Cluster headache

✨ Classification of TACs

TACs are a group of primary headache disorders characterised by unilateral head pain associated with ipsilateral cranial autonomic symptoms. They include:

Type	Typical Attack Duration	Frequency	Gender Ratio	Response to Indomethacin
Cluster Headache (CH)	15–180 min	1–8/day	M > F (3–4:1)	No
Paroxysmal Hemicrania	2–30 min	1–40/day	F > M	Yes
SUNCT/SUNA (Short-lasting unilateral neuralgiform headache attacks)	5–240 sec	Up to 200/day	M > F	No
Hemicrania Continua	Continuous	Superimposed exacerbations	F > M	Yes
Probable trigeminal autonomic cephalalgia	Criteria partially met for above	Variable	–	–

✨ Cluster Headache (CH)

Epidemiology

Prevalence: ~0.1% of general population
Sex Ratio: Males 3–4× more commonly affected than females
Age of Onset:
- Typically 20–40 years in males
- Onset peaks in 60s for females (notably in Black women)
Genetics:
- Autosomal dominant inheritance reported in ~5% of CH patients
- Linkage to chromosome 2q14 and hypothalamic dysfunction implicated

✨Pathophysiology

Hypothalamic activation (esp. posterior hypothalamus) → triggers trigeminal-autonomic reflex arc
Secondary activation of:
- Trigeminal nerve → nociception
- Parasympathetic fibers via sphenopalatine ganglion → cranial autonomic symptoms
Circadian rhythmicity suggests suprachiasmatic nucleus involvement
Pituitary pathology (e.g., microadenoma, meningioma) may mimic or precipitate cluster symptoms

✨ Clinical Features of Cluster Headache

Headache Characteristics

Feature	Description
Pain intensity	Excruciating, deep, stabbing, lancinating (often described as the “worst pain imaginable”)
Laterality	Strictly unilateral
Site	Orbital, supraorbital, temporal ± radiation to upper jaw, teeth, neck
Quality	Burning, drilling, or pulsating
Behaviour	Patient is agitated, restless, may pace or rock (contrast with migraine patients who seek dark, quiet rooms)

Attack Pattern

Frequency: 1 every other day to 8/day
Duration: 15 to 180 minutes (untreated)
Periodicity: Occurs in clusters over weeks to months, often with seasonal (spring/autumn) predilection
Chronobiology: Attacks often occur at the same time each day (nocturnal, REM-related onset common)

Associated Autonomic Symptoms (≥1 required for diagnosis):

Conjunctival injection (red eye)
Lacrimation (tearing)
Rhinorrhoea or nasal congestion
Eyelid oedema
Forehead/facial sweating or flushing
Miosis and/or ptosis (Horner’s syndrome, ~30%)
Sensation of fullness in ear

✨ Diagnostic Criteria (ICHD-3 Beta)

A. ≥5 attacks fulfilling criteria B–D
B. Severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15–180 min
C. At least one of the following ipsilateral autonomic symptoms:

Conjunctival injection/lacrimation
Nasal congestion/rhinorrhoea
Eyelid oedema
Forehead/facial sweating
Miosis/ptosis
Sense of restlessness/agitation
D. Frequency: 1 attack every other day to 8/day
E. Not better accounted for by another ICHD-3 diagnosis

✨ Triggers

Alcohol (almost universally provokes an attack during an active cluster period)
Nitroglycerin
Vasodilators
Strong smells: petroleum, nail polish, paint thinners
Sleep apnoea (OSA screening warranted in refractory cases)

✨Red Flags

Any atypical presentation (e.g., bilateral headache, prolonged duration) warrants imaging
Pituitary tumours or Rathke’s cleft cysts may mimic cluster headache → MRI brain with dedicated pituitary sequences is essential

✨ Differential Diagnosis

Condition	Distinguishing Features
Migraine	Photophobia, phonophobia, nausea common; prefers rest; longer duration; aura present in ~30%
Paroxysmal Hemicrania	Shorter attacks (2–30 min), more frequent, responds dramatically to indomethacin
Hemicrania Continua	Continuous unilateral pain with superimposed exacerbations; also indomethacin responsive
SUNCT/SUNA	Ultra-short (<4 mins), very high frequency (up to 200/day); eye redness and tearing prominent
Trigeminal Neuralgia	Electric-shock pain, triggered by touch, chewing, usually V2/V3 (vs CH which involves V1)
Tension-Type Headache	Bilateral, non-pulsating, mild-moderate, no autonomic signs
Secondary headache	Consider pituitary mass, carotid dissection, orbital pathology, sinus disease, AVM, etc.

✨ Acute Management of Cluster Headache

First-Line Abortive Therapies

Agent	Dose	Notes
Oxygen therapy	100% O₂ via non-rebreather mask at 12–15 L/min for 15–20 mins	Rapid relief in ~75%
Sumatriptan SC	6 mg SC	Relief within 10–15 min
Sumatriptan IN	20 mg (may repeat once in 24 hrs)	Less effective than SC
Rizatriptan	10 mg PO	Oral agents less reliable
Zolmitriptan	2.5–5 mg PO	Alternative if SC unavailable

Second-Line / Bridging Therapies

Intranasal lidocaine (4–10%)
- 1 mL IN or soaked cotton swab
- Onset in 5–15 mins
Indomethacin: Useful if diagnosis uncertain or overlapping with hemicrania
Capsaicin (intranasal): Desensitises C-fibers in trigeminal pathways

✨Preventive Management

First-Line: Verapamil

Best evidence-based agent for CH prophylaxis
Dosing strategy:
- Start: 80 mg TID for 1–2 weeks
- Titrate up to 120 mg TID → Max: 480–960 mg/day
- ECG monitoring required: risk of bradycardia, heart block

Bridging: Prednisolone

Start 50 mg/day × 5 days, taper by 12.5 mg every 3 days (per ETG/Australian guidelines)

Alternatives (Second-Line/Adjuncts)

Agent	Dose	Notes
Melatonin	9–10 mg nocte	Mild to moderate efficacy
Galcanezumab (Emgality)	300 mg SC monthly	Anti-CGRP monoclonal; PBS criteria may apply
Lithium carbonate	300 mg BID (target serum: 0.4–0.8 mmol/L)	Useful in chronic CH; monitor thyroid and renal function
Topiramate	25–100 mg daily	Consider cognitive side effects
Gabapentin	300–900 mg/day	Less evidence; may assist in overlapping neuralgiform pain
Occipital nerve block	Methylprednisolone + bupivacaine	Useful in episodic CH, especially during cluster bouts

✨ Refractory Cluster Headache

Occipital nerve stimulation
Sphenopalatine ganglion stimulation
Deep brain stimulation (posterior inferior hypothalamus)
➤ Reserved for intractable chronic CH under expert supervision