Key Facts

Cluster headache is the most painful primary headache disorder. Rapid treatment of acute attacks and effective prophylaxis during cluster periods are essential. Patients are often restless and agitated during attacks (unlike migraine where patients prefer to lie still).

Epidemiology

Prevalence ~0.1% (1 in 1,000). M:F 3-4:1. Mean age of onset 28-30 years. Episodic form (~80%): attacks cluster over 4-12 weeks, then remit for months-years. Chronic form (~20%): no remission for >3 months.

Aetiology

• Hypothalamic dysfunction is central to pathogenesis (circadian and circannual rhythms)
• Risk factors: male sex, smoking (>90% of patients are smokers), family history (14× risk in first-degree relatives), head trauma

Pathophysiology

Activation of the trigeminal-autonomic reflex: trigeminovascular pathway activation → pain; parasympathetic activation (via superior salivatory nucleus and sphenopalatine ganglion) → autonomic features. Hypothalamic activation (posterior hypothalamus — 'pacemaker' for attacks) explains circadian rhythmicity. PET imaging shows posterior hypothalamic grey matter activation during attacks.

Attack Features

• Excruciating unilateral orbital/supraorbital/temporal pain (often described as drilling, burning, stabbing)
• Duration: 15-180 minutes (usually 45-90 minutes)
• Frequency: 1-8 attacks per day
• Restlessness/agitation: patients pace, rock, bang head — CANNOT lie still (key distinction from migraine)

Ipsilateral Autonomic Features (≥1)

• Conjunctival injection and/or lacrimation
• Nasal congestion and/or rhinorrhoea
• Eyelid oedema
• Forehead/facial sweating
• Miosis and/or ptosis (partial Horner syndrome)

Temporal Pattern

• Episodic (~80%): cluster bouts lasting 4-12 weeks; remission periods ≥3 months
• Chronic (~20%): attacks continue for >1 year without remission (or remission <3 months)

Red Flags

• First-ever cluster-like headache with neurological signs → consider secondary causes (MRI to exclude pituitary tumour, cavernous sinus pathology)
• Atypical features or poor treatment response → neuroimaging mandatory

Clinical Diagnosis

• Diagnosis is clinical based on ICHD-3 criteria
• MRI brain (with pituitary views): NICE CG150 recommends in all cluster headache patients to exclude secondary causes (pituitary tumour, cavernous sinus pathology)

Monitoring During Treatment

• ECG: before and during verapamil (PR interval prolongation — check ECG at baseline and with each dose increase)
• Lithium levels: if on lithium (therapeutic range 0.4-0.8 mmol/L for headache)
• Renal function and TFTs: if on lithium

Acute Treatment (NICE CG150)

• 100% oxygen: 12-15 L/min via non-rebreather mask for 15-20 minutes; effective in ~80%; no side effects; first-line
• SC sumatriptan 6mg: rapid onset; effective in ~75%; max 2 injections/24h (separated by ≥1 hour)
• Intranasal sumatriptan 20mg or zolmitriptan 5mg nasal: alternatives if SC not tolerated
• Oral triptans are TOO SLOW for cluster headache (attack resolves before oral absorption)
• Do NOT use: opioids, paracetamol, NSAIDs (ineffective for cluster headache)

Transitional Prophylaxis (Bridge)

• Prednisolone: 60-100mg OD for 5 days then taper over 2-3 weeks; rapid onset of action while long-term prophylaxis takes effect
• Greater occipital nerve block: suboccipital injection of local anaesthetic ± steroid

Long-Term Prophylaxis

• Verapamil 240-960mg/day in divided doses: first-line; dose titrated every 2 weeks; ECG monitoring essential (PR prolongation, heart block)
• Lithium carbonate 400-800mg/day: especially for chronic cluster; monitor levels, renal function, TFTs
• Topiramate 50-200mg/day: second-line
• Melatonin 10mg ON: some evidence, well-tolerated

Refractory

• Galcanezumab 300mg SC monthly (anti-CGRP): NICE TA for episodic cluster headache
• Occipital nerve stimulation: NICE IPG for chronic refractory cluster headache
• Sphenopalatine ganglion stimulation: emerging therapy

Lifestyle

• Absolute alcohol avoidance during cluster period (potent trigger)
• Smoking cessation
• Maintain regular sleep pattern

Referral Criteria

• All cluster headache: neurology/headache clinic (NICE CG150)
• Refractory: specialist headache centre for neuromodulation

Episodic cluster headache: cluster bouts typically last 4-12 weeks; ~80% remain episodic. ~20% evolve to chronic form. Chronic cluster: may remit spontaneously in some. Cluster headache does not shorten life expectancy but causes profound disability during active periods. Suicide risk is elevated (termed 'suicide headache'). Most patients respond well to oxygen and verapamil. Significant diagnostic delay is common (mean ~5 years from onset to diagnosis).

Trigeminal Autonomic Cephalalgias Comparison