What is the differential diagnosis and treatment approach for a patient presenting with unilateral headache?

Differential Diagnosis for Unilateral Headache

The differential diagnosis for unilateral headache primarily includes migraine without aura, cluster headache, and tension-type headache as primary disorders, while secondary causes such as giant cell arteritis (if age >50), carotid dissection, and intracranial pathology must be systematically excluded based on red flag features. 1, 2

Primary Headache Disorders

Migraine Without Aura

Suspect migraine without aura when unilateral headache is pulsating, moderate-to-severe in intensity, lasts 4-72 hours, and is accompanied by nausea/vomiting and/or photophobia and phonophobia. 1

Key diagnostic features include:

• At least 5 lifetime attacks meeting specific criteria 1
• Pain characteristics: At least 2 of the following: unilateral location, pulsating quality, moderate-to-severe intensity, aggravation by routine physical activity 1
• Associated symptoms: Nausea/vomiting and/or photophobia and phonophobia 1
• Behavioral pattern: Patients prefer to lie still in a dark, quiet room 2, 3
• Family history is often positive and strengthens the diagnosis, particularly if onset occurred at or around puberty 1

Cluster Headache

Consider cluster headache when severe unilateral orbital/periorbital pain lasts 15-180 minutes with ipsilateral autonomic symptoms and restlessness during attacks. 2, 4

Distinguishing features include:

• Severe unilateral pain in orbital, supraorbital, or temporal region lasting 15-180 minutes (untreated) 1, 2
• Attack frequency: 1-8 attacks daily during cluster periods 1, 2
• Ipsilateral autonomic symptoms: At least one of lacrimation, nasal congestion, rhinorrhea, forehead/facial sweating, miosis, ptosis, or eyelid edema 1, 2
• Restlessness or agitation: Patients pace during attacks, unlike migraine patients who lie still 2, 4
• Clustering pattern: Attacks occur in bouts during specific times of year with remission periods 4

Tension-Type Headache

Tension-type headache typically presents bilaterally but can be unilateral, with pressing/tightening quality, mild-to-moderate intensity, and absence of autonomic features. 1, 2

Diagnostic criteria:

• Pain characteristics: At least 2 of pressing/tightening quality, mild-to-moderate intensity, bilateral location, no aggravation with routine activity 1
• Absence of features: No nausea/vomiting (anorexia may occur), no photophobia AND phonophobia together (may have one or the other) 1

Secondary Headache Disorders Requiring Exclusion

Giant Cell Arteritis (Age >50)

In patients over 50 years old with new-onset unilateral temporal headache, giant cell arteritis must be urgently excluded. 3

Key features differentiating from primary headaches:

• Continuous dull aching pain rather than episodic attacks 4
• Jaw claudication and systemic symptoms (fever, malaise, weight loss) 4
• Temporal artery tenderness on examination 4

Carotid Artery Dissection

Carotid dissection presents with continuous unilateral pain and focal neurological deficits, incompatible with episodic attack patterns. 4

Medication-Overuse Headache

Suspect medication-overuse headache when headache occurs ≥15 days/month in a patient with pre-existing headache disorder and regular overuse of acute medications for >3 months. 1

Specific criteria:

• Non-opioid analgesics: ≥15 days/month for ≥3 months 1
• Triptans, ergots, opioids, or combination medications: ≥10 days/month for ≥3 months 1

Red Flags Requiring Neuroimaging

Neuroimaging (MRI brain preferred) is indicated when any of the following red flags are present: 2, 5

• Focal neurological deficits on examination 2
• Atypical headache pattern or new headache in patient >50 years 2, 5
• Progressive worsening or abrupt-onset ("thunderclap") headache 2, 5
• New neurological symptoms or abnormal neurological examination 2
• Recent head or neck trauma 5
• Headache brought on by exertion or Valsalva maneuver/cough 5
• Systemic symptoms/signs or secondary risk factors (cancer, HIV) 5

Diagnostic Approach Algorithm

The medical history is the mainstay of diagnosis; physical examination is confirmatory, and investigations are required only when red flags suggest secondary causes. 1, 6, 7

Step 1: Characterize the headache

• Duration: 15-180 minutes suggests cluster; 4-72 hours suggests migraine 1, 2
• Quality: Pulsating suggests migraine; severe stabbing suggests cluster 1, 2
• Location: Strictly unilateral orbital/periorbital suggests cluster; unilateral or bilateral suggests migraine 1, 2
• Intensity: Severe suggests cluster or migraine; mild-to-moderate suggests tension-type 1, 2

Step 2: Identify associated symptoms

• Autonomic symptoms (lacrimation, rhinorrhea, ptosis): Cluster headache 2
• Nausea/vomiting, photophobia, phonophobia: Migraine 1
• Neither: Tension-type headache 1

Step 3: Assess behavioral response

• Restlessness/pacing: Cluster headache 2, 4
• Lying still in dark room: Migraine 2, 3

Step 4: Screen for red flags

• If any red flag present: Obtain neuroimaging (MRI brain preferred) 2, 5
• If normal neurological examination and no red flags: Diagnosis based on clinical criteria alone 1, 6

Common Pitfalls to Avoid

Do not assume all unilateral headaches are migraines—cluster headache requires different acute and preventive treatment strategies. 2

Do not overlook medication-overuse headache in patients with frequent headache days, as this perpetuates the headache cycle and requires medication withdrawal. 1

Do not miss giant cell arteritis in patients over 50 with new-onset temporal headache, as delayed diagnosis risks permanent vision loss. 3, 4

Do not order neuroimaging routinely—it is indicated only when red flags are present or the neurological examination is abnormal. 1, 2, 6