364.3 🏥 內科專科考前版

364.3.1 Mechanistic Deep Dive

364.3.1.1 CGRP Pathway

  • CGRP (calcitonin gene-related peptide) — potent vasodilator
  • Released during migraine attack from trigeminovascular system
  • Targets:
    • mAbs to CGRP ligand: fremanezumab, galcanezumab, eptinezumab
    • mAb to CGRP receptor: erenumab
    • Small-molecule receptor antagonists (gepants): ubrogepant, rimegepant, atogepant, zavegepant

364.3.1.2 Triptan Mechanism

  • 5HT-1B/1D agonist
  • Vasoconstriction + presynaptic inhibition of CGRP release
  • CV risk

364.3.1.3 Lasmiditan (Ditan) Mechanism

  • 5HT-1F agonist
  • No vasoconstriction
  • Safe in CAD
  • Sedation, dizziness

364.3.1.4 Migraine Pathophysiology

  • Cortical spreading depression (aura)
  • Trigeminovascular activation
  • Neurogenic inflammation
  • CGRP, PACAP, substance P
  • Central sensitization

364.3.2 Recent Trials & Updates

364.3.2.1 Anti-CGRP mAbs (2018-)

  • Erenumab approved 2018 (first)
  • Galcanezumab + fremanezumab 2018
  • Eptinezumab 2020
  • Reduce migraine days
  • Generally well tolerated
  • Side effects: constipation (erenumab), injection site, HTN possible

364.3.2.2 Gepants Acute Treatment

  • Ubrogepant (2019)
  • Rimegepant (2020) — also prevention
  • Zavegepant nasal (Zavzpret) FDA 2023

364.3.2.3 Atogepant (Qulipta) Prevention

  • 2021 FDA episodic, 2023 chronic
  • Daily oral
  • Effective preventive

364.3.2.4 Galcanezumab for Cluster

  • FDA 2019 episodic cluster
  • CONQUER trial
  • First mAb for cluster

364.3.2.5 Plasma CGRP

  • Elevated during attacks
  • Returns to normal with successful treatment
  • Investigational biomarker

364.3.2.6 Anti-PACAP

  • Lu AG09222 (Lundbeck)
  • Phase 3 trials
  • New mechanism

364.3.3 High-Yield Specialist Points

364.3.3.1 Hemiplegic Migraine

  • Rare, often familial
  • Motor aura
  • AVOID triptans + ergots (theoretical stroke risk)
  • Use gepants, lasmiditan
  • FHM mutations: CACNA1A, ATP1A2, SCN1A

364.3.3.2 Vestibular Migraine

  • Vertigo + migraine
  • May or may not have headache during episode
  • Vestibular symptoms 5 min - 72 hr
  • Treatment similar to migraine

364.3.3.3 Status Migrainosus

  • Severe migraine > 72 hours
  • ED treatment: fluids, antiemetics, NSAIDs, DHE
  • Hospitalization if needed

364.3.3.5 Migraine and Stroke

  • Migraine with aura → mild ↑ ischemic stroke risk
  • Avoid combined OCP if migraine with aura + smoking/age > 35
  • Hemiplegic migraine: more concern

364.3.3.6 CV Risk with Triptans

  • Theoretical, rarely clinically significant
  • Avoid if CAD, stroke, uncontrolled HTN
  • Lasmiditan and gepants alternative

364.3.3.7 Reversible Cerebral Vasoconstriction Syndrome (RCVS)

  • Thunderclap headache, recurrent
  • Postpartum, vasoactive drugs (cocaine, SSRI)
  • Beaded vessels on angiography
  • Self-limited, but can cause stroke/hemorrhage
  • Avoid vasoconstrictors

364.3.3.8 Cervical Artery Dissection

  • Trauma or spontaneous
  • Headache + neck pain + Horner (carotid) or vertigo (vertebral)
  • Stroke risk
  • CTA/MRA
  • Antiplatelet or anticoagulation

364.3.3.9 Headache in Cancer Patients

  • Brain metastases
  • LM disease (carcinomatous meningitis)
  • Cerebral venous sinus thrombosis (hypercoagulable)
  • Treatment-related (PD-1 inhibitor hypophysitis)

364.3.4 Pearls

  • SNOOP10 for red flags
  • Migraine acute: NSAIDs → triptans → gepants/lasmiditan if CV contraindication
  • Migraine preventive: traditional (topiramate, β-blocker, TCA, valproate, BTX-A) or CGRP-targeted (mAbs, atogepant, rimegepant)
  • Cluster acute: O2 + SC sumatriptan
  • Cluster preventive: verapamil + galcanezumab
  • Indomethacin response = paroxysmal hemicrania or hemicrania continua
  • GCA urgent steroids
  • IIH acetazolamide
  • Thunderclap → SAH workup
  • MOH identify + withdraw + bridge + preventive