1. Cluster Headache 3 rd BIENNIAL HULL-BASH NATIONAL MEETING ON HEADACHE Anish Bahra The National Hospital for Neurology and Neurosurgery Whipps Cross University Hospital

2. Lifetime prevalence Tension-type headache~ 60-80% Migraine headache 15% Cluster Headache 0.1%

3. IHS Classification for Cluster Headache (2004) Severe unilateral orbital, supraorbital and/or temporal painSevere unilateral orbital, supraorbital and/or temporal pain Associated symptoms:Associated symptoms: –Conjunctival injection / Lacrimation –Nasal congestion / Rhinorrhea –Eyelid oedema –Forehead and facial sweating –Ptosis and Miosis –A sense of restlessness / agitation 15-180 minutes duration15-180 minutes duration 1 / alternate days – 8 /day1 / alternate days – 8 /day

4. Cluster Headache – Defining features Strictly unilateral V1 pain + Autonomic features Restlessness / agitation Short-duration / daily / bouts

6. Cluster Headache – Laterality %

7. %

8. Site of pain →V 1 % Retro-orbital92Retro-orbital92 Temporal70Temporal70 Upper teeth50Upper teeth50 Forehead46Forehead46 Jaw45Jaw45 Cheek45Cheek45 % Lower teeth32Lower teeth32 Neck31Neck31 Nose20Nose20 Ear17Ear17 Shoulder13Shoulder13 Vertex7Vertex7 Occiput6Occiput6 Parietal1Parietal1 Bahra A et al. Neurology 2002; 58: 354-361

9. JawV 3JawV 3 CheekV 2CheekV 2 Lower teeth V 3Lower teeth V 3 NeckC 2/3NeckC 2/3 NoseV 2NoseV 2 EarC 2EarC 2 ShoulderC 3/4ShoulderC 3/4 VertexC 2VertexC 2 OcciputC 2OcciputC 2 ParietalC 2ParietalC 2 Retro-orbitalV 1Retro-orbitalV 1 TemporalV 1TemporalV 1 Upper teethV 2Upper teethV 2 ForeheadV 1ForeheadV 1

11. Autonomic Features %

12. % CH – 98% 1 Migraine – 25% 2 1. Torelli, 2001 n=553 2. Obermann, 2007 n=841

13. Attack Duration and Frequency N CH Migraine Duration 15-180 mins 4-72hrs Frequency 1 / day 1-2 / month

14. Additional Features % CH Migraine

15. IHS Classification Criteria for Cluster Headache Episodic Cluster Headache → 90% 7 days - One year Pain-free interval ≥ one month Chronic Cluster Headache → 10% ≥ one year without remission ≥ one year with remissions  one month

17. 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

18. Cluster Headache Paroxysmal hemicrania SUNCT M:F3:11:11.5:1 Episodic:Chronic90:1035:6510:90 Attack Duration15-180 mins2-30 mins5-250s Attack Frequency1-8/day> 5 /day1/day to 30/hr Restlessness90%80%65% PeriodicityPresentRareAbsent Alcohol Trigger+++–

19. All patients ? Cluster Headache & Imaging

20. Aneurysm of the ACA Pituitary tumour AVM of the occipital lobe Vertebral artery aneurysm Meningioma of the cervical canal (C2) Symptomatic Cluster Headache

21. Aneurysm of the ACA Pituitary tumour AVM of the occipital lobe Vertebral artery aneurysm Meningioma of the cervical canal (C2) Symptomatic Cluster Headache

22. Typical or atypical Response to treatment ≡ Primary CH ± Resolution with Rx of precipitating pathology Symptomatic Cluster Headache

23. Phenotype Rx Response Symptomatic Cluster Headache Cannot differentiate b/u Primary & Secondary CH

24. Locker at al. Headache. 2006 ( n = 558) / Ramirez-Lassepas. Arch Neurol. 1997 Predictors of Secondary Headache Predictors of Secondary Headache Any one → Sensitivity 98.6% Likelihood Ratio Age > 50 years* 2.34 Sudden Onset* 1.74 Abnormal neurological examination* 3.56 Additional Features 2.27

25. All patients ? → Need Data New onset Primary CCH Atypical history + Systemic / neurological features Cluster Headache & Imaging

26. Therapeutics

27.  The Sumatriptan Cluster Headache Study Group -1991 Success: 74% Sumatriptan 26% Placebo  Modest further benefit from 12mg  2 & 3mg are effective  No prophylactic benefit  Long term - Well tolerated.  No tachyphylaxis / MOH ABORTIVE THERAPY : SUMATRIPTAN S/C

28. Double-blind cross-over comparison of oxygen 100% inhalation with air 12l / min for 15 minutes ( n=76) * Success: 78% Oxygen 20% Placebo  Recommendation : 7 – 12 l/min for 15 minutes CONCLUSION : Safest treatment but impractical ABORTIVE THERAPY : OXYGEN Fogan, 1985. / Cohen, 2007*

29. Sumatriptan 20mg IN Zolmitriptan 5 and 10mg IN Zolmitriptan 5 and 10mg po Lidocaine IN ABORTIVE THERAPY

30. Sumatriptan 20mg IN Zolmitriptan 5 and 10mg IN Zolmitriptan 5 and 10mg po Lidocaine IN ABORTIVE THERAPY Response at 30 minutes

31. Double-blind placebo controlled cross-over study Lignocaine 10% Intranasal ( n = 9) 37 ± 7.8 mins Lignocaine } p < 0.01 59.3 ± 12.3 mins Placebo } A/Es – Unpleasant taste. Adequate self- administration 4% Lignocaine solution 3-4 drops intranasally ABORTIVE THERAPY : LIGNOCAINE IN Costa et. Al (2000) Cephalalgia ; 20 : 85

32. PREVENTATIVE THERAPY Multiple daily attacks → Prophylaxis

33. PREVENTATIVE THERAPY : VERAPAMIL 240-480mg daily Up to 1200mg daily Start at 80mg tds 40-80mg increments every 10-14 days ECG monitoring every two weeks –Lethargy –Constipation –Pedal oedema –Bradycardia Leone et al. (2000) Neurology ; 54 : 1382

34. Verapamil in Cluster Headache ArrhythmiasNo PatientsMean VPM(mg) Dose ±SD Patients on VPM217512 ± 279 ECGs108587 ± 264 1° Heart Block13578 ± 264 Other HB9604 ± 260 Total arrhythmias21567 ± 290 PR ≤ 0.2s9653 ± 275 Cohen, 2007

35. BradycardiaNo Patients Mean VPM(mg) Dose ±SD Heart Rate (mean) Total108591 ± 26466 Bradycardia39659 ± 25353 Bradycardia → Stop VPM 4495 ± 17249

36. Arrhythmias in patients on VPM + Other Drug Rhythm Lithium5(1)Junctional (after Lithium stopped) Methysergide1(1)1° Heart Block (after Methysergide stopped) Triptans49(8)1° HB (6), 2° HB (1), Junctional (1)

37. 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 –Fibrosis Weight gain Muscle cramps Mood changes

38. PREVENTATIVE THERAPY : LITHIUM 300-1500mg –Level at 4/7 after dose change –Weekly until dose constant for 4 weeks – Then 3 monthly 0.7-1.2 mmol/l Normal renal function and Na + (Li toxicity) Tremor GI side effects ↓ thyroid, euthyroid goitre Ataxia, nystagmus, dysarthria Diabetes Insipidus Drowsiness, confusion, seizures

39. 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 ABORTIVE THERAPY : CORTICOSTEROIDS Jammes (1975) Dis. Nerv. Syst. ; 36 : 375

40. Verapamil – 1200mg daily. ECG monitoring Methysergide – 12mg daily. Avoid > 6/12 use Lithium – 300-1500mg ( Level 0.7-1.2mmol/l) Steroids – 40-80mg. Max. 2 /52. Interim measure  Other considerations → Topiramate / Melatonin / Sodium Valproate / Gabapentin / Ergotamine Preventative Therapy

41. Trigeminal ganglion and nerve Sphenopalatine ganglion Greater superficial petrosal nerve Nervus intermedius Greater Occipital Nerve Hypothalamus SURGICAL THERAPY

42. Greater Occipital Nerve Block

43. Patients (N)No. InjectionsComplete response (N) Partial Response (N) 1922103 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)

44. Occipital Nerve Stimulation Duration (yrs) Mo since ONS Subjective outcome Estimated Change % Patient Recommend Triptan Use 1723Same-NoSame 2627Same-YesSame 3611Improved95YesLess 417 Improved60YesLess 51327Improved20-80YesSame 6248Improved90YesLess 71311Improved25YesSame 85432(23)*Improved40YesLess All13 (6-54) ⌘ 20 (9-27) ⌘ 75% Improved 60 (25-95) ⌘ 88% Yes38% Less Use Burns, The Lancet (2007)

45. CLUSTER HEADACHE PET VBM May et al. (1998) Lancet ; 352 : 275 May et al. (1999) Nat. Med; 5:836

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

47. Sumatriptan 6mg sc High flow oxygen IN Sumatriptan / IN or Po Zolmitriptan IN Lidocaine Verapamil Methysergide Lithium Topiramate Corticosteroids Local V / Upper Cervical nerve block Local V / Upper Cervical neurostimulation Central neurostimulation Cluster Headache