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MIGRAINE - MBBS Exam Notes

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DEFINITION

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EPIDEMIOLOGY

• Affects ~16% of the population (2nd most common primary headache after tension-type)
• Female > Male (3:1) - hormonal influence
• Strong genetic/familial predisposition
• Onset usually in adolescence or early adulthood

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CLASSIFICATION (ICHD-3)

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PHASES OF A MIGRAINE ATTACK

1. Prodrome (hours to days before)

• Mood changes (depression/euphoria), food cravings, yawning, fatigue, neck stiffness

2. Aura (20-60 minutes, reversible)

• Visual (most common): scintillating scotoma, fortification spectra, homonymous hemianopia
• Sensory: unilateral paresthesias/numbness spreading in "march" pattern
• Speech: dysphasia
• Motor: weakness (hemiplegic migraine)
• Mechanism: Cortical Spreading Depression (CSD) - a wave of neuronal depolarization followed by sustained suppression, moving at 3-5 mm/min across cortex, triggering aura symptoms

3. Headache Phase (4-72 hours)

• Unilateral (60%), throbbing/pulsating
• Moderate to severe intensity
• Worsened by physical activity
• Associated with: nausea, vomiting, photophobia, phonophobia, osmophobia
• Associated with cerebral vasodilation and lower-than-normal serotonin levels

4. Postdrome

• Fatigue, difficulty concentrating ("migraine hangover"), lasting hours to a day

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PATHOPHYSIOLOGY

Trigeminovascular Theory (Most accepted)

1. Trigeminal nerve innervates intracranial vessels and dura mater (trigeminovascular system)
2. Neurogenic inflammation: trigeminal nerve endings release CGRP (Calcitonin Gene-Related Peptide), Substance P, Neurokinin A
3. CGRP causes potent vasodilation + plasma protein extravasation into perivascular space
4. Perivascular edema → mechanical stretching → activation of pain endings in dura
5. Pain signals pass: Trigeminal ganglion → Trigeminocervical Complex (TCC) → Quintothalamic tract → Thalamus → Cortex

Key point: Migraine is a brain disorder - NOT a "vascular headache." Vascular changes are secondary events, not causative.

Serotonin (5-HT) Role

• Serotonin levels FALL during headache phase → vasodilation
• Platelet serotonin release during prodrome → vasoconstriction
• Migraine drugs act on 5-HT1B/1D receptors

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DIAGNOSTIC CRITERIA (IHS/ICHD-3)

Migraine WITHOUT Aura (≥5 attacks):

• Duration 4-72 hours (untreated)
• At least 2 of: Unilateral, Pulsating, Moderate/severe, Aggravated by routine activity
• At least 1 of: Nausea/vomiting OR Photophobia + Phonophobia

Migraine WITH Aura (≥2 attacks):

• One or more fully reversible aura symptoms
• Each aura lasts 5-60 minutes
• Headache during or following aura within 60 minutes

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TRIGGERS (Mnemonic: STRESS)

• S - Sleep changes (too much/too little)
• T - Tyramine-containing foods (cheese, red wine, chocolate)
• R - Red wine/alcohol
• E - Estrogen changes (menstruation, OCP)
• S - Stress (or let-down after stress)
• S - Sensory stimuli (bright lights, loud noise, strong smells)

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TREATMENT

Diagram Summary

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A. ACUTE (ABORTIVE) TREATMENT

Step 1 - Mild to Moderate Attacks

• Aspirin 600-900 mg, Ibuprofen 400-800 mg, Naproxen 500-1000 mg
• Paracetamol + Aspirin + Caffeine combination (FDA approved)
• Aspirin + Metoclopramide (comparable to oral sumatriptan)
• Take early in attack for best effect

Step 2 - Moderate to Severe Attacks

TRIPTANS (5-HT1B/1D Agonists) - DRUGS OF CHOICE

1. Activate presynaptic receptors on trigeminal nerve endings → inhibit release of CGRP, Substance P
2. Cause vasoconstriction of dilated intracranial vessels

• Oral bioavailability: ~15% (high first-pass)
• SC injection: fastest onset (relief in 30-60 min)
• Metabolized by MAO-A
• Do NOT combine with MAO inhibitors or ergotamine (within 24 hours)

• Coronary artery disease / ischemic heart disease (most important)
• Uncontrolled hypertension
• Cerebrovascular disease / history of stroke
• Hemiplegic/basilar migraine
• Pregnancy
• Peripheral vascular disease

• "Triptan sensations": chest tightness, tingling, flushing, neck pressure (usually benign but alarming)
• Nausea, dizziness
• Medication overuse headache (if used >10 days/month)

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ERGOT ALKALOIDS

• Most effective when given during prodromal phase
• DHE preferred over ergotamine (less nausea, less arterial spasm)

• Coronary artery disease
• Hypertension
• Peripheral vascular disease
• Pregnancy (oxytocic)
• Renal/hepatic impairment

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NEWER AGENTS

Gepants (CGRP Receptor Antagonists)

• Advantage over triptans: No vasoconstriction → safe in cardiovascular disease
• Avoid with strong CYP3A4 inhibitors (ubrogepant)
• Can be re-dosed at 2 hours (unlike triptans)

Ditans (5-HT1F Agonists)

• Lasmiditan 50-200 mg PO
• Does NOT cause vasoconstriction → safe in cardiovascular disease
• Causes CNS side effects (dizziness, sedation) - do not drive for 8 hours

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Antiemetics (Adjunctive)

• Metoclopramide 10 mg IV/IM - for severe nausea/vomiting; also enhances analgesic absorption
• Prochlorperazine - also has antimigraine properties
• Domperidone - enhances GI absorption of analgesics

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Clinical Guide: Which drug when?

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B. PROPHYLACTIC TREATMENT

• ≥2 attacks per month
• Attacks severely disabling despite acute treatment
• Contraindication to acute treatments
• Medication overuse headache
• Complicated migraine (hemiplegic, basilar)

First-Line Prophylactic Agents

Second-Line Prophylactic Agents

KD Tripathi Key Points for Exam:

• DOC for prophylaxis = Propranolol
• DOC for acute severe migraine = Sumatriptan
• Ergotamine is no longer first-line (replaced by triptans)
• Flunarizine - preferred calcium channel blocker for migraine prophylaxis in India

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NON-PHARMACOLOGICAL MANAGEMENT

• Identify and avoid personal triggers (keep headache diary)
• Regular sleep schedule, meals, exercise
• Stress management: yoga, meditation, biofeedback, relaxation therapy
• Avoid excess caffeine/alcohol
• Non-invasive vagus nerve stimulation, transcranial magnetic stimulation (newer options)

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SPECIAL SITUATIONS

Migraine in Pregnancy

• Avoid: Ergotamine (oxytocic), triptans (limited data), valproate (teratogenic), NSAIDs in 3rd trimester
• Safe options: Paracetamol, Metoclopramide, Magnesium
• Prophylaxis: Propranolol (if needed), Amitriptyline

Menstrual Migraine

• Occurs 1-2 days before to 3 days after onset of menstruation
• Due to estrogen withdrawal
• Perimenstrual prophylaxis: Frovatriptan, Estrogen patches, Naproxen, Rimegepant

Status Migrainosus (attack >72 hours)

• IV hydration, IV Metoclopramide, IV Valproate, IV Dihydroergotamine
• Short course of corticosteroids (Dexamethasone)

Medication Overuse Headache (MOH)

• Occurs with >10 days/month use of triptans or >15 days/month of analgesics
• Treatment: Withdraw offending drug; bridge with NSAIDs or corticosteroids; start prophylaxis

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QUICK REVISION TABLE - Drugs Acting on 5-HT in Migraine

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HIGH-YIELD EXAM POINTS (KD Tripathi Style)

1. Triptans MOA: 5-HT1B/1D agonists → vasoconstriction + inhibit CGRP/SP release
2. Sumatriptan CI: Coronary artery disease (vasoconstriction risk)
3. Ergotamine + Triptan should NOT be combined (additive vasoconstriction - gap of 24 h)
4. Sumatriptan + MAO inhibitor - contraindicated (reduced metabolism → toxicity)
5. CGRP is the key neuropeptide in migraine pathophysiology
6. Frovatriptan - longest half-life (26 h), preferred for menstrual migraine
7. Naratriptan - best tolerated triptan, least headache recurrence
8. Propranolol = DOC for migraine prophylaxis
9. Topiramate = anticonvulsant used in migraine prophylaxis (also causes weight loss)
10. Valproate - avoid in pregnancy (teratogen - neural tube defects)
11. Gepants - safe in CVS disease (no vasoconstriction); can be re-dosed at 2 h
12. Botulinum toxin - prophylaxis for chronic migraine (≥15 days/month)
13. Cortical spreading depression (CSD) - mechanism of aura
14. Medication overuse headache - warn patients using triptans/NSAIDs too frequently
15. Migraine is a BRAIN disorder - NOT a vascular headache

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