What is the differential diagnosis, evaluation, and treatment for a 57-year-old female smoker with hypertension and a family history of stroke, presenting with a 2-week history of gradual, unilateral, throbbing headache, nausea, and photophobia, with elevated blood pressure (hypertension)?

Differential Diagnoses for 57-Year-Old Female with Unilateral Throbbing Headache

Four Key Differential Diagnoses

1. Migraine Without Aura (Most Likely)

This patient's presentation is most consistent with migraine without aura, given the unilateral, throbbing, gradual-onset headache lasting 2 weeks with nausea and photophobia 1, 2. The International Headache Society criteria require at least 5 lifetime attacks lasting 4-72 hours with at least 2 pain characteristics (unilateral, pulsating, moderate-to-severe intensity, aggravation by activity) and at least 1 associated symptom (nausea/vomiting or photophobia AND phonophobia) 1, 3. While this appears to be a prolonged single attack rather than multiple discrete episodes, the symptom constellation strongly suggests migraine 4.

Critical caveat: The 2-week duration is atypical for standard migraine attacks (which typically last 4-72 hours) and raises concern for status migrainosus or an alternative diagnosis 1.

2. Giant Cell Arteritis (GCA)

GCA must be urgently excluded in any patient over 50 years with new-onset unilateral temporal headache 1, 5. This patient's age (57), unilateral temporal location, and vascular risk factors (hypertension, smoking, family history of stroke) place her at risk 5. GCA can present atypically without classic features like jaw claudication or visual symptoms 5. The gradual onset over 2 weeks is consistent with GCA's subacute presentation 1.

3. Secondary Headache from Hypertensive Emergency

The elevated BP (162/94 mmHg) could represent either a hypertensive urgency or early hypertensive emergency 4. Hypertensive encephalopathy presents with headache, but typically includes altered consciousness, seizures, or cortical blindness 4. The absence of these features makes this less likely, though BP of 162/94 does not meet criteria for hypertensive emergency (≥180/110 mmHg with acute organ damage) 4.

4. Cerebrovascular Disease (Stroke/TIA)

Given her multiple vascular risk factors (age 57, hypertension, smoking, family history of stroke), cerebrovascular disease must be considered 4, 6. Headache occurs in 7-65% of strokes, more commonly with hemorrhagic than ischemic stroke 6. However, the gradual onset over 2 weeks, absence of focal neurological deficits, and presence of migraine features make acute stroke less likely 4, 6. The suddenness of onset, not severity, is the characteristic feature distinguishing stroke-related headache 6, 7.

---

Diagnostic Evaluation

Immediate Laboratory Testing

• ESR and CRP: Essential to evaluate for GCA in this patient over 50 years with new-onset headache 1. However, ESR can be normal in 10-36% of GCA cases, so normal values do not exclude the diagnosis 1.
• Complete metabolic panel: Assess renal function and electrolytes, particularly given hypertension 4.
• CBC: Evaluate for anemia or thrombocytosis that may accompany GCA 5.
• Fasting glucose and HbA1c: Screen for diabetes given stroke risk factors 4.
• Lipid panel: Assess cardiovascular risk 4.
• TSH and free T4: If symptoms suggest hypothyroidism 1.

Neuroimaging

MRI brain with and without contrast is the preferred initial imaging modality 1. MRI provides higher resolution without ionizing radiation and is superior for detecting:

• Acute/subacute ischemic stroke
• Intracranial masses
• Vascular malformations
• Signs of vasculitis 1

Non-contrast CT head should be obtained emergently if:

• Thunderclap headache presentation (subarachnoid hemorrhage) 1, 7
• Acute trauma 1
• Patient cannot undergo MRI 1

CT sensitivity for subarachnoid hemorrhage is 95% on day 0 but drops to 74% by day 3, making early imaging critical if this is suspected 1.

Vascular Imaging

• CT angiography or MR angiography of head and neck: Evaluate for:

  • Cervical artery dissection
  • Intracranial stenosis
  • Aneurysm
  • Vasculitis 4, 5

• Ultrasound of temporal and vertebral arteries: If GCA is suspected, look for the hypoechoic concentric "halo" sign around vessel walls 5. This should be performed urgently before starting corticosteroids, as treatment can normalize findings within days 5.

Additional Testing Based on Initial Results

• Lumbar puncture: If imaging is negative but subarachnoid hemorrhage or CNS infection remains suspected 4, 7.
• Temporal artery biopsy: Gold standard for GCA diagnosis if clinical suspicion remains high despite negative ultrasound 5. Do not delay corticosteroid treatment while awaiting biopsy 5.

---

Treatment Approach

Immediate Management (Emergency Department/Urgent Care)

Blood Pressure Management

The elevated BP (162/94 mmHg) should NOT be aggressively lowered in the acute setting 8. This level does not meet criteria for hypertensive emergency 4. In acute stroke, BP is typically left untreated up to 220/120 mmHg to maintain cerebral perfusion 8. Initiate or optimize oral antihypertensive therapy for outpatient management, targeting <140/90 mmHg 4.

Acute Headache Treatment

If migraine is the working diagnosis after excluding red flags:

1. First-line: NSAIDs (ibuprofen 400-800 mg or naproxen 500-1000 mg) or acetaminophen 1000 mg 1, 2

   • Limit use to ≤2 days per week or maximum 10 days per month to prevent medication-overuse headache 2

2. Second-line (if NSAIDs fail or pain is moderate-to-severe): Triptans (sumatriptan 50-100 mg PO, rizatriptan 10 mg) 2, 9

   • Critical contraindications: Ischemic heart disease, uncontrolled hypertension, cerebrovascular disease, peripheral vascular disease 9
   • This patient requires cardiovascular risk assessment before triptan use given age >50, hypertension, smoking, and family history of stroke 9
   • Consider administering first dose in supervised setting with post-dose ECG 9

3. Antiemetics: Metoclopramide or prochlorperazine for nausea 1

If Giant Cell Arteritis is Suspected

Immediately initiate high-dose corticosteroids (prednisone 40-60 mg/day or methylprednisolone 250-1000 mg IV) BEFORE temporal artery biopsy 5. Delaying treatment risks permanent vision loss 1, 5. Urgent rheumatology referral is mandatory 1.

Outpatient Management and Follow-Up

Lifestyle Modifications

• Smoking cessation: Strongly encourage with counseling, nicotine replacement, and formal programs 4. Smoking increases stroke risk 1.8- to 6-fold 4.
• Dietary modifications: 5 servings of fruits/vegetables daily may reduce stroke risk 4.
• Exercise: Moderate aerobic activity (brisk walking, cycling) 4.
• Alcohol limitation: ≤1 drink/day for women 4.

Preventive Therapy for Migraine

Consider preventive medications if:

• Attacks occur frequently enough to impair quality of life
• Acute treatments are ineffective or contraindicated
• Patient is at risk for medication-overuse headache 2

Options include:

• Beta-blockers (propranolol)
• Antiepileptics
• Antidepressants (amitriptyline is most widely researched) 2, 10
• CGRP monoclonal antibodies
• OnabotulinumtoxinA 2

These reduce migraine frequency by 1-3 days per month relative to placebo 2.

Cardiovascular Risk Reduction

• Statin therapy: Consider given age, hypertension, smoking, and family history of stroke 4. Statins reduce stroke risk by 24% in high-risk patients 4.
• Antiplatelet therapy: Low-dose aspirin may be considered once BP is controlled, as uncontrolled hypertension increases hemorrhagic stroke risk 4.
• ACE inhibitor or ARB: Preferred for hypertension management given stroke risk 4. The LIFE study showed 21% stroke reduction with ARBs in hypertensive patients 4.

Referral Indications

Emergency Admission (Immediate)

• Any red flag present: thunderclap headache, focal neurological deficits, altered consciousness, neck stiffness, fever 1, 3
• Patient unable to self-care without help 1
• Suspected subarachnoid hemorrhage, stroke, or hypertensive emergency 4

Urgent Referral (Within 48 Hours)

• Suspected spontaneous intracranial hypotension 1
• Suspected GCA with elevated inflammatory markers 1, 5

Routine Neurology Referral (2-4 Weeks)

• Suspected primary headache disorder with uncertain diagnosis 1
• First-line treatments fail 1, 2
• Atypical features requiring specialist evaluation 1

---

Critical Clinical Pearls

Do not assume this is "just migraine" without excluding secondary causes 1, 3. The combination of age >50, new-onset headache, vascular risk factors, and 2-week duration mandates thorough evaluation 1, 5.

The absence of "thunderclap" onset does not exclude serious pathology 6, 7. GCA, cervical artery dissection, and even some strokes can present with gradual onset 6, 5.

Hypertension and migraine commonly coexist—the presence of elevated BP does not exclude migraine 3. However, BP must be controlled before considering triptan therapy 9.

Medication-overuse headache should be considered if the patient has been using over-the-counter analgesics frequently (≥15 days/month for non-opioid analgesics or ≥10 days/month for other acute medications for >3 months) 1.