What is the diagnosis of a unilateral headache in an adult with no significant past medical history?

Unilateral Headache Diagnosis

A unilateral headache in an adult with no significant past medical history is most commonly migraine without aura, which characteristically presents with unilateral location as one of its defining features. 1

Primary Diagnostic Considerations

Migraine Without Aura

Migraine without aura is the most likely diagnosis when a unilateral headache meets specific criteria: at least 5 attacks lasting 4-72 hours, with at least 2 of the following characteristics: unilateral location, pulsating quality, moderate-to-severe intensity, or aggravation by routine physical activity, plus at least one associated symptom (nausea/vomiting or both photophobia and phonophobia). 1

• The unilateral location alone does not define migraine—it must be accompanied by other qualifying features to meet diagnostic criteria. 1
• Approximately 60% of migraine attacks present with unilateral pain, though the pain can be bilateral in some cases. 1
• A positive family history of migraine strongly supports the diagnosis, as migraine has a significant genetic component. 1

Cluster Headache

Cluster headache presents with severe unilateral periorbital/orbital pain lasting 15-180 minutes, accompanied by ipsilateral autonomic symptoms such as lacrimation, rhinorrhea, ptosis, or miosis. 2, 3

• The key distinguishing features are the shorter attack duration (15-180 minutes vs. 4-72 hours for migraine), excruciating severity, and prominent autonomic symptoms. 2, 3
• Patients with cluster headache are typically restless and agitated during attacks, whereas migraine patients prefer to lie still in a dark, quiet room. 2, 3
• Cluster headache predominantly affects males and has a prevalence of only 0.5-1.0 per 1,000, making it much rarer than migraine. 3
• Attacks often occur at the same time each day, particularly at night, and may be triggered by alcohol during active periods. 3

Other Unilateral Headache Disorders

Primary stabbing headache, paroxysmal hemicrania, and SUNCT syndrome are less common causes of unilateral headache that require specific diagnostic criteria. 4

• Primary stabbing headache was the most common diagnosis among uncommon unilateral headaches in one series, presenting with brief jabs of pain. 4
• Paroxysmal hemicrania responds dramatically to indomethacin (the "indo-test"), which can be both diagnostic and therapeutic. 4
• Almost half of patients with unilateral headaches beyond migraine and cluster headache cannot be classified according to standard criteria, highlighting diagnostic challenges. 4

Critical Diagnostic Approach

Essential Clinical Features to Assess

Systematically document attack frequency, duration, pain characteristics, associated symptoms, and temporal patterns using ICHD-3 criteria as a checklist. 1, 5

• Attack duration: 4-72 hours suggests migraine; 15-180 minutes suggests cluster headache; seconds to minutes suggests primary stabbing headache or paroxysmal hemicrania. 1, 2, 3, 4
• Pain quality: Pulsating favors migraine; severe, boring, or burning favors cluster headache. 1, 3
• Associated symptoms: Nausea, photophobia, and phonophobia suggest migraine; lacrimation, rhinorrhea, and restlessness suggest cluster headache. 1, 2
• Behavioral response: Lying still in a dark room suggests migraine; pacing or rocking suggests cluster headache. 2
• Triggers: Light, stress, or hormonal changes suggest migraine; alcohol during active periods suggests cluster headache. 1, 3

When to Obtain Neuroimaging

Neuroimaging is mandatory when red flags are present or when the presentation is atypical, as secondary causes can mimic primary unilateral headaches. 2, 4, 6

• Red flags requiring immediate imaging: Sudden onset ("thunderclap"), first headache after age 50, progressive worsening, persistent neurological deficits, fever, or loss of consciousness. 2, 5
• In one series of uncommon unilateral headaches, imaging revealed causally related lesions in 8 of 63 patients (13%), including frontal sinusitis, pontine venous angioma, and vascular compression of the trigeminal nerve. 4, 6
• Normal neuroimaging and absence of red flags are crucial in confirming a primary headache disorder. 2

Common Diagnostic Pitfalls

Failing to systematically apply diagnostic criteria leads to misdiagnosis, as no objective biomarkers exist for primary headache disorders. 5

• Not counting attacks systematically—migraine without aura requires at least 5 qualifying attacks before definitive diagnosis. 5, 7
• Missing the gradual onset of aura symptoms (spreading over ≥5 minutes), which distinguishes migraine from vascular events like TIA. 1, 5
• Overlooking that unilateral location can occur in tension-type headache, though it is less common and typically presents with bilateral pressing/tightening pain. 2
• Assuming all side-locked headaches are secondary—primary headaches can be persistently unilateral, though this is more common in short-lasting headaches. 8
• Not recognizing that chronic cluster headache can shift sides in 51% of cases, which should be considered before proposing surgical interventions. 8