Residency · Residency · Neurology
Trigeminal Autonomic Cephalalgias
Introduction
The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders characterized by unilateral head pain with prominent ipsilateral cranial autonomic features. Despite being less common than migraine, TACs cause extreme suffering, and accurate classification is essential because each subtype responds to different treatments.
| Feature | Cluster Headache | Paroxysmal Hemicrania | SUNCT/SUNA | Hemicrania Continua |
|---|---|---|---|---|
| Duration | 15–180 min | 2–30 min | 1–600 sec | Continuous |
| Frequency | 1–8/day | ≥ 5/day | Up to 200/day | Continuous with exacerbations |
| Sex predominance | Male 3:1 | Female | Equal or male | Female |
| Key treatment | O2, SC sumatriptan | Indomethacin (absolute) | Lamotrigine | Indomethacin (absolute) |
| Prevention | Verapamil | Indomethacin | Lamotrigine, topiramate | Indomethacin |
Shared Features of TACs
All TACs share strictly unilateral pain in the trigeminal (V1) distribution accompanied by ipsilateral cranial autonomic symptoms including lacrimation, conjunctival injection, nasal congestion or rhinorrhea, eyelid edema, forehead and facial sweating, miosis, and ptosis. The underlying mechanism involves activation of the trigeminal-autonomic reflex, in which trigeminal afferents activate the superior salivatory nucleus, producing parasympathetic outflow via the sphenopalatine ganglion. The posterior hypothalamus is the putative pacemaker driving attack periodicity.
Cluster Headache
Epidemiology
Cluster headache has a prevalence of approximately 0.1% with a 3:1 male-to-female ratio. Onset is typically between ages 20 and 40. The episodic form (90% of cases) consists of cluster periods lasting weeks to months separated by remission periods of 3 months or more. The chronic form (10%) involves attacks occurring for more than 1 year without remission or with remission shorter than 3 months.
Clinical Features
The pain is excruciating, strictly unilateral, and located in the periorbital or temporal region. Attack duration is 15-180 minutes, typically 45-90 minutes. Attacks occur 1-8 times per day, often at the same time daily (circadian regularity). Prominent ipsilateral autonomic features include lacrimation, conjunctival injection, nasal congestion, ptosis, and miosis. Patients characteristically exhibit restlessness and agitation during attacks, in contrast to migraine patients who prefer stillness. Triggers during the cluster period include alcohol, nitroglycerin, and strong odors.
Acute Treatment
High-flow oxygen (100% at 12-15 L/min via non-rebreather mask for 15-20 minutes) is first-line and effective in approximately 78% of attacks. Sumatriptan 6 mg subcutaneous is effective within 15 minutes, limited to 2 injections per day. Zolmitriptan 5 mg nasal spray is an alternative. Oral triptans are too slow for cluster headache attacks. Intranasal lidocaine (4%) provides adjunctive therapy targeting the sphenopalatine ganglion.
Preventive Treatment
Verapamil (240-960 mg/day) is the first-line preventive, with baseline and serial ECGs required due to the risk of heart block at the high doses used. Short-course corticosteroids (prednisone 60-80 mg tapering over 2-3 weeks) serve as transitional bridge therapy. Lithium (600-1200 mg/day) is effective for chronic cluster headache but requires monitoring of levels, renal function, and thyroid function. Galcanezumab (300 mg subcutaneously monthly) is FDA-approved for episodic cluster headache as the first CGRP monoclonal antibody approved for this indication. Greater occipital nerve block using local anesthetic plus corticosteroid provides transitional therapy.
Paroxysmal Hemicrania
Clinical Features
Paroxysmal hemicrania produces unilateral severe pain in the periorbital or temporal region. Attack duration is 2-30 minutes (shorter than cluster). Frequency is 5 or more attacks per day (more frequent than cluster). Prominent cranial autonomic features are present. Unlike cluster headache, it affects women more than men.
Diagnosis and Treatment
An absolute response to indomethacin is a defining diagnostic criterion according to ICHD-3. Dosing starts at 25 mg three times daily, titrated to 50-75 mg three times daily at the lowest effective dose. GI prophylaxis with a proton pump inhibitor is recommended. For indomethacin-intolerant patients, celecoxib, verapamil, or topiramate may be considered (limited evidence). The "indotest" using rapid IV or IM indomethacin challenge can confirm the diagnosis.
Short-Lasting Unilateral Neuralgiform Headache Attacks
SUNCT and SUNA
SUNCT (Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing) requires both conjunctival injection and lacrimation. SUNA (Short-lasting Unilateral Neuralgiform headache attacks with cranial Autonomic symptoms) requires only one or neither of conjunctival injection or lacrimation. Attack duration is 1-600 seconds (typically 5-240 seconds). Frequency can reach up to 200 attacks per day. Attacks can be triggered by cutaneous stimuli, mimicking trigeminal neuralgia.
Treatment
Acute treatment is impractical due to the ultra-short attack duration. For prevention, lamotrigine (200-400 mg/day) is first-line. Topiramate, gabapentin, and carbamazepine may also be effective. Refractory cases may benefit from occipital nerve stimulation or deep brain stimulation.
Hemicrania Continua
Hemicrania continua is a continuous, strictly unilateral headache with fluctuating intensity. There is mild-to-moderate baseline pain with exacerbations of moderate-to-severe pain. Ipsilateral autonomic features accompany the exacerbations. Like paroxysmal hemicrania, it shows an absolute response to indomethacin. It must be distinguished from chronic migraine, which can also be unilateral with autonomic features.
Diagnostic Approach
Evaluation requires a detailed headache diary documenting attack duration, frequency, laterality, and autonomic features. MRI brain with pituitary protocol should be performed to exclude structural lesions, especially in atypical presentations. An indomethacin trial is indicated for suspected paroxysmal hemicrania or hemicrania continua. ESR and pituitary function tests should be obtained when indicated.
Clinical Pearls
Attack duration is the most useful feature for distinguishing TAC subtypes: cluster headache lasts 15-180 minutes, paroxysmal hemicrania 2-30 minutes, and SUNCT/SUNA 1-600 seconds. Oxygen and subcutaneous sumatriptan are first-line acute treatments for cluster headache; oral triptans are too slow. An absolute response to indomethacin defines paroxysmal hemicrania and hemicrania continua; indomethacin should always be trialed in suspected cases. Verapamil requires ECG monitoring due to the risk of heart block at the high doses used for cluster headache prevention.
References
- May A, Schwedt TJ, Magis D, et al. Cluster headache. Nat Rev Dis Primers. 2018;4:18006.
- Goadsby PJ, Cittadini E, Burns B, Cohen AS. Trigeminal autonomic cephalalgias: diagnostic and therapeutic developments. Curr Opin Neurol. 2008;21(3):323-330.
- Cittadini E, Matharu MS, Goadsby PJ. Paroxysmal hemicrania: a prospective clinical study of 31 cases. Brain. 2008;131(4):1142-1155.
- Goadsby PJ, Dodick DW, Leone M, et al. Trial of galcanezumab in prevention of episodic cluster headache. N Engl J Med. 2019;381(2):132-141.