Trigeminal Autonomic Cephalalgias
Trigeminal Autonomic Cephalalgias
What You'll Learn
- TACs: unilateral headache + ipsilateral cranial autonomic features mediated by the trigeminal-parasympathetic reflex
- Cluster headache: male predominance (3–4:1), 15–180 min attacks, circadian/circannual periodicity; acute: 100% O2 12–15 L/min + sumatriptan 6 mg SC; preventive: verapamil (requires ECG monitoring)
- Paroxysmal hemicrania: female predominance, shorter attacks (2–30 min), >5/day, absolute indomethacin response (diagnostic criterion)
- SUNCT/SUNA: shortest attacks (1–600 sec), highest frequency (3–200/day), first-line treatment lamotrigine; must exclude pituitary adenoma
- Hemicrania continua: continuous unilateral headache with exacerbations + autonomic features; absolute indomethacin response (diagnostic criterion)
- Key differentiator: cluster = restlessness/pacing; migraine = lying still in dark
- Indomethacin-responsive TACs: PH and HC (NOT cluster)
HighYield Pearls
- TAC definition: ALL TACs = strictly unilateral pain + ipsilateral cranial autonomic features (conjunctival injection, lacrimation, rhinorrhea/congestion, ptosis/miosis, facial sweating/flushing, eyelid edema) ± restlessness; bilateral pain should prompt reconsideration
- Cluster headache: unilateral orbital/temporal severe pain 15–180 min, 1–8 attacks/day, circadian + circannual periodicity (nocturnal “alarm-clock”), MALE predominance (3:1), restlessness/agitation (paces)
- Cluster acute: HIGH-FLOW O2 12–15 L/min via NRB ×15 min + SC SUMATRIPTAN 6 mg; AVOID opioids
- Cluster prevention: VERAPAMIL (high-dose, ECG monitoring for PR prolongation/AV block), galcanezumab (only CGRP mAb FDA-approved for episodic CH), brief steroid bridge, greater occipital nerve block
- Paroxysmal hemicrania (PH): unilateral 2–30 min ×5–40+/day, FEMALE predominance, ABSOLUTE response to INDOMETHACIN (diagnostic); celecoxib/topiramate if intolerant
- SUNCT vs. SUNA: ultra-short attacks 1–600 sec, 3–200/day; SUNCT = conjunctival injection AND tearing; SUNA = one or neither but with another autonomic feature; LAMOTRIGINE first-line; IV lidocaine for status
- Hemicrania continua (HC): CONTINUOUS unilateral pain + episodic exacerbations with autonomic features ± migrainous features; ABSOLUTE response to INDOMETHACIN (diagnostic); side-locked
- Indomethacin-responsive headaches: PH and HC (mnemonic: “PHat HC”) — absolute response is diagnostic; 25 mg TID titrated to 75 mg TID with GI prophylaxis
- MRI brain + pituitary (microadenoma, posterior fossa neurovascular conflict) is mandatory in SUNCT/SUNA; in cluster headache, image when atypical features are present (refractory, abnormal neurologic exam, older onset, side-locked new headache, suspicion for secondary TAC) — not required for every typical cluster
- Differential traps: trigeminal neuralgia (V2/V3 stabs, no autonomic features, refractory period present); cavernous sinus / pituitary macroadenoma / ICA dissection / posterior fossa lesion as secondary causes
🔍 Quick ReferenceClinical · Treatment / response pattern
Clinical phenotype
- “Alarm-clock” nocturnal attacks + restlessness/pacing + male → Cluster headache
- “Worst headache, like an ice pick or hot poker behind the eye” → Cluster headache
- Alcohol triggers attacks only during a cluster bout + seasonal/circannual pattern → Cluster headache
- V1 distribution pain + partial Horner syndrome (ptosis/miosis) ipsilateral → Cluster headache (can persist between bouts)
- Brief 2–30 min attacks, many per day, female → Paroxysmal hemicrania
- Ultra-brief 1–600 sec stabs with conjunctival injection AND tearing → SUNCT
- Ultra-brief stabs with only one (or neither) of injection/tearing but another autonomic feature → SUNA
- Cutaneous triggers (light touch, chewing, brushing teeth, wind) with NO refractory period → SUNCT/SUNA (refractory period present = trigeminal neuralgia)
- Continuous side-locked unilateral baseline pain + autonomic exacerbations → Hemicrania continua
Treatment / response pattern
- High-flow O2 12–15 L/min + SC sumatriptan 6 mg aborts attack → Cluster headache
- Verapamil first-line preventive (ECG for PR prolongation) → Cluster headache
- Greater occipital nerve block as bridge to verapamil → Cluster headache
- Galcanezumab / CGRP mAb FDA-approved for prevention → Episodic cluster headache
- ABSOLUTE response to indomethacin (diagnostic) → Paroxysmal hemicrania & Hemicrania continua (“PHat HC”)
- Lamotrigine first-line (slow titration for SJS risk) → SUNCT/SUNA
- IV lidocaine for refractory status → SUNCT/SUNA
- Mandatory pituitary MRI for SUNCT-like presentation → SUNCT/SUNA (microadenoma mimic)
- Opioids ineffective / avoid in ALL TACs → All TACs
TAC Overview & Pathophysiology
Trigeminal-Parasympathetic Reflex
- Afferent: V1 (ophthalmic) trigeminal afferents → trigeminal nucleus caudalis
- Central relay: trigeminal nucleus → superior salivatory nucleus (pons)
- Efferent: VII nerve parasympathetic outflow → pterygopalatine ganglion → cranial autonomic symptoms
- This reflex arc is the shared mechanism for autonomic features across all TACs
Hypothalamic Role
- Posterior hypothalamus = "pacemaker" — activated in cluster headache (PET, fMRI studies)
- Explains circadian (same time daily) and circannual (seasonal) periodicity
- Basis for deep brain stimulation (DBS) of posterior hypothalamus in refractory cluster
- Hypothalamic activation also seen in PH, SUNCT — suggests shared central generator
Cranial Autonomic Features
| Feature | Mechanism | Notes |
|---|---|---|
| Lacrimation | Parasympathetic (VII → lacrimal gland) | Most common autonomic feature |
| Conjunctival injection | Parasympathetic vasodilation | Key feature in SUNCT |
| Nasal congestion / rhinorrhea | Parasympathetic (VII → nasal mucosa) | Often misdiagnosed as "sinus headache" |
| Ptosis / miosis | Sympathetic dysfunction (partial Horner) | Can become persistent between attacks |
| Eyelid edema | Parasympathetic vasodilation + venous congestion | Ipsilateral only |
| Forehead / facial sweating | Sympathetic dysfunction | Ipsilateral to pain |
💎 Board Pearl
- All TACs are strictly unilateral — bilateral pain should prompt reconsideration of the diagnosis
- Partial Horner syndrome (ptosis + miosis without anhidrosis) can persist between cluster periods — do NOT mistake for a new Horner requiring workup
Cluster Headache
ICHD-3 Diagnostic Criteria
- Pain: severe to very severe, unilateral, orbital/supraorbital/temporal
- Duration: 15–180 minutes (untreated)
- Frequency: 1 every other day to 8 per day
- ≥1 ipsilateral autonomic feature OR sense of restlessness/agitation
- ≥5 attacks fulfilling criteria
Subtypes
| Subtype | Definition |
|---|---|
| Episodic cluster | ≥2 cluster periods lasting 7 days–1 year, separated by remission ≥3 months |
| Chronic cluster | No remission period ≥3 months for ≥1 year (or remissions <3 months) |
Epidemiology & Clinical Features
- Male:female = 3–4:1 (most male-predominant primary headache)
- Onset typically age 20–40 years
- Strong association with smoking (up to 65% of patients)
- Circadian periodicity: attacks at same time daily, often nocturnal (1–2 AM) — "alarm clock headache"
- Circannual periodicity: cluster bouts in spring and fall
- Restlessness/agitation: pacing, rocking, head banging — key distinction from migraine (where patients lie still in dark)
- Alcohol triggers attacks only during a cluster period (not during remission)
Acute Treatment
| Treatment | Dose / Route | Details |
|---|---|---|
| 100% O2 | 12–15 L/min via non-rebreather | First-line; 78% response within 15 min; no side effects; few contraindications (caution in severe COPD/CO2 retention; fire hazard with smoking — high-risk in cluster population) |
| Sumatriptan SC | 6 mg subcutaneous | First-line pharmacologic; fastest triptan onset (5–15 min); can repeat ×1 in 24 h |
| Zolmitriptan intranasal | 5 mg nasal spray | Alternative to SC sumatriptan; effective within 15–30 min |
| Lidocaine intranasal | 4–10% ipsilateral nostril | Adjunctive; targets sphenopalatine ganglion |
Transitional (Bridge) Therapy
- Prednisone burst: 60–100 mg/day ×5 days, then taper over 2–3 weeks
- Greater occipital nerve (GON) block: suboccipital injection of local anesthetic ± corticosteroid
- Purpose: rapid suppression while waiting for preventive agents to reach therapeutic effect
Preventive Treatment
| Agent | Details | Monitoring |
|---|---|---|
| Verapamil | First-line preventive; doses often 240–960 mg/day; slow titration | ECG before initiation and with every dose increase (PR prolongation, AV block) |
| Lithium | More effective for chronic cluster; 600–1200 mg/day | Lithium levels, renal function, thyroid |
| Galcanezumab | FDA-approved for episodic cluster (300 mg SC monthly, administered as 3 consecutive 100-mg SC injections; continue monthly while bout is active); only CGRP mAb with this indication | Injection site reactions |
| Topiramate | Third-line; 100–200 mg/day | Cognitive effects, kidney stones, weight loss |
| Melatonin | 10 mg at bedtime; adjunctive; reflects hypothalamic mechanism | Minimal side effects |
💎 Board Pearl
- Verapamil requires ECG monitoring with each dose increase — risk of PR prolongation and heart block; doses in cluster often exceed standard cardiology doses
- Cluster headache + restlessness/agitation = key distinguishing feature from migraine (patients pace, rock, or bang head)
- Galcanezumab is the only FDA-approved CGRP mAb for episodic cluster headache
Clinical Pearl
- Oral triptans are generally too slow for cluster attacks (15–180 min duration) — always use SC sumatriptan or intranasal zolmitriptan
- Cluster patients frequently present to the ER — high-flow O2 should be tried before opioids (which are ineffective)
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