What is the differential diagnosis and recommended work‑up for a headache persisting for one week?

Differential Diagnosis for Week-Long Headache

Primary Headache Disorders

A headache persisting for one week most commonly represents either tension-type headache (which can last 30 minutes to 7 days), migraine (lasting 4-72 hours untreated, but may evolve into status migrainosus if exceeding 72 hours), or the early presentation of chronic daily headache. 1

Tension-Type Headache

• Bilateral, pressing/tightening quality with mild-to-moderate intensity 2, 1
• Not aggravated by routine physical activity and lacks nausea/vomiting 2, 1
• Does not present with both photophobia and phonophobia together 2, 1
• Duration is highly variable, ranging from 30 minutes up to 7 days 1

Migraine Without Aura

• Requires at least 5 lifetime attacks lasting 4-72 hours when untreated 1, 3
• Must have ≥2 pain characteristics: unilateral location, pulsating quality, moderate-to-severe intensity, or aggravation by routine activity 1, 3
• Must have ≥1 associated symptom: nausea/vomiting OR both photophobia and phonophobia 1, 3
• Photophobia together with nausea strongly supports migraine over tension-type headache 1

Status Migrainosus

• A single migraine attack that does not resolve and exceeds 72 hours 1
• Warrants evaluation for both prolonged migraine and possible secondary causes 1

Chronic Migraine (Evolving)

• Defined as ≥15 headache days per month for >3 months, with ≥8 days meeting migraine criteria 1, 4
• A week-long continuous headache may represent the transition from episodic to chronic migraine 4

Medication-Overuse Headache

• Occurs with ≥15 headache days per month and regular overuse of acute medications for >3 months 2, 1
• Non-opioid analgesics used ≥15 days/month or triptans/ergots/combination analgesics used ≥10 days/month 1, 4
• Often develops from excessive treatment of migraine attacks and can perpetuate chronic daily headache 2, 1

Secondary Headache Disorders (Red Flags)

Life-Threatening Causes Requiring Immediate Evaluation

Subarachnoid Hemorrhage

• Thunderclap headache ("worst headache of life") with abrupt onset 1, 5
• May present with altered taste sensation 1
• Non-contrast CT head is 95% sensitive on day 0 but drops to 74% by day 3 and 50% at 1 week 6
• If CT is normal and clinical suspicion remains, lumbar puncture is mandatory to detect xanthochromia 6, 7

Meningitis

• Headache with neck stiffness and unexplained fever 2, 1
• Requires immediate CSF analysis 7, 8

Giant Cell Arteritis

• New-onset headache in patients >50 years with scalp tenderness or jaw claudication 1, 5
• ESR can be normal in 10-36% of cases, so clinical suspicion should drive temporal artery biopsy 6
• Referral to rheumatology is indicated 1

Other Secondary Causes to Consider

Brain Tumor or Space-Occupying Lesion

• Progressive headache that awakens from sleep 1
• Worsens with Valsalva maneuver or cough 1, 7
• May present with focal neurological symptoms 1

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 neurology referral within 48 hours 1

Increased Intracranial Pressure

• Headache worsening with coughing, sneezing, or exercise 1, 7

Coccidioidal Meningitis (in endemic areas)

• Lumbar puncture with CSF analysis is recommended for patients with unusual, worsening, or persistent headache lasting beyond one week, especially with altered mental status, unexplained nausea/vomiting, or new focal neurologic deficits 2
• Headache from uncomplicated coccidioidal pneumonia typically dissipates in approximately one week; persistent or progressive headache requires lumbar puncture 2

Recommended Work-Up

History and Physical Examination

Critical Historical Elements 1, 3

• Frequency and timing: Document exact duration (one week continuous vs. intermittent)
• Pain characteristics: Location (unilateral vs. bilateral), quality (pulsating vs. pressing), severity
• Associated symptoms: Nausea, vomiting, photophobia, phonophobia, autonomic symptoms
• Aggravating factors: Routine activity, Valsalva, cough, exertion, postural changes
• Medication history: Document all acute and preventive medications to assess for overuse

Red Flags Requiring Immediate Investigation 2, 1, 7, 5

• Thunderclap or abrupt-onset headache
• New-onset headache after age 50
• Progressive worsening over time
• Headache awakening patient from sleep
• Headache brought on by Valsalva, cough, or exertion
• Focal neurological symptoms or signs on examination
• Unexplained fever, neck stiffness, or limited neck flexion
• Altered consciousness, memory, or personality
• Recent head or neck trauma
• Papilledema on fundoscopic examination

Neurological Examination 3, 6

• A normal neurological examination yields only 0.2% probability of serious intracranial pathology in migraine patients 1
• Any unexplained abnormal neurological finding significantly increases probability of clinically significant pathology and warrants neuroimaging 1

Diagnostic Tools

Headache Diary 1, 3

• Document frequency, duration, character, triggers, accompanying symptoms, and medication use
• Reduces recall bias and increases diagnostic accuracy 1
• If diary entries consistently fail to meet ICHD-3 criteria over multiple attacks, migraine is ruled out 1

Validated Screening Instruments

• ID-Migraine questionnaire (3-item): Sensitivity 0.81, specificity 0.75, positive predictive value 0.93 1
• Migraine Screen Questionnaire (5-item): Sensitivity 0.93, specificity 0.81, positive predictive value 0.83 1

Neuroimaging

When Neuroimaging Is NOT Indicated 2, 1, 3

• Normal neurological examination with typical primary headache features does not require neuroimaging 1, 3
• The yield of neuroimaging in patients with headache and normal neurological examination is extremely low: brain tumors 0.8%, AVMs 0.2%, aneurysms 0.1% 6

When Neuroimaging IS Indicated 2, 1, 7, 5

• Any red flag present on history or examination
• MRI brain with and without contrast is preferred for subacute presentations: higher resolution, no ionizing radiation 1, 7
• Non-contrast CT head if presenting <6 hours from acute severe headache onset (to rule out subarachnoid hemorrhage) 1, 5
• CT head for acute trauma or abrupt-onset headache 1, 8

Laboratory Testing

When Laboratory Tests Are Indicated 1

• ESR/CRP: If temporal arteritis suspected (patients >50 years with new-onset headache); note ESR can be normal in 10-36% of giant cell arteritis cases 6
• Morning TSH and free T4: If cold intolerance or lightheadedness present (hypothyroidism) 1
• Thyroid peroxidase (TPO) antibodies: If biochemical hypothyroidism confirmed 1

Lumbar Puncture

Indications for Lumbar Puncture 2, 7, 8

• Persistent or progressive headache beyond one week with altered mental status, unexplained nausea/vomiting, or new focal neurologic deficits 2
• Normal CT scan with high clinical suspicion for subarachnoid hemorrhage 6, 7, 8
• Suspected meningitis (fever, neck stiffness) 7, 8
• Suspected increased or decreased intracranial pressure 7, 8

Management Algorithm

If Red Flags Present

• Emergency admission for any red flag or patient unable to self-care without help 1
• Non-contrast CT head immediately if thunderclap headache or acute severe onset 1, 5
• Lumbar puncture if CT normal but subarachnoid hemorrhage suspected, or if meningitis suspected 6, 7, 8
• Urgent neurology referral (within 48 hours) for suspected spontaneous intracranial hypotension 1

If No Red Flags and Normal Examination

• Initiate headache diary to document pattern over 4 weeks 1, 3
• Apply validated screening tools (ID-Migraine or Migraine Screen Questionnaire) 1
• Assess for medication overuse: triptans/ergots ≥10 days/month or simple analgesics ≥15 days/month for ≥3 months 1, 4
• Routine neurology referral (2-4 weeks) if diagnosis uncertain or first-line treatments fail 1

Common Pitfalls to Avoid

• Do not assume all week-long headaches are tension-type: A migraine can evolve into status migrainosus (>72 hours) or represent early chronic migraine 1
• Do not overlook medication-overuse headache: Always document frequency of acute medication use, as overuse perpetuates chronic daily headache and prevents response to preventive therapy 2, 1, 4
• Do not delay lumbar puncture in endemic areas: In regions with coccidioidomycosis, persistent headache beyond one week warrants CSF analysis, as untreated meningitis is nearly always fatal 2
• Do not rely solely on ESR for giant cell arteritis: ESR can be normal in 10-36% of cases; clinical suspicion should drive temporal artery biopsy 6
• Do not order neuroimaging reflexively: In the absence of red flags and with a normal neurological examination, neuroimaging has extremely low yield and can lead to unnecessary procedures and patient anxiety 2, 1, 3, 6