1. Trigeminal Autonomic Cephalalgias
Manjit S Matharu
Headache Group, Institute of Neurology &
The National Hospital for Neurology and Neurosurgery
London UK
Third Biennial Hull-BASH Headache Meeting
23rd January 2009

2. Trigeminal Autonomic Cephalgias
Cluster Headache
Paroxysmal Hemicrania
SUNCT (Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing)
Unilateral head pain, predominantly V1
Very severe / excruciating
Cranial autonomic symptoms
Parasympathetic h
Sympathetic i
Attack frequency and duration differs
Treatment responses differ

3. Paroxysmal Hemicrania IHS CLASSIFICATION CRITERIA
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 indomethacin

4. Trigeminal Autonomic Cephalgias
Cluster
Headache
Paroxysmal Hemicrania
SUNCT
Attack frequency (daily)
1-8
1-40
3-200
Duration of attack
15-180mins
2-30mins
5-240secs
Pain quality
Sharp, throbbing
Stabbing, burning
Autonomic features
+++
+++*
Restless or agitated
90%
80%
65%

5. Trigeminal Autonomic Cephalgias
Cluster
Headache
Paroxysmal Hemicrania
SUNCT
Migrainous features ++ +
Triggers
Alcohol
NTG
Cutaneous
+++ -
Circadian periodicity
70%
45%
Absent
Episodic : Chronic
90:10
35:65
10:90

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

7. Paroxysmal Hemicrania DIFFERENTIAL DIAGNOSIS
Symptomatic Paroxysmal Hemicrania
Cluster headache
SUNCT syndrome
Hemicrania continua

8. Symptomatic Paroxysmal Hemicrania
Vascular
ICA aneurysm
Subclavian artery dilatation
Parietal AVM
MCA Stroke
Occipital infarction
Inflammatory or Infection
Collagen vascular disease
Ophthalmic herpes zoster
Iatrogenic
Surgical sympathectomy
Tumours
Pituitary tumours
Frontal tumour
Tuber cinereum hamartoma
Sella turcica gangliocytoma
Cavernous sinus meningioma
Multiple parotid ca. Metastasis
Non-Hodgkin’s lymphoma
Pancoast syndrome
Miscellaneous
Essential thrombocythaemia
Intracranial hypertension
Maxillary cyst

9. Trigeminal Autonomic Cephalgias Pituitary and TACs
Cittadini and Matharu, Neurologist 2009
Literature review of symptomatic TACs published between
Identified 37 symptomatic cases of CH
50% had typical presentation
33% poor response to treatments
Cause CH
N=24 PH
N=3
SUNCT
N=10
Vascular lesions 8
Tumours
Pituitary tumour 12 7 3 10
Miscellaneous
Idiopathic granulomatous hypophysitis 4 1

10. Trigeminal Autonomic Cephalgias Pituitary and TACs
Levy et al, Brain 2005
84 pituitary tumour patients with headaches studied
9% had TACs
Functioning adenomas more likely to cause TACs
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 routine MRI
1 in 500 have a macro-adenoma

11. Trigeminal Autonomic Cephalgias Pituitary and TACs
Difficult to draw up definitive guidelines from retrospective reviews
Pituitary imaging should be performed in:
Atypical phenotype/abnormal examination
Treatment resistant cases
Do typical cases require neuroimaging?
Increases likelihood of identifying incidental lesion
Implication of data on pituitary lesions?
Need prospective community based study in CH patients
Carefully elicit symptoms related to pituitary disease in all TAC patients but only perform MRI scans of the pituitary and a basal pituitary hormone profile in:
patients with atypical features (including pituitary related symptoms)
abnormal examination
poor response to appropriate treatments.

12. Paroxysmal Hemicrania DIFFERENTIAL DIAGNOSIS
Symptomatic Paroxysmal Hemicrania
Cluster headache
SUNCT syndrome
Hemicrania continua

13. Cluster Headache Vs Paroxysmal Hemicrania
Trial of Indomethacin if:
Attack frequency > 5 daily
Attack duration < 30 minutes
Chronic subtypes
Feature CH PH
Gender (M:F)
2.5-7:1
1:1
Duration (min)
2 – 30
Frequency (attacks/day)
1- 8
1 - 40
Indomethacin - +

14. Paroxysmal Hemicrania DIFFERENTIAL DIAGNOSIS
Symptomatic Paroxysmal Hemicrania
Cluster headache
Hemicrania continua
SUNCT syndrome

15. Hemicrania Continua Unilateral headache
Forehead, temple, orbit and occiput
Continuous, moderate pain
Exacerbations:
lasting from 20 min to several days
accompanied by autonomic and migrainous features
occur in 75%
Lack of precipitating factors
Complete response to indomethacin

16. Paroxysmal Hemicrania TREATMENTS
Indomethacin:
Oral Indomethacin trial
25mgs tds
50mgs tds
If high index of suspicion: 75mgs tds
Lower doses for 3 days; maximum dose for 7 days
Indotest (Intramuscular indomethacin)
N=77

17. Paroxysmal Hemicrania INDOTESThr
Time
Indomethacin 50mgs intramuscularly hr
Time
Indomethacin 100mgs intramuscularly
N=77
Adapted from Antonaci et al. Headache 1998;38:122-8

18. Paroxysmal Hemicrania TREATMENTS
Indometacin
Persistence of efficacy
23% develop GI side effects with chronic treatment
Other NSAIDS: Aspirin, naproxen, piroxicam
COX-II Inhibitors: Celecoxib, Rofecoxib
Topiramate
Verapamil
Greater occipital nerve injection
N=77

19. Neuralgiform attacks with Conjunctival injection and Tearing
SUNCT
Short-lasting
Unilateral
Neuralgiform attacks with
Conjunctival injection and
Tearing

20. SUNCT IHS CLASSIFICATION CRITERIA
Unilateral orbital, supraorbital or temporal pain
Stabbing or pulsating pain
seconds duration
Attack frequency from 3-200/day
Pain is accompanied by conjunctival injection and lacrimation

21. Trigeminal Autonomic Cephalgias
Cluster
Headache
Paroxysmal Hemicrania
SUNCT
Attack frequency (daily)
1-8
1-40
3-200
Duration of attack
15-180mins
2-30mins
5-240secs
Pain quality
Sharp, throbbing
Stabbing, burning
Autonomic features
+++
+++*
Restless or agitated
90%
80%
65%

22. Trigeminal Autonomic Cephalgias
Cluster
Headache
Paroxysmal Hemicrania
SUNCT
Migrainous features ++ +
Triggers
Alcohol
NTG
Cutaneous
+++ -
Circadian periodicity
70%
45%
Absent
Episodic : Chronic
90:10
35:65
10:90

23. Trigeminal Autonomic Cephalgias
Cluster
Headache
Paroxysmal Hemicrania
SUNCT
Lifetime prevalence
1/1000
1/50,000*
F:M ratio 1:
1:1
1:1.5
Age
Mean
Range 30
6-67 37
5-68 48
19-75

24. SUNCT DIFFERENTIAL DIAGNOSIS
Secondary causes
Posterior fossa pathology
Pituitary tumours
Trigeminal neuralgia
Primary stabbing headache
Paroxysmal hemicrania

25. SUNCT Vs Trigeminal Neuralgia
Feature
SUNCT TN
Gender (M:F)
1.5:1
1:2
Site of pain V1
V2/3
Duration (secs)
5-240
<5
Autonomic features
Prominent
Sparse
Refractory period
Absent
Present
Trigeminal Vascular loop 7%
47-90%

26. SUNCT DIFFERENTIAL DIAGNOSIS
Primary Stabbing Headache
Stabbing or jabbing pain
Ophthalmic trigeminal distribution
Last a few seconds (rarely up to 1 minute)
Occurs at irregular intervals
Site of pain varies from attack to attack
Spontaneous attacks only
Autonomic features absent
Attacks subside with indomethacin

27. MRI (including pituitary views) Pituitary hormone profile
SUNCT INVESTIGATIONS
MRI (including pituitary views)
Pituitary hormone profile
Trial of indomethacin

28. Greater occipital nerve injection 8 63%
SUNCT TREATMENTS
Doses
Number
Efficacy
Lamotrigine
mg/d 25
68%
Topiramate
50-400mg/d 21
52%
Gabapentin
mg/d 22
45%
IV lidocaine
mg/kg/hr 11
100%
Greater occipital nerve injection 8
63%
Cohen et al. Migraine Trust Symposium, September 2006

29. SUNCT TREATMENTS Topiramate in SUNCT
Cross-over RCT of topiramate 50 bd vs placebo
Primary endpoint was reduction in attack frequency by 50%
Secondary endpoint was reduction in ‘attack load’
N=5
Results
Beneficial in 2 – one had complete cessation of attacks, and one had a 71% reduction in attack load.
Placebo response in one
Two had no benefit
Cohen, Matharu, Goadsby. IHS, 2007

30. Hypothalamic Stimulator
SUNCT TREATMENTS
Hypothalamic Stimulator
Leone M, Ann Neurol 2005.

31. Trigeminal Autonomic Cephalgias PATHOPHYSIOLOGY
Cluster Headache
PET Study
May et al, Lancet 1998
Ipsilateral hypothalamic activation in CH

32. Paroxysmal Hemicrania
Trigeminal Autonomic Cephalgias PATHOPHYSIOLOGY
Paroxysmal Hemicrania
PET Study
Matharu et al, Ann Neurol 2006
Contralateral hypothalamic activation in PH

33. Trigeminal Autonomic Cephalgias PATHOPHYSIOLOGY
SUNCT
fMRI Studies
May et al, Ann Neurol 1999
Sprenger et al, Pain 2005
Cohen et al, Cephalalgia 2004
Hypothalamic activation in SUNCT

34. Functional Neuroimaging of Primary Headaches Headache Phase
Episodic and Chronic Migraine
Spontaneous
Episodic Migraine
Spontaneous
Episodic Migraine
Chronic
Migraine
Weiller et al, Nature 1995
Afridi et al, Arch Neurol 2005
Matharu et al, Brain 2004
Specific dorsal rostral pontine activation in migraine

35. Trigeminal Autonomic Cephalgias PATHOPHYSIOLOGY
Hemicrania Continua
PET Study
Posterior Hypothalamus
Dorsal Rostral Pons
Matharu et al, Headache 2004

36. Functional Neuroimaging of Primary Headaches
Activation pattern in primary headaches
Migraine CH
SUNCT PH HC
Posterior hypothalamus ü
Dorsal rostral pons
Primary headaches can be pathophysiologically differentiated on the basis of distinct patterns of brain activation
Dorsal pontine and hypothalamic activation are markers of migrainous symptoms and cranial autonomic features, respectively
These structures that likely play a pivotal role in the pathophysiology of primary headache syndromes

37. “Pain is a more terrible lord of mankind than even death itself”
Albert Schweitzer