Manjit S Matharu
Headache Group, Institute of Neurology &
The National Hospital for Neurology and Neurosurgery
London
UK
HULL-BASH Headache Meeting
20 th January 2011

ABSOLUTE RESPONSE
Paroxysmal Hemicrania
Hemicrania Continua
PARTIAL RESPONSE
Primary stabbing headache
Valsalva-induced headache
Primary cough headache
Primary exertional headache
Primary sex headache
Hypnic headache

• Introduced in clinical practice in 1963
• Non-steroidal anti-inflammatory drug (NSAID)
• Anti-inflammatory, anti-pyretic and analgesic effects
MECHANISM OF ACTION IN INDOMETACIN-RESPONSIVE HEADACHES
• Basis of specific action unknown:
1.
Inhibits cyclooxygenase 1 and cyclooxygenase 2 (therefore, the generation of prostaglandins) and leukocyte activity
2.
Decreases both cerebral blood flow and CSF pressure
3.
Indometacin also affects melatonin secretion
4.
Indometacin may have an effect on nitrinergic mechanisms
(David Dodick, 1998)

ABSOLUTE RESPONSE
Paroxysmal Hemicrania
Hemicrania Continua
PARTIAL RESPONSE
Primary stabbing headache
Valsalva-induced headache
Primary cough headache
Primary exertional headache
Primary sex headache
Hypnic headache

Cluster Headache
Paroxysmal Hemicrania
SUNCT (Short-lasting
Unilateral Neuralgiform headache with Conjunctival injection and Tearing)
Unilateral head pain, predominantly V
1
Very severe / Excruciating
Cranial autonomic symptoms
Parasympathetic h
Sympathetic i
Attack frequency and duration differs
Treatment responses differ

• Severe
• Unilateral
• Orbital, supraorbital or temporal pain
• 2-30 minutes duration
• >5 attacks daily at least 50% of the time
• Associated symptoms:
-Conjunctival injection
-Lacrimation
-Ptosis
-Miosis
-Eyelid oedema
-Nasal congestion
-Rhinorrhea
-Forehead and facial sweating
• Stopped completely by indometacin

Lifetime prevalence
F:M ratio
Age
• Mean
• Range
Cluster
Headache
1/1000
Paroxysmal
Hemicrania
SUNCT
1/50,000* 1/15,000
1:2.5-7.2
1:1 1:1.5
30
6-67
37
5-68
48
19-75

Attack frequency (daily)
Duration of attack
Pain quality
Pain intensity
Cluster
Headache
1-8
Paroxysmal
Hemicrania
1-40
SUNCT
3-200
15-180mins 2-30mins 5-240secs
Sharp, throbbing
Sharp, throbbing
Stabbing, burning
Very severe Very severe Very severe
Circadian periodicity 70% 45% Absent

Autonomic features
Migrainous features
Restless or agitated
Aura
Triggers
• Alcohol
• Cutaneous
Episodic : Chronic
Cluster
Headache
+++
++
90%
14%
+++
-
90:10
Paroxysmal
Hemicrania
+++
++
80%
Rare
+
-
35:65
SUNCT
+++*
+
65%
Rare
-
+++
10:90

EVIDENCE FOR HYPOTHALAMIC DYSFUNCTION
Cluster Headache
PET Study
Paroxysmal Hemicrania
PET Study
SUNCT fMRI Study
May et al, Lancet 1998 Matharu et al, Ann Neurol 2004 May et al, Ann Neurol 1999
Posterior hypothalamic region activation in all trigeminal autonomic cephalalgias

Posterior Hypothalamus
Ventral Midbrain
Matharu et al , Ann Neurol 2006

Oral Indometacin trial
25mgs tds for 3 days
50mgs tds for 3 days
75mgs tds for 7 days
Indotest (Intramuscular indometacin)
11.1+3.5 hr
Indomethacin 100mgs intramuscularly
Adapted from Antonaci et al. Headache 1998;38:122-8
Time

FEATURE
Duration (min)
Frequency (attacks/day)
Indometacin
CH
15 - 180
1- 8
-
Trial of Indometacin if:
• Attack frequency > 5 daily
• Attack duration < 30 minutes
• Chronic subtypes
• Medically intractable
PH
2 – 30
1 - 40
+

INVESTIGATIONS
Cittadini and Matharu, Neurologist 2009
Literature review of symptomatic TACs published between 1975-2007
Identified 37 symptomatic cases of TACs (CH 24, PH 3, SUNCT 10)
Pituitary tumours: CH 7, PH 3, SUNCT 7
Levy et al, Brain 2005
84 pituitary tumour patients with headaches
Studied in TERTIARY REFERRAL NEUROSURGICAL CENTRE
4% had CH; 5% had SUNCT (76% had migraine)
Investigate all TAC patients for pituitary tumours?
Prevalence of pituitary tumours in TACs is unknown
1 in 10 of the population have an incidental pituitary micro-adenoma (< 1cm diameter) on MRI pituitary
1 in 500 have a macro-adenoma

Indometacin
Persistence of efficacy; investigate if efficacy wears off
23% develop GI side effects with chronic treatment
Other NSAIDs
COX-II inhibitors
Topiramate
Verapamil
Greater occipital nerve blocks
Neuromodulation
Occipital nerve stimulation
Posterior hypothalamic region (midbrain tegmentum) DBS

A. Headache for >3 months
B. All of the following characteristics:
1. unilateral pain without side-shift
2. daily and continuous, without pain-free periods
3. moderate intensity, but with exacerbations of severe pain
C. At least one of the following autonomic features occurs during exacerbations and ipsilateral to the side of pain:
1. conjunctival injection and/or lacrimation
2. nasal congestion and/or rhinorrhoea
3. ptosis and/or miosis
D. Complete response to therapeutic doses of indomethacin

Burns B, Watkins L, Goadsby PJ. Lancet Neurol 2008
Results
5/6 (83%) reported meaningful benefit
Degree of Improvement
Substantial
Moderate
Worse *
%
80-95%
30%
-20%
Benefit built up over 2 days -3 months
Worsened rapidly when stimulator off
Number
4
1
1
*
Patient has migraine not hemicrania continua

Posterior Hypothalamus
Dorsal Rostral Pons Ventrolateral Midbrain
Matharu et al , Headache 2004

Not especially rare – 3% of general population, 42% of migraineurs.
Also commoner in cluster, HC, TTH
Stabbing or jabbing pain
Ophthalmic trigeminal distribution
Last a few seconds (rarely up to 1 minute)
May be unifocal or move around the head
Occurs at irregular intervals
Important to differentiate from:
Trigeminal Neuralgia: TN is triggerable, V ii
/V iii
SUNCT – longer runs of stabbing pain, cranial autonomic symptoms
Treatment (if required): Indometacin
Celecoxib
Melatonin
Gabapentin

Previously known as benign cough headache, Valsalva headache
Sudden headache triggered (not worsened) by coughing/Valsalva
Lasts 1 second-30mins
Associated features uncommon
Approx 40% of cough headache is secondary, usually due to Chiari malformation
Essential to exclude structural lesions, especially in posterior fossa
Mean age of onset 67 (range 44-81 in one series)
Treatment: Indometacin
Acetazolamide, Methysergide
Lumbar puncture – can be curative, may need repeating

IHS criteria:
Pulsating headache
Lasting from 5 minutes to 48 hours
Brought on by and occurring only during or after physical exertion
Not attributed to another disorder
On first occurrence, essential to exclude SAH/dissection
Treatment: Indomethacin
Propranolol
Ergotamine (pre-emptive)
Flunarizine

Preorgasmic Headache:
Dull ache in the head and neck associated with awareness of neck and/or jaw muscle contraction
Occurs during sexual activity and increases with sexual excitement
Orgasmic Headache:
Sudden severe ("explosive") headache occurring at orgasm
On first occurrence, essential to exclude SAH/dissection
Treatment: Pre-emptive or prophylactic Indometacin
Propranolol/Metoprolol
Diltiazem
Naratriptan 2.5mg

A. Dull headache
B. Develops only during sleep, and awakens patient
C. At least two of the following characteristics:
1.
occurs >15 times per month
2.
lasts ≥15 minutes after waking
3.
first occurs after age of 50 years
D. No autonomic symptoms and no more than one of nausea, photophobia or phonophobia
Caffeine, Indometacin, Lithium, Flunarizine

Strictly unilateral paroxysmal or continuous headaches
Short-lasting unilateral or bilateral headaches