Neurologic Emergencies: Rapid Diagnosis and Intervention

Dr Neeraj Manikath , claude.ai

Abstract

Neurologic emergencies represent some of the most time-sensitive conditions in critical care medicine, where delays in diagnosis and treatment can result in irreversible disability or death. This review addresses three critical domains: stroke mimics and chameleons that lead to diagnostic errors, contemporary management of refractory status epilepticus, and a systematic approach to the comatose patient. We emphasize practical clinical pearls, common pitfalls, and evidence-based interventions that enhance diagnostic accuracy and therapeutic outcomes.

Introduction

The phrase "time is brain" has become axiomatic in neurocritical care, yet the true challenge lies not merely in speed but in accuracy. Misdiagnosis rates in neurologic emergencies remain stubbornly high, with stroke mimics accounting for up to 30% of suspected strokes presenting to comprehensive stroke centers.¹ Meanwhile, status epilepticus carries mortality rates approaching 20%, with outcomes heavily dependent on rapid escalation of therapy.² The comatose patient presents perhaps the ultimate diagnostic challenge, requiring systematic evaluation to identify reversible causes while avoiding premature therapeutic nihilism.

Stroke Mimics and Chameleons: Avoiding Pitfalls

The Magnitude of the Problem

Stroke mimics—conditions that present with stroke-like symptoms but have alternative etiologies—represent a significant diagnostic challenge. Common mimics include seizures with Todd's paresis, hemiplegic migraine, functional neurologic disorders, hypoglycemia, and septic encephalopathy. Conversely, stroke chameleons are actual cerebrovascular events that present atypically, leading to missed diagnoses.³

Pearl #1: The "FAST" paradigm (Face-Arm-Speech-Time), while excellent for public awareness, has poor sensitivity for posterior circulation strokes. Isolated vertigo, diplopia, or dysarthria without limb weakness are frequently missed.⁴

High-Yield Stroke Mimics

Seizures and Postictal States: Todd's paresis can persist for 24-48 hours and is indistinguishable from stroke on clinical examination. The key discriminator is history—witnesses reporting rhythmic movements or a known seizure disorder should raise suspicion. However, be cautious: seizures can be the presenting symptom of acute stroke in 2-3% of cases.⁵

Hypoglycemia: Perhaps the most critical "don't miss" mimic, as it's immediately reversible. Point-of-care glucose testing should be reflexive for any altered patient.

Hack #1: In patients with unilateral weakness and altered mental status, if glucose < 60 mg/dL, administer dextrose first and reassess before activating the stroke team. However, if glucose is normal and clinical suspicion for stroke remains high, proceed with neuroimaging without delay.

Functional Neurologic Disorder (FND): Historically termed "conversion disorder," FND accounts for 10-15% of stroke mimics.⁶ Clinical clues include "give-way" weakness, Hoover's sign positivity, and neuroanatomically implausible patterns. However, caution is warranted—diagnostic anchoring on FND has led to missed basilar artery occlusions with catastrophic outcomes.

Oyster #1: Never diagnose FND in the emergency setting without neuroimaging. Even positive functional signs don't exclude organic pathology—patients with FND can have concurrent strokes.

Dangerous Stroke Chameleons

Posterior Circulation Strokes: These account for 20% of ischemic strokes but are misdiagnosed in up to 35% of cases initially.⁷ Isolated vertigo from vertebrobasilar insufficiency can mimic benign peripheral vestibulopathy. The HINTS examination (Head Impulse, Nystagmus, Test of Skew) has superior sensitivity and specificity compared to early MRI for acute vestibular syndrome.⁸

Pearl #2: A normal head impulse test in a patient with acute vestibular syndrome suggests central pathology (stroke) rather than peripheral vestibular dysfunction. This counterintuitive finding is critical—peripheral lesions show corrective saccades, central lesions do not.

Lacunar Syndromes: Pure sensory stroke, isolated dysarthria-clumsy hand syndrome, or ataxic hemiparesis are easily dismissed as peripheral neuropathies or functional complaints. Maintain a high index of suspicion in patients with vascular risk factors.

Imaging Considerations

Non-contrast CT has limited sensitivity for acute ischemic stroke (sensitivity 26-39% in first 3 hours).⁹ MRI with diffusion-weighted imaging (DWI) is superior but still misses 10-15% of acute strokes, particularly in the posterior fossa or with imaging within 6 hours of symptom onset.

Hack #2: When clinical suspicion for stroke is high but initial imaging is negative, repeat MRI at 24-48 hours or proceed with CT/MR angiography to evaluate for large vessel occlusion that may benefit from intervention despite negative parenchymal imaging.

Status Epilepticus: Second- and Third-Line Agents

Defining Refractory Status Epilepticus

Status epilepticus (SE) is defined as continuous seizure activity for >5 minutes or recurrent seizures without return to baseline. Refractory SE (RSE) persists despite adequate doses of benzodiazepines and one second-line antiseizure medication.¹⁰ Super-refractory SE (SRSE) continues for >24 hours despite anesthetic agents.

First-Line Failures: When to Escalate

The established sequence—benzodiazepines followed by phenytoin/fosphenytoin, valproate, or levetiracetam—fails in 30-40% of cases.¹¹ The critical error is delayed escalation due to reluctance to intubate or administer anesthetic agents.

Pearl #3: Once RSE is diagnosed (failure of benzodiazepines plus one second-line agent), do not serially add antiseizure medications. Proceed directly to continuous infusion anesthetic agents with EEG monitoring.

Second-Line Agents: The Evidence

Levetiracetam vs. Fosphenytoin vs. Valproate: The ESETT trial demonstrated equivalent efficacy (~50% seizure cessation) among these three agents for benzodiazepine-refractory SE.¹² However, safety profiles differ:

• Levetiracetam: Safest profile, no loading-related adverse effects, no drug interactions
• Fosphenytoin: Risk of hypotension, cardiac arrhythmias (requires cardiac monitoring); avoid in patients with heart block
• Valproate: Contraindicated in hepatic dysfunction, pregnancy, and mitochondrial disorders

Hack #3: In undifferentiated SE without IV access, consider intramuscular (IM) fosphenytoin (20 PE/kg) or intranasal midazolam while establishing access. IM levetiracetam is not FDA-approved but has been used off-label.

Third-Line Agents: Anesthetic Management

When second-line agents fail, continuous infusion anesthetics are indicated. The three main options are:

Midazolam: Loading dose 0.2 mg/kg, infusion 0.1-0.4 mg/kg/hr. Advantages include rapid onset and offset. Disadvantages include tachyphylaxis requiring escalating doses and propylene glycol toxicity with prolonged high-dose infusions.¹³

Propofol: Loading dose 1-2 mg/kg, infusion 20-200 mcg/kg/min. Rapid onset/offset allows neurologic assessments. Major concern is propofol infusion syndrome (PRIS), characterized by metabolic acidosis, rhabdomyolysis, cardiac failure, and death. Risk increases with doses >80 mcg/kg/min for >48 hours.¹⁴

Oyster #2: Monitor triglycerides, lactate, and creatine kinase in patients receiving propofol >48 hours. Development of metabolic acidosis or elevated triglycerides (>500 mg/dL) should prompt immediate discontinuation.

Pentobarbital: Loading dose 5-15 mg/kg, infusion 0.5-5 mg/kg/hr. Most effective for SRSE but carries significant risks: profound hypotension requiring vasopressor support, immunosuppression with infection risk, and prolonged wake-up time (days to weeks) after discontinuation.

Pearl #4: EEG monitoring during anesthetic treatment should target burst suppression (interburst interval 2-10 seconds) rather than complete suppression, which offers no additional benefit and increases complications.¹⁵

Emerging and Alternative Therapies

Ketamine: NMDA receptor antagonist with theoretical advantages for seizures mediated by NMDA receptor upregulation in RSE. Typical dosing: 1-2 mg/kg bolus, 0.3-5 mg/kg/hr infusion. Increasingly used as adjunctive therapy, though high-quality evidence is limited.¹⁶

Immunotherapy: Consider in patients with SRSE without clear etiology after infectious and metabolic workup. Empiric treatment with methylprednisolone, IVIG, or plasmapheresis may be beneficial in autoimmune encephalitis-associated SE.¹⁷

Hack #4: Send autoimmune encephalitis panel (NMDA receptor, LGI1, CASPR2, AMPA receptor antibodies) early in unexplained SE, as results take weeks. Don't wait for results before initiating immunotherapy if clinical suspicion is high.

The Comatose Patient: A Structured Diagnostic Approach

Initial Assessment: The First Five Minutes

Coma represents a medical emergency requiring simultaneous assessment and stabilization. The structured approach prevents cognitive bias and ensures critical reversible causes are not missed.

The ABCDE of Coma Management:

• Airway: Secure if GCS ≤8 or absent gag reflex
• Breathing: Ensure adequate oxygenation and ventilation
• Circulation: Address hypotension (target MAP >65 mmHg)
• Dextrose: Check glucose immediately; treat if <60 mg/dL
• Examination: Focused neurologic examination

Pearl #5: Administer empiric thiamine (500 mg IV) before dextrose administration in any patient with suspected alcohol use disorder or malnutrition to prevent precipitating Wernicke encephalopathy.

The COMA Mnemonic for Differential Diagnosis

• Carbonopathies (CO2 retention, hypoglycemia, hyperglycemia)
• Opiates and other drugs (toxidromes)
• Metabolic (hepatic, uremic, endocrine)
• Anatomic (stroke, hemorrhage, trauma, increased ICP)

Neurologic Examination Pearls

Pupillary Response: The most reliable examination finding, as pupillary reflexes are preserved even in metabolic encephalopathies until late stages.

• Pinpoint pupils: Opioid toxicity or pontine hemorrhage
• Midposition fixed pupils: Midbrain injury or severe anoxic brain injury
• Unilateral dilated fixed pupil: Uncal herniation until proven otherwise

Oyster #3: Beware of pharmacologic pupil dilation from topical medications or systemic anticholinergics. A dilated unreactive pupil in a patient who received atropine during resuscitation may not represent herniation.

Ocular Movements: Roving eye movements suggest intact brainstem and cortical suppression (metabolic). Absent doll's eyes (oculocephalic reflex) or cold calorics (oculovestibular reflex) indicate brainstem dysfunction—but never test oculocephalic reflex until cervical spine injury is excluded.

Motor Response: Purposeful movement to noxious stimuli suggests supratentorial dysfunction. Decerebrate or decorticate posturing indicates severe injury but preserved brainstem function. Absent motor response is the most ominous finding.

Breathing Patterns:

• Cheyne-Stokes: Bilateral hemispheric dysfunction or heart failure
• Central neurogenic hyperventilation: Midbrain/pontine lesion
• Apneustic breathing: Pontine injury
• Ataxic breathing: Medullary dysfunction (pre-arrest pattern)

Critical Investigations

Immediate Laboratory Tests: Glucose, complete metabolic panel, arterial blood gas, complete blood count, liver function tests, ammonia, troponin, toxicology screen, serum osmolality with osmolar gap calculation.

Hack #5: Calculate the osmolar gap. If elevated (>10 mOsm/kg) with high anion gap metabolic acidosis, consider toxic alcohol ingestion (methanol, ethylene glycol) and initiate fomepizole empirically while awaiting confirmatory levels.

Neuroimaging: Non-contrast CT is the initial study of choice to exclude hemorrhage, herniation, and large infarcts. MRI with DWI is superior for acute ischemic stroke, posterior fossa pathology, encephalitis, and anoxic brain injury but requires patient stability.

Lumbar Puncture: Indicated when infection or subarachnoid hemorrhage is suspected and CT is non-diagnostic. Check opening pressure. Always send cell count, glucose, protein, Gram stain, culture, and consider HSV PCR if encephalitis is possible.

Pearl #6: In suspected bacterial meningitis with coma or papilledema, administer antibiotics and dexamethasone immediately, obtain blood cultures, and defer LP until after CT. Do not delay antibiotics to obtain imaging or LP—mortality increases by 30% for each hour delay in antibiotic administration.¹⁸

Prognostication Pitfalls

Premature prognostication in coma is a leading cause of inappropriate withdrawal of life-sustaining treatment. The American Academy of Neurology recommends waiting at least 72 hours after cardiac arrest (and after normothermia in patients who underwent targeted temperature management) before discussing poor prognosis based on neurologic examination alone.¹⁹

Oyster #4: Sedative medications, particularly propofol and benzodiazepines, can persist for days in critically ill patients with renal or hepatic dysfunction. Always consider pharmacologic confounders before prognosticating. Quantitative EEG monitoring can help distinguish sedation from structural injury.

Conclusion

Neurologic emergencies demand diagnostic precision married to therapeutic urgency. Stroke mimics and chameleons teach us that clinical gestalt, while valuable, must be supplemented by systematic evaluation and appropriate imaging. Refractory status epilepticus requires early escalation to anesthetic agents with continuous EEG monitoring rather than serial addition of antiseizure medications. The comatose patient benefits from a structured approach that addresses reversible causes while avoiding premature prognostic nihilism. Mastery of these domains separates competent from exceptional neurointensive care and ultimately determines whether patients face disability or recovery.

Key Take-Home Points

1. Always check glucose in altered patients—it's the only stroke mimic that's immediately reversible
2. HINTS examination outperforms early MRI for acute vestibular syndrome
3. Escalate to continuous infusion anesthetics after failure of one second-line agent in status epilepticus
4. Monitor for propofol infusion syndrome when using doses >80 mcg/kg/min for >48 hours
5. Defer prognostication for at least 72 hours post-arrest, accounting for pharmacologic confounders

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Disclosure: The author has no conflicts of interest to declare.