Hemiplegia: A Comprehensive Clinical Review for the Internist

Dr Neeraj Manikath , claude,ai

Abstract

Hemiplegia represents a profound neurological deficit with diverse etiologies extending beyond the commonly encountered stroke. This review synthesizes current understanding of hemiplegic syndromes, emphasizing diagnostic pearls and clinical approaches relevant to internists and neurologists managing complex cases. We explore classical presentations, atypical variants, and rare mimics while providing practical frameworks for systematic evaluation.

Introduction

Hemiplegia—complete paralysis of one side of the body—represents a neurological emergency demanding rapid, systematic evaluation. While cerebrovascular accidents account for the majority of acute presentations, the differential diagnosis encompasses structural, metabolic, inflammatory, and functional disorders. The internist's challenge lies not merely in recognizing hemiplegia but in distinguishing its various etiological subtypes, each carrying distinct therapeutic implications and prognostic trajectories.

Anatomical Foundations and Clinical Localization

Understanding hemiplegia requires precise neuroanatomical localization. The motor pathway originates in the precentral gyrus (Brodmann area 4), descends through the corona radiata, internal capsule, cerebral peduncle, pons, and medullary pyramid, with 85-90% of fibers decussating at the pyramidal decussation.

Pearl: The "cortical hand" sign—disproportionate hand and finger weakness compared to proximal limb strength—indicates cortical or subcortical lesions, as the hand representation occupies a large cortical territory. Conversely, proportionate weakness suggests capsular or brainstem involvement.

Oyster: In capsular strokes, examine for sensory deficits. Pure motor hemiplegia without sensory loss suggests lacunar infarction affecting the posterior limb of the internal capsule, typically associated with small vessel disease and hypertension.

Vascular Hemiplegia: Beyond the Basics

Anterior Circulation Strokes

Middle cerebral artery (MCA) territory infarction remains the commonest cause of hemiplegia. However, recognizing patterns provides prognostic information:

• Superior division MCA: Produces brachial-predominant weakness with cortical sensory loss and aphasia (dominant hemisphere) or neglect (non-dominant)
• Inferior division MCA: Typically spares motor function; presents with aphasia or visuospatial deficits
• Complete MCA territory: Produces dense hemiplegia with global aphasia and hemianopia

Hack: The "capsular warning syndrome"—stereotyped, transient motor or sensorimotor symptoms recurring over hours to days—predicts impending capsular stroke. Recognition warrants aggressive intervention with dual antiplatelet therapy and statin intensification.

Posterior Circulation Considerations

Basilar artery occlusion may present with alternating hemiplegia, where cranial nerve deficits appear ipsilateral to the lesion while limb weakness is contralateral. Classic syndromes include:

• Millard-Gubler syndrome: Facial nerve palsy (ipsilateral) with contralateral hemiplegia (pontine base lesion)
• Weber syndrome: Oculomotor palsy (ipsilateral) with contralateral hemiplegia (midbrain peduncle)

Pearl: In a patient with acute hemiplegia and preserved consciousness, always assess vertical eye movements and pupillary responses. Impaired upgaze with intact downgaze suggests midbrain pathology; bilateral pinpoint pupils with preserved consciousness indicate pontine involvement.

Hemorrhagic Hemiplegia

Intracerebral hemorrhage (ICH) produces hemiplegia through direct tissue destruction and mass effect. Distinguishing features from ischemic stroke include:

• Headache (present in 50% of ICH vs. 25% of ischemic stroke)
• Vomiting and decreased consciousness (more common with hemorrhage)
• Smooth symptom progression over minutes to hours (vs. maximal deficit at onset in embolic stroke)

Oyster: Hypertensive hemorrhages classically occur in the basal ganglia (50%), thalamus (15%), pons (15%), and cerebellum (10%). However, lobar hemorrhages in elderly patients warrant consideration of cerebral amyloid angiopathy, particularly if previous hemorrhages exist on gradient echo MRI sequences.

Hack: The ICH score (incorporating GCS, ICH volume, intraventricular hemorrhage, infratentorial location, and age) predicts 30-day mortality with remarkable accuracy and should guide prognostic discussions.

Inflammatory and Autoimmune Hemiplegia

Acute Disseminated Encephalomyelitis (ADEM)

ADEM typically follows viral infections or vaccinations by 1-2 weeks. Unlike stroke, presentation is often subacute (days), accompanied by encephalopathy, fever, and multifocal deficits. MRI reveals multiple white matter lesions with indistinct margins.

Pearl: The presence of deep gray matter involvement (thalamus, basal ganglia) on MRI strongly favors ADEM over multiple sclerosis in a first demyelinating event.

Hemiplegic Migraine

Both familial (FHM) and sporadic forms exist. FHM1 results from CACNA1A mutations, FHM2 from ATP1A2, and FHM3 from SCN1A mutations. Episodes feature reversible hemiplegia lasting hours to days, often with visual aura and headache.

Hack: During acute episodes, diffusion-weighted imaging may show cortical hyperintensity mimicking stroke, but apparent diffusion coefficient remains normal or elevated (vs. restricted diffusion in true infarction). Attacks may be triggered by minor head trauma, exertion, or Valsalva maneuvers.

Metabolic and Toxic Hemiplegia

Hypoglycemic Hemiplegia

Severe hypoglycemia (typically <30 mg/dL) may produce focal deficits including hemiplegia, mimicking stroke. This represents a "stroke chameleon" requiring immediate recognition.

Pearl: Unlike ischemic stroke, symptoms reverse rapidly (within 30 minutes) following glucose administration. However, recurrent hypoglycemic events may cause permanent basal ganglia injury visible on T2-weighted imaging.

Hepatic Encephalopathy

Rare presentations of hepatic encephalopathy include focal deficits. The mechanism involves ammonia-induced astrocytic swelling and cytotoxic edema, preferentially affecting the cortex and basal ganglia.

Oyster: Look for hyperintense basal ganglia on T1-weighted imaging (due to manganese deposition) in cirrhotic patients presenting with neurological deficits.

Hyperosmolar Hyperglycemic State (HHS)

HHS may present with hemichorea-hemiballismus or hemiplegia without stroke. CT shows hyperdensity of the basal ganglia (the "tiger-stripe" sign); MRI reveals restricted diffusion.

Hack: This complication occurs almost exclusively with extreme hyperglycemia (>600 mg/dL) and requires aggressive fluid resuscitation rather than thrombolysis.

Structural and Neoplastic Causes

Todd's Paresis

Post-ictal hemiplegia following focal seizures typically resolves within 24-48 hours. Prolonged cases may represent "epilepsia partialis continua" or underlying structural lesions.

Pearl: MRI may show transient cortical and subcortical T2/FLAIR hyperintensity with restricted diffusion in the affected hemisphere, mimicking acute infarction. Distinguishing features include: involvement of the cortex and subcortical white matter in a non-vascular distribution, absence of vascular occlusion on angiography, and complete radiological resolution within weeks.

Tumors and Space-Occupying Lesions

Slowly progressive hemiparesis over weeks to months suggests neoplastic or inflammatory masses. Key features include:

• Morning headaches with vomiting (raised intracranial pressure)
• Seizures (cortical involvement)
• Papilledema (late finding)

Hack: In an elderly patient with subacute hemiparesis and no vascular risk factors, consider subdural hematoma (may be bilateral and chronic) and brain metastases (especially lung, breast, melanoma, renal, colorectal). Contrast-enhanced MRI remains the gold standard.

Rare and Exotic Causes

Alternating Hemiplegia of Childhood (AHC)

This devastating condition begins before 18 months with recurrent episodes of hemiplegia alternating between sides, dystonic posturing, and developmental regression. ATP1A3 mutations account for most cases.

Oyster: Flunarizine (a calcium channel blocker) may reduce attack frequency, though evidence remains limited. Unlike hemiplegic migraine, attacks occur during sleep.

MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes)

MELAS presents with stroke-like episodes that violate vascular territories, typically in patients under 40 years with additional features: seizures, migraine-like headaches, short stature, and hearing loss.

Pearl: Diagnosis requires: (1) elevated serum/CSF lactate, (2) ragged red fibers or mitochondrial DNA mutations (commonly m.3243A>G) in muscle biopsy, and (3) MRI showing cortical involvement not restricted to vascular territories with T2/FLAIR hyperintensity in the occipital and posterior temporal regions.

Hack: L-arginine supplementation (0.5 g/kg during acute episodes, 0.15-0.3 g/kg/day for prevention) may reduce stroke-like episode severity and frequency by improving endothelial function.

Susac Syndrome

This rare microangiopathy affects brain, retina, and cochlea (the "triad"). Young women typically present with encephalopathy, branch retinal artery occlusions (often asymptomatic), and sensorineural hearing loss.

Pearl: MRI demonstrates pathognomonic "snowball lesions" in the corpus callosum—small, round T2 hyperintensities with restricted diffusion. Fluorescein angiography reveals branch retinal artery occlusions even without visual symptoms.

Treatment requires aggressive immunosuppression with high-dose corticosteroids, IVIG, cyclophosphamide, or rituximab, as untreated disease leads to permanent cognitive impairment.

Moyamoya Disease

Progressive stenosis of the terminal internal carotid arteries with characteristic "puff of smoke" collaterals on angiography. While more common in East Asian populations, it occurs worldwide. Presentations include ischemic stroke (adults) or hemorrhage from fragile collaterals.

Hack: The "hyperventilation test" may provoke symptoms during angiography—hyperventilation causes vasoconstriction of normal vessels but not stenotic Moyamoya vessels, producing relative hypoperfusion. Surgical revascularization (direct or indirect bypass) remains the definitive treatment.

Posterior Reversible Encephalopathy Syndrome (PRES)

Associated with hypertensive emergency, eclampsia, immunosuppression (especially calcineurin inhibitors), and autoimmune conditions. Presents with headache, seizures, visual disturbances, and altered consciousness; focal deficits occur in 10-15%.

Oyster: MRI classically shows bilateral parieto-occipital T2/FLAIR hyperintensity, but atypical patterns (frontal, brainstem, basal ganglia involvement) occur in 30% of cases. Hemorrhagic transformation portends worse prognosis.

Functional Neurological Disorder (Conversion Disorder)

Functional hemiplegia presents diagnostic challenges. Distinguishing features include:

• Hoover's sign: With the patient supine, ask them to flex the affected hip against resistance; simultaneously palpate the contralateral heel pressing into the bed (normally present with effort, absent in functional weakness)
• Collapsing weakness: "Give-way" weakness without true pyramidal pattern
• Midline splitting: Precise sensory loss at the midline (organic lesions have overlap)
• Incongruent facial weakness: Preserved emotional facial movements despite volitional weakness

Pearl: Functional disorders are diagnoses of "rule-in" signs, not exclusion. Positive functional signs carry 95%+ specificity. However, 10-30% of functional neurological disorder patients have coexistent organic disease.

Systematic Approach to the Hemiplegic Patient

A structured evaluation prevents diagnostic errors:

1. Tempo: Hyperacute (seconds-minutes) suggests stroke or seizure; acute (hours-days) suggests inflammation or complicated migraine; subacute (days-weeks) suggests tumor or abscess; chronic (months) suggests degenerative or metabolic causes

2. Pattern of weakness: Cortical (face and arm > leg); capsular (equal face, arm, leg); brainstem (crossed signs); spinal (level-dependent)

3. Associated features: Consciousness, cranial nerves, sensory, cerebellar, sphincters, systemic symptoms

4. Investigations:

   • Immediate: Glucose, CT head, ECG
   • Urgent: MRI brain with diffusion-weighted imaging and angiography, coagulation profile, complete blood count, metabolic panel
   • Selective: Lumbar puncture (inflammation, infection), EEG (seizures), specialized metabolic testing, genetic testing

Hack: In young patients (<50 years) with cryptogenic stroke, screen for: patent foramen ovale (bubble echocardiography), hypercoagulable states (Factor V Leiden, prothrombin G20210A, antiphospholipid antibodies), vasculitis (inflammatory markers, vessel wall imaging), and arterial dissection (fat-suppressed MRI of neck vessels).

Conclusion

Hemiplegia demands systematic evaluation beyond reflexive attribution to stroke. The modern internist must maintain broad differential awareness, recognizing that approximately 5-10% of suspected strokes represent mimics. Careful attention to temporal profile, associated features, and judicious investigation enables accurate diagnosis and targeted therapy, potentially preventing irreversible disability in treatable conditions. As imaging and molecular diagnostics advance, our recognition of rare hemiplegic syndromes will continue to evolve, demanding ongoing educational vigilance.

Key Clinical Pearls Summary

1. Capsular warning syndrome predicts impending stroke—treat aggressively
2. Cortical hand sign indicates cortical/subcortical lesions
3. Hypoglycemic hemiplegia reverses within 30 minutes of glucose
4. Snowball lesions in corpus callosum are pathognomonic for Susac syndrome
5. Todd's paresis should resolve within 48 hours—longer duration warrants reassessment
6. Hoover's sign has >95% specificity for functional hemiplegia
7. MELAS stroke-like episodes violate vascular territories
8. Alternating hemiplegia with cranial nerve involvement localizes to brainstem

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Note: This review synthesizes current clinical knowledge. For publication in a peer-reviewed journal, formal literature review with systematic citation of primary sources would be required. Key areas for reference inclusion would include: current stroke guidelines (AHA/ASA), diagnostic criteria for rare conditions (International Headache Society for hemiplegic migraine, diagnostic criteria for MELAS, Susac syndrome, etc.), and landmark studies on stroke mimics and functional neurological disorders.