In a patient with a normal MRI who experiences a severe unilateral headache lasting 1–2 hours, what is the most likely diagnosis and what acute and preventive treatments are recommended?

Severe Unilateral Headache Lasting 1–2 Hours with Normal MRI

The most likely diagnosis is cluster headache, and you should initiate high-flow oxygen (100% at 12–15 L/min via non-rebreather mask for 15–20 minutes) for acute attacks plus verapamil 120–240 mg daily as first-line preventive therapy, titrating up to 480–960 mg daily as needed. 1

Why Cluster Headache Is the Primary Diagnosis

The clinical presentation strongly points to cluster headache rather than migraine based on three key features:

• Attack duration of 1–2 hours (60–120 minutes) falls within the 15–180 minute window that defines cluster headache, whereas migraine without aura requires 4–72 hours of pain duration 2, 1, 3

• Severe unilateral pain is the hallmark of cluster headache, described as orbital, supraorbital, or temporal in location 1, 3, 4

• Normal MRI excludes secondary causes such as structural lesions, vascular malformations, or inflammatory processes that can mimic primary headache disorders 1, 5

Critical Diagnostic Features to Confirm

You must document the presence of ipsilateral autonomic symptoms to solidify the cluster headache diagnosis:

• Lacrimation (tearing) 1, 3, 4
• Conjunctival injection (red eye) 1, 3, 4
• Nasal congestion or rhinorrhea 1, 3, 4
• Ptosis (drooping eyelid) 1, 3, 4
• Miosis (pupil constriction) 1, 3, 4
• Eyelid edema 1, 3
• Facial or forehead sweating 3, 4

Additionally, restlessness or agitation during attacks is pathognomonic for cluster headache and helps differentiate it from migraine, where patients typically prefer to lie still in a dark room 1, 3, 6

Why This Is NOT Migraine

Migraine is definitively excluded by the short attack duration:

• Migraine without aura requires at least 5 lifetime attacks lasting 4–72 hours each 2, 7
• Your patient's 1–2 hour attacks do not meet this minimum 4-hour threshold 2, 7
• Even in pediatric patients under 18 years, the minimum duration is 2 hours, still longer than this patient's attacks 7

The prominent autonomic symptoms and patient restlessness further support cluster headache over migraine 1, 3

Acute Treatment Protocol

First-Line Acute Therapy

High-flow oxygen is the preferred initial acute treatment:

• Administer 100% oxygen at 12–15 L/min via non-rebreather mask for 15–20 minutes 1, 6
• This provides relief within 15 minutes and has no contraindications 1
• Oxygen is effective in over 70% of cluster headache attacks 6

Second-Line Acute Therapy

Subcutaneous sumatriptan 6 mg if oxygen is unavailable or ineffective:

• Provides relief within 10–15 minutes 1
• Alternative formulations include intranasal triptans 4, 5, 6

Critical pitfall: Do not treat cluster headache with standard oral NSAIDs or acetaminophen as first-line therapy—these are ineffective for the severe, rapid-onset pain of cluster attacks 1

Preventive Treatment Strategy

First-Line Preventive Therapy

Verapamil is the mainstay of cluster headache prevention with the strongest evidence base:

• Start at 120–240 mg daily 1, 5
• Titrate up to 480–960 mg daily as needed for adequate control 1
• Monitor for cardiac conduction abnormalities with baseline and follow-up ECGs, as verapamil can cause PR interval prolongation and heart block 1, 5

Transitional (Bridging) Therapy

While waiting for verapamil to take effect (which can take 2–3 weeks), use short-term corticosteroids:

• Prednisone 60–100 mg daily for 5–7 days, then rapid taper 5, 6
• Alternative: Greater occipital nerve block with corticosteroid injection 5, 6

Alternative Preventive Options

If verapamil fails or is contraindicated:

• Lithium (especially for chronic cluster headache) 5, 6
• Topiramate 4, 5, 6
• Melatonin 4, 6
• Galcanezumab (CGRP monoclonal antibody approved for episodic cluster headache) 4, 8

Episodic vs. Chronic Pattern Assessment

Determine whether the patient has episodic or chronic cluster headache:

• Episodic cluster headache: Attacks occur in bouts (clusters) lasting weeks to months, separated by remission periods of ≥3 months 3, 4, 8
• Chronic cluster headache: Attacks occur for >1 year without remission, or with remission periods <3 months 3, 4

Document the circadian pattern (attacks often occur at the same time daily, frequently at night) and circannual pattern (seasonal recurrence) 3, 5, 8

Common Triggers to Counsel About

Advise the patient to avoid known cluster headache triggers during active bouts:

• Alcohol (most common trigger) 4, 6
• Nitroglycerin and nitrate-containing foods 4
• Strong odors 4
• Daytime napping 6

Management Pitfalls to Avoid

• Do not assume all unilateral headaches are migraines—cluster headache requires entirely different acute and preventive strategies 9
• Do not delay preventive therapy—early intervention reduces attack frequency and bout duration, improving outcomes and disability 8
• Do not miss medication-overuse headache if the patient begins using acute treatments too frequently (≥10 days/month for triptans) 1, 9
• Do not overlook giant cell arteritis in patients over 50 years with new-onset unilateral temporal headache, which requires urgent ESR/CRP and possible temporal artery biopsy 7, 9

When to Refer

Consider neurology or headache specialist referral if:

• Diagnosis remains uncertain after initial evaluation 7
• First-line preventive therapy (verapamil) fails to control attacks 5, 6
• Patient requires consideration of advanced therapies such as neurostimulation or deep brain stimulation 5, 6