Nervous System & Special Senses

Migraine: acute treatment and preventive therapy

Clinical Overview and When to Suspect Migraine

— Unilateral location

— Pulsating quality

— Moderate-severe intensity

— Aggravation by routine activity

AND ≥1 of: nausea/vomiting OR photophobia + phonophobia.

— Recurrent disabling unilateral throbbing headache with photophobia, relieved by sleep in a dark room

— Premonitory symptoms (yawning, food cravings, mood change) 24–48 h prior

— Family history (~70% positive)

— Triggers: menses, missed meals, sleep disruption, red wine, weather change, stress letdown

Board pearl: A recurrent stereotyped disabling headache with normal exam between attacks in a young woman is migraine until proven otherwise — imaging is not required for a typical history meeting ICHD-3 criteria and a normal neurologic exam (ACR Choosing Wisely).

Migraine is a primary headache disorder defined by recurrent attacks of moderate-to-severe head pain with associated autonomic, sensory, and gastrointestinal features; it affects ~18% of US women and ~6% of men, peaking ages 25–55.

Core pathophysiology: cortical spreading depression triggers trigeminovascular activation, CGRP release, neurogenic inflammation, and central sensitization — the rationale for triptans, gepants, and anti-CGRP biologics.

ICHD-3 diagnostic criteria (migraine without aura) — ≥5 attacks lasting 4–72 hours with ≥2 of:

Migraine with aura: ≥2 attacks with reversible visual, sensory, speech, motor, brainstem, or retinal symptoms developing over ≥5 min, lasting 5–60 min, followed within 60 min by headache.

Chronic migraine: headache ≥15 days/month for >3 months, with ≥8 days meeting migraine features — a key threshold for initiating preventive therapy and a billing-relevant distinction for onabotulinumtoxinA coverage.

When to suspect in the FM clinic:

Red flag screen ("SNOOP10"): Systemic symptoms, Neurologic deficits, Onset sudden/thunderclap, Older age >50 first headache, Pattern change, Positional, Precipitated by Valsalva, Papilledema, Progressive, Pregnancy/postpartum — any positive demands neuroimaging.

Presentation Patterns and Key History

— Prodrome (hours-2 days before): yawning, irritability, neck stiffness, food cravings, polyuria — often misattributed to "triggers"

— Aura (5–60 min): visual scintillating scotoma/fortification spectra most common; sensory tingling spreading hand→face; dysphasic aura

— Headache (4–72 h): unilateral pulsating, worsened by movement, nausea, photo/phonophobia, osmophobia

— Postdrome ("migraine hangover"): fatigue, cognitive fog, scalp tenderness for up to 24 h

— Frequency (headache days/month), duration, peak severity, functional impairment (work/school missed)

— Medications already tried, doses, response, days/month of acute medication use

— Headache diary for ≥1 month is the single most useful pre-visit tool

— Menstrual relationship: pure menstrual migraine occurs days −2 to +3 in ≥2/3 cycles, exclusively perimenstrual

— Sleep, caffeine, alcohol, hydration, exercise, stressors

— Mood (PHQ-9), anxiety (GAD-7) — comorbid in 30–50%

— Brainstem aura (formerly basilar): vertigo, diplopia, dysarthria, tinnitus, ataxia — contraindicates triptans/ergots

— Hemiplegic migraine: unilateral motor weakness during aura, often familial (CACNA1A, ATP1A2, SCN1A) — also a triptan contraindication

— Retinal migraine: monocular visual loss — requires ophthalmology and stroke workup first time

Step 3 management: A patient using sumatriptan 12+ days/month with worsening daily headache has MOH — the answer is to taper the overused agent and start a preventive, not to add another acute.

Four phases (not all present in every attack):

Key history elements for the FM visit:

Validated tools: MIDAS (Migraine Disability Assessment) and HIT-6 quantify disability and track preventive response.

Aura subtypes to recognize:

Medication overuse headache (MOH): ≥15 headache days/month with regular overuse — triptans/opioids/combination analgesics ≥10 days/month, or simple analgesics ≥15 days/month, for >3 months.

Physical Exam Findings (and Vital/Neurologic Assessment)

— Pallor, diaphoresis, mild tachycardia

— Photophobia (patient prefers dark room), allodynia (cutaneous brushing painful — marker of central sensitization, predicts poor triptan response if dosed late)

— Cranial autonomic features (less prominent than cluster): mild lacrimation, conjunctival injection, ptosis on the pain side — overlap with TACs

— Neck stiffness/myofascial tenderness (60%) — does not mean meningitis if no fever and normal mentation

— Vitals including BP in both arms (hypertensive urgency mimic; also baseline for triptan candidacy)

— Funduscopy → rule out papilledema (IIH, mass)

— Cranial nerves, visual fields by confrontation

— Pronator drift, strength, reflexes, gait, Romberg

— Palpate temporal arteries in >50 yo (GCA), TMJ, cervical paraspinals, occipital nerve (Tinel at greater occipital notch)

— Auscultate for cranial/carotid bruits (AVM, dissection)

— Papilledema → urgent MRI/MRV, LP with opening pressure (IIH, venous sinus thrombosis)

— Horner syndrome with neck pain → carotid dissection CTA neck

— Focal deficit persisting >60 min after aura → MRI to exclude migrainous infarction or stroke mimic

— Fever + meningismus → LP after imaging

— Asymmetric pupils, papilledema, AMS → emergent CT

Key distinction: Aura symptoms march and spread over minutes (cortical spreading depression at 3 mm/min); TIA/stroke deficits are maximal at onset. A negative visual scotoma that appears instantaneously is more concerning for embolic/vascular cause than migraine aura.

Board pearl: New unilateral neck pain with ipsilateral headache and Horner syndrome in a young adult after chiropractic manipulation → carotid artery dissection — order CTA, not "migraine prophylaxis."

Between attacks: exam is normal — this is a diagnostic feature. Persistent abnormal neurologic findings demand a secondary cause workup.

During an attack you may see:

Required exam at the diagnostic visit:

Findings that change the diagnosis (secondary headache red flags):

Diagnostic Workup — Initial Labs / Imaging / ECG

— Any SNOOP10 red flag

— First or worst headache, thunderclap onset → non-contrast CT then LP/CTA for SAH; consider RCVS

— New headache after age 50 → MRI + ESR/CRP for GCA

— Progressive frequency/severity despite optimization

— New aura features, especially motor or brainstem

— Headache awakening from sleep, worse with Valsalva, positional

— Immunocompromised, cancer history, pregnancy/postpartum (consider CVT — MRV)

— Atypical aura >60 min or persistent neurologic deficit

— ESR/CRP if >50 yo (GCA)

— CBC, BMP, TSH for baseline before starting preventives

— Pregnancy test before topiramate, valproate, or imaging with contrast

— LFTs before valproate; BUN/Cr before NSAIDs and topiramate

Step 3 management: A 52-yo new daily headache, jaw claudication, scalp tenderness → STAT ESR/CRP, start prednisone 60 mg empirically, temporal artery biopsy within 1–2 weeks — do not wait for biopsy to treat suspected GCA.

Migraine is a clinical diagnosis — routine labs and imaging are not indicated when the history meets ICHD-3 and the neurologic exam is normal (ACR Choosing Wisely, AAN, AHS).

When to image (MRI brain preferred over CT for non-emergent eval):

MRI brain with and without contrast is the modality of choice for non-emergent eval; add MRA for aneurysm/AVM concern and MRV for venous sinus thrombosis (especially postpartum, OCP use, hypercoagulable).

Labs to consider when secondary cause suspected:

ECG: obtain before starting triptans in patients with cardiovascular risk factors (age ≥40 men, ≥55 women, HTN, DM, hyperlipidemia, smoking, family history) — triptans are contraindicated in CAD, prior MI, stroke, PAD, uncontrolled HTN, Prinzmetal angina.

LP indicated if SAH suspected and CT negative within 6 h (and beyond), or if meningitis/IIH considered — measure opening pressure.

Diagnostic Workup — Advanced or Confirmatory Studies

— With contrast when ruling out neoplasm, infection, inflammatory/demyelinating disease, leptomeningeal process

— MRV for postpartum, hypercoagulable, papilledema, ear/sinus infection adjacent — rule out cerebral venous sinus thrombosis

— MRA head and neck for thunderclap (after negative CT/LP for SAH) → RCVS, dissection, unruptured aneurysm, AVM

— High-resolution vessel wall imaging in young stroke with possible vasculitis vs RCVS

— Opening pressure >25 cm H₂O in non-obese, >25 in obese (some use >25 across the board) supports IIH

— Xanthochromia/RBCs for delayed SAH presentation

— Cell count, glucose, protein for meningitis

— Diagnostic uncertainty

— Failure of ≥2 preventive classes at adequate dose/duration

— Hemiplegic, brainstem, or persistent aura

— Status migrainosus >72 h

— Suspected MOH requiring withdrawal

— Pregnancy with severe disabling migraine

Board pearl: Young obese woman with daily headache, transient visual obscurations, pulsatile tinnitus, and papilledema → idiopathic intracranial hypertension — MRI/MRV first to exclude CVT, then LP with opening pressure; treat with acetazolamide and weight loss is disease-modifying.

MRI brain protocol choice:

CT angiography acceptable when MRI contraindicated or unavailable; DSA reserved for AVM/aneurysm characterization.

Lumbar puncture:

EEG: not routinely indicated for migraine — only when seizure suspected (migralepsy, occipital epilepsy mimicking visual aura).

Genetic testing: consider for familial hemiplegic migraine (CACNA1A, ATP1A2, SCN1A) when motor aura recurs — affects family counseling and avoidance of triptans.

Sleep study: if daily morning headaches, snoring, BMI elevated — OSA can drive chronic migraine and treating it improves headache frequency.

Specialist referral triggers (neurology):

Headache diary remains the most important "advanced" tool — captures frequency, triggers, treatment response, menstrual correlation; digital apps (Migraine Buddy, N1-Headache) acceptable.

Risk Stratification and First-Line Management Logic

— Acute (abortive) plan — what to take at headache onset

— Preventive (prophylactic) plan — daily/monthly therapy to reduce frequency

— ≥4 headache days/month with some impairment

— ≥2 headache days/month with severe disability (MIDAS ≥11)

— Acute therapy contraindicated, ineffective, overused, or adverse effects

— Special circumstances: hemiplegic migraine, brainstem aura, migrainous infarction, persistent aura, frequent prolonged aura

— Patient preference

— Mild-moderate: NSAIDs (naproxen 500 mg, ibuprofen 400–800 mg, diclofenac powder 50 mg) or acetaminophen 1000 mg; combo APAP/ASA/caffeine

— Moderate-severe or NSAID failure: triptan ± NSAID (sumatriptan 85 mg + naproxen 500 mg combo has strongest evidence)

— Triptan failure or contraindication: gepant (ubrogepant, rimegepant), ditan (lasmiditan), or DHE

— Adjunct antiemetic (metoclopramide, prochlorperazine) for nausea — also have intrinsic antimigraine effect

— Triptans, ergots, opioids, combination analgesics: <10 days/month

— Simple analgesics/NSAIDs: <15 days/month

— Regular sleep, meals, hydration, aerobic exercise

— Trigger identification via diary (but avoid over-restriction)

— CBT, biofeedback, relaxation training — Level A evidence

— Limit caffeine to <200 mg/day

Step 3 management: Patient with 5 migraine days/month and MIDAS 22 has a clear indication for preventive therapy — picking only "stronger triptan" without offering prevention is the wrong answer on Step 3.

Two parallel decisions at every migraine visit:

Indications for preventive therapy (AHS 2021):

Acute treatment stratified care (preferred over step care):

Early treatment principle: treat within 20–60 min of onset, before allodynia, to maximize response and reduce recurrence.

Acute medication frequency limits (to prevent MOH):

Non-pharmacologic foundation (recommend at every visit):

Pharmacotherapy — Acute (Abortive) Drug Regimen

— Naproxen 500–550 mg PO, ibuprofen 400–800 mg, diclofenac potassium 50 mg powder, ketorolac 30 mg IM/IV in ED

— Avoid in CKD, PUD, third-trimester pregnancy

— Sumatriptan 50–100 mg PO, 6 mg SC (fastest onset, ~10 min), 5–20 mg intranasal

— Rizatriptan 10 mg ODT (fastest oral onset), eletriptan 40 mg (highest efficacy oral), zolmitriptan, almotriptan, naratriptan/frovatriptan (longer half-life, menstrual prophylaxis)

— May redose at 2 h; max 2 doses/24 h

— Contraindications: CAD, prior MI, stroke/TIA, PAD, uncontrolled HTN, Prinzmetal, hemiplegic or brainstem aura, pregnancy (relative), ergot or MAOI within 24 h

— Switch triptan if one fails — try ≥2 before declaring class failure

— Ubrogepant 50–100 mg, may repeat once at 2 h

— Rimegepant 75 mg ODT — also approved for prevention (every other day)

— Zavegepant intranasal — fast onset

— Safe in CV disease — preferred over triptans when triptan contraindicated

Board pearl: A 58-yo man with HTN and prior MI needs acute migraine therapy → gepant or lasmiditan, NOT a triptan. Pick ubrogepant 100 mg.

NSAIDs (first-line for mild-moderate):

Triptans (5-HT1B/1D agonists — first-line moderate-severe):

Gepants (small-molecule CGRP receptor antagonists — no vasoconstriction):

Ditans: Lasmiditan 50–200 mg (5-HT1F selective, no vasoconstriction) — CNS depression, driving restriction 8 h, Schedule V

Ergots: DHE nasal/SC/IV — effective but more nausea; same vascular contraindications as triptans; do not combine with triptan within 24 h

Antiemetics: metoclopramide 10 mg, prochlorperazine 10 mg PO/IV (watch akathisia/QT), ondansetron

Avoid: butalbital combinations and opioids — promote MOH, poor evidence, sedation; reserve only for rescue when nothing else tolerated.

Pharmacotherapy — Preventive Therapy and Procedures

— Beta-blockers (Level A): propranolol 80–240 mg/d, metoprolol, timolol — first-line; avoid in asthma, bradycardia, depression

— Topiramate (Level A): 25 mg qHS titrated to 50–100 mg BID; SE paresthesias, cognitive fog, weight loss, kidney stones, teratogenic (cleft palate, low birth weight) — avoid in pregnancy and counsel contraception; reduces OCP efficacy >200 mg

— Valproate (Level A): 500–1500 mg/d — contraindicated in pregnancy (neural tube defects, IQ reduction) and women of childbearing potential without robust contraception

— Amitriptyline (Level B): 10–50 mg qHS — good for comorbid insomnia/depression; anticholinergic, QT

— Venlafaxine (Level B): 75–150 mg — useful with comorbid anxiety

— Candesartan (Level B): 16 mg — well tolerated

— Memantine, magnesium 400–600 mg, riboflavin 400 mg, CoQ10 100 mg TID, butterbur (avoid — hepatotoxicity)

— Monoclonal antibodies: erenumab (anti-receptor), fremanezumab, galcanezumab, eptinezumab (IV q3mo) — monthly/quarterly SC

— Oral gepants for prevention: rimegepant qod, atogepant 10–60 mg daily

— Indicated when ≥2 oral preventives fail or are contraindicated; insurers often require step therapy

— OnabotulinumtoxinA (Botox) — FDA-approved for chronic migraine only (≥15 days/month); 155 units across 31 sites q12 weeks (PREEMPT protocol)

— Greater occipital nerve block — bridge therapy, status migrainosus, pregnancy

— Sphenopalatine ganglion block, neuromodulation devices (Cefaly, gammaCore, Nerivio) — adjuncts

Step 3 management: Chronic migraine (≥15 d/mo) failing topiramate and propranolol → next step is onabotulinumtoxinA or anti-CGRP mAb — both are evidence-based; insurance typically requires documentation of prior preventive failures.

Oral preventives — start low, titrate slowly, trial ≥8 weeks at target dose:

CGRP-targeted preventives (paradigm shift — well-tolerated, migraine-specific):

Procedures:

Menstrual migraine mini-prophylaxis: frovatriptan 2.5 mg BID or naproxen 550 mg BID days −2 to +3.

Special Populations — Elderly and Renal/Hepatic Impairment

— ESR/CRP for GCA

— MRI brain for mass, subdural, stroke

— Review medications (nitrates, PDE5 inhibitors, CCBs cause headache)

— Triptans relatively contraindicated in ≥65 with CV risk factors — perform CV risk assessment, obtain ECG; consider stress test if multiple risk factors

— Gepants and lasmiditan preferred in CV disease — no vasoconstriction

— NSAIDs limited by CKD, PUD, antiplatelet/anticoagulant interactions, HF

— Acetaminophen up to 3 g/d safer in this population

— Avoid amitriptyline (Beers — anticholinergic, falls, delirium) — if needed use lowest dose or nortriptyline

— Topiramate — cognitive SE worse; start 12.5 mg; monitor for confusion, metabolic acidosis

— Beta-blockers — caution with bradycardia, AV block, orthostasis

— Candesartan and CGRP mAbs well-tolerated options

— Avoid NSAIDs in eGFR <30; cautious use 30–60

— Topiramate dose-reduce 50% if CrCl <70; avoid in severe impairment (calculi, acidosis risk)

— Gabapentin/pregabalin (not first-line but used adjunctively) — dose by CrCl

— Triptans: eletriptan avoided in severe renal impairment; sumatriptan generally safe

— Avoid valproate, divalproex (hepatotoxicity, hyperammonemia)

— Acetaminophen max 2 g/d if cirrhosis or active drinking

— Eletriptan and rimegepant contraindicated in severe hepatic impairment

— Erenumab/fremanezumab/galcanezumab no hepatic dose adjustment — favorable in cirrhosis

Board pearl: New-onset "migraine" in a 70-yo with scalp tenderness and ESR 95 is giant cell arteritis — start high-dose prednisone immediately and biopsy within 1–2 weeks.

New-onset headache after age 50 is NOT migraine until proven otherwise — workup mandatory:

Migraine prevalence declines after 60; persistent or new migraine in elderly should prompt evaluation for secondary causes including cervicogenic, GCA, medication-induced, and hypnic headache.

Acute therapy in elderly:

Preventives in elderly:

Renal impairment:

Hepatic impairment:

Special Populations — Pregnancy, Lactation, and Pediatrics

— First-line acute: acetaminophen 1000 mg, plus metoclopramide 10 mg for nausea

— NSAIDs: OK in 2nd trimester; avoid in 1st (miscarriage signal) and after 20 weeks (oligohydramnios, premature ductal closure — FDA 2020 warning)

— Triptans: registry data reassuring (especially sumatriptan); use if benefit > risk — discuss with patient

— Avoid: ergots (uterotonic, vasoconstriction — contraindicated), valproate (NTDs, neurocognitive), topiramate (cleft palate, low birth weight)

— Preventives in pregnancy: propranolol (monitor for fetal growth restriction, neonatal bradycardia/hypoglycemia in 3rd trimester), amitriptyline; magnesium, riboflavin, CoQ10 supplements; CGRP mAbs not recommended (long half-life, limited safety data)

— Nerve blocks (occipital) with lidocaine — safe, effective bridge

— New severe headache postpartum → urgent workup for preeclampsia/eclampsia, cerebral venous sinus thrombosis, RCVS, PRES, pituitary apoplexy — check BP, MRI/MRV

— Compatible: acetaminophen, ibuprofen, sumatriptan, eletriptan, propranolol, magnesium

— Limited data: gepants, mAbs

— Avoid: aspirin (Reye), ergots

— Diagnosis: shorter duration allowed (2–72 h), often bilateral frontal/temporal, prominent GI symptoms

— Acute: ibuprofen 10 mg/kg first-line; triptans approved ≥6 yo (almotriptan, rizatriptan, sumatriptan/naproxen, zolmitriptan nasal) — avoid in <6

— Preventives (CHAMP trial): amitriptyline and topiramate showed no benefit over placebo in children — emphasize CBT, lifestyle; consider preventives only with significant disability

— Childhood periodic syndromes: cyclic vomiting, abdominal migraine, benign paroxysmal vertigo — migraine equivalents

Step 3 management: Pregnant woman with severe migraine refractory to acetaminophen → IV metoclopramide + IV magnesium ± occipital nerve block with lidocaine; avoid ergots and valproate entirely.

Pregnancy — migraine often improves in 2nd/3rd trimester (estrogen stabilization); worsens postpartum.

Postpartum:

Lactation:

Pediatric migraine:

Complications and Adverse Outcomes

— Outpatient: SC sumatriptan 6 mg, oral steroid burst (dexamethasone 4 mg or prednisone 10-day taper to reduce 24–72 h recurrence)

— ED/inpatient: IV fluids, IV metoclopramide or prochlorperazine + diphenhydramine, IV ketorolac, IV magnesium 1–2 g, IV valproate, DHE q8h (Raskin protocol), greater occipital nerve block

— Single-dose dexamethasone 10 mg IV reduces recurrence at 24–72 h

— Most common cause of refractory daily headache

— Withdraw the offending agent (abrupt for triptans/NSAIDs; taper for opioids/butalbital to prevent withdrawal seizure)

— Bridge with steroids, naproxen scheduled, or nerve blocks

— Start a preventive simultaneously (topiramate, mAb)

— Depression, anxiety, suicidality

— Cardiovascular disease (especially women with aura)

— Patent foramen ovale association (no benefit to PFO closure for migraine — MIST, PREMIUM)

— Epilepsy, IBS, fibromyalgia, restless legs

— Sleep disorders, OSA

— Topiramate: nephrolithiasis, oligohidrosis, acute angle-closure glaucoma, metabolic acidosis

— Valproate: hepatotoxicity, pancreatitis, thrombocytopenia

— Triptans: serotonin syndrome with SSRI/SNRI (rare in practice, FDA warning persists)

CCS pearl: For status migrainosus in CCS, order IV NS, metoclopramide 10 mg IV, diphenhydramine 25 mg IV, ketorolac 30 mg IV, magnesium 2 g IV, and dexamethasone 10 mg IV; reassess at 1 h; if persists, neurology consult and admit for DHE protocol.

Status migrainosus: debilitating migraine >72 hours despite treatment.

Medication overuse headache (MOH):

Migrainous infarction: aura symptoms persisting >60 min with imaging-confirmed ischemic stroke in corresponding territory, typically posterior circulation, in patient with migraine with aura — diagnosis of exclusion.

Increased stroke risk in migraine with aura — OR ~2x, higher with smoking and combined OCP use in women <55 — avoid estrogen-containing contraceptives; use progestin-only or non-hormonal.

Persistent aura without infarction: aura symptoms >1 week without imaging stroke — bilateral, suggests recurrent CSD.

Migraine-related comorbidities (screen and manage):

Medication-specific AEs:

When to Escalate Care — ED, Consult, or Inpatient Triage

— Thunderclap headache (peak severity <1 min) — SAH, RCVS, dissection

— First or worst headache

— Fever + meningismus + AMS

— Focal neurologic deficit persisting beyond aura window

— Headache after head trauma with concerning features

— Pregnancy/postpartum with BP elevation or new headache

— Status migrainosus failing outpatient therapy

— Suspected GCA with visual symptoms — emergent ophthalmology

— Diagnostic uncertainty

— ≥2 preventive classes failed at therapeutic dose for ≥8 weeks

— Need for onabotulinumtoxinA or CGRP mAb prior authorization support

— Hemiplegic, brainstem, prolonged, or persistent aura

— Suspected secondary headache requiring further workup

— Need for inpatient DHE protocol or refractory MOH withdrawal

— Status migrainosus refractory to ED treatment

— Severe dehydration from intractable vomiting

— Suspected secondary cause requiring inpatient workup (CVT, RCVS, infection, mass)

— Opioid/butalbital withdrawal management

— IV DHE infusion protocol (some centers outpatient)

— Visit cadence: 4–6 weeks during preventive titration, then q3 months stable

— Headache diary review every visit

— MIDAS/HIT-6 at baseline and 3 months

— Reassess CV risk before each triptan continuation in patients aging into risk

— Behavioral health for CBT/biofeedback

— Physical therapy for cervicogenic component, posture

— Sleep medicine if OSA suspected

— Ophthalmology if visual aura atypical or vision change persistent

— Dental/TMJ if jaw-related triggers

Step 3 management: Patient calls clinic with "worst headache of life, sudden onset 1 hour ago" — answer is send to ED via EMS for non-contrast CT and possible LP, not "take sumatriptan and call back."

Send to ED when:

Neurology consult/referral when:

Inpatient admission criteria:

Outpatient pathway intensification in FM clinic:

Multidisciplinary referrals:

Key Differentials — Same-Category Primary Headaches

— Bilateral, pressing/tightening (non-pulsatile), mild-moderate, no nausea, no aggravation by activity

— May have photo OR phonophobia (not both)

— First-line acute: NSAIDs/acetaminophen; preventive (chronic TTH): amitriptyline

— Strictly unilateral periorbital/temporal, excruciating, 15–180 min, occurs 1–8x/day in clusters lasting weeks-months

— Ipsilateral autonomic features: lacrimation, conjunctival injection, rhinorrhea, ptosis, miosis, agitation/restlessness (vs migraine — patient seeks quiet)

— Male predominance, smokers, alcohol trigger during cluster

— Acute: 100% O₂ 12–15 L/min via NRB for 15 min, SC sumatriptan 6 mg, intranasal zolmitriptan

— Preventive: verapamil 240–480 mg/d (ECG for AV block), prednisone bridge, galcanezumab (FDA-approved for episodic cluster), occipital nerve block

Key distinction: Migraine patient lies still in a dark room; cluster patient paces and rocks. Migraine attacks last hours; cluster attacks last <3 hours but recur multiple times daily during a cluster period.

Board pearl: Strictly unilateral headache with autonomic features that disappears with indomethacin → paroxysmal hemicrania or hemicrania continua — not migraine, not cluster.

Tension-type headache (TTH):

Cluster headache (trigeminal autonomic cephalalgia):

Paroxysmal hemicrania: similar to cluster but shorter (2–30 min), more frequent (>5/day), absolute response to indomethacin — diagnostic.

SUNCT/SUNA: very brief (seconds-minutes), high frequency, autonomic features; lamotrigine first-line.

Hemicrania continua: continuous unilateral pain with exacerbations and autonomic features — also indomethacin-responsive.

New daily persistent headache (NDPH): daily from a clearly remembered onset day, often refractory.

Primary cough/exertional/sexual headaches: image first time to exclude Chiari, AVM, SAH.

Hypnic headache: elderly, awakens from sleep at consistent time — caffeine or lithium responsive.

Key Differentials — Secondary Headache Causes

— Subarachnoid hemorrhage: thunderclap, "worst ever," meningismus, AMS — CT then LP for xanthochromia

— Cerebral venous sinus thrombosis: postpartum, OCP, hypercoagulable; subacute progressive headache, papilledema, seizures, focal deficits — MRV

— Carotid/vertebral dissection: neck pain + ipsilateral headache, Horner, after manipulation/trauma — CTA/MRA

— RCVS (Call-Fleming): recurrent thunderclap over days-weeks, postpartum, vasoactive drugs — segmental vasoconstriction on angiography

— Stroke/TIA: focal deficit maximal at onset

— Giant cell arteritis: >50, scalp/temporal tenderness, jaw claudication, vision loss, ESR/CRP elevated

— Brain tumor: progressive, worse with Valsalva, morning headache, focal deficits, papilledema

— Chiari malformation: occipital, cough-triggered

— Colloid cyst: positional, sudden

— IIH (pseudotumor cerebri): young obese women, papilledema, transient visual obscurations, pulsatile tinnitus, CN VI palsy

— Spontaneous intracranial hypotension: orthostatic headache worse upright, CSF leak — pachymeningeal enhancement on MRI

CCS pearl: Postpartum day 7 with new severe headache, seizure, focal weakness — order MRI/MRV brain, CBC, coags, D-dimer; if CVT confirmed, start heparin/LMWH even if hemorrhagic transformation present and transition to warfarin for 3–6 months.

Vascular:

Infectious: meningitis, encephalitis, abscess, sinusitis (true sinusitis has purulent discharge, fever)

Structural/mass effect:

Intracranial pressure:

Toxic/metabolic: CO poisoning (winter, multiple household members), hypoxia, hypercapnia, hypoglycemia, hyponatremia, hypothyroidism, pheochromocytoma, sleep apnea

Medication-induced: nitrates, PDE5 inhibitors, CCBs (amlodipine), OCPs, immunotherapies, withdrawal (caffeine, opioids), MOH

Cervicogenic: unilateral, neck movement triggered, restricted ROM — PT, occipital nerve block

Trigeminal neuralgia: lancinating, seconds, V2/V3, trigger zones — carbamazepine

Secondary Prevention / Long-Term Plan and Discharge Considerations

— Preventive success = ≥50% reduction in headache days/month at 3 months

— Acute success = pain-free at 2 h, sustained at 24 h, return to function

— Disability metric improvement (MIDAS, HIT-6) more meaningful than count alone

— Continue effective preventive 6–12 months then attempt slow taper if well-controlled

— Many patients require indefinite therapy; CGRP mAbs allow drug holidays

— Sleep: consistent 7–9 h, treat OSA

— Exercise: aerobic 30–40 min, 3–5x/week — Level B evidence

— Eat: regular meals, hydration, limit alcohol/caffeine

— Diary: monthly headache log

— Stress: CBT, mindfulness, biofeedback

— Migraine with aura + estrogen-containing contraceptive = contraindicated (stroke risk) — switch to progestin-only, copper IUD, or barrier

— Migraine without aura + low-risk = combined OCPs acceptable; use continuous dosing to reduce withdrawal migraines

— Perimenopause often worsens migraine; continuous low-dose transdermal estradiol may stabilize

— Treat depression/anxiety (consider venlafaxine, amitriptyline as dual-purpose)

— Address HTN with candesartan or beta-blocker (dual-purpose)

— Weight loss for chronic migraine + obesity — improves frequency

Step 3 management: 28-yo woman with migraine with aura wants contraception → levonorgestrel IUD, copper IUD, DMPA, or progestin-only pill — combined estrogen-containing methods are contraindicated.

Long-term migraine management is bidirectional: optimize acute treatment efficacy while reducing frequency through prevention.

Set realistic goals with patient:

Preventive duration:

Lifestyle prescription (the "SEEDS" mnemonic):

Hormonal considerations:

Comorbidity management:

Vaccination/preventive care visits: integrate USPSTF screening (BP, lipids, depression, cancer screens) at migraine follow-ups — these patients see PCP frequently.

Follow-Up, Monitoring Parameters, and Counseling

— Initial preventive titration: 4–6 week intervals until target dose reached

— Stabilization phase: 3 months

— Maintenance: every 6 months with diary review

— CGRP mAb users: 3 months for response assessment (continue if ≥50% reduction)

— Topiramate: baseline and annual BMP (bicarbonate for metabolic acidosis), weight, mood, paresthesias, cognition; pregnancy test before initiation in WOCBP; eye exam if visual symptoms (angle closure)

— Valproate: baseline and periodic LFTs, CBC (thrombocytopenia, hyperammonemia), weight; pregnancy test and reliable contraception mandatory

— Propranolol: HR, BP, mood, asthma symptoms, glucose in DM (masks hypoglycemia)

— Amitriptyline: ECG if >50 or cardiac history (QT), anticholinergic SE, weight, mood

— OnabotulinumtoxinA: q12-week injections; document headache day reduction

— CGRP mAbs: BP (erenumab can elevate BP, ~1% develop HTN), constipation, injection-site reactions, hypersensitivity

— Treat acute attack early — within 20–60 min, before allodynia

— Track acute medication days to prevent MOH

— Preventives take 8–12 weeks for full effect — don't quit early

— Identify but don't over-restrict triggers — leads to anxiety and avoidance

— Rescue plan: when to escalate to ED (status >72 h, atypical features)

— Work/school absenteeism

— MIDAS quarterly

— Patient-reported global impression of change

Board pearl: Patient on erenumab develops new HTN with SBP 150s after 3 months → check BP, address per JNC8/ACC; erenumab can cause de novo or worsening hypertension (FDA warning 2020) — monitor BP at every visit.

Follow-up cadence:

Monitoring by agent:

Counseling points:

Functional outcome tracking:

Shared decision-making on prevention class — discuss SE profiles, cost, dosing burden, comorbidities

Ethical, Legal, and Patient Safety Considerations

— Valproate and topiramate are Category D/teratogens — documented informed consent and reliable contraception are standard of care in women of childbearing potential

— In many states valproate use in WOCBP requires REMS-like documentation and pregnancy testing

— Topiramate doses >200 mg reduce OCP efficacy — counsel on backup or alternative method

— Migraine with aura + estrogen = WHO MEC Category 4 (contraindicated) — documenting the conversation and alternative options is a defensible-practice essential

— Lasmiditan — patients must not drive for 8 hours after dosing (FDA boxed-style warning); document counseling

— Topiramate, amitriptyline cognitive impairment — caution

— Opioids and butalbital are not recommended for migraine — promote MOH, dependence, and worse outcomes

— State PDMP check before any controlled substance; CDC opioid guideline applies

— Document rationale if rescue opioid is ever used

— ED visit for migraine → ensure PCP follow-up within 1–2 weeks, share discharge summary, reconcile new prescriptions (especially steroids, antiemetics)

— Pregnancy planning visit → proactive switch off teratogens before conception, not after positive test

— Chronic migraine qualifies for ADA workplace accommodations (lighting, schedule flexibility, breaks); physician documentation often required

— FMLA paperwork is a legitimate clinical task — document headache days and functional limitations

Step 3 management: Before prescribing topiramate to a 26-yo woman, document pregnancy test, contraception plan, and counseling on cleft palate risk — failure to do so is a documented safety lapse.

Teratogenicity counseling and contraception:

Combined hormonal contraceptive prescribing:

Driving and machinery:

Opioid stewardship:

Transitions of care:

Disability and accommodations:

Mandatory reporting context: severe headache in a pediatric patient with bruising, retinal hemorrhage, or AMS — consider non-accidental trauma and report per state law.

Equity/access: CGRP mAbs and onabotulinumtoxinA are expensive; prior authorization documentation, patient assistance programs, and step-therapy adherence are part of competent management.

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: Triptans + SSRIs/SNRIs carry an FDA serotonin syndrome warning but clinical risk is very low — don't reflexively avoid the combination; counsel and monitor.

Migraine with aura ↑ ischemic stroke risk ~2x — additive with smoking and estrogen contraceptives.

PFO is associated with migraine with aura but closure does NOT reduce migraine frequency (MIST, PREMIUM, PRIMA trials — negative).

CGRP is the dominant neuropeptide of trigeminovascular activation; CGRP infusion triggers migraine in migraineurs.

Cortical spreading depression propagates at ~3 mm/min — explains the slow march of visual aura.

Indomethacin-responsive headaches: paroxysmal hemicrania, hemicrania continua, primary cough/exertional/sexual.

100% oxygen 12–15 L/min via non-rebreather for 15 minutes = acute cluster headache, NOT migraine.

Frovatriptan and naratriptan (longest half-lives) → menstrual mini-prophylaxis.

Sumatriptan SC 6 mg is the fastest-onset triptan formulation (~10 min).

Eletriptan has highest oral efficacy.

Rizatriptan ODT has fastest oral onset.

Dexamethasone single dose after ED migraine reduces 24–72 h recurrence.

CHAMP trial: amitriptyline and topiramate not superior to placebo in pediatric migraine.

Topiramate: paresthesias, weight loss, cognitive fog, kidney stones, acute angle-closure glaucoma, metabolic acidosis, cleft palate.

Valproate: hepatotoxicity, pancreatitis, NTDs, weight gain, hair loss, tremor.

Propranolol: avoid in asthma, depression, cocaine-using patients.

Erenumab: anti-CGRP receptor mAb; others target ligand; erenumab specifically associated with constipation and HTN.

OnabotulinumtoxinA — FDA-approved for chronic migraine ONLY (≥15 d/mo), not episodic.

MOH threshold: triptans/opioids/combinations ≥10 d/mo; simple analgesics ≥15 d/mo, >3 months.

SNOOP10 red flags — memorize for board questions about when to image.

Pregnancy migraine treatment ladder: acetaminophen → metoclopramide → occipital nerve block → consider triptan if disabling.

GCA pearl: jaw claudication has highest LR+ for biopsy-positive disease.

Board Question Stem Patterns

— Answer: Switch to progestin-only or non-hormonal contraception; start a preventive (propranolol or topiramate); continue triptan for acute.

— Answer: Medication overuse headache — taper triptan, initiate preventive, bridge with NSAID or steroid burst.

— Answer: Ubrogepant or lasmiditan for acute; triptans contraindicated.

— Answer: IV metoclopramide, IV magnesium, ± occipital nerve block; avoid valproate, ergots, NSAIDs after 20 weeks.

— Answer: High-dose prednisone now, temporal artery biopsy within 1–2 weeks — GCA, not migraine.

— Answer: CT head non-contrast → LP if CT negative; rule out SAH.

— Answer: OnabotulinumtoxinA or anti-CGRP mAb.

— Answer: MRV — cerebral venous sinus thrombosis; anticoagulate.

— Answer: Cluster headache — 100% O₂ + SC sumatriptan; verapamil prevention.

— Answer: Acute angle-closure glaucoma — stop topiramate, ophthalmology emergent.

— Answer: Blood pressure (HTN signal); also constipation.

Step 3 management: Stems that pair "5+ migraine days/month with disability" or "acute therapy contraindicated" expect you to initiate preventive therapy — passing on prevention is the wrong answer.

Stem 1: 28-yo woman with 6 disabling unilateral throbbing headaches/month, photophobia, nausea, MIDAS 24 — wants to use combined OCPs; she has aura.

Stem 2: 35-yo using sumatriptan 15 days/month with worsening daily headache.

Stem 3: 58-yo man with HTN, DM, prior MI, has migraine without aura.

Stem 4: Pregnant woman at 28 weeks with severe migraine unresponsive to acetaminophen.

Stem 5: 65-yo woman with new headache, scalp tenderness, jaw claudication, ESR 88.

Stem 6: 22-yo with sudden "thunderclap" headache, peak in <1 min.

Stem 7: Chronic migraine ≥15 days/month, failed propranolol and topiramate at adequate doses.

Stem 8: Postpartum day 10 with progressive headache, papilledema, seizure.

Stem 9: Strictly unilateral periorbital pain 8x/day, 30 min each, with lacrimation, ptosis, agitation.

Stem 10: 30-yo on topiramate develops blurred vision, eye pain.

Stem 11: Patient on erenumab 3 months — what to monitor?

One-Line Recap

Migraine is a clinical diagnosis whose long-term outcome hinges on early-onset, stratified acute therapy combined with preventive treatment when headache days or disability cross threshold — all built on lifestyle optimization and vigilance for red-flag mimics.

Board pearl: When in doubt on a migraine question, the answer is usually (1) start a preventive when criteria are met, (2) switch contraception in aura patients, (3) work up red flags before calling it migraine, or (4) stop the overused acute medication — these four moves resolve the majority of Step 3 migraine vignettes.

Acute: NSAIDs for mild, triptans (or gepants/ditans if CV disease) for moderate-severe; add antiemetic; treat early; cap acute days to prevent MOH (<10 d/mo triptans, <15 d/mo simple analgesics).

Preventive indications: ≥4 headache days/month with impairment OR ≥2 with severe disability OR contraindication/failure of acute therapy — choose by comorbidity (propranolol for HTN, topiramate for obesity, amitriptyline for insomnia/depression, candesartan for renal-sparing); escalate to onabotulinumtoxinA (chronic only) or CGRP mAbs after ≥2 oral preventive failures.

Red flags (SNOOP10) mandate neuroimaging: sudden/thunderclap, age >50 new onset, focal deficits, papilledema, systemic symptoms, progressive pattern, postpartum, immunocompromised — never call new headache after 50 "migraine" without an ESR/CRP and MRI.

Special populations: migraine with aura + estrogen contraception = contraindicated; valproate and topiramate teratogenic — document contraception; lasmiditan = 8-hour driving restriction; erenumab = monitor BP; opioids and butalbital have no place in routine migraine care.