltage and more sharp morphology in underlying EEG, afster frequencies more accentuated


Mu rhythm:  benign normal variant in healthy individuals, 7-11 Hz arciform waveforms over central head regions; attenuates with movement or thought of movement of contralat hand


EEG criteria for seizures:  clear evolution in frequency, morphology or location of an ongoing EEG pattern

N20 waveform:  AAN (2006), bilateral absence of N20 component of median nerve SEP 3d after CPR predicts poor outcome; N9 (Erb’s point) waveform – peripheral nerve activity through brachial plexus; N13 waveform – activity in dorsal horns of SC; N20 waveform – activity in thalamocortical radn / sensory cortex


EEG in Brain death:  irreversible loss of function of brain, including brainstem; definition is simple, difficulty in confirming “irreversible”;  no requirement for EEG or SSEP testing ;  EEG: at least 30mins, use of minimum of 16 channels, minimum of gain of 2 uV/mm (magnifies any electrocerebral activity); electrocerebral inactivity (ECI): most common EEG pattern in brain death (80%, 20% have some electrical activity), but not diagnostic (brain death is a clinical diagnosis)


EEG during CEA Surgery:  EEG + median n. SSEP + post tib n. SSEP; EEG can detect new cortical ischemia, assesses large areas of cortex; new ischemia = ipsi slowing  or amplitude attenuation or both; normal CBF 50ml/100g/min, mild hypoperf >22 well tolerated; when <22, EEG starts showing slowing / amplitude attenuation, decrease to 7-15 result in suppression of EEG activity;  80% patients have adequate collateral flow, 20% with significant ischemia on cross-clamping


EEG in NCSE:  seizure duration predicts mortality; if <10h, 60% home 10% died, if >20h none home, 85% died.


EEG in SDH / EDH: focal slowing, amplitude attenuation (underlying cortical malfunction and increased distance between brain and electrode), focal sharp waves or spikes, PLEDS, seizures (irritation from blood)


Rationale for cEEG:  EEG linked to metabolism, EEG sensitive to ischemia, EEG detects reversible neuronal dysfunction, EEG detects neuronal recovery (cf phy exam), EEG detects seizures, cEEG dynamic, EEG localizes;  EEG important for:  sz, epileptiforma ctivity, post SAH VSP, focal ischemia, early increased ICP, monitor depth of anesthesia, monitor for periodic patterns with prognostic value (PLEDS or GPEDS)


EEG in Encephalopathy:  typical EEG progression:  mild slowing of occipital dom rhythm (alpha) in wakefulness à theta range à diffuse fragmentary or more sustained theta and delta activity à alpha rhythm and frontal beta will be lost, diffuse theta and delta more prominent and sustained à normal sleep architecture lost (K complexes / spindles) à diffuse amplitude attenuation and FIRDA à normal variability and state transitions lost à unreactive to ext stimuli à diffuse BS pattern à ECI




ALS:  lithium ineffective; effective treatments (to delay progression) include: NIV, PEG nutritional support, riluzole;  FTD: in 15% of ALS,


Ipecac:  excessive use – progressive myopathy, CMP; suspect if with h/o eating disorder


Succinylcholine:  can induce hyperkalemia in these cases: musc dystrophy, ms inflam, disuse atrophy, denervation, thermal trauma, severe infection; mechanism:  spread of AChRs, upregulation of AChRs à efflux of K during activation of receptors à hyperK


Myasthenia gravisanti MUSK Ab:  40% of seroneg MG neg for AChR Ab have MUSK Ab, pred women, distinct features: prominent facial weakness, atrophy, signif pharyngeal and resp involvement, frequent crises, good response to plasma exchange for acute, rituximab for long-term immunosuppression;  cholinergic crisis:  paradoxical worsening due to high-dose steroids;  Treatment:  IVIg comparable to plasma exchange in mod to sev MG; indications for mech vent:  FVC <=15ml/kg (N=>60), NIF <=20cm H20 (N>=100), do not wait for abnormal ABG


SCI:  sensory level with extensor plantar responses (CS tract dysfn), sudden

MS:  same findings with long-tract signs

PNS disorder: loss of reflexes

CIDP:  same findings, but more insidious; 8 weeks symptoms, progressive


GBS:  acute ascending paralysis, nadir at 2-4wks then recovery, immune-mediated d/o of PNS, most common post-infectious neuromuscular paralysis; most common: C. jejuni, EBV, CMV, HIV, M. pneumoniae; life-threatening:  resp. failure, dysautonomia; variants: AIDP, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, acute pandysautonomia, Miller Fisher syndrome; albuminocytologic dissociation:  elevated CSF Pr, normal CSF cell count; always exclude infection, CSF studies can be normal first 2 weeks; other studies:  EMG (assess axonal injury, esp latter phases), NCV (prolonged H reflex / F wave latencies or absent F wave responses); repeat NCV in 2 weeks if normal; evaluation of infectious disease: stool cultures, serology for C. jejuni, HIV, EBV, mycoplasma pneumonia, CMV; SIADH in GBS: pathophysio unknown, ?downward osmotic resetting / enhanced renal tubular sensitivity to ADH; GBS may be more severe in Pt with SIADH;  cardiac Cx: due to autonomic neuropathy; arrhythmias, BP lability, myocaritis, stunned myocardium, CHF, ACS, EKG changes


MFS:  ophthalmoplegia, ataxia, hyporeflexia, descending rather than ascending





Serotonin Syndrome:  (+) exposure à agitation /confusion, fever, HTN, tachycardia, diaphoresis, mydriasis, tremor, akathisia, clonus, ms rigidity, increased bowel function (diarrhea); common agents: SSRIs, MAOis, antidep, opiates (meperidine, tramadol), lithium, triptans; cf NMS: NMS with normal pupil size, rigidity all limbs, hyporeflexia, quiet delirium or mutism


Lithium toxicity:  dysarthria, ataxia, nystagmus, n/v, diarrhea, nephrogenic DI


NMStreatment: dantrolene (ms relaxant, decrease release of intracellular Ca from SR) 1-2.5mg/Kg IV, bromocriptine (dopamine receptor agonist), lorazepam first line agent for sedation / ms relaxation, fluids (possible rhabdomyolysis)


EKGOsborn waves:  J point elevation ~1mm end of QRS complex found in hypothermia; height of wave inversely related to body temperature;  benzodiazepine overdose – AV block; TCA overdose – QT prolong QRS prolong; SAH – ST elev/dep, inverted or peak T, Q waves, prolonged QTc; severe hyperCa – shortened QTc


TCA poisoning:  Na HCO3  to goal pH of 7.45-7.55 in patients with widened QRS / prolonged QTc, evidence only from case series / animal studies


Naloxone: half life 60-90 mins, duration as long as half-life


Malignant Hyperthermia:  syndrome of ms hypermetabolism after succinylcholine or inhaled anesthetics; ms protein abnormalities – ryanodine receptor mutation; symptoms:  high fever, tachycardia, cyanosis, masseter ms spasm, pipe rigidity, hyporeflexia, rise in ETCO2, rhabdomyolysis; treatment:  dantrolene is mainstacy (decreased excitation-contraction coupling by reducing Ca release from SR, no effect on NMJ), benzos not helpful


Heat exhaustion:  gen weakness, n/v, syncope, no neuro dysfunction / tissue damage; elevated core T

Heat syncope:  syncope due to peripheral vasodilation

Heat cramp:  exertional cramping in heat due to DHN

Heat stroke: loss of thermoregulation à extremely elevated core body T (>40.6C), neuro dysfunction (delirium, lassitude, sz, coma) and anhidrosis; signs of end-organ damage (ARF, elevated LFTs, cardiac conduction defects, DIC, rhabdo); treat early, decrease core T to <38.9 within 30mins; 2 types: exertional (healthy persons exercising or working hot environment) and nonexertional (debilitated or elderly with prolonged exposure to heat)


Drug abusePCP: hallucinogen, antagonizes NMOA receptors, inhibits MOA reuptake, cholinergic effects via nicotinic and muscarinic; periods of super human strength, anesthesized; ataxia + nystagmus; HTN and tachycardia; miosis, salivation, bronchospasm, diaphoresis;  Cocaine or Amphetamines:  sympathomimetic + paranoia, no ataxia or nystagmus;  opiates: sedation, depressed RR, miosis, constipation, analgesia; MDMA: stimulant and hallucinogen; increased release of serotonin, dopamine, norepinephrine; severe hyperthermia, sympathomimetic effects, paranoia, hallucinations


Sarin attack:  organophosphate, inhibits AChase à cholinergic crisis, in PNS and CNS, both nicotinic and muscarinic receptors; symptoms: neuromusc weakness, loss of DTRs, fasciculations, sz, AMS, miosis, BOV, ocular pain, tachy / brady, SLUDGE symptoms (salivation, lacrimation, urination, diarrhea, GI upset, emesis); pralidoxime: antidote, give up to 6 hours of exposure


Barbiturates: gastroparesis, immunosupression, resp failure, hypotension, poikilothermia, hypokalemia, rebound hyperkalemia, decreased VT / torsades





Multiple Sclerosis:  RRMS: 2 oral therapies approved – fingolimod (US/Russ) and cladribine (Au / Russ);  phase3 trials (BG-12, laquinimod, terifluonmide); fingolimod: activated when phosphorylated by sphingokinase, alters lympho tracking by trapping them in peripheral LN, lymph counts reduce rapidly, return to normal within 6 weeks after stopping treatment

NMDA encephalitissymptoms: prominent neuropsych, seizures, dyskinesias, hypoventilation, autonomic instability, in young; dramatic presentation then 1-3 relapses, then death or recovery; pathology: Ab against N R1 and N R2 heteromers of NMDA receptor, may be assoc with ovarian teratoma; treatment: tumor removal, immunotherapy

NMO:  classic presentation of optic neuritis and acute transverse myelitis; ON can be severe and steroid-resistant, spinal cord attacks often severe, spans 3 or more segments on MRI, bilateral limb paresis, sensory syndromes, bowel and bladder dysfunction; BS involvement – refractory n/v, hiccups (pericanal region of medulla / area postrema and medial/lat portions of nucleus tractus solitarius; Diagnostic criteria:  NMO IgG (aquaporin 4) Ab; 2 elements based on neuroimaging; normal brain MRI or nonspecific WM lesions, (+) longitudinal extensive spinal cord lesion (acute transverse myelitis) – contiguous T2 hyperintensity over 3 or more vert segments of SC and have core of T1 hypointensity; Treatment:  IV steroids (methylpred), oral azathioprine, chimeric antiCD20 monoclonal Pr rituximab

Behcet’s disease: relapsing inflammatory disorder, no definite cause, CNS affectation: preference for BS and diencephalon; vasculitis in 1/3, narrowing, occlusion and aneurysm formation; may be viral or autoimmune, ?familial cases assoc with HLAB5, HLAB1   [HLADR15 MS, HLADQB1-0602 narcolepsy, c-ANCA Wegener’s, HLAB27 AS]


Progressive Systemic Sclerosis:  thickening of skin and SQ tissues + sm ms atrophy + fibrosis of internal organs (GI tract, lungs, heart, kidneys); Dxics:  (+) ANA nucleolar pattern, (+) Scl-70 (specific); CNS affectation: global cognitive decline or focal lesion; enceph, migraine, psych change, sz, focal deficits


Drugs and CNSaseptic meningitis: PCN / ceph; benign intracranial hypertension: Ampho B / nalidixic acid; cerebellar ataxia and ON: ethambutol; cochlear and vest damage: vancomycin; neurotoxicity: tacrolimus, cyclosporine, immunosuppression;


GCA:  temporal arteritis; large vessel, T-cell mediated vasculitis, CD4 cells aggregate on internal elastic lamina; symptoms: pain, HA, scalp tenderness, jaw claudication, neck pain; ESR >30mm/hr, Sx x 2 weeks; confirm with Bx


Progressive multifocal leukoencepalopathy:  opportunistic infection by JC virus; occurs in late HIV, associated with use of natalizumab in MS, symptoms: depends on where lesion is, commonly cognitive deficits, focal paralysis, generalized weakness, visual disturbance, gait abnormalities; most common manif in AIDS is hemiparesis; MRI: hyperintense T2 subcortical WM multifocal lesions beginning at GW junction, coalesce to form confluenct lesions, hypointense in T1; no enhancement (unlike active MS); prognosis better with natalizumab-associated vs AIDS; Dx: CSF analysis (+) JC Virus PCR (Sn >80%, Sp >90%); Treatment: plasma exchange to remove natalizumab;  pathology:  confluent demyelination juxtacortical WM or near deep GM (in MS, periventricular); histopath – enlarged oligos with virions, reactive astrocytosis, bizarre giant astrocytes



Marburg’s variant: ?rapidly progressive demyelinating process, multifocal, cerebral hemispheres, BS, optic nerves; pseudotumor variant? HA vomiting AMS focal deficits; contrast uptake homogenous cf tumefactive form; pathology: extensive necrosis, massive macrophage infiltration in acute lesions, severe extensive demyelination;  CSF:  mononuclear pleocytosis, oligoclonal bands absent


Rituximab:  infusion reaction, cytokine release, common with first time infusions; treatment: wait 30-60 mins, steroids prior to starting infusion at half previous rate, titrate to tolerance (unless severe / true anaphylaxis)


Tumefactive MS:  mimics clinical and MRI chars of glioma or cerebral abscess; >50% lesions are gad-enhancing, respond to IV steroids; diagnosis: biopsy (shows demyelinating disease)


Acute partial transverse myelitis (APTM):  greater chance of converting to MS; asymmetric patchy SC abnormal signal; length of lesion typically shorter than 2 vert segments


ADEM: monophasic demyelinating disorder, 6w after viral infection / immunization (DPT, MMR, influenza, tetanus, yellow fever); measles highest risk; rapid multifocal / focal neuro symptoms: prodrome (HA, LG fever, myalgia, malaise), then motor ffd by sensory deficits, BS signs, cerebellar signs, enceph, stupor, coma, meningismus, seizures; MRI:  enlarged and confluenct WM edematous lesions, enhance simultaneously;


GBS: PNS demyelinating disease


Neurosarcoidosis: elevated ACE in CSF and serum, may present as recurrent steroid-dependent ON; confirm with gallium 67 scan, biopsy


SLE:  50% have neuropsych presentation, most common sx: acute confusional state, psychosis, dementia; stroke, venous thrombosis, ataxia, movement disorders



CPM:  associated with rapid correction of hyponat or hypoosmolar states; symptoms: quadriplegia and pseudobulbar palsy; partial forms = confusion, dysarthria, disturbances of conjugate gaze without quadriplegia; diagnostics: MRI (symmetric high signal intensity in pons on T2W, lesions outside brainstem occasionally; correct Na gradually 10 mmol/L within 24h and 20 within 48h





Diabetes Insipiduscauses: meningitis (uncommon) central trauma, brain surgery (esp TSP), sellar and suprasellar tumors, pit apoplexy, sarcoidosis; lab findings: hypernatremia, low UOsm, normal UNa, low USG;  central DI: impaired production of ADH; DDAVP: 50% decrease in UOsm in DI, 5% increase in Uosm without DI, no change with nephrogenic DI


VHL Syndrome: AD, cerebellar and spinal cord hemangioblastomas, retinal angiomas, renal cell carcinoma, pheochromocytoma


Pheocyromocytoma:  diagnostics: plasma metanephrines most useful test, normal excludes diagnosis, mild elevations false positives; renal US with Doppler (rule out RAS, FMD)


Lithium: s/e hypothyroidism, may present as myxedema coma


Thyroid storm: symptoms: seizure, RVR, hyperthermia; amiodarone associated with 2 major thyrotoxicosis: type 1 (associated underlying thyroid abnormality), type 2 (no intrinsic thyroid abnormality); TreatmentPTU: inhibits production of thyroid hormones, inhibits conversion of T4 to T3; Lugol’s solution: inhibits release of thyroid hormones, start 1 hour after first dose of antithyroid drug; Propranolol: B-adrenergic blocker, large doses >240mg can inhibit conversion of T4 to T3


Myxedema coma: extreme hypothyroidism, coma / lethargy with bradycardia, hypothermia, hyponatremia, resp failure, precipitated by infection, CHF, amiodarone; high MR; Treatment: ventilator support, cautious rewarming, hydrocortisone 50-100mg q6h, hemodynamic support


Hyponatremia: drugs: CMZ, SSRIs, opiates, lamotrigine; euvolemic:  SIADH, hypothyroidism, adrenal insufficiency; Uosm >100 (usually>300), UNa>30; polydipsia, inapproate water administration: Uosm<100, UNa>30;  hypovolemic: vomiting, diarrhea, third spacing; UOsm  >300, UNa <20 FENa<1%); hypervolemic: CHF, Cirrhosis (UOsm >300, UNa <20, FENa <1%); excessive diuretic use:  UOsm>300 UNa >20, FENA>1%


CSW:  extracellular volume depletion due to renal sodium transport abnormality in patients with intracranial disease and normal adrenal and thyroid function; associated with: TB meningitis, metastatic adenoacarcinoma of lung, TBI, SAH; pathology: increased BNP; treatment: fluid replacement, maintain positive salt balance, fludrocortisones if refractory; main diff with SIADH: hypovolemia and negative Na balance; SIADH is eu or hypervolemia; random urine Na >100 in CSW; SIADH rarely leads to random urine >100


SIADH / CSW: hyponatremia, high UOsm, high UNa; high Pr diet / oral urea induces osmotic dieresis; demeclocycline: blocks ADH action (inhibits cAMP generation) and increases free water secretion, contraindicated in renal disease, hepatic cirrhosis or CHF; conivaptan: short-term use only; tolvaptan: selective V2 receptor blocker, long-term oral use

Psychogenic Polydipsia:  hyponatremia, low to normal UOsm, low to normal UNa


ODS:  rapid corection of Na, demyelination of neurons in pons; symptoms: spastic paralysis, pseudobulbar palsy, dysarthria, horiz gaze paralysis, dec consciousness over hours to days; risk factors: chronic ETOH, malnutrition, renal insufficiency, liver cirrhosis; majority <=105, nearly all <120; animal experiments: no brain damage when hyponatremia <1d is rapidly corrected; max rate:  0.5 mmol/L/hr, 10-12 mmol/L in first 24h and no more than 18 in first 48 hours






MeningitisTiming of ABx in meningitis:  no prospective data, retrospective studies show benefit in outcome and survival if antibiotic started prior to deterioration of LOC <10 GCS, and reduction in mortality with early Abx; delayed CSF sterilization after 24h of ABx risk factor for subsequent neuro sequelae; steroids:  outcome correlates with severity of inflammation; early dexamethasone in acute bacterial meningitis improves outcomes, [mortality RR 0.6  p=0.002] [neuro sequelae RR 0.6 p=0.05]; most apparent in pneumococcal meningitis, [reduced case fatality of 21%], not significant in meningococcal meningitis; rifampin:  good CSF penetration, excellent agent but used alone resistance rapidly develops; ampicillin: for treatment of L. monocytogenes; aminoglycosides: poor CSF penetration, needs extended dosing regiments of 7mg/Kg IBW or adjusted BW


Coumadin:  vit K dep factors (10, 9, 7, 2) require gamma carboxylation to be activated, Coumadin diminishes Vit K and results in undercarboxylated proteins; PT prolongation during first few days is due to reduction of F7 (half life 6 hours), subsequent due to depletion of F10 (45h) and F2 (60h); also inhibits carboxylation of regulatory proteins (C, S, Z) and has ability to be a procoagulant; 2 enantiomers: S- and R-enantiomer; drug-drug interaction:  S 5x more potent than R, amiodarone inhibits both enantiomers (greater anticoagulation); rifampin, CMZ and barbiturates increase clearance (lesser anticoagulation)


Anticoagulation post-stroke: Afib + stroke – recurrent ischemic stroke in first 2 weeks = 5%; start Coumadin 2-3d after stroke, full anticoagulation by day 7-10, avoid period of hemorrhagic transformation


Vit K: give PO if no significant risk for bleeding; PO more effective than SQ; SQ has unpredictable absorption; anaphylactoid reactions variable (intravenous), likely due to different dispersants used; give IV only when actively bleeding or significant risk; give no faster than 1mg/min; most infuse 10mg over 30 mins


Protamine: 1mg neutralizes 115 USP units of UFH; dose to neutralize 100 units of heparin:  (based on time since heparin discontinued); immediately after d/c = 1.0-1.5mg; 30-60 mins later, 0.5-0.75 mg; 2 hours or greater – 0.25-0.375 mg; infusion rate:  infuse 20-25mg slowly ffd by remainder of dose over 8-16 hours; for LOVENOX:  reduced by only 60-75%; 1mg protamine:1mg enoxaparin; if PTT prolonged 2-4h after first dose, additional protamine at 0.5mg/mg enoxaparin may be given


Dabigatran:  T1/2 12-14h; low protein binding, most effective reversal is dialysis; 50-60% removed over 4 hours HD


Benzodiazepine:  potentiates CNS GABA (inhibitory); anxiolysis and anterograde amnesia, sedation, anticonvulsant, but NOT analgesic; limited effects on cerebrovascular tone, decrease in cerebral metabolic O2 demand with decrease in cerebral blood flow


Midazolam: rapid onset, short duration of action; limit to 48-72h continuous infusions; prolonged sedation with accumulation of active metabolite (hydroxymidazolam or conjugated salt), esp in renal function; prlonged in obese, and low serum albumin


Flumazenil: reversal for benzos, does not reverse resp or cardiac depression, does not reverse CNS of other agents that affect GABAergic neurons (barbiturates, ETOH, anesthetics)


Fentanyl: less BP effects, does not promote release of histamine; side effects:  hypotension at high doses, bradycardia, can cause jaw / abd / chest wall rigidity (high dose or rapid administration)


Naloxone:  reverses narcotics, not direct effect on opioid receptors;  adverse events: hypo or hypertension, tachycardia, vent arrhythmias, restlessness, seizures, n/v/d, pulmonary edema, pain, cardiac arrest;  0.4mg IV push, or may dilute in normal saline and given at 1ml increments


Propofol:  emulsion in phospholipid vehicle, 1:1 Kcal/ml; long term infusions cause hypertriglyceridemia; phospholipid vehicle can cause infections – change tubing q12h, add preservative to decrease potential for overgrowth; causes green urine (phenolic derivative, chemical reaction); elevation of pancreatic enzymes; propofol infusion syndrome: high doses (>83 ug/kg/min) x >48h associated with lactic acidosis, bradycardia, inc risk of cardiac arrest


23.4%:  30mL = 120 mEq Na Cl; 3%, 5%, 14.6% contain 0.51, 0.86, 2.5 mEq/mL of NaCl; 3% 235 mL, 5% 140mL, 14.6% 48mL


Acyclovir: dose based on ideal KgBW, 10mg/Kg/dose; acute renal failure can occur if actual body weight used in obese; poor protein binding; max solubility should not exceed 2.5mg/mL or acyclovir may precipitate in renal tubules causing AKI; frequency of acyclovir crystal 12-48%, rapid bolus may also contribute, AKI occurs within 24-48h


Valacyclovir:  prodrug, esterified acyclovir, greater bioavailability (55% vs 15-30% acyclovir); rapidly converted to acyclovir by intestinal / hepatic metabolism; oral dose 1g q8h


Ganciclovir: DOC for CMV, competitive inhibitor of vDNA polymerase and chain terminator; triphosphate form more stable and lower catabolism than acyclovir; 10x greater concentrations in infected cells; incorporated into human DNA, resulting in neutropenia, granulocytopenia, thrombocytopenia; side effects: seizures, retinal detachment


Cidofovir: treatment of CMV retinitis in AIDS; administer with probenecid and saline hydration – potential for nephrotoxicity


Nosocomial UTI:  E coli 31%, pseudomonas / GNB 10%, Kleb 9%, staph 6% proteus 5% enterococcus 2%; fungal UTI 14%;


Vasopressinreceptors: V1 in vascular sm muscle (vasoconstriction); V2 in kidney collecting ducts (increase water permeability, resorption in distal tubule and collecting ducts); V3 in pituitary (increase in ACTH and cortisol production)


Milrinone:  peripheral vasodilation, decreases SVR, (+) inotrope; MOA: inhibits cAMP breakdown in heart (increases CO) and in vasc sm ms (decreases SVR)


Succinylcholine: the only avail depolarizing agent; relaxes sk ms; rapid onset (10-15s), short duration (10-15m); depolarization = K goes out of cells, serum K increases by 0.5-1; contraindication: caution in kidney disease, patients with neuromuscular diseases (GBS, MG) prolonged immobility (SCI) – triggers severe hyperkalemia à use nondepolarizing agents instead (atracurium, cisatracurium, rocuronium, vecuronium) with slower onset (1-4m) longer duration (20-60m)


Nondepolarizing agents:  cis/atracurium  preferred – organ-independent hofmann elimination and eliminated by plasma esterases; pan / vec accumulate in hepatic and renal dysfunction; roc accumulates in hepatic dysfunction; titrate based on train-of-four monitoring; tolerance: common with cis/atracurium; laudanosine: metabolic of cis/atra, predisposes to seizures; histamine release: associated with atracurium; tachycardia common with pancuronium; prolonged ms weakness:  quadriplegic myopathy syn, critical illness polyneuropathy, acute myopathy of critical care reported after d/c of NMBA, risk related to use of NMBA with concurrent drug therapy (steroids) and MOF


Carbamazepine: induces cytochrome P450 3A4 (CYP3A4), also a substrate for this enzyme; stimulates metabolism of other CYP3A4 substrates, also autoinduces its own metabolism; autoinduction effect lasts 1 month; MOA: inhibits Na channel receptors; indications: partial seizures with complex symptomatology, GTC, mixed seizure patterns, trigeminal neuralgia


Fosphenytoin: phosphate ester prodrug of phenytoin; highly water soluble, IM or IV with less risk of tissue damage / venous irritation; rapidly absorbed, converted to phenytoin by phosphatase enzymes; rate: 150mg PE/min


Phenytoin:  infusion-related adverse reactions occur due to sodium hydroxide, propylene glycol and alcohol content; complications: hypotension and arrhythmias with rapid IV infusion (>50mg/min)


Lacosamide: indication: partial onset of seizures, in combi with other AEDs; caution in patients with cardiac conduction abnormalities or severe cardiovascular disease; EKG before starting and after titration to steady state


VPA:  substrate of cytochrome P450 system; numerous case reports of interaction between meropenem and VPA – coadministration decreases serum concentration of VPA


Benzodiazepines:  bind to GABA-A, increases affinity of GABA and its receptor;  GABA: inhibitory neurotransmitter; promotes opening of post synaptic receptor GABA-A, increases conductance of chloride ions à membrane hyperpolarization à neuronal inhibition


Side effects of antipsychotic meds:


QTc:  all antipsychotic drugs can prolong QTc; ziprasidone prolongs QTc longer than haldol / risperdal / olanzapine / seroquel; criteria for QTc prolongation: (guidelines from Committee for Proprietary Medicinal Products) – increase by 60 msec above baseline or >450 in males or >470 in females


EPS:  acute dystonia / parkinsonism / akathisia occur early after initiation of treatment; tardive dyskinesia, tardive dystonia, tardive akathisia occur later (years of treatment); typical with haldol and fluphenazine; quetiapine has lowest risk for EPS


Weight gain: most significant s/e with atypical antipsychotics; MOA:  antagonistic effect on H1 receptors and serotonin 5HT2; seen with clozapine and olanzapine, intermediate with risperidone and quetiapine; low with ziprasidone and aripiprazole


Anticholinergic effects: more common with atypicals; dry mouth, constipation, urinary retention


Hyperprolactinemia: more common with typical antipsychotics (higher affinity to dopamine receptors) inhibition of dopamine receptor in tuberoinfundibular tract, elevates serum prolactin; risperidone and olanzapine




Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s

%d bloggers like this: