What is the differential diagnosis for a patient presenting with a persisting headache?

Differential Diagnosis for Persisting Headache

The differential diagnosis for persisting headache must systematically distinguish between primary headache disorders (migraine, tension-type, cluster) and secondary causes requiring urgent intervention, with red flag features mandating immediate evaluation for life-threatening conditions such as subarachnoid hemorrhage, intracranial mass, meningitis, temporal arteritis, or spontaneous intracranial hypotension. 1

Primary Headache Disorders

Chronic Migraine

• Headache occurring ≥15 days per month for >3 months, with migraine features on ≥8 days per month 1, 2
• Characterized by unilateral throbbing pain, photophobia, phonophobia, nausea, and worsening with physical activity 3
• Affects approximately 12% of the population and is the most disabling primary headache disorder 3

Episodic Migraine

• Fewer than 15 headache days per month with typical migraine features 1
• May present with aura, sensitivity to smells or sounds, and family history of migraine 4

Tension-Type Headache

• Bilateral, pressing/tightening quality, mild to moderate intensity, without autonomic features 1
• Most common primary headache disorder, affecting 38% of the population 3
• Does not worsen with routine physical activity 3

Cluster Headache

• Severe unilateral pain lasting 15-180 minutes with ipsilateral autonomic symptoms (lacrimation, nasal congestion, ptosis), occurring 1-8 times daily in clusters 1
• Requires neurological referral for all cases 1

New Daily Persistent Headache

• Abrupt onset of daily headache that becomes continuous within 24 hours and persists 5
• May initially present with orthostatic quality suggesting spontaneous intracranial hypotension 5

Secondary Headache Disorders Requiring Urgent Evaluation

Subarachnoid Hemorrhage

• Thunderclap headache: sudden onset peaking within 1 second to 1 minute 5, 1
• Requires immediate non-contrast head CT; if negative and suspicion remains high, lumbar puncture for xanthochromia is mandatory 5
• Misdiagnosis carries grave consequences including death and severe disability 5

Spontaneous Intracranial Hypotension (SIH)

• Orthostatic headache: absent or mild (1-3/10) on waking, onset within 2 hours of becoming upright, >50% improvement within 2 hours of lying flat 5
• Associated symptoms include neck pain, tinnitus, hearing changes, photophobia, nausea, and dizziness 5
• Differential includes postural tachycardia syndrome (PoTS), orthostatic hypotension, cervicogenic headache, and migraine 5
• Requires brain MRI to confirm diagnosis and spine imaging to localize CSF leak source 5

Intracranial Mass or Tumor

• Progressively worsening headache over days to weeks 1
• Headache worsened by Valsalva maneuver (coughing, straining, bending) 1, 6
• Headache awakening patient from sleep 1, 6
• Nearly all children with brain tumors have abnormal neurologic findings or papilledema at diagnosis 5

Meningitis/Encephalitis

• Fever or signs of infection with headache 1
• Requires urgent evaluation with lumbar puncture after neuroimaging excludes mass effect 6

Temporal Arteritis (Giant Cell Arteritis)

• New headache after age 50 1, 6
• May present with jaw claudication, visual symptoms, and elevated inflammatory markers 1
• Requires urgent assessment to prevent permanent vision loss 1

Pseudotumor Cerebri (Idiopathic Intracranial Hypertension)

• Severe headaches with papilledema, typically in overweight females of childbearing age 5
• Can occur in obese males and prepubertal children 5
• MRI shows empty sella, dilated optic sheaths, flattening of posterior globes 5

Cervicogenic Headache

• Headache provoked by cervical movement rather than posture, with reduced cervical range of motion and myofascial tenderness 5
• Requires presence of cervical pathology for diagnosis 5

Critical Red Flags Requiring Immediate Evaluation

• Abnormal neurological examination findings or focal neurological deficits 1, 6
• Recent head or neck trauma 6
• Headache brought on by exertion or sexual activity 6
• Pregnancy with new headache 6
• Immunosuppression or active cancer 3, 4
• Impaired consciousness 4
• Papilledema with focal neurologic signs 4
• Meningeal irritation on physical examination 4

Diagnostic Approach

Immediate Imaging Indications

• Non-contrast head CT for thunderclap headache, acute trauma, or suspected acute intracranial hemorrhage 5, 4
• MRI brain (preferred modality) when any red flags present, unexplained abnormal neurologic examination, or atypical features 1, 6
• Lumbar puncture after negative CT if subarachnoid hemorrhage suspected, with spectrophotometric analysis for xanthochromia (sensitivity 100%, specificity 95.2%) 5

Specialist Referral Criteria

• All cluster headaches, chronic migraine, and headache with motor weakness require neurology referral 1
• Suspected SIH: refer to neurologist within 2-4 weeks if self-caring; within 48 hours if unable to self-care with help; emergency admission if unable to self-care without help 5

Medication Overuse Headache

• Triptans, ergots, or combination analgesics ≥10 days per month for ≥3 months 2
• Simple analgesics ≥15 days per month for ≥3 months 2
• Medication overuse can transform episodic headache into chronic daily headache 7
• Requires complete cessation of overused medications 7