Cluster HeadacheCluster Headache

Anish BahraAnish Bahra

The National Hospital for Neurology and Neurosurgery

Whipps Cross University Hospital

Classification of Headache DisordersClassification of Headache Disorders

1.1. MigraineMigraine

2.2. Tension-Type HeadacheTension-Type Headache

3.3. Trigeminal Autonomic CephalalgiasTrigeminal Autonomic Cephalalgias

4.4. Other Primary HeadachesOther Primary Headaches

Trigeminal Autonomic CephalalgiasTrigeminal Autonomic Cephalalgias

• Cluster Headache Cluster Headache

• Paroxysmal HemicraniaParoxysmal Hemicrania

• SUNCT SUNCT Short-lasting Unilateral Neuralgiform attacks Conjunctival injection & Short-lasting Unilateral Neuralgiform attacks Conjunctival injection & TearingTearing

Goadsby PJ, Lipton RB. Brain 1997;120:193-209Goadsby PJ, Lipton RB. Brain 1997;120:193-209

1.1. MigraineMigraine 15-18%15-18%

2.2. Tension-Type HeadacheTension-Type Headache ~ 60-80%~ 60-80%

3.13.1 Cluster HeadacheCluster Headache 0.1%0.1%

3.23.2 Paroxysmal HemicraniaParoxysmal Hemicrania LessLess

3.33.3 SUNCTSUNCT

4.14.1 Stabbing HeadacheStabbing Headache

4.24.2 Cough HeadacheCough Headache

4.34.3 Exertional HeadacheExertional Headache

4.44.4 Sexual HeadacheSexual Headache

4.54.5 Hypnic HeadacheHypnic Headache

4.64.6 Thunderclap HeadacheThunderclap Headache

4.74.7 Hemicrania ContinuaHemicrania Continua

4.84.8 New persistent Daily HeadacheNew persistent Daily Headache

Diagnosis of Cluster HeadacheDiagnosis of Cluster Headache

Trigeminal Autonomic CephalalgiasTrigeminal Autonomic Cephalalgias

• Strictly unilateral head and facial pain (V1)Strictly unilateral head and facial pain (V1)

• Ipsilateral autonomic featuresIpsilateral autonomic features

• Short-lived attacksShort-lived attacks

• Multiple daily attacksMultiple daily attacks

• Active bouts and remissions / no remissions Active bouts and remissions / no remissions

Cluster Headache – Laterality%

• JawJaw 4545

• CheekCheek 4545

• Lower teeth 32Lower teeth 32

• NeckNeck 3131

• NoseNose 2020

• EarEar 1717

• ShoulderShoulder 1313

• VertexVertex 77

• OcciputOcciput 66

• ParietalParietal 11

• Retro-orbitalRetro-orbital 92 92 %%

• TemporalTemporal 7070• Upper teethUpper teeth 5050• ForeheadForehead 4646

Bahra A et al. Neurology 2002; 58: 354-361

Autonomic FeaturesAutonomic Features

NN 230 23011 180 18022 10510533

• Lacrimation %Lacrimation % 9191 84 84 86 86

• Conjunctival injectionConjunctival injection 7777 58 58 88 88

• Nasal congestionNasal congestion 7575 48 48 71 71

• RhinorrhoeaRhinorrhoea 7272 43 43 - -

• Ptosis / Eye-lid swellingPtosis / Eye-lid swelling 7474 57 57 - -

1. Bahra A et al. Neurology 2002; 58: 354 → Prospective2. Manzoni et al. Cephalagia 1983; 3: 213. Ekbom. Acta. Neurol. Scand. 1970; 46 (suppl.41)

Ipsilateral autonomic featuresIpsilateral autonomic features

• Conjunctival injection Conjunctival 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 CephalalgiasTrigeminal Autonomic Cephalalgias

• Strictly unilateral head and facial pain (V1)Strictly unilateral head and facial pain (V1)

• Ipsilateral autonomic featuresIpsilateral autonomic features

• Short-lived attacksShort-lived attacks

• Multiple daily attacksMultiple daily attacks

• Active bouts and remissions / no remissions Active bouts and remissions / no remissions

Attack Duration and FrequencyAttack Duration and Frequency

NN 18018022 423 42333 105 10544

DurationDuration 30-120 30-12030-120 30-120 < 30- < 30-180180

Freq/dayFreq/day <1 to >5 2/wk to >8/day <1 to >3 <1 to >5 2/wk to >8/day <1 to >3

Trigeminal Autonomic CephalalgiasTrigeminal Autonomic Cephalalgias

• Strictly unilateral head and facial pain (V1)Strictly unilateral head and facial pain (V1)

• Ipsilateral autonomic featuresIpsilateral autonomic features

• Short-lived attacksShort-lived attacks

• Multiple daily attacksMultiple daily attacks

• Episodic / ChronicEpisodic / Chronic

Cluster Headache : Active Bouts & RemissionsCluster 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 painInterictal pain

N(230)

Ever

y 2

yrs

Ever

y 18

/12

1 / y

ear

2 / y

ear

4 / y

ear

3 / y

ear

Bouts per yearBouts per year

Bahra et al. Neurology 2002

Other Distinctive Features Other Distinctive Features

• RestlessnessRestlessness

• Periodicity Periodicity –– Diurnal and Seasonal Diurnal and Seasonal

• Alcohol TriggeringAlcohol Triggering

Cluster periodonsets (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 ProvocationCluster Headache Attack Provocation

Cluster HeadacheCluster Headache

Severe unilateral Severe unilateral orbital, supraorbital and/or temporal orbital, supraorbital and/or temporal painpain

Conjunctival injection Conjunctival injection LacrimationLacrimationNasal congestionNasal congestionRhinorrheaRhinorrheaEye-lid oedemaEye-lid oedemaForehead & facial sweatingForehead & facial sweating

Ptosis and miosisPtosis and miosis

15min to 3 hours attack duration15min to 3 hours attack duration

1 / alternate days - 8 attacks / day 1 / alternate days - 8 attacks / day

~ Daily 7 days - 1 yr with ~ Daily 7 days - 1 yr with ≥ one month ≥ one month remission (~ 90%)remission (~ 90%)

A sense of restlessness / agitationA sense of restlessness / agitation

Differential Diagnosis of Differential Diagnosis of Cluster HeadacheCluster Headache

Differential Diagnosis

MigraineMigraine CHCH PHPH SUNCTSUNCT Trigeminal Trigeminal NeuralgiaNeuralgia

MigraineMigraine CHCHStrictly unilateral Strictly unilateral 30 99

NauseaNausea 82 45

VomitingVomiting 50 20

Motion Motion ~ 90 ~ 90

PhotophobiaPhotophobia 83 60

PhonophobiaPhonophobia 86 30

AuraAura 80 18

LacrimationLacrimation 44 95

Conjunctival injectionConjunctival injection 24 62

Nasal CongestionNasal Congestion 25 45

RhinorrhoeaRhinorrhoea 22 65

Rasmussen 1991, Ekbom 1970

MigraineMigraine CHCHStrictly unilateral Strictly unilateral 30 99

NauseaNausea 82 45

VomitingVomiting 50 20

Motion Motion ~ 90 ~ 90

PhotophobiaPhotophobia 83 60

PhonophobiaPhonophobia 86 30

AuraAura 80 18

LacrimationLacrimation 44 95

Conjunctival injectionConjunctival injection 24 62

Nasal CongestionNasal Congestion 25 45

RhinorrhoeaRhinorrhoea 22 65

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 HeadacheSymptomatic Cluster Headache

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% & specificity 34.4%

Likelihood Ratio

Age > 50 years*Age > 50 years* 2.34

Sudden Onset*Sudden Onset* 1.74

Abnormal neurological examination*Abnormal neurological examination* 3.56

Additional Features Additional Features 2.27

N

Treatment of Cluster HeadacheTreatment of Cluster Headache

Abortive Therapy : Sumatriptan 6mg scAbortive Therapy : Sumatriptan 6mg sc

The Sumatriptan Cluster Headache Study Group -1991

• Modest > benefit from 12mg

• 2 & 3mg are effective

• No prophylactic benefit

• Long term - Well tolerated.

• No medication overuse

74

26

Abortive Therapy : OxygenAbortive Therapy : Oxygen

Cohen 2007

• Oxygen 100% 12l/min

• Mask holes covered

• For multiple daily attacks

• Safe but impractical

• http://www.impressresp.com/

‘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 ABORTIVE THERAPY

Sumatriptan 20mg IN (A)

Zolmitriptan 5 and 10mg IN (A/B)

Zolmitriptan 5 and 10mg po (B)

Lidocaine IN (B)

ABORTIVE THERAPY ABORTIVE THERAPY

Response at

30 minutes

PREVENTATIVE THERAPY : VERAPAMILPREVENTATIVE THERAPY : VERAPAMIL

• 240 – 960mg 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

Verapamil in Cluster HeadacheVerapamil in Cluster Headache

Arrhythmias No Patients Mean VPM(mg) Dose ±SD

Patients on VPM 217 512 ± 279

ECGs 108 587 ± 264

1° Heart Block 13 578 ± 264

Other HB 9 604 ± 260

Total arrhythmias 21 567 ± 290

PR ≤ 0.2s 9 653 ± 275

Cohen, 2007

PREVENTATIVE THERAPY : METHYSERGIDEPREVENTATIVE 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 : LithiumPreventative Therapy : Lithium

• Tremor

• GI side effects

• ↓ thyroid, euthyroid goitre

• Ataxia, nystagmus, dysarthria

• Diabetes Insipidus

• Caution re Drug Interactions

Preventative Therapy : LithiumPreventative Therapy : Lithium

• 600-1500mg

• 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)

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 TherapyPreventative Therapy : : CorticosteroidsCorticosteroids

Jammes (1975) Dis. Nerv. Syst. ; 36 : 375

• Topiramate (B)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 TherapyPreventative Therapy

EFNS Guidelines for the Management of Cluster Headache 2006

• Topiramate Topiramate 800mg800mg

• Ergotamine tartrate Ergotamine tartrate 10mg 10mg

• Valproic acid Valproic acid 2g2g

• Melatonin Melatonin 15 mg15 mg

• Gabapentin Gabapentin 3.6g3.6g

• Pizotifen Pizotifen 4mg4mg

Preventative TherapyPreventative Therapy

• Trigeminal ganglion and nerve

• Sphenopalatine ganglion

• Greater superficial petrosal nerve

• Nervus intermedius

• Greater Occipital Nerve

• Hypothalamus

Surgical TherapySurgical Therapy

Cervicotrigeminal Modulation

Greater Occipital Nerve BlockGreater Occipital Nerve Block

Patients (N) No. Injections Complete response (N)

Partial Response (N)

19 22 10Mean 17 days

3Mean 52 days

AUDIT. Afridi et al. Pain 2006

Patients N=23 Treatment Group Placebo

Complete response at 1/52 11 None

Complete response at 4/52 8 None

Ambrosini et al. Pain (2005)

Occipital Nerve Stimulation Cluster HeadacheOccipital Nerve Stimulation Cluster Headache

Burns et al. Lancet, 2007Improvement

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: SummarCluster Headache: Summaryy

•Strictly unilateral head Strictly unilateral head pain + autonomic featurespain + autonomic features

•15-180mins & daily15-180mins & daily

• Restless during attacksRestless during attacks

•Woken early hours a.mWoken early hours a.m

•Active bouts & Active bouts & remissionsremissions

AcuteAcute

• Sc Sumatriptan (A)

• High flow oxygen (A)

PreventionPrevention

• Verapamil (A)

• Methysergide (B)

• Lithium (B)

• Steroids (A)

• Topiramate (B)

• Occipital nerve block

Cluster Headache: SummarCluster Headache: Summaryy

AcuteAcute

• Sc Sumatriptan (A)

• High flow oxygen (A)

PreventionPrevention

• Verapamil (A)

• Methysergide (B)

• Lithium (B)

• Steroids (A)

• Topiramate (B)

• Occipital nerve block