02 — Disease States
Management Pathways
Time-critical, stepwise approaches across the neurocritical care spectrum — status epilepticus, the three intracranial hemorrhages, ischemic stroke, CNS infection, sodium disorders, and more. Where steps are numbered, the sequence carries clinical meaning.
Emergency Status Epilepticus
1
0–5 min · StabilizationABCs, glucose, IV access, start the clock
Airway, oxygen, hemodynamics. Point-of-care glucose (dextrose + thiamine if low), labs and AED levels. Document seizure onset time — it drives every subsequent decision.
2
5–20 min · First lineBenzodiazepine at an adequate dose
IV lorazepam, IM midazolam, or IV diazepam. Under-dosing is the most common error — give a full weight-based dose before declaring failure.
3
20–40 min · Second lineIV antiseizure agent at a therapeutic load
Levetiracetam 60 mg/kg, fosphenytoin 20 mg PE/kg, or valproate 40 mg/kg — ESETT found roughly equivalent efficacy. Choose by patient factors; dose to the full target.
4
40+ min · RefractoryContinuous infusion + cEEG
Anesthetic infusion (midazolam, propofol, or pentobarbital) titrated to seizure suppression or burst-suppression on continuous EEG, with the airway secured.
Emergency Myasthenic Crisis
1
ImmediateRespiratory monitoring
Serial NIF and vital capacity; low threshold for ICU and airway support. Avoid medications known to worsen neuromuscular transmission.
2
AcuteRapid immunotherapy
IVIG or plasma exchange as first-line crisis therapy, with corticosteroids (watch for early transient worsening).
3
OngoingTrigger identification & symptomatic care
Identify and treat precipitants (infection, offending drugs). Symptomatic pyridostigmine as tolerated; manage secretions.
Ambulatory Migraine
1
AcuteAbortive therapy
NSAIDs/acetaminophen for mild attacks; triptans as first-line migraine-specific therapy; gepants or ditans and antiemetic adjuncts where triptans are contraindicated or ineffective.
2
PreventiveWhen to prevent
Consider prophylaxis with frequent or disabling attacks. Options include CGRP monoclonal antibodies, topiramate, and beta-blockers — matched to comorbidities.
3
RefractoryStatus migrainosus
For prolonged, refractory attacks: IV approaches (DHE protocols, antiemetics, hydration) and specialist referral.
Emergency Intracranial Hemorrhage — ICH vs SDH vs SAH
Three distinct entities that share an emergency workup but diverge sharply in cause, imaging, and management. Differentiating them drives every downstream decision — especially the role of nimodipine and vasospasm surveillance, which apply only to aneurysmal SAH.
Differentiating the three
| Feature | Intracerebral (ICH) | Subdural (SDH) | Subarachnoid (SAH) |
|---|
| Compartment | Within brain parenchyma | Between dura and arachnoid | Subarachnoid space / CSF |
| Usual source | Small perforating arteries | Bridging veins | Ruptured saccular aneurysm |
| Typical cause | Chronic hypertension; amyloid angiopathy in the elderly | Trauma; falls in the elderly and anticoagulated | Aneurysm rupture; trauma is a separate category |
| CT appearance | Focal parenchymal hyperdensity | Crescentic, crosses suture lines | Blood in basal cisterns, sulci, fissures |
| Hallmark presentation | Focal deficit, depressed consciousness | Fluctuating consciousness; may be subacute | Thunderclap "worst headache of life" |
| Distinctive therapy | Tight BP control, reversal, ICP | Reversal, surgical evacuation, ICP | Nimodipine + vasospasm surveillance |
Shared acute priorities
1
Blood pressureControl, but avoid over-lowering
For spontaneous ICH, initiate smooth control with a titratable agent (nicardipine, clevidipine) targeting roughly 130–150 mmHg systolic; ATACH-2 showed that driving below 130 adds renal harm without outcome benefit. In aneurysmal SAH before the aneurysm is secured, control systolic pressure (commonly below ~160) to limit rerupture.
2
ReversalReverse anticoagulation by agent
4F-PCC plus IV vitamin K for warfarin; idarucizumab for dabigatran; andexanet alfa or 4F-PCC for factor Xa inhibitors. SDH in an anticoagulated elderly patient is the most common real-world reversal scenario. See the andexanet, 4F-PCC, and idarucizumab cards for detail.
3
ICPManage intracranial pressure and herniation
Head-of-bed to 30°, normocapnia, treat pain and agitation. For herniation or elevated ICP: hyperosmolar therapy with hypertonic saline (preferred if hypovolemic or hypotensive) or mannitol (avoid if hypovolemic — it diuresis). Neurosurgical consultation for evacuation, EVD, or decompression.
4
SeizuresSeizure prophylaxis — selectively, not routinely
Routine antiseizure prophylaxis is not recommended for ICH and does not improve outcomes. Treat clinical or electrographic seizures. Consider cEEG when consciousness is depressed out of proportion to imaging. Lobar location and cortical involvement raise seizure risk; levetiracetam is the usual agent when prophylaxis is chosen.
Aneurysmal SAH — the distinct pathway
5
Secure the aneurysmEarly clipping or coiling
Definitive securing of the aneurysm within 24–72 hours prevents catastrophic rebleeding. Until then, strict BP control and avoidance of antithrombotics.
6
21 daysNimodipine for every aneurysmal SAH
Nimodipine 60 mg every 4 hours for 21 days improves neurologic outcome — the only pharmacologic therapy proven to do so. The benefit is neuroprotective, not simply antivasospastic. Never give it intravenously; the boxed warning follows fatal IV errors. See the nimodipine card.
7
Days 4–14Delayed cerebral ischemia surveillance
Vasospasm and delayed cerebral ischemia peak in the second week. Monitor with serial exams and transcranial Dopplers; maintain euvolemia and treat symptomatic vasospasm with induced hypertension and, where needed, endovascular therapy.
Highest-yield distinction: nimodipine and vasospasm surveillance belong to aneurysmal SAH alone. Giving nimodipine for ICH or SDH is a common conceptual error — the evidence base and mechanism are specific to subarachnoid aneurysmal bleeding.
Emergency Acute Ischemic Stroke — Cardioembolic & Atherosclerotic
The hyperacute reperfusion decision is identical regardless of mechanism. Everything afterward — antiplatelet versus anticoagulation, and the entire secondary-prevention regimen — depends on whether the stroke was cardioembolic or atherosclerotic. Establishing the mechanism is the central task.
Hyperacute reperfusion (mechanism-independent)
1
0–4.5 hIV thrombolysis
Alteplase 0.9 mg/kg or tenecteplase 0.25 mg/kg within 4.5 hours of last known well. Blood pressure must be below 185/110 before treatment and below 180/105 for 24 hours after. Tenecteplase is a single bolus and is now a reasonable alternative, with an advantage before transfer for thrombectomy. See both drug cards.
2
Up to 24 hMechanical thrombectomy for large-vessel occlusion
Endovascular thrombectomy for anterior-circulation large-vessel occlusion, up to 24 hours in selected patients with favorable perfusion imaging (DAWN, DEFUSE-3). Thrombolysis and thrombectomy are complementary, not either-or.
3
First 24 hPermissive hypertension if not thrombolysed
When thrombolysis is not given, do not treat blood pressure unless it exceeds roughly 220/120 or there is end-organ injury — cerebral perfusion depends on it. This is the opposite of the hemorrhage approach, and confusing the two is dangerous.
Mechanism-directed prevention — the fork in the road
| Cardioembolic | Atherosclerotic (large-artery) |
|---|
| Typical source | Atrial fibrillation, LV thrombus, mechanical valve | Carotid, intracranial, or aortic plaque |
| Antithrombotic | Anticoagulation (DOAC or warfarin) | Antiplatelet therapy |
| Acute regimen | Start timing by infarct size — the 1-3-6-12 rule | Short-course DAPT for minor stroke / high-risk TIA (21 days) |
| Anti-lipid | Statin if concurrent atherosclerosis | High-intensity statin, LDL target below 70 |
| Procedural | LAA occlusion if anticoagulation contraindicated | Carotid endarterectomy or stenting for symptomatic stenosis |
| Key trials | ELAN, TIMING (timing of DOAC) | CHANCE, POINT, THALES, SAMMPRIS, SPARCL |
Cardioembolic timing (the 1-3-6-12 rule): anticoagulation is deferred by infarct size to avoid hemorrhagic transformation — roughly day 1 for TIA, day 3 for small, day 6 for moderate, and day 12 for large infarcts. ELAN found earlier initiation was safe, and practice is trending earlier for smaller strokes.
Atherosclerotic DAPT (CHANCE / POINT): aspirin plus clopidogrel started within 24 hours for minor stroke (NIHSS ≤3) or high-risk TIA, but for only 21 days — benefit is front-loaded while bleeding risk accumulates. For symptomatic intracranial stenosis, SAMMPRIS supports 90 days of DAPT plus aggressive risk-factor control over stenting. See the DAPT and statin cards.
Emergency Bacterial Meningitis & CNS Infection
A true time-critical emergency where the sequence — dexamethasone with or just before the first antibiotic, and never delaying antibiotics for the lumbar puncture — determines outcome. Under-dosing and mistimed steroids are the recurring errors.
Lumbar puncture & CSF interpretation
| CSF parameter | Normal | Bacterial | Viral | Fungal / TB |
|---|
| Opening pressure | 10–20 cm H₂O | Elevated | Normal or mildly high | Elevated |
| White cells | <5 /µL | Hundreds–thousands | Tens–hundreds | Tens–hundreds |
| Predominant cell | Lymphocytes | Neutrophils | Lymphocytes | Lymphocytes |
| Glucose (CSF:serum) | >0.6 | Low (<0.4) | Normal | Low |
| Protein | <45 mg/dL | Markedly high | Mildly high | High |
CT before LP only for specific risk features — immunocompromise, CNS disease history, new seizure, papilledema, or focal deficit. Otherwise imaging wastes time. Critically, obtaining a CT never justifies delaying antibiotics — draw cultures, give antibiotics and dexamethasone, then image and tap.
Empiric therapy & timing
1
Minute 0Dexamethasone with the first antibiotic
Dexamethasone 0.15 mg/kg IV, given 10–20 minutes before or concurrent with the first antibiotic dose. It reduces mortality and hearing loss in pneumococcal meningitis (European Dexamethasone Study), but the benefit is lost if given after antibiotics. Continue only if pneumococcus is confirmed. See the dexamethasone card.
2
Minute 0Empiric antibiotics at meningeal doses
Ceftriaxone 2 g every 12 hours plus vancomycin (CNS dosing) for resistant pneumococcus. The single most common error is once-daily ceftriaxone — meningitis demands 2 g q12h. See the ceftriaxone and vancomycin cards.
3
Add if at riskAmpicillin for Listeria coverage
Add ampicillin 2 g every 4 hours in patients over 50, immunocompromised, pregnant, or with alcohol use disorder — cephalosporins have zero Listeria activity, and omitting this leaves a lethal gap. See the ampicillin card.
4
If encephalitis featuresEmpiric acyclovir for HSV
Add acyclovir 10 mg/kg every 8 hours if encephalitis is suspected. Untreated HSV encephalitis carries roughly 70% mortality, so start empirically and de-escalate on CSF PCR. See the acyclovir card.
When intraventricular antibiotics become necessary
Reserved, per IDSA 2017 guidance on healthcare-associated ventriculitis and meningitis, for situations systemic therapy cannot solve: persistently positive CSF cultures despite adequate IV therapy; multidrug-resistant gram-negative CNS infection; EVD- or shunt-associated infection; or organisms whose CSF penetration is inadequate relative to their MIC.
The governing principle is the inhibitory quotient — dose to achieve a CSF trough at least 10–20 times the organism's MIC, not a fixed milligram amount. Only preservative-free formulations may be instilled; the drain is clamped 15–60 minutes after administration; and dosing frequency drops when daily EVD output is high, since drainage removes drug. Device removal is usually required alongside. See the intraventricular antibiotics card for agent-specific dosing.
Neurocritical Sodium Disorders
In neurocritical care, sodium is a therapeutic tool as much as a lab value. The unifying safety principle across hyponatremia is the same: the rate of correction, not the absolute number, determines whether the brain is harmed.
Hyponatremia — rate is everything
1
Severe symptomsHypertonic saline bolus for seizures or coma
For severe symptomatic hyponatremia (seizures, obtundation): 3% saline 100–150 mL IV over ~10 minutes, repeated up to two or three times until symptoms abate, aiming to raise sodium by 4–6 mEq/L acutely. This small, rapid rise reverses cerebral edema without overcorrecting.
2
First 24 hRespect the correction ceiling
Limit total correction to no more than 8 mEq/L in 24 hours — 6 mEq/L in patients at high risk for osmotic demyelination (malnutrition, alcohol use disorder, hypokalemia, liver disease, chronic hyponatremia). Overcorrection of chronic hyponatremia causes osmotic demyelination syndrome.
3
If overcorrectingRelower with desmopressin and free water
If sodium is rising too fast, actively relower: desmopressin plus D5W. The proactive "DDAVP clamp" — fixing water handling up front with scheduled desmopressin alongside hypertonic saline — makes the correction rate predictable rather than reactive. See the desmopressin card.
4
Etiology-directedTreat the cause
SIADH: fluid restriction first-line; tolvaptan (V2 antagonist) for refractory cases — but never fluid-restrict during the first 24 hours of tolvaptan, which drives overcorrection. Hypovolemic hyponatremia: isotonic saline. Hypervolemic: treat the underlying heart failure or cirrhosis. See the tolvaptan card.
Hypernatremia & diabetes insipidus
1
AssessCalculate the free water deficit
Replace with enteral free water or IV D5W / hypotonic fluids. Correct chronic hypernatremia no faster than ~10 mEq/L per 24 hours to avoid cerebral edema.
2
If polyuricDistinguish central from nephrogenic DI
Central DI (common after pituitary or hypothalamic injury, or brain death physiology): desmopressin corrects it. Nephrogenic DI: desmopressin does not work — address the cause and use thiazides or amiloride. The desmopressin response is itself the diagnostic test.
Ambulatory Dementia & Alzheimer Disease
Two therapeutic layers: long-established symptomatic agents that modestly slow decline, and the new disease-modifying anti-amyloid antibodies that carry real benefit, real risk, and real infrastructure demands.
Symptomatic therapy by stage
| Stage | First-line | Add / combine | Note |
|---|
| Mild | Cholinesterase inhibitor (donepezil, rivastigmine, galantamine) | — | Symptomatic benefit is modest; set expectations |
| Moderate | Cholinesterase inhibitor | Add memantine | Combination is standard |
| Severe | Donepezil | Memantine | Continue if meaningful function is preserved |
Watch the cholinergic downside: donepezil-induced bradycardia and syncope are an under-recognized cause of falls, especially with concurrent beta-blockers. See the donepezil and memantine cards.
Disease-modifying anti-amyloid antibodies
1
Confirm eligibilityEarly disease with proven amyloid
Lecanemab and donanemab are indicated only for mild cognitive impairment or mild dementia due to Alzheimer disease, with amyloid confirmed by PET or CSF. Obtain baseline MRI and APOE genotyping before starting.
2
Counsel on ARIAAPOE status changes the risk conversation
Amyloid-related imaging abnormalities — edema (ARIA-E) and microhemorrhage (ARIA-H) — are the defining risk. APOE e4 homozygotes carry markedly higher risk, including fatal events, and warrant explicit shared decision-making. Serial surveillance MRI is mandatory.
3
Highest-stakes interactionAnticoagulation dramatically raises hemorrhage risk
Concurrent anticoagulation substantially increases intracerebral hemorrhage risk; anticoagulated patients were generally excluded from trials, and deaths have been reported. A patient on an anti-amyloid antibody who develops ICH or needs thrombolysis is a genuine dilemma — a place where the neuro and neurocritical worlds collide. See the lecanemab and donanemab cards.
Effect size in context: CLARITY-AD (lecanemab) and TRAILBLAZER-ALZ 2 (donanemab) both showed statistically robust slowing of decline — roughly a quarter to a third on their cognitive scales at 18 months — while the clinical meaningfulness of that magnitude remains actively debated. Donanemab offers a finite course, stopping once amyloid is cleared.
