Cluster Headache Anish Bahra The National Hospital for Neurology and Neurosurgery Whipps Cross University Hospital

Classification of Headache Disorders 1. Migraine Migraine 2. Tension-Type Headache Tension-Type Headache 3. Trigeminal Autonomic Cephalalgias Trigeminal Autonomic Cephalalgias 4. Other Primary Headaches Other Primary Headaches

Trigeminal Autonomic Cephalalgias Cluster HeadacheCluster Headache Paroxysmal HemicraniaParoxysmal Hemicrania SUNCT Short-lasting Unilateral Neuralgiform attacks Conjunctival injection & TearingSUNCT Short-lasting Unilateral Neuralgiform attacks Conjunctival injection & Tearing Goadsby PJ, Lipton RB. Brain 1997;120:

1. Migraine Migraine15-18% 2. Tension-Type Headache Tension-Type Headache ~ 60-80% 3.1 Cluster Headache Cluster Headache0.1% 3.2 Paroxysmal Hemicrania Paroxysmal HemicraniaLess 3.3 SUNCT SUNCT 4.1 Stabbing Headache 4.2 Cough Headache Cough Headache 4.3 Exertional Headache Exertional Headache 4.4 Sexual Headache Sexual Headache 4.5 Hypnic Headache Hypnic Headache 4.6 Thunderclap Headache Thunderclap Headache 4.7 Hemicrania Continua Hemicrania Continua 4.8 New persistent Daily Headache New persistent Daily Headache

Diagnosis of Cluster Headache

Trigeminal Autonomic Cephalalgias Strictly unilateral head and facial pain (V1) Strictly unilateral head and facial pain (V1) Ipsilateral autonomic features Ipsilateral autonomic features Short-lived attacksShort-lived attacks Multiple daily attacks Multiple daily attacks Active bouts and remissions / no remissions Active bouts and remissions / no remissions

Cluster Headache – Laterality %

Jaw45Jaw45 Cheek45Cheek45 Lower teeth 32Lower teeth 32 Neck31Neck31 Nose20Nose20 Ear17Ear17 Shoulder13Shoulder13 Vertex7Vertex7 Occiput6Occiput6 Parietal1Parietal1 Retro-orbital92 %Retro-orbital92 % Temporal70Temporal70 Upper teeth50Upper teeth50 Forehead46Forehead46 Bahra A et al. Neurology 2002; 58:

Autonomic Features N Lacrimation % Lacrimation % Conjunctival injection Conjunctival injection Nasal congestion Nasal congestion Rhinorrhoea Rhinorrhoea Ptosis / Eye-lid swelling Ptosis / Eye-lid swelling Bahra A et al. Neurology 2002; 58: 354 → Prospective 2.Manzoni et al. Cephalagia 1983; 3: 21 3.Ekbom. Acta. Neurol. Scand. 1970; 46 (suppl.41)

Ipsilateral autonomic features Ipsilateral autonomic features Conjunctival injectionConjunctival injection LacrimationLacrimation Nasal congestionNasal congestion RhinorrheaRhinorrhea Eye-lid oedemaEye-lid oedema Forehead & facial sweatingForehead & facial sweating Ptosis and miosisPtosis and miosis Parasympathetic Sympathetic

Trigeminal Autonomic Cephalalgias Strictly unilateral head and facial pain (V1) Strictly unilateral head and facial pain (V1) Ipsilateral autonomic features Ipsilateral autonomic features Short-lived attacksShort-lived attacks Multiple daily attacks Multiple daily attacks Active bouts and remissions / no remissions Active bouts and remissions / no remissions

Attack Duration and Frequency N Duration < Freq/day 5 2/wk to >8/day 3

Trigeminal Autonomic Cephalalgias Strictly unilateral head and facial pain (V1) Strictly unilateral head and facial pain (V1) Ipsilateral autonomic features Ipsilateral autonomic features Short-lived attacksShort-lived attacks Multiple daily attacks Multiple daily attacks Episodic / Chronic Episodic / Chronic

Cluster Headache : Active Bouts & Remissions Episodic Cluster Headache 7 days - One year Pain-free interval ≥ one month Chronic Cluster Headache ≥ one year without remission ≥ one year with remissions  one month * Interictal pain

N (230) Every 2 yrs Every 18 /12 1 / year2 / year4 / year3 / year Bouts per year Bahra et al. Neurology 2002

Other Distinctive Features RestlessnessRestlessness Periodicity – Diurnal and SeasonalPeriodicity – Diurnal and Seasonal Alcohol TriggeringAlcohol Triggering

Cluster period onsets (n) Month Kudrow (1987) Headache

1mg s/l nitroglycerine provocation During (n=28) and out (n=15) of active bout Attack precipitated in ALL during active bout No attack precipitated out of the bout Ekbom, K. Arch Neurol 1968; 19: 487 Cluster Headache Attack Provocation

Cluster Headache Severe unilateral orbital, supraorbital and/or temporal pain Conjunctival injection Lacrimation Nasal congestion Rhinorrhea Eye-lid oedema Forehead & facial sweating Ptosis and miosis 15min to 3 hours attack duration 1 / alternate days - 8 attacks / day ~ Daily 7 days - 1 yr with ≥ one month remission (~ 90%) A sense of restlessness / agitation

Differential Diagnosis of Cluster Headache

Differential Diagnosis MigraineCHPHSUNCT Trigeminal Neuralgia

MigraineCH Strictly unilateral 3099 Nausea8245 Vomiting5020 Motion  ~ 90  ~ 90  Photophobia8360 Phonophobia8630 Aura8018 Lacrimation4495 Conjunctival injection 2462 Nasal Congestion 2545 Rhinorrhoea2265 Rasmussen 1991, Ekbom 1970

MigraineCH Strictly unilateral 3099 Nausea8245 Vomiting5020 Motion  ~ 90  ~ 90  Photophobia8360 Phonophobia8630 Aura8018 Lacrimation4495 Conjunctival injection 2462 Nasal Congestion 2545 Rhinorrhoea2265 Rasmussen 1991, Ekbom 1970

Aneurysm of the ACA Pituitary tumour AVM of the occipital lobe Aneurysm of the vertebral artery Meningioma of the cervical canal (C2) Symptomatic Cluster Headache

Locker at al. Headache ( n = 558) / Ramirez-Lassepas. Arch Neurol Predictors of Secondary Headache Predictors of Secondary Headache * Any one → Sensitivity 98.6% & specificity 34.4% Likelihood Ratio Age > 50 years* 2.34 Sudden Onset* 1.74 Abnormal neurological examination* 3.56 Additional Features 2.27

N

Treatment of Cluster Headache

Abortive Therapy : Sumatriptan 6mg sc The Sumatriptan Cluster Headache Study Group Modest > benefit from 12mg 2 & 3mg are effective No prophylactic benefit Long term - Well tolerated. No medication overuse 74 26

Abortive Therapy : Oxygen Cohen 2007 Oxygen 100% 12l/min Mask holes covered For multiple daily attacks Safe but impractical ‘Rationalising oxygen use to improve patient safety and reduce waste’ 78 20

Sumatriptan 20mg IN (A) Zolmitriptan 5 and 10mg IN (A/B) Zolmitriptan 5 and 10mg po (B) Lidocaine IN (B) ABORTIVE THERAPY

Sumatriptan 20mg IN (A) Zolmitriptan 5 and 10mg IN (A/B) Zolmitriptan 5 and 10mg po (B) Lidocaine IN (B) ABORTIVE THERAPY Response at 30 minutes

PREVENTATIVE THERAPY : VERAPAMIL 240 – 960mg daily Start at 80mg tds 40-80mg increments every days ECG monitoring every two weeks –Lethargy –Constipation –Pedal oedema –Bradycardia Leone et al. (2000) Neurology ; 54 : 1382

Verapamil in Cluster Headache ArrhythmiasNo PatientsMean VPM(mg) Dose ±SD Patients on VPM ± 279 ECGs ± 264 1° Heart Block13578 ± 264 Other HB9604 ± 260 Total arrhythmias21567 ± 290 PR ≤ 0.2s9653 ± 275 Cohen, 2007

PREVENTATIVE THERAPY : METHYSERGIDE 3-6mg : Increase in one week Then 1mg / week Up to 12mg daily BNF – 6 months then drug holiday –Nausea and vomiting –Abdominal discomfort –Vasoconstrictive effects –Organ Fibrosis Weight gain Muscle cramps Mood changes

Preventative Therapy : Lithium Tremor GI side effects ↓ thyroid, euthyroid goitre Ataxia, nystagmus, dysarthria Diabetes Insipidus Caution re Drug Interactions

Preventative Therapy : Lithium mg Level at 4/7 after dose change Weekly until dose constant for 4 weeks Then 3 monthly mmol/l Normal renal function and Na + (Li toxicity)

Short-term use for multiple daily attacks Attacks recur once the dose is decreased 40-80mg for 5 – 7 days Taper thereafter over 2 weeks Simultaneously introduce a suitable prophylactic Preventative Therapy : Corticosteroids Jammes (1975) Dis. Nerv. Syst. ; 36 : 375

Topiramate (B) Ergotamine tartrate (B) Ergotamine tartrate (B) Valproic acid (C) Valproic acid (C) Melatonin (C) Melatonin (C) Gabapentin (C) Gabapentin (C) Pizotifen (C) Pizotifen (C) Preventative Therapy EFNS Guidelines for the Management of Cluster Headache 2006

Topiramate 800mg Ergotamine tartrate 10mg Ergotamine tartrate 10mg Valproic acid 2g Valproic acid 2g Melatonin 15 mg Melatonin 15 mg Gabapentin 3.6g Gabapentin 3.6g Pizotifen 4mg Pizotifen 4mg Preventative Therapy

Trigeminal ganglion and nerve Sphenopalatine ganglion Greater superficial petrosal nerve Nervus intermedius Greater Occipital Nerve Hypothalamus Surgical Therapy

Cervicotrigeminal Modulation

Greater Occipital Nerve Block Patients (N)No. InjectionsComplete response (N) Partial Response (N) Mean 17 days 3 Mean 52 days AUDIT. Afridi et al. Pain 2006 Patients N=23Treatment GroupPlacebo Complete response at 1/5211None Complete response at 4/528None Ambrosini et al. Pain (2005)

Occipital Nerve Stimulation Cluster Headache Burns et al. Lancet, 2007 Improvement

Leone et al. (2001) NEJM ; 345 : 1428 Cluster Headache - Stereotactic Stimulation of the Posterior Hypothalamic Gray Matter May et al. (1998) Lancet ; 352 : 275

Cluster Headache: Summar y Strictly unilateral head pain + autonomic featuresStrictly unilateral head pain + autonomic features mins & daily15-180mins & daily Restless during attacks Restless during attacks Woken early hours a.mWoken early hours a.m Active bouts & remissionsActive bouts & remissions Acute Sc Sumatriptan (A) High flow oxygen (A)Prevention Verapamil (A) Methysergide (B) Lithium (B) Steroids (A) Topiramate (B) Occipital nerve block

Cluster Headache: Summar y Acute Sc Sumatriptan (A) High flow oxygen (A)Prevention Verapamil (A) Methysergide (B) Lithium (B) Steroids (A) Topiramate (B) Occipital nerve block