Headache is the most common neurologic symptom, affecting people across all ages. While ~90% of headaches are benign (migraine, tension-type, cluster), they may also indicate life-threatening neurologic or systemic disease, such as intracranial hemorrhage, infection, or acute glaucoma. A systematic clinical approach is essential to differentiate primary headaches from secondary causes that require urgent intervention.

Pathophysiology — mechanisms you must keep in mind

• Migraine (neurovascular): Cortical spreading depression (CSD) → transient cortical neuronal/glial depolarization → trigeminovascular activation → release of CGRP and other neuropeptides → meningeal vasodilation, sterile inflammation, central sensitization → pain, photophobia, phonophobia, nausea.

• Tension-type headache: Pericranial myofascial nociception + central sensitization (chronic). Muscle contraction is not the only mechanism; psychophysiologic factors and reduced pain inhibition contribute.

• Trigeminal autonomic cephalalgias (cluster): Hypothalamic dysfunction with activation of trigeminal-autonomic reflex (ipsilateral cranial autonomic features).

• Medication-overuse headache (MOH): Repeated analgesic/triptan exposure induces changes in pain modulation (rebound/central sensitization).

• Raised intracranial pressure / mass effect: Increased intracranial volume → stretch/ischemia of pain-sensitive intracranial structures → positional/worse-on-Valsalva headaches, morning prominence, papilledema.

• Subarachnoid hemorrhage / intracranial bleeding: Acute meningeal irritation from blood → severe “thunderclap” pain, meningeal signs, rapid neurologic decline.

• Meningitis / encephalitis: Infection → meningeal/brain parenchymal inflammation → severe diffuse headache ± fever, stiff neck, altered mental status.

• Lumbar puncture headache: Low CSF pressure → orthostatic headache due to traction on pain-sensitive structures.

Headache Types

Diagnostic features, exam, acute & preventive treatment

Secondary causes

Organized table (condition → distinguishing clinical features → initial investigations/urgency)

“Red flags” you must memorize (SNOOP⁴ mnemonic, high-yield)

• S: Systemic symptoms (fever, weight loss), Secondary risk (HIV, cancer)

• N: Neurologic signs (focal deficits, seizures, confusion) or new neuro exam abnormality

• O: Onset sudden, abrupt, “thunderclap”

• O: Older age at onset (>50), or new onset in elderly

• P: Previous headache history atypical (progressive change) or Papilledema

• Additional: positional headaches, immunosuppression, anticoagulation, trauma, pregnancy/postpartum

If any red flag → lower threshold for neuroimaging and urgent workup.

Focused diagnostic approach — quick algorithm (practical)

1. Triage: Are there red flags? If yes → urgent CT head (noncontrast) or MRI + labs, consult neurosurgery/ID/ophthalmology as appropriate.

2. If no red flags and features of primary headache: treat symptomatically, document triggers, assess for prophylaxis need (>4 migraine attacks/month or disability).

3. If new focal signs or atypical pattern but not emergent: MRI brain ± MRV, labs (CBC, ESR/CRP), consider lumbar puncture if infection or SAH suspected and CT negative.

4. If frequent analgesic use: evaluate for MOH; plan withdrawal and preventive therapy.

Diagnostic tests — when and what (table)

Immediate / emergency interventions — by cause (table)

Treatment overview (practical prescriptions and cautions)

Acute migraine

• NSAIDs (naproxen 500–1000 mg), aspirin, acetaminophen.

• Triptans (sumatriptan 50–100 mg PO, 6 mg SC or intranasal) — contraindicated with ischemic heart disease, uncontrolled hypertension, pregnancy (some).

• Anti-emetics (metoclopramide, prochlorperazine) for nausea & to augment absorption.

• Ditans (lasmiditan) and gepants (rimegepant, ubrogepant) are newer choices (review contraindications).

Chronic / frequent migraine prevention

• Beta-blockers (propranolol, metoprolol) — contraindicated in asthma/heart block.

• Anti-epileptics (topiramate, valproate) — monitor weight, cognitive effects, teratogenicity.

• TCAs (amitriptyline) — useful also for tension-type.

• Botox injections for chronic migraine (≥15 headache days/month) in specialist setting.

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) — consider in refractory cases.

Tension-type

• Acute: NSAIDs/acetaminophen; nonpharm: physio, posture correction, relaxation, CBT.

• Chronic prophylaxis: low-dose amitriptyline.

Cluster

• Acute: 100% oxygen (first line) or SC sumatriptan; prevent with verapamil (monitor ECG) or lithium.

MOH

• Stop overused medication (withdrawal), symptomatic bridge, start preventive therapy if indicated.

Intracranial infection / SAH / hemorrhage

• Manage per neurosurgery/infectious disease protocols — antibiotics/antivirals, surgical drainage, blood pressure control.

Pediatric & Geriatric specific guidance

• Pediatrics: High index of suspicion for tumor if new, persistent headache in child >3 yrs. Migraines common but may present atypically. Use age-appropriate dosing and consult pediatrics/neurology early.

• Geriatrics: New headache >50 yrs → urgent evaluate for temporal arteritis, mass lesion, or secondary cause. Be cautious with triptans and other agents because of cardiovascular risk and polypharmacy.

Physical exam pearls (quick)

• Papilledema = raised ICP until proven otherwise.

• Horner’s syndrome + unilateral periorbital pain = consider cluster / carotid dissection.

• Jaw claudication / scalp tenderness = temporal arteritis.

• Fixed mid-dilated pupil + cloudy cornea = acute angle-closure glaucoma.

• Fever + nuchal rigidity = meningitis/SAH until proven otherwise.

• Thunderclap onset = SAH until proven otherwise.

Documentation & patient counseling (what to tell patients)

• Record onset, quality, duration, frequency, triggers, red flags, medication use (frequency & names).

• Educate patients on trigger management (sleep, hydration, caffeine moderation), safe analgesic use to avoid MOH, and indications for urgent return (sudden severe headache, focal deficits, fever with neck stiffness, visual loss).

• For chronic headaches, set realistic goals: reduce frequency, improve function, avoid overuse, address comorbid anxiety/depression.

References

1. ICHD-3: International Classification of Headache Disorders (ICHD-3), 2018.

2. AHS (American Headache Society) and EHF/NICE guidelines on migraine and chronic headache management.

3. Evers S, Jensen R. EFNS guideline — medication overuse headache (2011).

4. UpToDate reviews on acute headache management (consult current local guidelines).

5. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (ICHD-3). Cephalalgia. 2018;38(1):1-211. ICHD-3

6. Evers S., Jensen R. Treatment of Medication Overuse Headache — Guideline of the EFNS Headache Panel. European Journal of Neurology. 2011;18(9):1115-1121.

7. Diener HC, Antonaci F, Braschinsky M, Evers S, Jensen RH, Lainez M, et al. European Academy of Neurology Guideline on the Management of Medication-Overuse Headache. Eur J Neurol. 2020;27(7):1102-1116.

8. Silberstein SD, Blumenfeld AM, Cady RK, Turner IM, Lipton RB, Diener HC, et al. OnabotulinumtoxinA for treatment of chronic migraine: PREEMPT 24-week pooled subgroup analysis. Journal of the Neurological Sciences. 2013;331(1-2):48-56.

9. Olesen J., Steiner TJ., Walter S., et al. The Lancet Neurology Commission on headache: current understanding, future directions. The Lancet Neurology. 2018;17(1):25-32. (Also from ICHD-3 introduction)