CASE

REPORT

Symptomatic Trigeminal Autonomic Cephalalgia

Associated with Allodynia in a Patient with
Multiple Sclerosis
Fang-Chun Liu, Jong-Ling Fuh, Shuu-Jiun Wang*
Neurological Institute, Taipei Veterans General Hospital and National Yang-Ming University School of
Medicine, Taipei, Taiwan, R.O.C.

A patient with symptomatic trigeminal autonomic cephalalgia (TAC) provides a chance to understand the pathophysiology
and anatomic correlates of TAC. A 28-year-old woman experienced intermittent sharp and excruciating pain over her right
temporal, ear and neck regions for 3 days. The headaches lasted 1020 minutes each, occurred 12 times a day, and
were accompanied by prominent ipsilateral lacrimation and conjunctival injection. The patient had hiccups, 4-limb numbness and impaired visual acuity in both eyes. She had also had 3 episodes of left-side optic neuritis in the past half year.
Neurologic examination showed brushing allodynia over the right face and scalp during the headache attacks. The visual
acuity of her right eye was 6/60 and that of the left eye was 1/60. Brain magnetic resonance imaging showed nonenhancing lesions on the right lateral tegmentum of the lower pons where the spinal trigeminal nucleus is located and the
floor of the 4th ventricle. The patient was diagnosed as having multiple sclerosis with symptomatic TAC. Her headaches,
autonomic signs and allodynia subsided 3 days after pulse therapy and gabapentin treatment were given. We suggest
that the spinal trigeminal nucleus lesion was responsible for the symptomatology of TAC and cutaneous allodynia in our
patient. [J Chin Med Assoc 2008;71(11):583586]
Key Words: allodynia, multiple sclerosis, trigeminal autonomic cephalalgia

Introduction
Trigeminal autonomic cephalalgia (TAC) is a primary
headache syndrome that is characterized by severe
short-lasting unilateral headaches with ipsilateral cranial autonomic symptoms. Based on the International
Classification of Headache Disorders, 2nd edition
(ICHD-2),1 this group includes cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and
tearing. The pathophysiology is still poorly understood.
The hypothalamus and trigeminovascular system have
been implicated.2
Several reports have described the association of
TAC-like headache with intracranial lesions. Pituitary
adenomas were the most common lesions.3 Other lesions, such as arteriovenous malformation of temporal

and frontal lobes, brain tumor in posterior fossa, vertebral artery aneurysm, and orbitosphenoidal aspergillosis, were also reported.3 Most of the lesions were
located around the sella region or posterior cranial
fossa. Rarely, parenchymal lesions and sphenoid sinus
infection were also noted.
Cutaneous allodynia is common during migraine
attacks. It is related to sensitization of neurons in the
trigeminal nucleus caudalis and/or thalamus.4 The association between allodynia and TAC such as cluster
headache is disputed,5 and the location responsible
for allodynia in TAC is not clear.
In this report, we present a patient with multiple
sclerosis, whose clinical features resembled TAC with
allodynia. To the best of our knowledge, this is the first
case report of spinal trigeminal nucleus as the underlying anatomic correlation.

*Correspondence to: Dr Shuu-Jiun Wang, Neurological Institute, Taipei Veterans General Hospital,
201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C.
E-mail: sjwang@vghtpe.gov.tw
Received: March 31, 2008
Accepted: June 2, 2008

J Chin Med Assoc November 2008 Vol 71 No 11

2008 Elsevier. All rights reserved.

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F.C. Liu, et al

Case Report
A 28-year-old woman presented with an excruciating
pain that was initially localized to the right ear and then
spread to her right temporal and neck regions. The
pain began 3 days before admission. The headaches
lasted for approximately 1020 minutes each and occurred 12 times a day. It was accompanied by marked
ipsilateral lacrimation, conjunctival injection, nausea
and vomiting, but not rhinorrhea, nasal stuffiness or
ptosis. In addition, the patient found that touching
the right side of her face and scalp would induce severe
pain during the headache attacks, which did not happen when the headache subsided. TAC was tentatively
diagnosed. In addition to the headaches, she also complained of persistent hiccup, 4-limb numbness and
impaired visual acuity.
The patient had had 3 recurrent episodes of optic
neuritis of her left eye in the past half year. The visual
acuity of the left eye during the last attack was only
counting fingers but recovered to 6/20 2 weeks later.
The magnetic resonance imaging (MRI) finding of the
left optic nerve at that time (Figure 1) was compatible
with optic neuritis, but no brain parenchymal abnormalities were noted. Cerebrospinal fluid studies including
IgG index were normal.
Neurologic examination showed impaired pinprick
sensation over distal limbs. Other sensory modalities,
such as light touch, position and vibration were normal. The visual acuity of the right eye deteriorated
from 6/6 to 6/60, and that of the left from 6/60 to
1/60. Fundoscopy showed temporal pale on the left
optic disc. No focal weakness or impairment of other
cranial nerves was detected. Tendon reflexes were normal
and bilaterally symmetrical. Brush-evoked allodynia,
A

tested by repetitively applying a 4 4-inch gauze pad,

was found on the patients right face (trigeminal nerve
1st and 2nd branches distribution) and scalp during
the headache attacks.
Brain MRI showed non-enhancing T1 isointense
and T2 high signal lesions on the right lateral tegmentum of the lower pons, bilateral optic nerves and the
floor of the 4th ventricle (Figure 2A). These lesions had
not been seen on the brain MRI done 2 months previously. There were no hemisphere white matter lesions.
Cerebrospinal fluid studies including oligoclonal band
and IgG index were normal. Autoimmune markers such
as ANA, ds-DNA, SS-A and SS-B were negative. Based
on the clinical, neuroimaging and laboratory findings,
the diagnosis of definite multiple sclerosis was made.
The headaches, autonomic symptoms and allodynia
subsided gradually within 3 days after steroid pulse
therapy (1,000 mg/day methylprednisolone) and gabapentin were given. Of note, her hiccups were also
controlled when the dosage of gabapentin reached
800 mg/day. Gabapentin was tapered 1 month later.
However, the hiccups and nausea recurred 1 week
after gabapentin withdrawal. Therefore, gabapentin
was reinstituted, which relieved the hiccups immediately. As of the last visit 9 months after this attack, no
further symptoms had occurred. Follow-up brain MRI
4 months later disclosed that the lesion had markedly
resolved (Figure 2B).

Discussion
Our patient presented with paroxysmal unilateral headaches and ipsilateral autonomic symptoms, which were
compatible with TAC. Brain MRI showed a lesion
B

Figure 1. (A) Axial T2-weighted magnetic resonance imaging shows abnormal high signals at the left optic nerve. (B) Axial T1-weighted
imaging with gadolinium shows patchy enhancement in the segment just anterior to the optic canal and the prechiasmatic segment of
the left side optic nerve.

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J Chin Med Assoc November 2008 Vol 71 No 11

Symptomatic TAC with allodynia

CST

ML

VI Nu.

Figure 2. (A) Axial magnetic resonance fluid-attenuated inversionrecovery imaging (MRI FLAIR) shows a hyperintense lesion in the
right lateral tegmentum of the lower pons. (B) The lesion is under
resolution markedly on MRI FLAIR 4 months later. (C) The lesion
was suspected as spinal trigeminal nucleus (STN). STT = spinal
trigeminal tract; CST = corticospinal tract; ML = medial lamiscus.

involving the right spinal trigeminal nucleus. Since

this lesion was only shown during this attack but not
2 months previously, we considered it to be responsible
for both her TAC and cutaneous allodynia.
Only 3 patients with multiple sclerosis presenting
with TAC have been reported before. The first case
was a 42-year-old man with headache lasting for 23
hours, which was initially localized to the right orbit, and
then spread to the homolateral maxillary and temporal
regions.6 Ipsilateral tearing, rhinorrhea and eye reddening were found. His lesions were around the lateral
ventricles and root entry zone of the right trigeminal
nerve. The second case was a 53-year-old man with
stabbing pain, shooting from his left upper lip to above
and medial to his left eye for 15 seconds, followed by
a piercing pain over the left cheek for 20 seconds.7
Profuse tearing and eye congestion were also noted.
No abnormality was found on imaging studies. The
third case was a 42-year-old man with right temporal
stabbing pain that lasted 530 seconds.8 Ipsilateral tearing and conjunctival injection were found. The lesions
were on the anterior pons, right cerebral peduncle and
medulla. The lesions of our patient and the first and
probably the third cases described above all involved
the trigeminal system. In contrast to previous cases,
only our patient presented with cutaneous allodynia.

Functional imaging has confirmed an activation of

the hypothalamic grey matter in induced or spontaneous
cluster headaches.2,9 Sympathetic nerves surrounding
carotid arteries10 and the trigeminal systems11 might
also be possible locations for autonomic symptoms.
In our and other multiple sclerosis cases,6,8 the involvement of the trigeminal system but not the hypothalamus
on brain MRI suggested that a trigeminal nerve system
lesion itself could present as TAC. Furthermore, allodynia has been linked to the sensitization of the 2ndorder neurons in the spinal trigeminal nucleus and/or
3rd-order neurons in the thalamus in migraine patients.4
It is not known whether this is also true in TAC patients.
Nevertheless, the ipsilateral spinal trigeminal nucleus
lesion in our patient supports this speculation.
Gabapentin has been reported to be effective in
the treatment of trigeminal neuralgia in patients with
multiple sclerosis.12 Both headaches and allodynia subsided after pulse therapy and gabapentin treatment in
our patient. In addition to pulse therapy, we could
not exclude the possibility that gabapentin might play
a role in relieving both TAC and allodynia in our
patient.
In conclusion, our patient is the first reported case
presenting with both symptomatic TAC and allodynia. This case demonstrated that the spinal trigeminal

STT
STN

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VII Nu.

585

F.C. Liu, et al

nucleus itself could activate both the trigeminoautonomic reflex and allodynia pathway.

4.

Acknowledgments

5.

This study was supported, in part, by a grant from Taipei

Veterans General Hospital (V96C1-041), Taipei,
Taiwan.

6.
7.
8.

References
1. The International Classification of Headache Disorders: 2nd
edition. Cephalalgia 2004;24(Suppl):9160.
2. Goadsby PJ. Pathophysiology of cluster headache: a trigeminal
autonomic cephalgia. Lancet Neurol 2002;1:2517.
3. Favier I, van Vliet JA, Roon KI, Witteveen RJ, Verschuuren JJ,
Ferrari MD, Haan J. Trigeminal autonomic cephalgias due to

586

9.
10.

11.
12.

structural lesions: a review of 31 cases. Arch Neurol 2007;64:

2531.
Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH.
An association between migraine and cutaneous allodynia.
Ann Neurol 2000;47:61424.
Ladda J, Straube A, Forderreuther S, Krause P, Eggert T.
Quantitative sensory testing in cluster headache: increased
sensory thresholds. Cephalalgia 2006;26:104350.
Leandri M, Cruccu G, Gottlieb A. Cluster headache-like pain
in multiple sclerosis. Cephalalgia 1999;19:7324.
Davey R, Al-Din A. Secondary trigeminal autonomic cephalgia
associated with multiple sclerosis. Cephalalgia 2004;24:6057.
Vilisaar J, Constantinescu CS. SUNCT in multiple sclerosis.
Cephalalgia 2006;26:8913.
May A. Cluster headache: pathogenesis, diagnosis, and management. Lancet 2005;366:84355.
Hardebo JE. How cluster headache is explained as an intracavernous inflammatory process lesioning sympathetic fibers.
Headache 1994;34:12531.
Frese A, Evers S, May A. Autonomic activation in experimental
trigeminal pain. Cephalalgia 2003;23:678.
Khan OA. Gabapentin relieves trigeminal neuralgia in multiple
sclerosis patients. Neurology 1998;51:6114.

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