ABCD2 Score



Table: ABCD2 Score


TIA Prognosis and Key Mx Considerations by National Stroke Association

ABCD2 Score:

  • Discharge low risk scores (ABCD 0-3)
    • outpatient work-up within 1-2 days (alternate option: admit for work-up)
      • carotid imaging (US, CTA, MRA)
      • Consider TTE; if high suspicion for cardioembolic source / bilateral infarcts, obtain TEE
      • Consider 30-d ambulatory cardiac monitor to detect cryptogenic Afib
    • smoking cessation
      • Start antiplatelet therapy:
        • ASA 81mg/day or
        • Clopidogrel 75mg/day or
        • ASA 25mg/ER dipyridamole 200mg BID
      • start high-intensity statins
        • Atorvastatin 40-80mg/d or
        • Rosuvastatin 20-40mg/day
      • *consider moderate intensity statins if >75y/o
        • Atorvastatin 10-20mg/d or
        • Rosuvastatin 5-10mg/d or
        • Simvastatin 20-40mg/d or
        • Pravastatin 40-80mg/d
      • Consider OAC or LMWH if rhythm shows atrial fibrillation – calculate CHADSVASC and HAS BLED score to guide therapy

    Admit high risk TIAs (ABCD2 scores >3)

    • Admit to hospital
    • Permissive hypertension (up to 220/120mm Hg) and gradually lower over 24-48h

Reference: (2017). [online] Available at: [Accessed 31 Jul. 2017].

Gross, Hartmut, and Noah Grose. 2017. “Emergency Neurological Life Support: Acute Ischemic Stroke”. Neurocritical Care 27 (S1): 102-115. doi:10.1007/s12028-017-0449-9.

Heads up Maneuver

Clinical scenario:  Patient with stroke comes in with large vessel occlusion and neuro deficits; he was placed supine for CT scan and NIHSS improved.  Vascular imaging still shows clot, but deficits are now nondisabling and NIHSS is low.  Should you proceed with thrombectomy?

Small study from UCLA used the Heads Up maneuver to select patients who should proceed to thrombectomy.


Patients included:

  1. stroke within 7.5h onset
  2. disabling neuro deficit on presentation
  3. improved while on CT to nondisabling deficit
  4. evidence (in MRA) of persisting large vessel occlusion


Heads up Maneuver: (performed in angio suite)

  1. position 90 degrees upright x 30 minutes, monitor BP/HR q5-10mins
  2. if worsened –> lower to supine, proceed with angio
  3. if remained stable –> lower to supine or 30 deg HOB; transfer to stroke unit


Pathophysiology of Delayed Collateral Failure:

STROKE –> increased CO / SVR –> improved flow to peri-infarct regions –> MI / CHF / dysrhythmias / sepsis / dysautonomia / drugs –> reduced CPP –> delayed collateral failure –> expansion of core infarct


Heads Up:

Head position influences collateral flow by increasing flow velocity in affected MCA. Impaired autoregulation allows perfusion to collateral channels to become passive-pressure dependent.  Head flat position increases CPP by 20%, improves neurologic function in 15% of patients.  Risk of aspiration PNA with head flat position is <5%.



The study found that heads up maneuver can be used to stress collateral systems and identify those patients who are vulnerable to hemodynamic failure.

  1. Only 5 patients included in the series – all had high NIHSS on arrival, improved during MRI scanning.
  2. Two patients tolerated 30 minutes, no thrombectomy performed, had excellent outcome with just medical therapy.
    1. *Spontaneous recanalization occurred within 72h (assumed that vigorous collaterals promoted recanalization).
  3. Three patients worsened with manuever and had successful recanalization and excellent outcomes as well.



Ali, L., Weng, J., Starkman, S., Saver, J., Kim, D., Ovbiagele, B., Buck, B., Sanossian, N., Vespa, P., Bang, O., Jahan, R., Duckwiler, G., Viñuela, F. and Liebeskind, D. (2016). Heads Up! A Novel Provocative Maneuver to Guide Acute Ischemic Stroke Management. Interventional Neurology, 6(1-2), pp.8-15.

Mt. Fuji Sign

The Mt. Fuji sign is a radiologic finding seen in tension pneumocephalus.  Bilateral hypoattenuating collections are seen in the frontal subdural space, which causes compression and separation of the frontal lobes.




Notice the widening of the interhemispheric space between the tips of the frontal lobes which resembles the silhouette of Mt. Fuji.  


In tension pneumocephalus, air enters into the cranial vault through disruption of the skull or skull base.  Air pressure increases within the subdural space due to a ball-valve mechanism, where air enters into subdural space but egress of air is blocked by an obstruction.

Tension pneumocephalus may occur after surgical evacuation of SDH (2.5-16%), skull base surgery, paranasal sinus surgery, posterior fossa surgery in sitting position, or head trauma.

To diagnose tension pneumocehpalus, CT findings should correlate with clinical signs of deterioration.

Peaking sign” (compression of frontal lobes without separation of frontal lobes) has also been linked to tension pneumocephalus.

Treatment includes:

  1. emergent decompression to alleviate pressure
    1. drilling burr holes
    2. craniotomy
    3. needle aspiration
    4. EVD placement
  2. administration of 100% oxygen
  3. closure of dural defects
  4. careful monitoring for clinical signs of deterioration
  5. serial CT scanning of brain

This is Mt. Fuji in Japan




Michel, Steven J. “The Mount Fuji Sign.” Radiology 232.2 (2004): 449-450.


Upper Extremity Veins

Deep Veins:


1. paired ulnar, radial and interosseous veins in forearm
2. paired brachial veins of upper arm
3. axillary vein (continues as subclavian vein)


Superficial Veins:



  1. cephalic vein
  2. basilic vein



“Deep Veins Of The Upper Extremity.” Web. 27 July 2017.

“Primary (Spontaneous) Upper Extremity Deep Vein Thrombosis.” 27 July 2017.

Diabetes Insipidus

Production of arginine vasopressin – by magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus.  Transported to the neurohypophysis via hypothalamo-hypophyseal tract.  Injury to these structures leads to DI.




Triphasic response in DI:

  1. First phase – DI caused by “stunning” of the magnocellular neurons, no AVP secretion.
  2. Second phase – injured hypothalamic cells degenerate and release their stored AVP
  3. Third phase – if majority of these neurons are destroyed, permanent phase of DI begins






Schreckinger, Matthew, Nicholas Szerlip, and Sandeep Mittal. “Diabetes Insipidus Following Resection Of Pituitary Tumors”. Clinical Neurology and Neurosurgery 115.2 (2013): 121-126.



RANDOM NOTES ON Diabetes insipidus (DI)

Nephrogenic DI – renal insensitivity to vasopressin, acquired or genetic; lithium

Central DI – deficiency in production of ADH

  • Related to extent of excision
  • Usually transient phenomenon after surgery
  • SIADH in second phase – follow serum Na on day 7
  • Symptoms: polyuria, nocturia, polydipsia / thirst


Patients with DI, especially if drowsy and unable to maintain adequate fluid intake, can rapidly become dehydrated.



Measure Is and Os hourly, sum every 6 hours

Foley catheter

Onset of dilute polyuria UOP >250cc/hr x2  hours

Check other reasons:

  1. diuretics
  2. large resuscitation
  3. mannitol
  4. hyperglycemic
  5. salt wasting


  1. USG <1.005
  2. UOsm 50-200 (<serum)
  3. Hypernatremia

? rountine serum Na – every 6 hours on day 1, then every 12h until stable, then daily x 1 week

Replace fluids

  1. normal saline to replace previous hour output, switch to 0.45% saline if UO 4-6ml/kg/h, switch to D5W if >6 ml/kg/h
  2. if awake, fluids ad libidum; may be able to maintain fluid balance by drinking to satiety, still DDAVP so patients can sleep comfortably at night

DDAVP (1-desamino-8-D-argnine vasopressin)

  • DDAVP: activates V2R – water reabsorption in kidney; mobilizes water channel aquaporin to luminal membrane of DCT and CD
  • Liquid form – given intranasal; oral tablet form; parenteral form


  Tablets Spray Solution for injection
Dose comparison 100 mcg 2.5 mcg N/A
200 mcg 5 mcg Less than 0.5 mcg
400 mcg 10 mcg Less than 1 mcg


  • Usual dose 1 ug q12h
  • Empiric – give minimum dose required to control polyuria; goal to control nocturia, partial control of polyuria during the day
  • Water retention à hyponatremia is a potential risk; patient education, serum NaHS



Post-op complications: hematomas, epistaxis, HCP, CSF leaks, meningitis

Preop labs with hypopituitarism – stress doses of hormonal replacement; keep on physiological dose until outpatient assessment

Lab tests post-op for evidence of early endocrinological remission

Cushing – no steroids unless necessary; serum cortisol q6h until nadir; if <5 + symptoms, start glucocorticoid therapy and then transition to maintenance doses until outpatient reassessment

Normal cortisol function prior to surgery – no steroids; assess post-o with AM fasting cortisol on POD1 or POD2; new start steroid replacement if cortisol <10 until reassessed outpatient

Acromegaly – POD1 serum GH level predicts early remission; delayed IGF1 level 6 weeks after

Prolactinomas – POD 1 AM prolactin level normalizes with remission


Classification and Severity of Diabetes Insipidus

Interesting classification of DI, taken from Neurology India, groups DI into mild and severe based on some clinical and lab findings.




This was their protocol for diagnosis and management of DI in patients who underwent craniopharyngioma surgery.


Protocol for diabetes insipidus

  • Diagnosis:  UO > 4ml/kg/h over 6 h perior OR Na >145 mEq/L with USG <1.005
  • Monitoring
    • if drowsy, unable to drink – measure Is and Os hourly, sum every 6 hours
    • Foley until UO reasonably controlled
    • intraop Na if surgery >6h determines type of IV fluids and if pitressin required in OR
    • measure Na q6h day 1
    • measure Na q12h day 2 until stable x 3 days
    • measure Na daily x 1 week
  • Treatment
    • Fluids until patient is awake and demonstrates intact thirst mechanism
      • 0.45% saline when UO 4-6 ml/Kg/h
      • D5W when UO >6ml/kg/h
    • DDAVP
      • day 1 – 5 unit IV boluses of pitressin
      • started as early as possible, usually on 2nd day, oral DDAVP 100 ug tablets of fractions of tablets
  • Adequacy of control
    • based on serum Na rather than Is and Os
      • check frequency >150 or <130 or inc/dec by >10mEg/L in 1 day


Other pearls:

  • Adipsia may be complication of hypothalamic damage
    • diminished thirst sensation
    • higher risk of developing hpyernatremia
    • require round the clock DDAVP
    • need to be trained to drink 2-3L water per day
    • gradually resolves with partial or complete thirst recovery by 9 months
  • Polydipsic with high UO
    • patient compensating with increased PO intake, normal or low Na
    • at risk for water intoxication or hyponatremia
    • use oral rehydration solution rather than plain water



Chacko, AriG et al. “Evaluation Of A Protocol-Based Treatment Strategy For Postoperative Diabetes Insipidus In Craniopharyngioma”. Neurology India 63.5 (2015): 712.

Moyamoya Direct Bypass Surgery

Technique for Direct Bypass Surgery:



  • Map out STA anterior to zygomatic arch for 8-9cm, using Doppler.



  • Dissect STA and vascular cuff under microscope.



  • Incise temporalis muscle in H-shaped fashion.
  • Create 6x6cm craniotomy over frontotemporal region.



  • Open dura wide over Sylvian fissure, under high magnification, identify M4 recipient artery.




  • Cut distal STA at 45 degrees, place temporary clips on recipient artery.
  • Make an elliptical arteriotomy over M4 branch.
  • Perform end-to-side anastomosis using 10 to 0 interrupted suture under high magnification.
  • Remove temporary clips from recipient and proximal STA once bypass completed.



  • Place STA and vascularized cuff in close apposition to cortical surface to facilitate delayed collateralization



Liu, Jonathan J., and Gary K. Steinberg. “Direct Versus Indirect Bypass For Moyamoya Disease”. Neurosurgery Clinics of North America 28.3 (2017): 361-374.

Decompressive Hemicraniectomy,

Evidence for DHC:



Mortality Reduction in Percentages:



Mortality at 12months after malignant MCA infarction. Forest plot presenting risk difference and 95% confidence interval (CI) for a pooled analysis of mortality at 12months from RCTs comparing DC and best medical care:

Surgical Technique:

  • Place head in rigid 3-pin fixation
  • A large reverse question mark flap is turned to allow access to a large part of the hemicranium.
  • Large craniectomy of frontotemporoparietal region
  • Avoid frontal air sinus
  • Take the inferior bone cut as low as possible to the floor of the middle fossa and ronguer/drill additional bone to accomplish this
  • typical craniectomy flap measures at least 15 cm anteroposteriorly and 10 to 12 cm craniocaudal
  • dura is opened in a C-shaped or stellate manner
  • When the anterior temporal lobe is infarcted and tentorial herniation is present or impending, perform an anterior temporal lobectomy with resection of the uncus and visualization of the tentorial edge, third nerve, and midbrain
  • lax duraplasty with autologous pericranial graft, closure must be capacious; be able to pick up and freely slide the lax dural sac
  • Muscle reapproximated loosely or not at all
  • Scalp is closed in layers (drains optional but preferred)
  • parenchymal or subdural ICP monitor optional
  • bone flap typically discarded (prefer delayed cranioplasty with a custom implant) or store bone flap in abdominal wall or cryopreserve
  • transfer to NSICU without extubation.
Post-op Management:
  • standard ICU ICP management
  • attempt early extubation without gagging
  • early enteral nutrition by POD1
  • SQH after 24 hours unless with C/I
  • early trach / PEG if needed
  • if stable post-op CT, ASA after 24 h
  • aggressive PT, speech, rehab


While technical details certainly vary between individual surgeons or centers, this brief outline describes a typical operation: the procedure is performed in a supine position with the head rotated to the contralateral side. A wide curved incision is performed either beginning behind or in front of the ear. The scalp flap and temporalis muscle are then deflected to expose the skull. Burr holes are created and subsequently connected to achieve an anterior to posterior diameter of the craniectomy area of at least 12 cm, with the recommended diameter in adult TBI

patients being 15 cm. The DC is finally extended to expose the floor of the middle cranial fossa. An adequately sized craniectomy is essential in achieving the desired decompressive effect. Moreover, a suboptimal DC will lead to exacerbated external brain her niation and shear forces at the bone edges, which can cause intraparenchymal hemorrhage and kinking of the cerebral

veins. After sufficient bony decompression has been achieved, the dura is incised to create a large dural opening. For coverage of the exposed brain, allogenic or autologous dural grafts can be used.


  • Hygroma / subdural fluid collection most common (50-58%), most clinically insignificant
  • delayed HCP in 7-12%
  • infection 2-7%
  • sinking flap syndrome (syndrome of trephined)


Operative technique of supratentorial DC. Artist’s rendition of a human head with a typical incision line for DC (gray line).

3D reconstruction of a human skull demonstrating burr holes (gray circles), craniectomy (gray area), and additional osteoclastic decompression of the middle cranial fossa floor (hatched area) as well as typical dural incision (red lines).

3D reconstruction of a human skull with a typical hemicraniectomy skull defect:

Intraoperative photography of a human brain after DC:

stepwise reduction in ICP after decompressive hemicraniectomy:

Suboccipital or Infratentorial Decompressive Craniectomy

In comparison with supratentorial DC, the technical details of suboccipital or infratentorial DC are less clearly established. Important aspects such as overall craniectomy size, laterality of the decompression, and necessity of resection of the posterior arch of the atlas all vary in the published literature. However, the basic surgical aim is decompression above the swollen cerebellum. In general, this procedure is performed with the patient in a prone or semi-prone/lateral position. A linear midline incision is made from the inion to the upper cervical spine, and the muscular layers are subsequently separated in the midline avascular plane, exposing the suboccipital skull, atlanto-occipital membrane, and posterior arch of the atlas. A wide craniectomy is performed extending into the foramen magnum. As the next step, to avoid tonsillar herniation, we routinely remove the posterior arch of the atlas. The dura is then usually opened in a Y-shaped fashion, and an expansion duroplasty is performed.

2018 AHA ASA Guidelines:

The guideline recommends early transfer of patients at risk of malignant cerebral edema to a center with neurosurgical expertise. Patient-centered preferences in shared decision-making regarding the interventions and limitations of care should be ascertained at an early stage. With regard to neurosurgical management, the guideline states that in patients ≤ 60 years of age, who deteriorate neurologically (defined as a decrease in the level of consciousness attributed to brain swelling despite medical therapy) within 48 h after MCA infarction, DC with expansion duroplasty is reasonable. In patients > 60 years of age, the same approach may be considered. For patients with cerebellar malignant stroke, the guideline recommends sub-occipital DC with expansion duroplasty upon neurological deterioration despite medical therapy, with concurrent EVD insertion to treat obstructive hydrocephalus.


Gupta, Aman et al. “Hemicraniectomy For Ischemic And Hemorrhagic Stroke”. Neurosurgery Clinics of North America 28.3 (2017): 349-360.

Beez, T., Munoz-Bendix, C., Steiger, H. and Beseoglu, K. (2019). Decompressive craniectomy for acute ischemic stroke. Critical Care, 23(1).

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