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Linear Pontine Trigeminal Root Lesions in Multiple Sclerosis
Clinical and Magnetic Resonance Imaging Studies in 5 Cases
Ichiro Nakashima, MD;
Kazuo Fujihara, MD;
Teiko Kimpara, MD;
Naoshi Okita, MD;
Sadao Takase, MD;
Yasuto Itoyama, MD
Arch Neurol. 2001;58:101-104.
ABSTRACT
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Background Magnetic resonance imaging (MRI) is useful for demonstrating demyelinating
lesions in patients with multiple sclerosis (MS). Magnetic resonance imaging
studies show that MS lesions are generally not uniform in shape, size, or
distribution. Linearly shaped lesions at the trigeminal root entry zone have
been occasionally reported in single cases of MS, but, to our knowlege, the
frequency and the clinical features of such patients have not been comprehensively
characterized.
Objective To describe the frequency and the clinical and laboratory features of
patients with MS who had linearly shaped lesions at the trigeminal root as
seen on MRI.
Design and Setting A retrospective review of medical records and MRI films of Japanese
patients with MS admitted to a university hospital and its affiliated hospital
in Sendai, Japan.
Patients and Methods Brain MRI films of 74 consecutive Japanese patients with MS (51 females
and 23 males) were studied retrospectively and the clinical and laboratory
features of the patients with linearly shaped lesions at the trigeminal root
were also investigated retrospectively.
Results Five patients (6.8%) were shown to have T1-weighted–hypointense,
T2-weighted–hyperintense, nonenhanced linear lesions in the pons on
MRI, and these were uniformly localized in the intramedullary portion of the
trigeminal root. All of these patients had clinically definite MS and had
various types of facial sensory disturbances, such as neuralgia (1 patient),
hypesthesia (2 patients), or paresthesia (3 patients). No other clinical or
laboratory feature was characteristic in these 5 patients.
Conclusions Linear pontine trigeminal root lesions were common in our patients with
MS. They were associated with various facial sensory symptoms. Since similar
lesions are formed in animal models of herpes simplex virus infection, further
study is needed to clarify whether these MS lesions are virally induced.
INTRODUCTION
MULTIPLE sclerosis (MS) lesions can be detected on magnetic resonance
imaging (MRI) as patchy plaques, which are generally not uniform in shape,
size, or distribution. Multiple sclerosis can involve any part of the white
matter of the central nervous system and the extent of these lesions is unrelated
to the neuroanatomical structure with the exception of some predominant localization
of lesions in periventricular areas. Several articles have described trigeminal
neuralgia in patients with MS that is associated with pontine MRI lesions
along the trigeminal nerve root.1, 2
In this study, we examine the frequency and clinical features of similar trigeminal
lesions within our patients with MS, and discuss potential pathogenetic mechanisms
that may account for these peculiar lesions.
PATIENTS AND METHODS
PATIENTS
We retrospectively reviewed the brain MRI and medical records of 74
consecutive MS cases (51 females and 23 males) from January 1, 1988, through
December 31, 1998. We identified 5 MS cases (6.8%) in which unique, linearly
shaped lesions lying in the pontine trigeminal root were confirmed on MRI.
Clinical, laboratory, and MRI findings of these 5 patients were analyzed in
this study.
MAGNETIC RESONANCE IMAGING
In each case, all of the available MRI films, which had been taken since
the onset of the illness, were examined. Two neurologists including one of
us (I.N.) and a blinded neuroradiologist evaluated each scan. Any T2-weighted–hyperintense
areas in the brainstem and cerebellum, which appeared on each T2-weighted
image with a moderately long repetition time of 2000 to 3000 milliseconds
and an echo time of 60 to 100 milliseconds, were considered abnormal.
REPORT OF CASES
CASE 1
A 26-year-old man developed a gait disturbance and numbness of the left
side of the face and right half of the body when he was 22 years old. On physical
examination, he had nystagmus, left-sided facial sensory loss, dysphagia,
right hemiparesis and hemiparesthesia, deep sensory disturbance, and truncal
ataxia. After the remission, weakness of the left arm and leg, and severe
numbness of the right half of the body recurred. He had nystagmus, diplopia,
dysphagia, left hemiparesis, right hemiparesthesia, and truncal ataxia and
was diagnosed as having clinically definite MS. His brain was scanned using
a 0.1-T MRI scanner at the time of recurrence. A linear lesion was detected
in the left side of the pons (Figure 1, A). The cerebrospinal fluid (CSF) study revealed
a normal cell count and protein level. There were 2 definite oligoclonal IgG
bands (OBs) in the CSF.
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T2-weighted magnetic resonance image at the middle pontine section
in each of our 5 patients with multiple sclerosis. A indicates patient 1;
B, patient 2; C, patient 3; D, patient 4; and E, patient 5. All patients had
a linearly shaped lesion at the trigeminal root that showed a high-intensity
signal (arrows). All patients also had ipsilateral trigeminal nerve symptoms
such as neuralgia, numbness, or paresthesia.
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CASE 2
A 35-year-old woman developed right leg weakness when she was 26 years
old. Three years later, spastic paraparesis, urinary dysfunction, and left-sided
facial pain also developed. The CSF study results were abnormal with an elevated
protein level and were positive for OBs. Since that time, the trigeminal neuralgia
has frequently recurred. The anti–herpes simplex virus (HSV) antibody
titer in the CSF was elevated when she developed intolerable facial pain at
the age of 35 years. However, polymerase chain reaction for HSV-DNA showed
no abnormalities. Magnetic resonance imaging using a 1.5-T scanner was performed
when she developed severe neuralgia. The MRI showed a hyperintensive linear
lesion along the left intramedullary trigeminal nerve root on T2-weighted
image (Figure 1, B). There were
several other lesions in the cerebral periventricular white matter, the basal
ganglia, and the corpus callosum shown on MRI.
CASE 3
A 28-year-old man developed bilateral visual disturbance, diplopia,
dysarthria, weakness of the whole body, gait disturbance, and urinary retention
after the remission of a high fever. At the time of admission to the hospital,
he had bilateral visual disturbance, oculomotor palsy, nystagmus, left-sided
facial paresthesia, left-sided facial palsy, dysphagia, moderate quadriparesis,
and cerebellar ataxia. The results of the CSF study were abnormal with marked
pleocytosis and an elevation of the protein level. The results of the OB test
were normal. Four years later, he developed mild paresthesia on the left side
of the head and was diagnosed as having probable MS. Magnetic resonance imaging
at the first episode showed lesions in the medulla oblongata, the left side
of the lower pons, the right edge of the upper pons, and the right cerebral
peduncle. Four years later when he had paresthesia on the left side of the
head, MRI showed a new lesion in the left intramedullary trigeminal nerve
root extending from the cerebellopontine angle to its entry zone (Figure 1, C).
CASE 4
A 28-year-old man developed diplopia, nystagmus, dysarthria, right hemiparesis,
and paresthesia of the whole face and extremities when he was 24 years old.
Magnetic resonance imaging (1.5 T) showed multiple lesions in the pons. Most
of the lesions were at the belly of the pons and a linear lesion was found
along the left trigeminal root (Figure 1,
D). There were no definite lesions in other regions of the brain. The CSF
study was normal with no OBs. Two years later, he developed paresthesia and
hypesthesia on the right side of the face. Magnetic resonance imaging showed
a round plaque lesion at the right trigeminal nerve nucleus of the lower pons.
CASE 5
A 15-year-old girl developed paresthesia of the left side of the face
and left fingers when she was 14 years old. Magnetic resonance imaging revealed
multiple brain lesions including a linear lesion of the intramedullary trigeminal
root (Figure 1, E). Two OBs were
seen in the CSF although the CSF cell count and protein level were normal.
The symptoms disappeared within a few weeks without any treatment. Six months
later, she developed diplopia and her condition was diagnosed as clinically
definite MS. Anti–HSV antibody titers and HSV-DNA levels in the CSF
were negative when studied at the recurrence.
RESULTS
CLINICAL AND MRI FINDINGS
Among the 74 consecutive patients with MS, 5 patients had a linearly
shaped MRI lesion in the pons, which corresponded neuroanatomically with the
intramedullary trigeminal root. These 5 patients had various kinds of facial
sensory manifestations, which are described in the "Report of Cases" section.
None of the other patients had asymptomatic linear pontine lesions. Four other
patients had rather round and larger plaque lesions near the cerebellopontine
angle in the pons, which included the intramedullary trigeminal root and the
surrounding regions. These 4 patients tended to have some additional cranial
nerve symptoms, such as facial nerve palsies or hearing disturbances, besides
facial sensory manifestations.
The clinical features of the 5 patients (2 females and 3 males) with
linearly shaped pontine lesions are listed in Table 1. The mean age of the 5 patients was 26.4 years and the mean
duration of the disease was 4.2 years. Four of them had 2 relapses of MS and
the remaining patient (case 2) had more than 5 relapses of MS. All 5 patients
had facial sensory disturbances on the same sides as the pontine lesions.
These were facial neuralgia (1 patient), facial paresthesia (3 patients),
and facial hypesthesia (2 patients). All of the linearly shaped pontine lesions
were observed as hyperintense lesions on T2-weighted images and as hypointense
lesions on T1-weighted images along the intramedullary trigeminal root (Figure 1). Gadolinium enhancement was not
observed in any of the lesions.
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Clinical Features of 5 Patients With Multiple Sclerosis (MS) Who Had
Linear Trigeminal Root Lesions*
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In the CSF study, only 1 (case 3) of these 5 patients had marked pleocytosis
and an elevated protein content, while the other 4 had normal CFS cell counts
and protein levels. Oligoclonal IgG bands were detected in 3 patients. A patient
with trigeminal neuralgia (patient 2) had an elevated anti–HSV antibody
titer both in the serum and the CSF during the acute phase of the second bout
of MS.
COMMENT
Magnetic resonance imaging is useful for demonstrating and monitoring
demyelinated lesions of the brain and spinal cord in patients with MS.3, 4 It is known that MRI findings are well
correlated with the pathological localization of MS lesions.4, 5
Multiple sclerosis lesions are usually not uniform in shape, size, and localization;
tend to be round, oval, or irregular in appearance; pin-point or large; and
isolated or disseminated, although they show some predominance of localization
near periventricular areas.4, 6
These MRI features of MS lesions are generally recognized. Therefore, such
linearly shaped pontine lesions as shown in this study are unique for the
shape of the MS lesions and their neuroanatomical localization.
Similarly shaped pontine MRI lesions have been reported in a few cases
of MS, especially in those patients with symptoms and signs related to the
trigeminal nerve. Gass et al2 described 2 patients
with MS who showed linearly shaped MRI lesions along the trigeminal root from
among 6 patients with various diseases who reported trigeminal neuralgia.
Meaney et al1 also described 1 patient with
MS who had trigeminal neuralgia and a similar MRI lesion in the intramedullary
trigeminal root. Such lesions corresponded only to the pontine trigeminal
root, not to other intramedullary cranial nerve roots.7
It is known that trigeminal neuralgia occurs more commonly in persons with
MS than in the general population,2, 8, 9
and especially in younger persons with MS who have bilateral trigeminal nerve
involvement.2 In general, idiopathic trigeminal
neuralgia is thought to be causally associated with vascular compression on
the trigeminal nerve or its root entry zone.10
However, a different mechanism such as one involving demyelinative changes
has to be presumed in MS. Very rare postmortem examinations of the brains
of patients with MS who had trigeminal neuralgia have shown demyelinative
changes in the pons at the root entry zone.1, 11
In this study of 5 patients with MS, we emphasize the uniqueness of
the shape and localization of the pontine MS lesions and the relation of such
lesions to the trigeminal nerve manifestations. They were linear in shape
and neuroanatomically corresponded closely to the intramedullary trigeminal
root, which extends from the root entry zone to the fifth nerve nuclei close
to the fourth ventricle. Although such pontine trigeminal linear lesions have
been observed in some previous reports,1, 2
the pathogenetic mechanisms of the lesion formation have never been discussed.
Why does such a demyelinating lesion develop linearly along the course of
the intramedullary trigeminal fascicular fibers?
The shape, size, and localization of such demyelinated lesions in these
5 patients with MS has been observed in central nervous system demyelinating
lesions of experimental HSV type 1–infected animal models. It is well
known that, after an experimental inoculation of HSV type 1 in the cornea
of mice or a rabbit, the virus spreads transaxonally to the central nervous
system through the first branch of the trigeminal nerve and induces selective
central nervous system demyelination in the intramedullary trigeminal root.11, 12, 13 The similarities
in the localization and shape of these lesions suggest that a common pathogenetic
mechanism may be present in both conditions. If so, it will be important to
verify whether an infection of HSV plays an active role in developing these
unique MS lesions or whether inflammatory responses in MS induce a reactivation
of HSV. In 1 of the 5 patients with MS who had a history of recurrent trigeminal
neuralgia, we found increased anti–HSV antibody titers in the serum
and CSF. The increased anti–HSV antibodies were demonstrated during
an episode of recurrent trigeminal neuralgia. However, polymerase chain reaction
to HSV-specific DNA was negative in her CSF. Thus, the trigeminal root might
have been previously damaged by herpetic infections, and increased anti–HSV
antibodies could be the result of nonspecifically activated antigen-specific
HSV B cells during an attack of MS and not necessarily a new herpetic recrudescence.
It is well known that HSV resides in latent form in the trigeminal ganglia
and that HSV-DNA is detected in the trigeminal ganglia in more than half of
control subjects,14 and HSV-DNA is also often
detected in the brains of persons with MS.15, 16
It will be necessary to study the presence of HSV in the pontine trigeminal
lesions.17
CONCLUSION
We studied 5 patients with MS who had peculiar MRI lesions at the intramedullary
trigeminal root from among 74 consecutive patients, and they had various facial
sensory manifestations. The pathogenetic mechanisms of such unique demyelinative
lesions in MS may be related to HSV infection.
AUTHOR INFORMATION
Accepted for publication September 1, 2000.
This work was supported by a grant-in-aid for General Scientific Research
(09470150) from the Ministry of Education, Science, and Culture, a grant from
the Neuroimmunological Research Committee, Kyoto, Japan (Dr Fujihara), and
a research subsidy from the Japan Foundation for Neuroscience and Mental Health,
Tokyo, (Dr Itoyama).
We thank Brent Bell for reading the manuscript.
From the Departments of Neurology, Tohoku University School of Medicine
(Drs Nakashima, Fujihara, Kimpara, and Itoyama) and Kohnan Hospital (Drs Okita
and Takase), Sendai, Japan.
Corresponding author and reprints: Ichiro Nakashima, MD, Department
of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku,
Sendai 980-8574, Japan, (e-mail: inakashima{at}neurol.med.tohoku.ac.jp).
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