What is the differential diagnosis for headache?

Differential Diagnosis for Headache

Primary Headache Disorders

The differential diagnosis for headache is divided into primary headache disorders (migraine, tension-type, cluster) and secondary headache disorders (underlying pathology causing the headache), with the critical first step being identification of red flags that indicate life-threatening secondary causes requiring immediate evaluation. 1

Migraine Without Aura

• Recurrent moderate-to-severe unilateral, pulsating headache lasting 4-72 hours with nausea/vomiting, photophobia, and phonophobia that worsens with routine physical activity 1
• Requires at least 5 lifetime attacks meeting these criteria for diagnosis 1
• Typically begins at or around puberty 1

Migraine With Aura

• Same features as migraine without aura plus recurrent short-lasting visual or hemisensory disturbances (lasting <60 minutes) preceding or accompanying headache 1
• Aura symptoms spread gradually over ≥5 minutes with at least one unilateral symptom 1

Chronic Migraine

• ≥15 headache days per month for >3 months, with ≥8 days meeting migraine criteria 2, 1
• Represents a distinct entity with substantially greater disability and economic burden than episodic migraine 2
• Only 20% of patients fulfilling criteria are properly diagnosed 2

Tension-Type Headache

• Bilateral, mild-to-moderate pressing or tightening quality that lacks migraine features and is not aggravated by routine physical activity 2, 1
• Most prevalent primary headache disorder, affecting 38% of the population 3

Cluster Headache

• Strictly unilateral severe headache lasting 15-180 minutes with ipsilateral autonomic symptoms including lacrimation, conjunctival injection, nasal congestion, ptosis, or miosis 2, 1
• Affects approximately 0.1% of the general population 2
• Highly characteristic presentation with frequently recurrent but short-lasting attacks 2

Medication-Overuse Headache (MOH)

• ≥15 headache days per month with regular overuse of acute medications (non-opioid analgesics ≥15 days/month or other acute medications ≥10 days/month) for >3 months 1
• Important differential diagnosis for chronic migraine, as the two disorders are often conflated 2

Secondary Headache Disorders (Life-Threatening Causes)

Subarachnoid Hemorrhage

• Thunderclap headache ("worst headache of life") reaching maximum intensity within seconds to minutes 4
• May have altered taste sensation 5
• Non-contrast CT head is indicated if presenting <6 hours from onset (sensitivity 95% on day 0, declining to 74% on day 3 and 50% at 1 week) 1
• If CT negative but suspicion remains, lumbar puncture is required 4

Meningitis

• Headache with neck stiffness and unexplained fever 1, 4
• Requires immediate evaluation with neuroimaging and lumbar puncture 4

Brain Tumor or Space-Occupying Lesion

• Progressive headache that awakens patient from sleep and worsens with Valsalva maneuvers, coughing, or exercise 1, 5
• May present with focal neurological symptoms and altered consciousness, memory, or personality 1, 4

Giant Cell Arteritis (Temporal Arteritis)

• New-onset headache in patients >50 years with scalp tenderness and jaw claudication 1, 5
• ESR/CRP should be obtained, though ESR can be normal in 10-36% of cases 1
• Delay in treatment can lead to permanent vision loss 5

Stroke or Transient Ischemic Attack

• Atypical aura with focal neurological symptoms 1, 5
• Requires urgent neuroimaging 4

Increased Intracranial Pressure

• Headache worsening with coughing, sneezing, or exercise 1, 5
• May awaken patient from sleep 1, 4

Spontaneous Intracranial Hypotension

• Orthostatic headache (absent or mild on waking, onset within 2 hours of upright posture, >50% improvement within 2 hours of lying flat) 1
• Requires urgent referral to neurology within 48 hours 1

Critical Red Flags Requiring Immediate Evaluation

History Red Flags

• Thunderclap headache or "worst headache of life" 4
• New headache onset after age 50 1, 4
• Progressive headache worsening over time 4
• Headache awakening patient from sleep 1, 4
• Headache aggravated by Valsalva, coughing, sneezing, or exercise 4
• Recent head or neck trauma 4
• Atypical aura 1, 4
• Weight loss with change in memory or personality 4

Physical Examination Red Flags

• Focal neurological symptoms or signs 4
• Neck stiffness or limited neck flexion 4
• Unexplained fever 4
• Impaired memory, altered consciousness, or personality changes 4
• Witnessed loss of consciousness 4

Ottawa SAH Rule (for alert patients >15 years with new severe nontraumatic headache reaching maximum intensity within 1 hour)

Additional investigation required if any of:

• Age ≥40 years 4
• Neck pain or stiffness 4
• Witnessed loss of consciousness 4
• Onset during exertion 4
• Thunderclap headache 4
• Limited neck flexion on examination 4

Diagnostic Approach

Initial Assessment

• Ask patients: "Do you feel like you have a headache of some type on 15 or more days per month?" to identify chronic headache patterns 2
• Use headache diaries to document frequency, duration, character, triggers, accompanying symptoms, and medication use 1
• ID-Migraine questionnaire (3-item) has sensitivity 0.81, specificity 0.75, positive predictive value 0.93 2, 1
• Migraine Screen Questionnaire (5-item) has sensitivity 0.93, specificity 0.81, positive predictive value 0.83 2, 1

Neuroimaging Indications

• The only role for neuroimaging is to confirm or exclude secondary headache causes suspected based on red flags 2
• MRI brain with and without contrast is preferred for subacute presentations or suspected tumor/inflammatory process (higher resolution, no ionizing radiation) 1, 5
• Non-contrast CT head if presenting <6 hours from acute severe headache onset (subarachnoid hemorrhage) 1
• CT head for acute trauma or abrupt-onset headache 1

Additional Testing

• Dental panoramic radiographs if dental pathology or sinusitis suspected 1, 5
• ESR/CRP if temporal arteritis suspected in patients >50 years 1, 5
• Morning TSH and free T4 if cold intolerance or lightheadedness present 1
• Lumbar puncture if CT negative but subarachnoid hemorrhage still suspected 5

Common Pitfalls to Avoid

• Do not order neuroimaging routinely without red flags, as it can reveal clinically insignificant abnormalities (white matter lesions, arachnoid cysts, meningiomas) that alarm patients and lead to unnecessary interventions 2
• Do not rely solely on neuroimaging without considering the complete clinical picture 4, 5
• Do not miss temporal arteritis in elderly patients, as treatment delay causes permanent vision loss 5
• Patients often report only "severe headache days" and fail to mention milder headaches, leading to underdiagnosis of chronic migraine 2
• Do not dismiss metallic taste as benign without thorough evaluation, as it is not typical of primary headaches and may indicate subarachnoid hemorrhage or space-occupying lesion 5

Referral Guidelines

• Emergency admission: Any red flag present or patient unable to self-care without help 1
• Urgent referral to neurology (within 48 hours): Suspected spontaneous intracranial hypotension, patient unable to self-care but has help 1
• Routine referral to neurology (2-4 weeks): Suspected primary headache disorder, diagnosis uncertain, first-line treatments fail 1
• Referral to rheumatology: Suspected giant cell arteritis 1