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

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias

Cluster
Cluster Headache
Headache
Paroxysmal
Paroxysmal Hemicrania
Hemicrania
SUNCT
SUNCT (Short-lasting
(Short-lasting
Unilateral
Unilateral Neuralgiform
Neuralgiform
headache
headache with
with Conjunctival
Conjunctival
injection
injection and
and Tearing)
Tearing)

Unilateral
Unilateral head
head pain,
pain,
predominantly
predominantly V
V11
Very
Very severe
severe // excruciating
excruciating
Cranial
Cranial autonomic
autonomic symptoms
symptoms

Parasympathetic
Parasympathetic
Sympathetic
Sympathetic

Attack
Attack frequency
frequency and
and duration
duration
differs
differs
Treatment
Treatment responses
responses differ
differ

Paroxysmal
Paroxysmal Hemicrania
Hemicrania
IHS
IHS CLASSIFICATION
CLASSIFICATION CRITERIA
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

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias

Cluster
Headache

Paroxysmal
Hemicrania

SUNCT

1-8

1-40

3-200

15-180mins

2-30mins

5-240secs

Sharp,
throbbing

Sharp,
throbbing

Stabbing,
burning

Autonomic features

+++

+++

+++*

Restless or agitated

90%

80%

65%

Attack frequency (daily)

Duration of attack
Pain quality

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
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

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias

Lifetime prevalence
F:M ratio

Cluster
Headache

Paroxysmal
Hemicrania

SUNCT

1/1000

1/50,000*

1/50,000*

1:2.5-7.2

1:1

1:1.5

30
6-67

37
5-68

48
19-75

Age
Mean
Range

Paroxysmal
Paroxysmal Hemicrania
Hemicrania
DIFFERENTIAL
DIFFERENTIAL DIAGNOSIS
DIAGNOSIS

Symptomatic
Symptomatic Paroxysmal
Paroxysmal Hemicrania
Hemicrania
Cluster
Cluster headache
headache
SUNCT
SUNCT syndrome
syndrome
Hemicrania
Hemicrania continua
continua

Symptomatic
Symptomatic Paroxysmal
Paroxysmal Hemicrania
Hemicrania
Vascular

Tumours

ICA aneurysm
Subclavian artery dilatation
Parietal AVM
MCA Stroke
Occipital infarction

Pituitary tumours
Frontal tumour
Tuber cinereum hamartoma
Sella turcica gangliocytoma
Cavernous sinus meningioma
Multiple parotid ca. Metastasis
Non-Hodgkins lymphoma
Pancoast syndrome

Inflammatory or Infection
Collagen vascular disease
Ophthalmic herpes zoster

Iatrogenic
Surgical sympathectomy

Miscellaneous
Essential thrombocythaemia
Intracranial hypertension
Maxillary cyst

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias
Pituitary
Pituitary and
and TACs
TACs
Cittadini
Cittadini and
and Matharu,
Matharu, Neurologist
Neurologist 2009
2009
Literature
Literature review
review of
of symptomatic
symptomatic TACs
TACs published
published between
between 1975-2007
1975-2007
Identified
Identified 37
37 symptomatic
symptomatic cases
cases of
of CH
CH
Cause

CH
N=24

Vascular lesions

Tumours

12
7

Pituitary tumour

Miscellaneous
Idiopathic granulomatous
hypophysitis

50%
50% had
had typical
typical presentation
presentation
33%
33% poor
poor response
response to
to treatments
treatments

4
1

PH
N=3

SUNCT
N=10

10
7

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias
Pituitary
Pituitary and
and TACs
TACs

Levy
Levy et
et al,
al, Brain
Brain 2005
2005
84
84 pituitary
pituitary tumour
tumour patients
patients with
with headaches
headaches studied
studied
9%
9% had
had TACs
TACs
Functioning
Functioning adenomas
adenomas more
more likely
likely to
to cause
cause TACs
TACs
Investigate
Investigate all
all TAC
TAC patients
patients for
for pituitary
pituitary tumours?
tumours?

Prevalence
Prevalence of
of pituitary
pituitary tumours
tumours in
in TACs
TACs is
is unknown
unknown
11 in
in 10
10 of
of the
the population
population have
have an
an incidental
incidental pituitary
pituitary micromicroadenoma
adenoma (<
(< 1cm
1cm diameter)
diameter) on
on routine
routine MRI
MRI
11 in
in 500
500 have
have aa macro-adenoma
macro-adenoma

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias
Pituitary
Pituitary and
and TACs
TACs

Difficult
Difficult to
to draw
draw up
up definitive
definitive guidelines
guidelines from
from retrospective
retrospective reviews
reviews
Pituitary
Pituitary imaging
imaging should
should be
be performed
performed in:
in:

Atypical
Atypical phenotype/abnormal
phenotype/abnormal examination
examination
Treatment
Treatment resistant
resistantcases
cases

Do
Do typical
typical cases
cases require
require neuroimaging?
neuroimaging?
Increases
Increaseslikelihood
likelihood of
ofidentifying
identifyingincidental
incidental lesion
lesion

Implication
Implication of
of data
data on
on pituitary
pituitary lesions?
lesions?

Need
Need prospective
prospective community
community based
based study
study in
inCH
CH patients
patients
Carefully
Carefully elicit
elicit symptoms
symptomsrelated
related to
to pituitary
pituitary disease
disease in
inall
allTAC
TAC patients
patients but
but
only
only perform
performMRI
MRIscans
scansof
of the
the pituitary
pituitary and
and aa basal
basal pituitary
pituitary hormone
hormone profile
profile
in:
in:
patients
patientswith
with atypical
atypical features
features(including
(including pituitary
pituitary related
related symptoms)
symptoms)
abnormal
abnormal examination
examination
poor
poorresponse
response to
to appropriate
appropriate treatments.
treatments.

Paroxysmal
Paroxysmal Hemicrania
Hemicrania
DIFFERENTIAL
DIFFERENTIAL DIAGNOSIS
DIAGNOSIS

Symptomatic
Symptomatic Paroxysmal
Paroxysmal Hemicrania
Hemicrania
Cluster
Cluster headache
headache
SUNCT
SUNCT syndrome
syndrome
Hemicrania
Hemicrania continua
continua

Cluster
Cluster Headache
Headache Vs
Vs Paroxysmal
Paroxysmal Hemicrania
Hemicrania
Feature

CH

PH

Gender (M:F)

2.5-7:1

1:1

Duration (min)

15 - 180

2 30

1- 8

1 - 40

Frequency (attacks/day)
Indomethacin

Trial of Indomethacin if:

1.
2.

Attack frequency > 5 daily

Attack duration < 30 minutes

3.

Chronic subtypes

Paroxysmal
Paroxysmal Hemicrania
Hemicrania
DIFFERENTIAL
DIFFERENTIAL DIAGNOSIS
DIAGNOSIS

Symptomatic
Symptomatic Paroxysmal
Paroxysmal Hemicrania
Hemicrania
Cluster
Cluster headache
headache
Hemicrania
Hemicrania continua
continua
SUNCT
SUNCT syndrome
syndrome

Hemicrania
Hemicrania Continua
Continua

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

Paroxysmal
Paroxysmal Hemicrania
Hemicrania
TREATMENTS
TREATMENTS
Indomethacin:
Indomethacin:
Oral
Oral Indomethacin
Indomethacin trial
trial
25mgs
25mgs tds
tds
50mgs
50mgs tds
tds
IfIf high
high index
index of
of suspicion:
suspicion: 75mgs
75mgs tds
tds
Lower
Lower doses
doses for
for 33 days;
days; maximum
maximum dose
dose for
for 77 days
days

Indotest
Indotest (Intramuscular
(Intramuscular indomethacin)
indomethacin)

N=77

Paroxysmal
Paroxysmal Hemicrania
Hemicrania
INDOTEST
INDOTEST

8.2+4.2 hr
Time
Indomethacin 50mgs intramuscularly
11.1+3.5 hr
Time
Indomethacin 100mgs intramuscularly
N=77
Adapted from Antonaci et al. Headache 1998;38:122-8

Paroxysmal
Paroxysmal Hemicrania
Hemicrania
TREATMENTS
TREATMENTS
Indometacin
Indometacin
Persistence
Persistence of
of efficacy
efficacy
23%
23% develop
develop GI
GI side
side effects
effects with
with chronic
chronic treatment
treatment
Other
Other NSAIDS
NSAIDS::
COX-II
COX-II Inhibitors
Inhibitors::

Aspirin,
Aspirin, naproxen,
naproxen, piroxicam
piroxicam
Celecoxib,
Celecoxib, Rofecoxib
Rofecoxib

Topiramate
Topiramate
Verapamil
Verapamil
Greater
Greater occipital
occipital nerve
nerve injection
injection
N=77

SUNCT
SUNCT

Short-lasting
Unilateral
Neuralgiform attacks with
Conjunctival injection and
Tearing

SUNCT
SUNCT
IHS
IHS CLASSIFICATION
CLASSIFICATION CRITERIA
CRITERIA
Unilateral
Unilateral orbital,
orbital, supraorbital
supraorbital or
or temporal
temporal pain
pain
Stabbing
Stabbing or
or pulsating
pulsating pain
pain
10-240
10-240 seconds
seconds duration
duration
Attack
Attack frequency
frequency from
from 3-200/day
3-200/day
Pain
Pain isis accompanied
accompanied by
by conjunctival
conjunctival injection
injection and
and lacrimation
lacrimation

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias

Cluster
Headache

Paroxysmal
Hemicrania

SUNCT

1-8

1-40

3-200

15-180mins

2-30mins

5-240secs

Sharp,
throbbing

Sharp,
throbbing

Stabbing,
burning

Autonomic features

+++

+++

+++*

Restless or agitated

90%

80%

65%

Attack frequency (daily)

Duration of attack
Pain quality

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
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

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias

Lifetime prevalence
F:M ratio

Cluster
Headache

Paroxysmal
Hemicrania

SUNCT

1/1000

1/50,000*

1/50,000*

1:2.5-7.2

1:1

1:1.5

30
6-67

37
5-68

48
19-75

Age
Mean
Range

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

SUNCT
SUNCT Vs
Vs Trigeminal
Trigeminal Neuralgia
Neuralgia

Feature
Gender (M:F)
Site of pain
Duration (secs)
Autonomic features
Refractory period
Trigeminal Vascular loop

SUNCT

TN

1.5:1

1:2

V1

V2/3

5-240

<5

Prominent

Sparse

Absent

Present

7%

47-90%

SUNCT
SUNCT
DIFFERENTIAL
DIFFERENTIAL DIAGNOSIS
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

SUNCT
SUNCT
INVESTIGATIONS
INVESTIGATIONS

MRI (including pituitary views)

Pituitary hormone profile
Trial of indomethacin

SUNCT
SUNCT
TREATMENTS
TREATMENTS
Doses

Number

Efficacy

Lamotrigine

100-400mg/d

25

68%

Topiramate

50-400mg/d

21

52%

Gabapentin

600-3600mg/d

22

45%

IV lidocaine

1.3-3.3 mg/kg/hr

11

100%

63%

Greater occipital
nerve injection

Cohen et al. Migraine Trust Symposium, September 2006

SUNCT
SUNCT
TREATMENTS
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

SUNCT
SUNCT
TREATMENTS
TREATMENTS
Hypothalamic Stimulator

Leone M, Ann Neurol 2005.

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
Cluster Headache
PET Study

May et al, Lancet 1998

Ipsilateral hypothalamic activation in CH

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
Paroxysmal Hemicrania
PET Study

Matharu et al, Ann Neurol 2006

Contralateral hypothalamic activation in PH

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
SUNCT
fMRI Studies

May et al, Ann Neurol 1999

Sprenger et al, Pain 2005

Cohen et al, Cephalalgia 2004

Hypothalamic activation in SUNCT

Functional
Functional Neuroimaging
Neuroimaging of
of Primary
Primary Headaches
Headaches
Headache
Headache Phase
Phase
Episodic
Episodic and
and Chronic
Chronic Migraine
Migraine
Spontaneous
Episodic Migraine

Spontaneous
Episodic Migraine

Weiller et al, Nature 1995

Afridi et al, Arch Neurol 2005

Chronic
Migraine

Matharu et al, Brain 2004

Specific dorsal rostral pontine activation in migraine

Trigeminal
Trigeminal Autonomic
Autonomic Cephalgias
Cephalgias
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
Hemicrania
Hemicrania Continua
Continua
PET Study
Posterior Hypothalamus

Dorsal Rostral Pons

Matharu et al, Headache 2004

Functional
Functional Neuroimaging
Neuroimaging of
of Primary
Primary Headaches
Headaches
Activation
Activation pattern
pattern in
in primary
primary headaches
headaches
Migraine
Posterior hypothalamus
Dorsal rostral pons

CH

SUNCT

PH

HC

Primary
Primary headaches
headaches can
can be
be pathophysiologically
pathophysiologically differentiated
differentiated on
on the
the basis
basis of
of
distinct
distinct patterns
patterns of
of brain
brain activation
activation
Dorsal
Dorsal pontine
pontine and
and hypothalamic
hypothalamic activation
activation are
are markers
markers of
of migrainous
migrainous
symptoms
and
cranial
autonomic
features,
respectively
symptoms
and
cranial
autonomic
features,
respectively

These
These structures
structures that
that likely
likely play
play aa pivotal
pivotal role
role in
in the
the pathophysiology
pathophysiology of
of
primary
primary headache
headache syndromes
syndromes

Pain is a more
terrible lord of
mankind than
even death itself
Albert Schweitzer