What is the differential diagnosis for a patient presenting with a one-month headache followed by three days of left-sided weakness?

Differential Diagnosis: One-Month Headache Followed by Three Days of Left-Sided Weakness

The most critical diagnosis to exclude immediately is acute ischemic stroke in the right middle cerebral artery or internal carotid artery distribution, which requires emergent neuroimaging and consideration for thrombolytic therapy if presenting within the appropriate time window. 1

Immediate Life-Threatening Considerations

Acute Ischemic Stroke

• Left-sided weakness lasting three days strongly suggests ischemic stroke in the right internal carotid artery or middle cerebral artery distribution, as these symptoms persist longer than 24 hours by definition. 1
• The preceding one-month headache may represent warning TIAs or evolving vascular pathology. 1
• Associated symptoms to assess include left-sided sensory loss, left-sided neglect, abnormal visual-spatial ability, monocular blindness affecting the right eye, or right homonymous hemianopsia. 1
• Non-contrast head CT is the first-line imaging study in the acute setting, followed by CT angiography to assess both extracranial and intracranial circulation. 1, 2, 3

Cerebral Venous Thrombosis (CVT)

• CVT can present with prolonged headache (weeks to months) followed by acute focal neurological deficits, making this a critical consideration. 1
• The case series identified 36 cases where CVT was precipitated by spontaneous intracranial hypotension, presenting with non-orthostatic headaches followed by hemiparesis. 1
• CT venography or MR venography should be obtained if there is any suspicion for CVT, as standard CT may miss this diagnosis. 3
• Look for associated seizures, altered consciousness, or signs of increased intracranial pressure. 1

Intracranial Hemorrhage

• Subacute or chronic subdural hematoma can present with progressive headache followed by focal deficits. 1
• Intracerebral hemorrhage from various causes (hypertension, coagulopathy, vascular malformation, or underlying malignancy) must be excluded. 4
• Non-contrast CT will identify acute hemorrhage, but MRI with gradient echo sequences is more sensitive for chronic blood products. 1, 3

Age-Specific Critical Considerations

If Patient is Over 50 Years Old

• The threshold for neuroimaging should be lower in patients over 50 with new headache, even without classic red flags, as secondary headaches become substantially more common. 5
• Onset of apparent migraine after age 50 should arouse suspicion of an underlying cause rather than primary headache disorder. 5
• Giant cell arteritis (GCA) must be considered with temporal headache, elevated inflammatory markers (ESR, CRP), and temporal artery abnormalities, as it can cause ischemic stroke via vasospasm. 6
• Brain MRI with and without contrast is preferred when available for superior detection of masses, ischemia, and structural abnormalities. 5

Secondary Structural Causes

Space-Occupying Lesions

• Brain tumor (primary or metastatic) can present with progressive headache followed by focal deficits as mass effect increases. 5, 2
• Headache worsening when lying down or with Valsalva maneuver suggests increased intracranial pressure from mass lesion. 5, 2, 3
• Headache that awakens the patient from sleep or is progressively worsening are concerning features requiring neuroimaging. 5, 2
• Plasma cell myeloma has been reported as presenting with intracranial hemorrhage and focal deficits, though rare. 4

Cavernous Malformation with Hemorrhage

• Can present with focal neurological deficits that may be transient, persistent, or progressive. 1
• MRI with T2-weighted sequences is superior to CT for detection. 1
• Symptoms may fluctuate and include seizures. 1

Spontaneous Intracranial Hypotension

• Presents with non-orthostatic headaches that can precede CVT by weeks, as documented in multiple case series. 1
• MRI findings include smooth, diffuse dural and leptomeningeal enhancement. 1
• Can lead to life-threatening complications including CVT and intracerebral hemorrhage. 1

Vascular Causes Beyond Typical Stroke

Moyamoya Disease

• Progressive narrowing of major intracranial vessels can present with episodic headache and transient hemiparesis. 7
• More common in younger patients but should be considered with recurrent symptoms. 7
• Requires cerebral angiography for definitive diagnosis. 7

Vasculitis

• Giant cell arteritis in older patients (>50 years) with temporal headache, elevated ESR, and temporal artery abnormalities. 6
• Can cause ischemic stroke via vasospasm requiring steroid therapy. 6

Primary Headache Disorders with Mimicry

Hemiplegic Migraine

• Sporadic hemiplegic migraine can present with unilateral motor weakness lasting hours to days, clinically imitating stroke or TIA. 7, 8
• This is a diagnosis of exclusion requiring extensive workup to rule out secondary causes. 8
• However, given the three-day duration of weakness, stroke must be definitively excluded first before attributing symptoms to migraine. 9, 8

Essential Diagnostic Workup

Immediate Imaging

• Non-contrast head CT immediately to exclude hemorrhage and identify large territory infarction. 1, 2, 3, 9
• CT angiography from aortic arch to vertex to assess extracranial and intracranial vasculature. 1
• Consider CT venography if CVT is suspected. 3
• Brain MRI with and without contrast is preferred when available for superior detection of ischemia, masses, and vascular abnormalities. 5, 3

Laboratory Studies

• Complete blood count to evaluate for thrombocytopenia or polycythemia. 3, 6
• Comprehensive metabolic panel including renal function. 1, 3
• Coagulation studies (PT/INR, aPTT). 1, 3
• Inflammatory markers (ESR, CRP) if GCA suspected in older patients. 6
• D-dimer if CVT is being considered. 3

Additional Studies

• Electrocardiogram to evaluate for atrial fibrillation or other arrhythmias. 1
• Carotid ultrasound or CTA to assess for significant stenosis. 1
• Echocardiography if cardioembolic source suspected. 9

Critical Pitfalls to Avoid

• Do not assume primary headache disorder without thorough evaluation for secondary causes, especially in patients over 50. 5
• Do not dismiss persistent focal deficits as migraine without definitive exclusion of stroke, hemorrhage, or mass lesion. 9, 8
• Do not delay neuroimaging in any patient with new neurological deficits, regardless of headache characteristics. 5, 2, 3
• Do not miss CVT by relying solely on non-contrast CT; obtain venous imaging if clinical suspicion exists. 1, 3
• Be aware that delayed imaging may miss acute findings; timing of imaging relative to symptom onset affects sensitivity. 1