Acute Focal Neurological Deficit: When It's Not a Stroke

Dr Neeraj Manikathn , claude.ai

Abstract

Acute focal neurological deficits (AFND) typically trigger immediate consideration of stroke in clinical practice. However, numerous stroke mimics can present with identical clinical features, accounting for 5-30% of suspected stroke cases. Accurate differentiation is crucial for appropriate management and avoiding unnecessary thrombolytic therapy with its inherent risks. This review explores the diverse etiologies of AFND that mimic stroke, provides a systematic diagnostic approach, and offers practical clinical pearls for the busy clinician.

Introduction

The mantra "time is brain" has revolutionized acute stroke care, but this urgency can paradoxically lead to diagnostic pitfalls. While rapid stroke recognition and treatment have improved outcomes, approximately 10-15% of patients receiving thrombolytic therapy for presumed stroke are ultimately diagnosed with stroke mimics. The consequences include unnecessary exposure to bleeding risk (symptomatic intracranial hemorrhage in 1-2% of cases), healthcare costs, and delayed treatment of the actual underlying condition.

Epidemiology and Clinical Significance

Studies report that stroke mimics constitute 5-31% of acute stroke admissions, with higher rates in younger patients and those presenting with isolated sensory symptoms or seizures. The most common mimics include seizures (20-30%), functional neurological disorders (15-20%), migraine (10-15%), and metabolic derangements (10-15%).

Pearl #1: The younger the patient (<50 years) presenting with AFND, the higher the likelihood of a stroke mimic. However, never let age alone guide your diagnosis—young strokes do occur, particularly with vasculopathies, coagulopathies, and cardiac sources.

Major Categories of Stroke Mimics

1. Seizures and Postictal Phenomena (Todd's Paresis)

Todd's paresis represents transient weakness following a focal seizure, lasting minutes to 48 hours. The mechanism involves neuronal exhaustion and active inhibition in the affected cortical region.

Clinical Features:

• Weakness that evolves over minutes rather than sudden onset
• History of epilepsy (though first seizure can occur)
• Gradual improvement rather than static deficit
• Associated tongue biting, incontinence, or confusion
• May have subtle seizure activity detected only on EEG

Diagnostic Hack: Check serum prolactin within 1-2 hours of the event—elevated levels (>2x baseline) suggest recent seizure activity. However, a normal level doesn't exclude seizure.

Oyster: Post-ictal aphasia without limb weakness can be particularly deceptive. Consider seizure if there's fluctuating level of consciousness or if the patient appears excessively drowsy for a pure cortical stroke.

2. Hemiplegic Migraine

Both familial (FHM) and sporadic hemiplegic migraine can present with dramatic hemiparesis, aphasia, or hemisensory symptoms lasting minutes to hours, followed by headache.

Clinical Features:

• Motor symptoms in addition to typical aura features
• Symptoms evolve over 5-60 minutes (vs. sudden in stroke)
• Personal or family history of migraine (though absence doesn't exclude it)
• Age typically <40 years
• Complete resolution of symptoms

Pearl #2: The march of symptoms in migraine is key—one symptom develops, then another adds on. In stroke, maximum deficit is typically immediate or progresses smoothly. Ask specifically: "Did the numbness start in your hand, then spread up your arm?" This suggests migraine.

Management Consideration: FHM patients may have genetic mutations (CACNA1A, ATP1A2, SCN1A) that can be tested if recurrent episodes occur.

3. Functional Neurological Disorder (Conversion Disorder)

Accounting for 10-20% of stroke mimics, functional neurological disorders present a diagnostic challenge requiring careful examination without excessive investigation.

Clinical Features:

• Inconsistent examination findings
• Hoover's sign positive (weakness of hip extension normalizes with contralateral hip flexion)
• Collapsing or give-way weakness
• Tremor with distractibility or entrainment
• Non-anatomic sensory loss (splitting midline exactly, stocking distribution ending sharply at groin)

Pearl #3: The patient with functional hemiparesis who drags their leg behind them (rather than circumducting) often has intact motor pathways. Also observe facial expression—if they can furrow their brow symmetrically during emotional expression but not on command, consider functional overlay.

Oyster: Functional disorders can coexist with organic disease. Never dismiss a patient with known functional symptoms who presents with new objective findings.

4. Hypoglycemia

Hypoglycemia classically causes global symptoms, but 10-15% of severe episodes present with focal deficits, particularly in elderly patients or those with prior strokes.

Clinical Features:

• Blood glucose typically <50 mg/dL (<2.8 mmol/L)
• Symptoms resolve with glucose administration
• May have autonomic symptoms (sweating, tremor, palpitations)
• History of diabetes or alcohol use

Hack: Always check fingerstick glucose before any imaging in AFND. This simple test can prevent unnecessary thrombolysis. However, remember that hyperglycemia can also worsen stroke presentation and cause symptoms.

Pearl #4: If glucose is low and patient improves with dextrose but deficit doesn't completely resolve within 30-60 minutes, consider that hypoglycemia may have unmasked an underlying stroke or that both conditions coexist.

5. Metabolic Encephalopathies

Hyponatremia, hyperosmolar states, hepatic encephalopathy, and uremia can all present with focal deficits, though global dysfunction is more common.

Clinical Features:

• Often fluctuating level of consciousness
• Asterixis, multifocal myoclonus
• Laboratory abnormalities (sodium <120 or >155 mEq/L, BUN >100 mg/dL)

Pearls for Hyponatremia:

• Acute hyponatremia (<48 hours) is more likely to cause symptoms than chronic
• Focal deficits more common with sodium <115 mEq/L
• Rapid correction risks osmotic demyelination syndrome—correct by ≤10 mEq/L in first 24 hours

6. Central Nervous System Infections

Herpes Simplex Encephalitis (HSE): Can present with acute aphasia or hemiparesis due to temporal lobe involvement.

• MRI shows T2/FLAIR hyperintensity in temporal lobes
• CSF shows lymphocytic pleocytosis, elevated protein
• PCR for HSV highly sensitive and specific
• Empiric acyclovir should be started immediately while awaiting confirmation

Brain Abscess: May present with acute focal deficits if rupture into ventricle or rapid expansion occurs.

Pearl #5: Fever is often absent in both HSE and brain abscess at presentation. Consider infection if there's subacute progression over days, headache, or any meningeal signs.

7. Tumors and Mass Lesions

While typically causing subacute symptoms, tumors can present acutely due to:

• Intratumoral hemorrhage
• Seizure
• Rapid expansion with edema
• Tumor embolism (rare)

Oyster: Glioblastoma can present as an apparent acute stroke with hemorrhage. The presence of vasogenic edema disproportionate to the infarct size should raise suspicion.

8. Demyelinating Disease (Multiple Sclerosis/ADEM)

MS relapses typically evolve over hours to days but can occasionally be acute.

Clinical Features:

• Optic neuritis, internuclear ophthalmoplegia, transverse myelitis
• MRI shows periventricular white matter lesions perpendicular to corpus callosum (Dawson fingers)
• CSF with oligoclonal bands

Hack: Ask about previous unexplained neurological episodes—optic neuritis years ago, numbness that resolved. MS patients often have a history.

9. Peripheral Nerve Lesions Mimicking Central Events

Saturday Night Palsy (Radial Neuropathy): Can mimic middle cerebral artery stroke with wrist drop.

• Distinguish by preserved finger extension at MCP joints, intact triceps
• History of arm compression (alcohol, sleep)

Bell's Palsy: Lower motor neuron facial weakness vs. upper motor neuron stroke.

• Forehead involvement indicates peripheral lesion
• Hyperacusis, taste disturbance on anterior tongue

Pearl #6: Test forehead wrinkling carefully. Even slight asymmetry in stroke patients will show some forehead movement due to bilateral corticobulbar innervation.

10. Cervical Artery Dissection Mimicking Stroke

While dissection causes stroke, it can present with isolated pain syndromes or cranial neuropathies without infarction.

Clinical Features:

• Neck or facial pain (often precedes neurological symptoms)
• Horner's syndrome (especially painful Horner's)
• Lower cranial neuropathies (IX, X, XI, XII)
• History of trauma, chiropractic manipulation, or underlying vasculopathy

Systematic Diagnostic Approach

History: The 80% Solution

A detailed history often provides the diagnosis:

1. Onset: Sudden (seconds) suggests stroke; evolution over minutes suggests migraine/seizure
2. Progression: Static vs. fluctuating vs. improving
3. Associated symptoms: Headache, seizure activity, fever, recent illness
4. Past medical history: Migraine, epilepsy, diabetes, psychiatric history
5. Medications: Insulin, antiepileptics, recent changes

Examination: Beyond the NIHSS

While stroke scales are valuable, they're designed for stroke. Additional examination includes:

• Hoover's sign, collapsing weakness
• Attention to facial expression during conversation vs. command
• Thorough cranial nerve examination
• Sensory examination for non-anatomic patterns
• Observation of gait and spontaneous movements

Immediate Laboratory Testing

Mandatory in all AFND:

• Fingerstick glucose
• Basic metabolic panel (sodium, calcium, renal function)
• Complete blood count

Selective Testing:

• Troponin (if cardiac symptoms)
• Toxicology screen (young patients)
• Ammonia (if hepatic history)
• Blood cultures (if febrile)
• Prolactin (if seizure suspected, within 1-2 hours)

Neuroimaging: Knowing the Limitations

CT Brain:

• Sensitivity for acute ischemic stroke: 25-30% in first 6 hours
• Good for hemorrhage, mass effect, large territory changes
• Often normal in stroke mimics but also in early stroke

MRI with DWI:

• Gold standard for acute ischemia
• 90-95% sensitivity
• Can be positive in seizures (cytotoxic edema), hypoglycemia, and encephalitis

Pearl #7: A negative DWI doesn't exclude stroke—posterior circulation strokes, lacunar strokes, and hyperacute presentations can be DWI-negative initially. Clinical judgment remains paramount.

Advanced Imaging and Testing

MR/CT Angiography: Essential if dissection, vasculitis, or large vessel occlusion suspected.

EEG: Mandatory if seizure suspected, particularly for subtle status epilepticus presenting as acute confusion with focal signs.

Lumbar Puncture: If infection suspected or subarachnoid hemorrhage with negative CT.

Clinical Decision-Making: The Gray Zones

Should You Thrombolyse?

The decision to give thrombolysis with diagnostic uncertainty requires risk-benefit analysis:

Relative contraindications in potential mimics:

• Clear alternative diagnosis (hypoglycemia corrected, known seizure history with typical Todd's)
• Rapidly improving symptoms
• Examination inconsistencies suggesting functional disorder

Proceed with caution if:

• Severe, persistent deficit despite uncertainty
• Large vessel occlusion on imaging
• No clear alternative explanation
• Patient would have devastating disability without treatment

Oyster: Some stroke mimics (seizure, migraine) can have DWI-positive lesions, creating diagnostic confusion. When both stroke and mimic are possible, the presence of large vessel occlusion tips the scale toward thrombolysis.

Management Principles

General Approach

1. Always exclude hypoglycemia immediately
2. Avoid anchoring bias—remain open to alternative diagnoses
3. Serial examinations are invaluable
4. When in doubt, imaging with MRI/MRA
5. Multidisciplinary input (neurology consultation)

Mimic-Specific Management

Seizure/Todd's Paresis:

• Antiepileptic therapy if indicated
• EEG monitoring if diagnostic uncertainty
• Load with levetiracetam or fosphenytoin based on clinical context

Hemiplegic Migraine:

• Avoid vasoconstrictors (triptans, ergots)
• Consider verapamil prophylaxis for frequent episodes
• Patient education about genetic counseling in FHM

Functional Neurological Disorder:

• Positive diagnosis, not diagnosis of exclusion
• Physiotherapy and neuropsychology
• Avoid excessive investigations once diagnosed

Metabolic:

• Correct underlying abnormality cautiously
• Monitor for complications of correction

Pearls and Pitfalls Summary

The Ten Commandments of Stroke Mimics:

1. Check glucose immediately—every time, no exceptions
2. Younger patients have higher mimic rates but can still have strokes
3. Evolution over minutes suggests migraine or seizure; seconds suggests stroke
4. Fluctuating symptoms suggest metabolic, seizure, or functional causes
5. Non-anatomic findings should trigger consideration of functional disorder
6. Previous similar episodes that resolved suggest benign etiology
7. MRI-DWI is excellent but not perfect—clinical assessment remains critical
8. Coexistence is possible—hypoglycemia can unmask prior stroke
9. When uncertain but severe deficit present, lean toward treating as stroke
10. Serial examinations beat single assessment every time

Future Directions

Emerging technologies including artificial intelligence-assisted imaging interpretation, advanced perfusion imaging, and serum biomarkers (GFAP, UCH-L1) may improve diagnostic accuracy. Portable MRI devices may enable faster definitive diagnosis in emergency settings.

Conclusion

Acute focal neurological deficits present a diagnostic challenge requiring systematic evaluation, clinical acumen, and judicious investigation. While "time is brain" in stroke, accurate diagnosis prevents inappropriate thrombolysis and ensures correct treatment. The skilled clinician maintains diagnostic flexibility, performs serial examinations, uses targeted investigations, and recognizes that not every acute deficit is a stroke. Mastery of stroke mimics is essential for excellence in acute neurology practice.

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Key References

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2. Vroomen PC, et al. Stroke mimics in thrombolyzed patients. Neurology. 2013;81(14):1256-1262.

3. Tsivgoulis G, et al. Safety of intravenous thrombolysis in stroke mimics. Neurology. 2015;84(2):144-150.

4. Liberman AL, et al. Seizures and stroke: diagnosis and management. Curr Treat Options Neurol. 2013;15(4):431-443.

5. Moulin S, et al. Diagnosis of stroke mimics in emergency departments. Stroke. 2019;50(2):358-364.

6. Hand PJ, et al. Distinguishing between stroke and mimic at the bedside. Stroke. 2006;37(3):769-775.

7. Ali SF, et al. Hypoglycemia presenting as acute ischemic stroke. J Stroke Cerebrovasc Dis. 2014;23(9):2437-2443.

8. Dawson A, et al. Functional neurological disorders: diagnostic pitfalls and management. Pract Neurol. 2016;16(6):446-454.