Stroke Misses and Stroke Mimics: Navigating Diagnostic Challenges in Acute Neurological Presentations

Dr Neeraj Manikath , claude.ai

Abstract

The accurate and timely diagnosis of acute ischemic stroke remains one of the most critical challenges in emergency medicine and neurology. While rapid identification enables life-saving thrombolytic therapy, the consequences of misdiagnosis extend beyond missed treatment windows to include inappropriate administration of thrombolytics to patients with stroke mimics. This review examines the clinical presentations, diagnostic pitfalls, and systematic approaches to distinguish true strokes from mimics, while identifying common scenarios where strokes are missed. Understanding these diagnostic challenges is essential for all physicians managing acute neurological emergencies.

Introduction

The mantra "time is brain" has driven the development of streamlined acute stroke protocols worldwide. However, this urgency creates a diagnostic tension: the need for rapid treatment must be balanced against the risk of misdiagnosis. Studies suggest that 5-30% of patients receiving thrombolytic therapy for presumed stroke actually have stroke mimics, while conversely, 10-15% of actual strokes are initially misdiagnosed in emergency departments.

The stakes are high. Missed strokes lead to delayed treatment, potentially converting salvageable penumbra to irreversible infarction. Conversely, treating mimics with thrombolysis exposes patients to hemorrhagic risks without therapeutic benefit. This review provides a practical framework for navigating these diagnostic challenges.

The Spectrum of Stroke Mimics

Common Stroke Mimics

Seizures and Postictal States

Todd's paresis represents one of the most frequently encountered stroke mimics, occurring in 6-13% of patients with focal seizures. The clinical presentation of focal weakness, sensory changes, or aphasia following a seizure can be indistinguishable from stroke. The paresis typically resolves within 24-48 hours, though occasionally persists longer.

Pearl: Always obtain a detailed history about the onset. Stroke deficits are maximal at onset, while seizure-related symptoms often build up (positive phenomena like jerking) before the deficit appears. Postictal confusion is common and may obscure the history.

Hack: Check for lateral tongue biting, which is highly specific (though not sensitive) for generalized tonic-clonic seizures. Review the evolution of symptoms—did weakness spread from one body part to another (Jacksonian march)?

Functional Neurological Disorders (Conversion Disorder)

Functional neurological symptoms account for 10-20% of stroke mimics in some series. These patients may present with hemiparesis, sensory loss, visual disturbances, or speech difficulties that can closely mimic stroke. Distinguishing features include inconsistent examination findings, non-anatomical deficits, and the presence of positive signs such as Hoover's sign or give-way weakness.

Oyster: Don't dismiss functional presentations because they seem "too perfect" or dramatic. Some functional presentations can be remarkably subtle and convincing. The diagnosis is made by identifying positive signs of functional etiology, not just by exclusion.

Metabolic and Toxic Encephalopathies

Hypoglycemia remains the classic "must-not-miss" stroke mimic. Focal neurological deficits occur in approximately 3-5% of severe hypoglycemic episodes and can include hemiparesis, hemisensory loss, or aphasia. The mechanism involves regional metabolic vulnerability, particularly in watershed territories.

Pearl: Always check glucose immediately in any acute neurological presentation—it's the quickest reversible cause to identify. However, don't assume glucose normalization immediately resolves all symptoms; focal deficits may persist for hours after correction.

Hepatic encephalopathy can present with focal findings including asterixis predominantly affecting one limb, which may be mistaken for weakness. Wernicke's encephalopathy, though classically presenting with the triad of confusion, ataxia, and ophthalmoplegia, can manifest with isolated focal findings.

Structural Lesions

Brain Tumors and Subdural Hematomas

Primary or metastatic brain tumors may present acutely, mimicking stroke when hemorrhage, seizure, or sudden tumor expansion occurs. Chronic subdural hematomas can present with fluctuating deficits that wax and wane, particularly in elderly patients on anticoagulation.

Hack: The presence of headache, particularly if progressive over days to weeks, should raise suspicion for structural lesions. However, up to 25% of stroke patients report headache, so this finding is not discriminatory. Look for signs of elevated intracranial pressure on examination.

Complicated Migraine

Hemiplegic migraine can produce profound focal neurological deficits lasting hours to days. Migraine with brainstem aura (formerly basilar migraine) presents with vertigo, dysarthria, ataxia, and visual symptoms that can mimic posterior circulation stroke. The key distinguishing feature is the gradual evolution and positive sensory phenomena (spreading paresthesias) typical of migraine aura, contrasting with the sudden-onset deficit of stroke.

Oyster: Don't rely on the absence of headache to exclude migraine—the aura may precede the headache by hours, and in acephalgic migraine, no headache develops. A personal or family history of migraine increases diagnostic likelihood, but new-onset migraine can occur at any age.

Peripheral Nervous System Disorders

Bell's palsy causes acute facial weakness that, when isolated, should be readily distinguished from stroke. However, central facial weakness from stroke is sometimes mistaken for peripheral seventh nerve palsy.

Pearl: In central (upper motor neuron) facial weakness from stroke, forehead wrinkling is preserved due to bilateral cortical innervation of the frontalis muscle. In Bell's palsy, the entire half of the face is affected, including forehead weakness.

Acute vestibular syndrome presenting with vertigo, nausea, vomiting, and gait instability can mimic posterior circulation stroke. The HINTS (Head Impulse, Nystagmus, Test of Skew) examination is more sensitive than early MRI diffusion-weighted imaging for detecting posterior circulation stroke in the first 48 hours.

Hack: In acute vestibular syndrome with vertigo, a normal head impulse test (preserved vestibulo-ocular reflex) should raise concern for central causes including stroke. Peripheral vestibular disorders typically show an abnormal head impulse test.

Common Scenarios for Missed Strokes

Posterior Circulation Strokes

Posterior circulation strokes account for approximately 20% of all ischemic strokes but represent a disproportionate number of missed diagnoses. The diverse presentations of vertebrobasilar territory ischemia—including isolated vertigo, diplopia, ataxia, or dysarthria—may not trigger stroke protocols.

Pearl: Beware of isolated vertigo, particularly in patients with vascular risk factors. While most isolated vertigo is peripheral, stroke risk factors (age >50, hypertension, diabetes, atrial fibrillation) should raise suspicion for central causes. The ABCD² score has limited utility in posterior circulation events.

Cerebellar infarctions are particularly treacherous. Early symptoms may be mild ataxia and dizziness, easily dismissed as benign vertigo. However, posterior fossa edema can develop over 24-72 hours, causing brainstem compression and rapid deterioration. A "walk test" should be performed—inability to walk independently with acute vertigo suggests central pathology.

Oyster: Initial CT scans miss up to 80% of posterior fossa strokes due to bone artifact. If clinical suspicion is high, proceed directly to MRI or arrange close observation with repeat imaging.

Lacunar Strokes

Pure motor stroke, pure sensory stroke, ataxic hemiparesis, and dysarthria-clumsy hand syndrome represent classic lacunar syndromes. These small-vessel occlusions may present with subtle findings that don't immediately suggest emergent stroke.

Hack: Don't let "minor" symptoms fool you. Small strokes can herald large ones—approximately 5% of patients with TIA or minor stroke will have a major stroke within 48 hours without treatment. Even isolated dysarthria or facial weakness warrants urgent evaluation and treatment consideration.

Nonconvulsive Status Epilepticus

Nonconvulsive status epilepticus (NCSE) can present with focal deficits, altered consciousness, or aphasia mimicking stroke. Conversely, seizures may be the presenting feature of acute stroke (particularly cortical infarcts), occurring in 4-6% of acute ischemic strokes.

Pearl: The presence of fluctuating symptoms, subtle facial or limb twitching, or altered awareness beyond what the focal deficit would explain should prompt consideration of NCSE. An urgent EEG is diagnostic.

Rapidly Progressive Deficits

Not all stroke presentations are sudden. Some patients, particularly those with intracranial large vessel atherosclerosis or progressing thrombosis, develop stuttering or progressive symptoms over hours. These patients may not be recognized as stroke if the "sudden onset" criterion is strictly applied.

Hack: Pay attention to the temporal profile. Symptoms that worsen in a stepwise fashion over hours may represent stroke-in-evolution. These patients may still benefit from urgent intervention including revascularization strategies.

Diagnostic Approach: A Systematic Framework

Clinical Assessment

The cornerstone of accurate diagnosis remains a thorough history and examination. Key historical features include:

1. Timing and tempo: Sudden onset (seconds to minutes) strongly favors stroke. Gradual progression over minutes may suggest migraine. Fluctuating symptoms raise concern for seizure or metabolic causes.

2. Deficit pattern: Negative symptoms (loss of function) are typical of stroke, while positive symptoms (tingling, flashing lights, jerking) suggest seizure or migraine.

3. Level of consciousness: Altered consciousness is uncommon in anterior circulation stroke unless massive hemispheric infarction. Its presence suggests posterior circulation involvement, seizure, or metabolic causes.

4. Risk factor profile: The presence of atrial fibrillation, prior stroke/TIA, carotid stenosis, or recent cardiac procedures significantly increases stroke likelihood.

Validated Clinical Tools

The Recognition of Stroke in the Emergency Room (ROSIER) scale helps distinguish stroke from mimics (sensitivity 92%, specificity 86%). It awards positive points for asymmetric facial/arm/leg weakness, speech disturbance, and visual field defect, while subtracting points for seizure activity and loss of consciousness.

The FABS (Face-Arm-Speech-Blood pressure-Sugar) mnemonic systematizes the approach to potential stroke mimics, ensuring hypoglycemia is checked while vascular risk factors are considered.

Neuroimaging Strategy

CT vs. MRI: Noncontrast CT remains the first-line imaging modality in most centers due to speed and availability. While CT has low sensitivity for acute ischemia in the first hours (approximately 30% sensitivity in the first 6 hours), it effectively excludes hemorrhage and identifies some mimics (tumors, subdural hematomas).

MRI with diffusion-weighted imaging (DWI) has superior sensitivity for acute ischemia (88-100% in most series) but even DWI can be negative in small lacunar strokes, particularly in the first few hours, and in some posterior circulation strokes.

Pearl: A negative DWI-MRI does not exclude stroke, particularly in the hyperacute phase (<3 hours) or in small brainstem or lacunar infarcts. Clinical judgment remains paramount.

CT or MR angiography should be strongly considered to identify large vessel occlusions amenable to mechanical thrombectomy, and may reveal dissections or other vascular pathology contributing to stroke or mimics.

Advanced Imaging Considerations

CT perfusion and MR perfusion can identify ischemic penumbra and guide treatment decisions beyond traditional time windows. However, perfusion abnormalities can occur in migraine, seizures, and other stroke mimics, reducing specificity.

Oyster: Arterial spin labeling (ASL) MRI can show hyperperfusion in seizure foci and migraine, potentially helping distinguish these mimics from stroke, though availability is limited.

Special Populations and Challenging Scenarios

Young Patients

Stroke in patients under 50 years requires consideration of non-atherosclerotic etiologies including dissection, vasculitis, hypercoagulable states, and substance use (particularly cocaine and methamphetamine). However, functional neurological disorders and complicated migraine are also more common in younger populations, creating diagnostic complexity.

Hack: In young patients without obvious vascular risk factors, carefully examine the neck for signs of trauma or manipulation that might suggest dissection. Ask specifically about chiropractor visits, contact sports, or vigorous exercise preceding symptoms.

Wake-Up Strokes

Approximately 20-25% of strokes are "wake-up strokes" where the patient awakens with deficits. The time of onset is unknown, complicating treatment decisions. MRI with DWI-FLAIR mismatch (positive DWI with negative FLAIR) can identify patients likely within the treatment window, as FLAIR changes typically lag DWI by several hours.

Stroke Chameleons

Some stroke presentations are inherently difficult to diagnose because they present with atypical features. These "chameleons" include isolated vertigo, sudden confusion without focal findings, isolated ataxia, or monocular vision loss. Maintaining high clinical suspicion in patients with vascular risk factors is essential.

Pearl: Any acute neurological symptom in a patient with atrial fibrillation should be considered stroke until proven otherwise. The combination of atrial fibrillation and acute neurological symptoms has a positive predictive value exceeding 80% for stroke.

Clinical Decision-Making in Uncertain Cases

When diagnostic uncertainty persists despite imaging and clinical assessment, several principles guide management:

1. Risk stratification: Patients with high-risk features (atrial fibrillation, known carotid disease, multiple vascular risk factors, ABCD² score ≥4) warrant aggressive evaluation even if initial imaging is negative.

2. Short-interval observation: Patients with suspected TIA or minor stroke should undergo observation with repeat neurological assessments. Progression of symptoms may clarify diagnosis and indicate need for urgent intervention.

3. Multimodal assessment: Combining clinical judgment, imaging findings, and vascular risk factor assessment provides better diagnostic accuracy than any single element.

4. When to treat with thrombolytics: In cases of genuine uncertainty, the decision to administer thrombolytics should weigh the probability of stroke against the likelihood and risk profile of potential mimics. Seizure and migraine carry relatively low hemorrhagic risk with thrombolysis, while structural lesions carry higher risk.

Oyster: Approximately 1-2% of stroke mimic patients receiving thrombolytics experience symptomatic hemorrhage, compared to 6-7% of actual stroke patients. While not negligible, this risk is lower than commonly feared, and should be weighed against the devastating consequences of missing true stroke.

Systems-Based Approaches to Reduce Misdiagnosis

Institutions can implement strategies to minimize both missed strokes and overtreated mimics:

1. Stroke team consultation: Immediate neurology involvement improves diagnostic accuracy compared to emergency physician assessment alone.

2. Telemedicine: Telestroke networks provide expert consultation, particularly valuable in settings with limited neurology availability.

3. Structured protocols: Standardized assessments including validated scales (NIHSS, ROSIER) improve consistency.

4. Education: Regular case conferences reviewing both missed strokes and treated mimics enhance diagnostic acumen.

5. Post-thrombolysis review: Systematic review of patients treated with thrombolytics who turn out to have mimics provides valuable learning opportunities.

Conclusion

Distinguishing stroke from mimics and recognizing atypical stroke presentations requires synthesis of clinical acumen, structured assessment tools, appropriate imaging, and an understanding of diagnostic pitfalls. While "time is brain" necessitates rapid decision-making, systematic evaluation minimizes both missed strokes and inappropriate treatment of mimics.

The most critical principles include maintaining high clinical suspicion in patients with vascular risk factors, recognizing that negative initial imaging does not exclude stroke (particularly in posterior circulation), understanding that functional and metabolic causes can produce convincing focal deficits, and appreciating that some presentations are inherently ambiguous requiring observation and repeat assessment.

As imaging technology advances and treatment windows expand, the diagnostic challenge evolves but remains central to optimal stroke care. Continued education, structured protocols, and thoughtful clinical reasoning remain our most powerful tools in navigating these diagnostic challenges and optimizing outcomes for patients with acute neurological presentations.

Key Takeaway Pearls

• Always check glucose immediately—hypoglycemia is the quickest reversible stroke mimic
• Normal head impulse test in acute vertigo suggests central (stroke) rather than peripheral cause
• Negative MRI-DWI does not exclude stroke, especially early or in posterior circulation
• Any acute neurological symptom with atrial fibrillation is stroke until proven otherwise
• Forehead sparing distinguishes central (stroke) from peripheral facial weakness
• Stroke symptoms are maximal at onset; seizure symptoms typically build or spread

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Note: This review article synthesizes current evidence on stroke diagnosis and mimics. The references would include landmark studies such as the ROSIER scale validation studies, HINTS examination research, telestroke trials, and epidemiological data on stroke mimic prevalence. For journal submission, specific citations would be added to each clinical assertion following the target journal's reference format.