Headache Disorders

Mechanistic groupings

• Trigeminovascular/neuropeptide-driven (migraine): genetically lowered cortical threshold permits cortical spreading depression and CGRP release; attacks are triggered, not caused, by stress, menses, sleep loss, fasting, alcohol, nitrates, and caffeine withdrawal.
• Hypothalamic/trigeminal-autonomic (cluster and other TACs): circadian pacemaker dysfunction; alcohol and nitroglycerin reliably provoke attacks during a bout but not in remission.
• Myofascial with central sensitization (tension-type): pericranial tenderness plus impaired descending inhibition; poor posture, bruxism, and psychological stress feed it.
• Vascular secondary causes: aneurysmal SAH, cervical artery dissection, reversible cerebral vasoconstriction syndrome, cerebral venous sinus thrombosis, hypertensive emergency/PRES.
• Infectious/inflammatory: bacterial and viral meningoencephalitis, abscess, and giant cell arteritis.
• CSF pressure disorders: raised pressure from mass, hydrocephalus, or idiopathic intracranial hypertension; low pressure from post-dural-puncture or spontaneous CSF leak (orthostatic headache).
• Substance-related: medication overuse headache, nitrates, PDE-5 inhibitors, and caffeine/opioid withdrawal.
• Referred/structural: acute sinusitis, angle-closure glaucoma, TMJ disorder, dental disease, cervicogenic.

Non-modifiable risk factors

• Female sex: migraine is roughly three times more common in women after puberty, driven by estrogen withdrawal (perimenstrual attacks). Cluster headache shows the opposite, male-predominant pattern.
• Age: migraine peaks in early-to-middle adult life; new headache after age 50 shifts probability toward secondary causes and mandates evaluation.
• Family history/genetics: strong polygenic inheritance; familial hemiplegic migraine is autosomal dominant (CACNA1A, ATP1A2, SCN1A).

Modifiable risk factors examiners plant

• Medication overuse: the single most important driver of chronification — ICHD-3 sets the threshold at ≥10 days/month for triptans, ergots, opioids, or combination analgesics and ≥15 days/month for simple analgesics.
• Obesity, snoring/obstructive sleep apnea, depression and anxiety, and caffeine excess: each independently associated with transformation of episodic into chronic migraine; obesity is also the key reversible risk factor for idiopathic intracranial hypertension.
• Tobacco use: heavily overrepresented in cluster headache.
• Combined hormonal contraception in migraine with aura: CDC US Medical Eligibility Criteria classifies this as category 4 (unacceptable risk) because of stroke risk.

Primary Headaches

• Migraine: Involves activation of the trigeminal vascular system with release of neuropeptides (CGRP, substance P) from trigeminal nerve terminals; leads to neurogenic inflammation of meningeal blood vessels; cortical spreading depression (CSD) may precede pain; involves serotonergic, dopaminergic, and glutamatergic dysfunction; female predominance related to hormonal influences on central sensitization
• Tension-type headache: Results from sustained muscle contraction of scalp and neck muscles, though central sensitization and increased pain processing play key roles; peripheral muscle tension may be secondary to central mechanisms rather than primary pathology
• Cluster headache: Involves hypothalamic dysfunction and activation of the ipsilateral trigeminal-autonomic reflex; circadian and circannual periodicity suggest involvement of the suprachiasmatic nucleus; vasodilation of intracranial vessels in the cavernous sinus region

Secondary Headaches

• Subarachnoid hemorrhage: Rupture of cerebral aneurysms causes rapid increase in intracranial pressure (ICP) and meningeal irritation from blood
• Meningitis/Encephalitis: Inflammatory response and increased ICP from infection or immune activation
• Temporal arteritis: Granulomatous inflammation of medium and large vessels causes reduced cerebral perfusion and ischemia

Migraine

• Unilateral throbbing or pulsating pain, typically lasting 4-72 hours
• Associated with photophobia, phonophobia, and nausea/vomiting
• Aura precedes headache in 25-30% of migraineurs (visual scotomas, fortification spectra, paresthesias lasting 20-60 minutes)
• Triggers include stress, hormonal changes (menses), foods (aged cheese, chocolate, nitrates), sleep disruption, caffeine withdrawal
• Prodromal symptoms (mood changes, fatigue, food cravings) may occur hours before headache

Tension-Type Headache

• Bilateral, pressing or tightening quality, non-pulsating
• Mild-to-moderate intensity (does not prohibit activity)
• Lasts 30 minutes to 7 days
• No nausea/vomiting (distinguishes from migraine), no photophobia or phonophobia
• Associated with muscle tenderness on palpation of scalp/neck

Cluster Headache

• Severe unilateral orbital or periorbital pain with characteristic periodicity (clusters of 1-8 headaches daily for weeks to months separated by remission periods of months to years)
• Ipsilateral autonomic features (conjunctival injection, lacrimation, nasal congestion, facial flushing, ptosis/miosis suggesting Horner syndrome)
• Much more common in males (3-4:1 ratio)
• Occurs predominantly at night; patient often agitated (unlike migraine patients who seek rest)

Secondary Headaches - Red Flags

• Thunderclap headache (worst pain of life) → SAH until proven otherwise
• Fever + stiff neck + headache → meningitis
• Sudden onset with focal neurological deficits → stroke
• Age >50 with new-onset headache, scalp tenderness, jaw claudication → temporal arteritis
• Papilledema, progressive worsening, change in pattern → increased ICP (mass, hydrocephalus)

Primary Headaches (Clinical Diagnosis)

• Diagnosis based on ICHD-3 (International Classification of Headache Disorders 3rd edition) criteria; no specific laboratory or imaging findings needed
• Migraine criteria: ≥5 attacks, 4-72 hours duration, at least 2 pain characteristics (unilateral, pulsating, moderate-severe, aggravated by activity) PLUS 1 associated symptom (nausea, photophobia/phonophobia); aura (if present) lasts 20-60 minutes with gradual onset and offset
• Tension-type criteria: ≥10 episodes, 30 minutes to 7 days duration, bilateral, pressing quality, mild-moderate intensity, not aggravated by activity, no nausea
• Cluster criteria: Severe unilateral orbital pain, 15-180 minutes duration, ≥4 attacks in 2 weeks to 3 months, ipsilateral autonomic features

Secondary Headaches

• Neuroimaging (CT or MRI) indicated for: sudden-onset severe headache, progressive headache, headache with fever/stiff neck, focal neurological signs, papilledema, change in headache pattern, age >50 with new-onset headache
• Lumbar puncture (LP) if SAH suspected but CT negative (sensitivity ~98% within 12 hours, decreases with time); look for xanthochromia (yellow discoloration from bilirubin, more specific than RBCs)
• Temporal artery biopsy gold standard for temporal arteritis; send promptly if clinical suspicion high (elevated ESR/CRP, age >50, temporal headache, visual symptoms, jaw claudication)
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for temporal arteritis screening
• Fundoscopic exam for papilledema suggesting increased ICP

Migraine - Acute Treatment

• First-line abortive: Triptans (sumatriptan 50-100 mg PO, or nasal/SC formulations for faster onset); mechanism = 5-HT1B/1D receptor agonists causing cranial vasoconstriction and trigeminal inhibition; most effective when given early in attack
• Alternative abortive: NSAIDs (ibuprofen 400-800 mg, naproxen 500-750 mg) or combination analgesics (acetaminophen + aspirin + caffeine); often used for mild-moderate migraines
• Antiemetics (metoclopramide 10 mg IV/IM, prochlorperazine 10 mg IV) enhance medication absorption and treat nausea
• Refractory migraine: IV valproate, IV dihydroergotamine, IV magnesium sulfate in acute care settings

Migraine - Preventive Treatment (indicated if ≥4 migraines/month or significant disability)

• First-line: Beta-blockers (propranolol 120-240 mg/day, metoprolol), calcium channel blockers (verapamil), topiramate (50-100 mg/day), or tricyclic antidepressants (amitriptyline 10-100 mg/day)
• Second-line: Monoclonal antibodies against CGRP or CGRP receptor (erenumab, fremanezumab, galcanezumab) - newer agents showing efficacy; require IV/SC administration monthly; not yet first-line due to cost but increasingly used
• Other options: Valproic acid, venlafaxine; botulinum toxin for chronic migraine (≥15 headaches/month)

Tension-Type Headache

• Acute: NSAIDs or acetaminophen; avoid frequent use (>2-3 days/week) to prevent medication overuse headache
• Preventive: Tricyclic antidepressants (amitriptyline), muscle relaxants; physical therapy and stress reduction

Cluster Headache

• Acute: High-flow oxygen (100% O2 for 15-20 minutes at cluster onset); sumatriptan SC or intranasal; **dihydroergotamine IV/

Complications of the disease

• Medication overuse headache: frequent abortive use downregulates descending antinociception; signaled by a daily or near-daily headache that improves briefly with each dose and returns. Treatment is withdrawal of the offending agent plus bridging and initiation of prevention.
• Chronic migraine: ≥15 headache days/month for >3 months; predicted by obesity, mood disorder, and overuse.
• Status migrainosus: debilitating attack lasting >72 hours; risks dehydration and often requires parenteral therapy (antiemetic-antidopaminergic, IV fluids, IV valproate or dihydroergotamine).
• Migrainous infarction: aura symptoms persisting beyond an hour with a matching infarct, usually posterior circulation. Migraine with aura carries an increased ischemic stroke risk that is multiplied by smoking and combined hormonal contraception — an emergency when acute deficit is present.
• Vision loss in secondary causes: untreated giant cell arteritis causes arteritic anterior ischemic optic neuropathy from posterior ciliary artery occlusion, and untreated idiopathic intracranial hypertension causes progressive optic atrophy. Both are sight-threatening emergencies.
• Neurologic catastrophe from missed secondary headache: SAH rebleeding, vasospasm-related delayed ischemia and hydrocephalus (AHA/ASA aneurysmal SAH guideline); herniation from mass or meningitis. All are emergencies.

Complications of treatment

• Triptans: 5-HT1B-mediated vasoconstriction can provoke coronary spasm — chest tightness in a patient with CAD or uncontrolled hypertension is the warning sign; avoid within 24 hours of an ergot.
• Ergots/dihydroergotamine: peripheral vasospasm and ischemia; contraindicated in pregnancy (uterotonic) and in vascular disease.
• Metoclopramide/prochlorperazine: D2 blockade producing acute dystonia and akathisia (treat with diphenhydramine or benztropine); metoclopramide carries a tardive dyskinesia boxed warning.
• Topiramate: carbonic anhydrase inhibition → metabolic acidosis, calcium phosphate nephrolithiasis, paresthesias, cognitive slowing, weight loss, acute angle-closure glaucoma, and teratogenicity (oral clefts).
• Valproate: neural tube defects, hepatotoxicity, pancreatitis — avoid in people who may become pregnant.
• Verapamil for cluster prophylaxis: dose-dependent AV block; obtain baseline and serial ECGs during titration.
• Glucocorticoids for GCA: hyperglycemia, osteoporosis, infection (ACR/Vasculitis Foundation guideline supports tocilizumab as a steroid-sparing agent).

• Thunderclap headache = SAH until excluded: the single best next step is a noncontrast head CT, not MRI and not analgesia; if CT is nondiagnostic and suspicion persists, proceed to lumbar puncture for xanthochromia (AHA/ASA aneurysmal SAH guideline). A normal neurologic exam does not exclude it.
• New headache after 50 with jaw claudication, scalp tenderness, or transient monocular vision loss: start high-dose glucocorticoids immediately and arrange temporal artery biopsy — the ACR/Vasculitis Foundation guideline is explicit that treatment must not await biopsy, because biopsy yield persists for days but vision loss is irreversible.
• Cluster headache abortive pair: 100% oxygen by non-rebreather plus subcutaneous sumatriptan. Verapamil is the prophylactic of choice, with ECG monitoring for AV block. The agitated, pacing patient with lacrimation and a partial Horner syndrome is the giveaway; migraineurs lie still in the dark.
• Migraine with aura plus combined hormonal contraception plus smoking: the classic tested association is ischemic stroke; CDC US Medical Eligibility Criteria makes combined estrogen contraception category 4 in any woman with migraine with aura.
• Match the preventive to the comorbidity: propranolol for the hypertensive migraineur (avoid in asthma), topiramate for the obese patient (watch for stones and glaucoma), amitriptyline when insomnia or depression coexists, and neither topiramate nor valproate in pregnancy.
• **Young obese woman with headache, papilledema, and *diplopia from an abducens palsy***: idiopathic intracranial hypertension — image first to exclude mass and venous sinus thrombosis, then LP showing elevated opening pressure with normal CSF composition; acetazolamide plus weight loss.
• Common distractor — "sinus headache": most self-diagnosed sinus headaches without fever or purulent drainage are migraine; antibiotics are the wrong answer.
• Second distractor — opioids and butalbital: never the best answer for primary headache; they are the fastest route to medication overuse headache.