What are the differential diagnoses for a patient found asleep with new‑onset focal neurological deficits?

Differential Diagnosis for New-Onset Focal Neurological Deficits in a Patient Found Asleep

Acute ischemic stroke is the most likely diagnosis and must be assumed until proven otherwise, but stroke mimics account for up to 31% of cases presenting with focal neurological deficits, with seizures, conversion disorder, hypoglycemia, and complicated migraine being the most common alternatives. 1, 2, 3

Primary Diagnostic Considerations

Acute Ischemic Stroke (Most Common)

• Wake-up strokes represent up to 30% of all ischemic strokes and present as new focal neurological deficits discovered upon awakening. 4
• The time of symptom onset is defined as when the patient was last known to be awake and symptom-free or at baseline. 1
• Patients with recurrent stroke history have significantly elevated risk for intracranial pathology when presenting with altered mental status or new deficits. 5
• Stroke remains the most common cause of acute focal neurological deficits in adults. 1

Stroke Mimics (Up to 31% of Cases)

Seizure with Postictal Paralysis (Todd's Paralysis)

• Most frequently identified stroke mimic, particularly in patients treated with thrombolytics. 1, 2, 3
• Patients with seizure history present with seizure activity in 21% of stroke mimic cases vs. 0.7% in true stroke patients. 6
• Examination of the head and face may reveal signs of trauma or tongue biting suggesting seizure activity. 1
• Postictal state can produce focal weakness lasting hours that mimics stroke. 3

Conversion Disorder/Functional Neurological Disorder

• Second most common stroke mimic identified in fibrinolytic-treated patients. 1
• More common in younger patients without traditional vascular risk factors. 2, 3
• Neurological deficits may not follow anatomic vascular distributions. 3

Hypoglycemia and Metabolic Disturbances

• Can present with focal neurological deficits that completely resolve with correction. 1, 2, 3
• Blood glucose must be checked immediately in all patients with suspected stroke. 1
• Other metabolic causes include hyponatremia, hypercalcemia, and hepatic encephalopathy. 2, 3

Complicated Migraine (Hemiplegic Migraine)

• Presents with focal neurological deficits during or after migraine headache. 1, 2, 3
• History of similar episodes with complete resolution supports this diagnosis. 1
• More common in younger patients with migraine history. 1, 2

Intracranial Hemorrhage

• Must be excluded urgently as it presents identically to ischemic stroke but requires opposite management. 5
• Non-contrast head CT is first-line to exclude hemorrhage before considering thrombolysis. 5
• Patients with recurrent stroke history have higher risk for hemorrhagic transformation. 5

Brain Tumor or Space-Occupying Lesion

• Typically presents with gradual progression of symptoms rather than acute onset. 1
• May have seizure at onset or history of other primary malignancy. 1
• Can present acutely if hemorrhage into tumor occurs. 3

Central Nervous System Infection

• Includes encephalitis, meningitis, or brain abscess. 2, 3
• Fever, headache, and altered mental status may accompany focal deficits. 1
• Examination may reveal signs of infection or meningismus. 1

Drug Toxicity

• Lithium, phenytoin, and carbamazepine can cause focal neurological deficits. 1
• History of medication use or changes is critical. 1

Clinical Differentiation Strategy

History Red Flags for Stroke Mimics

• History of seizures increases stroke mimic probability (21% vs. 0.7% in true stroke). 6
• Younger age (mean 69.8 years for mimics vs. 74.8 years for stroke). 6
• Absence of atrial fibrillation (21% in mimics vs. 38.1% in stroke). 6
• Absence of hypertension (53.2% in mimics vs. 78.9% in stroke). 6
• Gradual symptom progression suggests tumor rather than stroke. 1

Physical Examination Findings Favoring True Stroke

• Weakness of face (70.9% in stroke vs. 42.7% in mimics) or arm (60.9% vs. 33.9%) strongly suggests stroke. 6
• Dysarthria present in 59.5% of stroke vs. 40.3% of mimics. 6
• Higher NIHSS scores (>14 in 25.8% of stroke vs. 11.3% of mimics). 6
• Carotid bruits, cardiac murmurs, or arrhythmias on auscultation. 1
• Signs of atrial fibrillation, congestive heart failure, or embolic skin lesions (Janeway lesions, Osler nodes). 1

Critical Physical Examination Components

• Examine head and face for signs of trauma or seizure (tongue biting, bruising). 1
• Auscultate neck for carotid bruits. 1
• Cardiac examination for murmurs, arrhythmias, and signs of heart failure. 1
• Skin examination for coagulopathy stigmata, platelet disorders, or embolic lesions. 1
• Complete NIHSS scoring to quantify deficits and aid in diagnosis. 1

Imaging Algorithm

Immediate Non-Contrast Head CT

• First-line imaging for all patients with acute focal neurological deficits to exclude hemorrhage and identify large infarcts. 5
• Mandatory before considering thrombolytic therapy. 5
• Particularly critical in patients with recurrent stroke history due to high risk of intracranial pathology. 5

MRI Brain (Second-Line)

• If CT is unrevealing and symptoms persist beyond 24-48 hours, obtain MRI with DWI, FLAIR, and SWI sequences. 5
• MRI detects 70% of ischemic strokes missed on CT, especially in patients presenting with altered mental status alone. 5
• Diffusion-weighted imaging (DWI) positive with FLAIR negative suggests stroke occurred within 3-4.5 hours, potentially allowing thrombolysis in wake-up stroke. 4
• MRI changes clinical management in 76% of patients with acute disorders of consciousness. 5

Critical Pitfalls to Avoid

• Do not defer imaging based on normal laboratory values—intracranial pathology occurs with normal blood tests. 5
• Do not assume metabolic cause in patients with recurrent stroke history, even without focal deficits on initial examination. 5
• Any sudden-onset, objective focal neurological deficit must be assumed acute stroke until proven otherwise. 2
• Do not delay neuroimaging for EEG unless non-convulsive status epilepticus is strongly suspected. 5
• Remember that 70% of patients with missed ischemic stroke present with altered mental status rather than classic focal deficits. 5
• Stroke mimics treated with thrombolytics have overwhelmingly better outcomes than true strokes, with only two reported cases of symptomatic intracranial hemorrhage in the literature. 1, 7