What are the differential diagnoses and recommended evaluation for a new, persistent pressure‑like headache with photophobia and nausea?

Differential Diagnosis for New Persistent Pressure-Like Headache with Photophobia and Nausea

This presentation most likely represents migraine without aura, which is the most common cause of disabling headache with photophobia and nausea, but you must systematically exclude life-threatening secondary causes before settling on this diagnosis. 1

Primary Differential Diagnoses

Migraine Without Aura (Most Likely)

• Migraine without aura requires at least 5 lifetime attacks lasting 4-72 hours, with at least 2 pain characteristics (unilateral location, pulsating quality, moderate-to-severe intensity, or aggravation by routine activity) AND at least 1 associated feature (nausea/vomiting OR both photophobia and phonophobia). 2, 1
• The "pressure-like" quality does not exclude migraine—many patients describe migraine pain as pressure or tightness rather than classic throbbing, and clinical overlap between migraine and tension-type features is common. 3
• Photophobia and nausea are hallmark migraine features that strongly support this diagnosis over tension-type headache. 2
• The fact that this headache "does not go away" suggests either a prolonged single attack (status migrainosus if >72 hours) or the beginning of chronic daily headache. 2

Tension-Type Headache (Less Likely Given Photophobia/Nausea)

• Tension-type headache presents with bilateral, pressing/tightening quality, mild-to-moderate intensity, NOT aggravated by routine activity, and explicitly lacks both nausea/vomiting AND the combination of photophobia plus phonophobia. 2, 1
• The presence of both photophobia and nausea essentially rules out pure tension-type headache. 4
• However, many patients have overlapping features, and what appears to be tension-type headache may actually be migraine with atypical presentation. 3

Critical Secondary Causes to Exclude Immediately

Life-Threatening Conditions Requiring Emergency Evaluation

Meningitis

• Headache with neck stiffness and unexplained fever is meningitis until proven otherwise—this requires immediate lumbar puncture after neuroimaging. 1, 5
• Examine specifically for nuchal rigidity and fever; their absence significantly reduces (but does not eliminate) this risk. 1

Subarachnoid Hemorrhage

• Thunderclap headache ("worst headache of life") with sudden onset reaching maximum intensity within seconds to minutes. 1
• If presenting <6 hours from onset, non-contrast CT head has 95% sensitivity; after 6 hours, sensitivity drops rapidly (74% at day 3,50% at 1 week), requiring lumbar puncture if CT is negative. 1

Increased Intracranial Pressure (Brain Tumor, Abscess, Hydrocephalus)

• Progressive worsening over weeks, awakens patient from sleep, worsens with Valsalva/cough/exertion. 1
• Any progressive pattern or headache that awakens from sleep mandates MRI brain with and without contrast. 1

Giant Cell Arteritis (If Age >50)

• New-onset headache after age 50 with scalp tenderness, jaw claudication, visual symptoms. 1
• ESR and CRP are mandatory, but note that ESR can be normal in 10-36% of cases—clinical suspicion alone warrants urgent rheumatology referral and consideration of temporal artery biopsy. 1

Cerebral Venous Sinus Thrombosis

• Can present identically to migraine with unilateral throbbing headache, nausea, photophobia, but typically progressive and unresponsive to triptans. 6
• Risk factors include oral contraceptive use, pregnancy, thrombophilia, dehydration. 6
• MRI brain with MR venography is diagnostic; this must be considered in any "first migraine" that fails to respond to appropriate treatment or exceeds 72 hours. 6

Structured Evaluation Approach

Red Flags Requiring Urgent Neuroimaging

• Thunderclap onset, new headache after age 50, progressive worsening, atypical aura (>60 minutes or focal neurological symptoms), recent head/neck trauma, awakening from sleep, Valsalva/cough/exertion provocation, focal neurological signs, unexplained fever, neck stiffness, altered consciousness/memory/personality, witnessed loss of consciousness. 1
• Any single red flag mandates emergency admission and urgent imaging. 1

History Elements to Elicit

• Duration of this specific episode: If >72 hours, this is status migrainosus or suggests secondary cause. 2, 6
• Prior similar episodes: Migraine requires at least 5 lifetime attacks; if this is truly the first episode, maintain higher suspicion for secondary causes. 1
• Medication history: Overuse of analgesics (≥15 days/month for non-opioids or ≥10 days/month for triptans/combination analgesics) for >3 months causes medication-overuse headache. 1
• Oral contraceptive use or thrombophilia risk factors: Raises concern for cerebral venous thrombosis. 6
• Age and temporal pattern: New headache after age 50 requires giant cell arteritis workup. 1

Physical Examination Priorities

• Complete neurological examination: Any abnormality significantly increases probability of serious intracranial pathology and mandates imaging. 1
• Neck flexion and Kernig/Brudzinski signs: Meningeal irritation. 1
• Fundoscopy: Papilledema suggests increased intracranial pressure. 1
• Temporal artery palpation and scalp tenderness: Giant cell arteritis in patients >50. 1

Diagnostic Testing Algorithm

If ANY Red Flag Present:

• Emergency CT head (non-contrast if <6 hours from thunderclap onset; otherwise CT or MRI). 1
• Lumbar puncture after imaging if meningitis or subarachnoid hemorrhage suspected. 1, 5
• ESR/CRP if age >50 with new-onset headache. 1

If No Red Flags but Diagnosis Uncertain:

• MRI brain with and without contrast is preferred over CT for subacute presentations—higher resolution, no radiation, better for inflammatory/tumor/vascular pathology. 1
• Consider MR venography if risk factors for thrombosis or if headache exceeds 72 hours without response to migraine treatment. 6

If Clinical Picture Consistent with Migraine:

• Use ID-Migraine questionnaire (3 items: photophobia, nausea, disability from headache; sensitivity 81%, specificity 75%, positive predictive value 93%) to support diagnosis. 1
• Headache diary documenting frequency, duration, character, triggers, and medication use over 4 weeks increases diagnostic accuracy. 1
• Neuroimaging is NOT routinely indicated for migraine with normal neurological examination—the yield is only 0.2%, no higher than asymptomatic volunteers. 1

Common Pitfalls to Avoid

• Do NOT attribute fever to migraine—fever is never a feature of primary migraine and mandates investigation for meningitis, encephalitis, or systemic inflammatory disease. 5
• Do NOT dismiss "pressure-like" quality as excluding migraine—pain quality varies widely, and photophobia plus nausea strongly favor migraine over tension-type headache. 3
• Do NOT assume first-ever headache is benign migraine—maintain higher suspicion for secondary causes, especially cerebral venous thrombosis in young women on oral contraceptives. 6
• Do NOT order neuroimaging reflexively for every headache—if neurological examination is normal and clinical features meet migraine criteria without red flags, imaging adds no value and delays appropriate treatment. 1
• Do NOT overlook medication-overuse headache—if patient uses acute headache medications ≥10-15 days/month, this perpetuates chronic daily headache and requires withdrawal before other treatments will work. 1

Management Based on Diagnosis

If Migraine Without Aura Confirmed:

• NSAIDs or acetaminophen for mild-to-moderate attacks; triptans for moderate-to-severe or when NSAIDs fail. 1
• Antiemetics for nausea. 1
• If headache frequency ≥15 days/month for >3 months with ≥8 days meeting migraine criteria, this is chronic migraine requiring preventive therapy and neurology referral. 2, 1

If Red Flags Present:

• Emergency admission for any patient unable to self-care or with red flag features. 1
• Urgent neurology referral within 48 hours for suspected spontaneous intracranial hypotension or patient unable to self-care but has support. 1

If Diagnosis Uncertain:

• Routine neurology referral within 2-4 weeks for suspected primary headache disorder with uncertain diagnosis or failure of first-line treatments. 1