Cluster HeadacheCluster Headache

3rd BIENNIAL HULL-BASH NATIONAL MEETING ON HEADACHE

Anish BahraAnish Bahra

The National Hospital for Neurology and Neurosurgery

Whipps Cross University Hospital

Lifetime prevalence

Tension-type headache ~ 60-80%

Migraine headache 15%

Cluster Headache 0.1%

IHS Classification for Cluster Headache (2004)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 / LacrimationConjunctival injection / Lacrimation

– Nasal congestion / RhinorrheaNasal congestion / Rhinorrhea

– Eyelid oedemaEyelid oedema

– Forehead and facial sweatingForehead and facial sweating

– Ptosis and MiosisPtosis and Miosis

– A sense of restlessness / agitationA sense of restlessness / agitation

• 15-180 minutes duration15-180 minutes duration

• 1 / alternate days – 8 /day1 / alternate days – 8 /day

Cluster Headache Cluster Headache – Defining features– Defining features

Strictly unilateral V1 pain + Autonomic featuresStrictly unilateral V1 pain + Autonomic features

Restlessness / agitationRestlessness / agitation

Short-duration / daily / boutsShort-duration / daily / bouts

0

10

20

30

40

50

60

70

Right Left Side-shiftbetween

bouts

Side-shiftwithin bout

Bahra, 2002 N=230

Manzoni, 1983 N=180

Kudrow, 1980 N=423

Cluster Headache – Laterality%

0

10

20

30

40

50

60

70

Right Left Side-shiftbetween

bouts

Side-shiftwithin bout

Bahra, 2002 N=230

Manzoni, 1983 N=180

Kudrow, 1980 N=423

Cluster Headache – Laterality%

Site of pain Site of pain →V→V11

%%• Retro-orbitalRetro-orbital 9292• TemporalTemporal 7070• Upper teethUpper teeth 5050• ForeheadForehead 4646• JawJaw 4545• CheekCheek 4545

%%• Lower teethLower teeth 3232• NeckNeck 3131• NoseNose 2020• EarEar 1717• ShoulderShoulder 1313• VertexVertex 77• OcciputOcciput 66• ParietalParietal 11

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

• JawJaw VV33

• CheekCheek VV22

• Lower teethLower teeth V V33

• NeckNeck CC2/32/3

• NoseNose VV22

• EarEar CC22

• ShoulderShoulder CC3/43/4

• VertexVertex CC22

• OcciputOcciput CC22

• ParietalParietal CC22

• Retro-orbitalRetro-orbital VV11

• TemporalTemporal VV11

• Upper teethUpper teeth VV22

• ForeheadForehead VV11

0

10

20

30

40

50

60

70

80

90

100

Lacrim

ation

Conju

nctiva

l Injec

tion

Nasal

Cong

estio

n

Rhinor

rhoe

a

Ptosis

/lid sw

ellin

gM

iosis

Bahra, 2002 N=230

Manzoni, 1983 N=180

Ekbom, 1970 N=105

Autonomic Features%

0

10

20

30

40

50

60

70

80

90

100

Lacrim

ation

Conju

nctiva

l Injec

tion

Nasal

Cong

estio

n

Rhinor

rhoe

a

Ptosis

/lid sw

ellin

gM

iosis

Bahra, 2002 N=230

Manzoni, 1983 N=180

Ekbom, 1970 N=105

Autonomic Features%

CH – 98%1

Migraine – 25%2

1. Torelli, 2001 n=553 2. Obermann, 2007 n=841

Attack Duration and FrequencyAttack Duration and Frequency

NN CH CH Migraine Migraine

DurationDuration 15-180 mins15-180 mins 4-72hrs 4-72hrs

FrequencyFrequency 1 / day1 / day 1-2 / month 1-2 / month

0

10

20

30

40

50

60

70

80

90

100

Nause

a

Vomiti

ng

Photop

hobia

Phonop

hobia

Aura

Cluster HeadacheBahra, 2002,Torelli, 2001,Ekbom, 1970,Kudrow, 1980MigraineRasmussen, 1991

Additional Features%

CH

Migraine

IHS Classification Criteria for Cluster HeadacheIHS 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

0

5

10

15

20

25

30

35

40

45

50

> 2years

Every 2years

Every18

months

1/year 2/year 3/year 4/year > 4/year

Bout Frequency

% o

f To

tal

50

55

60

65

70

75

80

85

90

95

100

F M A M J J A S O N D J F

• 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

Headache

Paroxysmal

hemicrania

SUNCT

M:F 3:1 1:1 1.5:1

Episodic:Chronic 90:10 35:65 10:90

Attack Duration 15-180 mins 2-30 mins 5-250s

Attack Frequency 1-8/day > 5 /day 1/day to 30/hr

Restlessness 90% 80% 65%

Periodicity Present Rare Absent

Alcohol Trigger ++ + –

• All patients ?

Cluster Headache & ImagingCluster Headache & Imaging

• Aneurysm of the ACA

• Pituitary tumour

• AVM of the occipital lobe

• Vertebral artery aneurysm

• Meningioma of the cervical canal (C2)

Symptomatic Cluster HeadacheSymptomatic Cluster Headache

• Aneurysm of the ACA

• Pituitary tumour

• AVM of the occipital lobe

• Vertebral artery aneurysm

• Meningioma of the cervical canal (C2)

Symptomatic Cluster HeadacheSymptomatic Cluster Headache

• Typical or atypical

• Response to treatment ≡ Primary CH

• ± Resolution with Rx of precipitating

pathology

Symptomatic Cluster HeadacheSymptomatic Cluster Headache

• Phenotype

• Rx Response

Symptomatic Cluster HeadacheSymptomatic Cluster Headache

Cannot differentiate b/uPrimary & Secondary CH

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*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

• All patients ? → Need Data

• New onset

• Primary CCH

• Atypical history

• + Systemic / neurological features

Cluster Headache & ImagingCluster Headache & Imaging

TherapeuticsTherapeutics

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/CABORTIVE THERAPY : SUMATRIPTAN S/C

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 : OXYGENABORTIVE THERAPY : OXYGEN

Fogan, 1985. / Cohen, 2007*

Sumatriptan 20mg IN

Zolmitriptan 5 and 10mg IN

Zolmitriptan 5 and 10mg po

Lidocaine IN

ABORTIVE THERAPY ABORTIVE THERAPY

Sumatriptan 20mg IN

Zolmitriptan 5 and 10mg IN

Zolmitriptan 5 and 10mg po

Lidocaine IN

ABORTIVE THERAPY ABORTIVE THERAPY

Response at

30 minutes

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 INABORTIVE THERAPY : LIGNOCAINE IN

Costa et. Al (2000) Cephalalgia ; 20 : 85

PREVENTATIVE THERAPYPREVENTATIVE THERAPY

Multiple daily attacks → Prophylaxis

PREVENTATIVE THERAPY : VERAPAMILPREVENTATIVE 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

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

Bradycardia No Patients

Mean VPM(mg) Dose ±SD

Heart Rate

(mean)

Total 108 591 ± 264 66

Bradycardia 39 659 ± 253 53

Bradycardia → Stop VPM

4 495 ± 172 49

Arrhythmias in patients on VPM + Other Drug

Rhythm

Lithium 5(1) Junctional (after Lithium stopped)

Methysergide 1(1) 1° Heart Block (after Methysergide stopped)

Triptans 49(8) 1° HB (6), 2° HB (1), Junctional (1)

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

– Fibrosis

Weight gain

Muscle cramps

Mood changes

PREVENTATIVE THERAPY : LITHIUMPREVENTATIVE 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

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 THERAPYABORTIVE THERAPY : : CORTICOSTEROIDSCORTICOSTEROIDS

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

• 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 TherapyPreventative Therapy

• Trigeminal ganglion and nerve

• Sphenopalatine ganglion

• Greater superficial petrosal nerve

• Nervus intermedius

• Greater Occipital Nerve

• Hypothalamus

SURGICAL THERAPYSURGICAL THERAPY

Greater Occipital Nerve Block

Greater Occipital Nerve BlockGreater Occipital Nerve Block

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

Partial Response (N)

19 22 10 3

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

Duration Duration (yrs)(yrs)

Mo since Mo since ONS ONS

Subjective Subjective outcomeoutcome

Estimated Estimated Change %Change %

Patient Patient RecommendRecommend

Triptan UseTriptan Use

1 7 23 Same - No Same

2 6 27 Same - Yes Same

3 6 11 Improved 95 Yes Less

4 17 17 Improved 60 Yes Less

5 13 27 Improved 20-80 Yes Same

6 24 8 Improved 90 Yes Less

7 13 11 Improved 25 Yes Same

8 54 32(23)* Improved 40 Yes Less

All 13 (6-54) ⌘ 20 (9-27) ⌘

75% Improved

60 (25-95) ⌘

88% Yes 38% Less Use

Burns, The Lancet (2007)

CLUSTER HEADACHE

PET VBM

May et al. (1998) Lancet ; 352 : 275 May et al. (1999) Nat. Med; 5:836

Leone et al. (2001) NEJM ; 345 : 1428

Cluster Headache - Stereotactic Stimulation of the Posterior Hypothalamic Gray Matter

May et al. (1998) Lancet ; 352 : 275

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