Harvey's Garden

Migraine

3 min read

Epidemiology

Etiology

Pathophysiology

  • Aura Phase: Caused by Cortical Spreading Depression (CSD), a self-propagating wave of neuronal depolarization across the cortex (~3-5 mm/min). This initial hyperactivity is followed by suppression, explaining the positive (e.g., scintillating scotoma) and negative (e.g., scotoma) features of aura.
  • Pain Phase: Caused by activation of the Trigeminovascular System (TVS).
    • CSD is believed to trigger the activation of trigeminal nerve afferents that innervate cranial blood vessels.
    • This activation causes the release of vasoactive neuropeptides, most importantly Calcitonin Gene-Related Peptide (CGRP).
  • Role of CGRP:
    • CGRP is a potent vasodilator and promotes neurogenic inflammation. This leads to sensitization of pain receptors on the meningeal vessels, causing the characteristic severe, throbbing headache.
    • CGRP levels are elevated during migraine attacks and normalize after successful treatment.
    • Pharmacologic Targets: Triptans inhibit CGRP release, while newer CGRP antagonists directly block the peptide or its receptor.

Clinical features

  • POUND Mnemonic:
    • Pulsatile/throbbing quality.
    • One-day duration (typically lasts 4–72 hours if untreated).
    • Unilateral location.
    • Nausea and/or vomiting.
    • Disabling intensity (moderate to severe), aggravated by routine physical activity.
  • Associated with photophobia (sensitivity to light) and phonophobia (sensitivity to sound).
  • Phases: Can include a prodrome (fatigue, mood changes), aura, headache, and postdrome (feeling drained).
  • Aura: Occurs in ~30% of patients. Usually transient (<60 mins) focal neurologic symptoms (e.g., scintillating scotoma, paresthesias) that precede or accompany the headache.

Diagnostics

Treatment

Abortive (Acute)

  • Goal: Stop an ongoing attack.
  • Mild: NSAIDs, Acetaminophen.
  • Moderate/Severe:
    • Triptans (Sumatriptan):
      • MOA: 5-HT1B/1D agonist → vasoconstriction & ↓neuropeptide release (e.g. CGRP).
      • CI: CAD, uncontrolled HTN, stroke (risk of vasospasm).
    • Ergotamines (e.g., Dihydroergotamine - DHE):
      • Mechanism: Non-selective 5-HT receptor agonist; causes vasoconstriction.
      • Use: For moderate to severe attacks, often when triptans fail or are contraindicated.
    • CGRP Antagonists (-gepants): Ubrogepant, Rimegepant. Good alternative if triptans are contraindicated.
  • Adjunct: Antiemetics (Prochlorperazine, Metoclopramide) for N/V.
  • Key Pitfall: Avoid using >2-3 days/week to prevent Medication Overuse Headache (MOH).

Prophylactic (Preventive)

  • Goal: Reduce frequency & severity.
  • Indications: ≥4 headache days/month, disabling attacks.
  • First-Line Agents:
    • Beta-blockers: Propranolol.
    • Anticonvulsants: Topiramate, Valproate (teratogenic).
    • TCAs: Amitriptyline.
  • Newer & Second-Line:
    • Anti-CGRP Monoclonal Antibodies: (e.g., Erenumab). First-line option specifically designed for migraine prevention.
    • Botox: For chronic migraine (≥15 headache days/month) only.

Abortive therapy for migraines

  • Treat nausea and vomiting, if present.
    • Accompanying vomiting makes absorption of oral medications (e.g., oral NSAIDs) unreliable.
    • IV fluids
    • Parenteral antiemetics: e.g., metoclopramide, prochlorperazine

Mild to moderate headache

  • First-line treatment consists of NSAIDs, acetaminophen, acetylsalicylic acid, or combinations including caffeine.

Moderate to severe headache

  • Parenteral antidopaminergics
  • Migraine-specific agents: triptans (e.g., sumatriptan) OR ergotamine; do not combine these agents!
    • Triptans
      • Sumatriptan
      • 5-HT1B/1D receptor agonists that cause:
        • Vasoconstriction of (dilated) cranial and basilar arteries
        • Inhibition of trigeminal nerve nociception
        • Inhibition of vasoactive peptide secretion
      • Adverse effects
        • Vasospasm of coronary vessels → coronary ischemia (rare)
        • Paresthesia and sensation of cold in the extremities
        • Serotonin syndrome (if taken with other 5-HT agonists)

Warning

Avoid opioids as first-line treatment for acute migraines, because they increase the risk of chronic migraine, carry a risk of dependence, and worsen nausea and vomiting.

Prophylactic therapy of migraine

  • Lifestyle modifications
    • Exercise in moderation
    • Maintain a healthy diet
    • Identify and try to avoid potential triggers
    • Follow a regular sleeping schedule
  • General prophylaxis
    • First-line
    • Second-line
      • Tricyclic antidepressant: amitriptyline
      • NSAIDs

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