Psychiatry and Clinical Neurosciences (1999), 53, 485–490

Regular Article

Multiple sclerosis with extensive lesions, left hemiplegia,
mental dysfunction and retrobulbar neuritis
KANA OGAWA, md, MASAHIKO KISHI, md, TERUYUKI KURIHARA, md,
KEN IKEDA, md, AND MASAO KINOSHITA, md
Fourth Department of Medicine,Toho University School of Medicine, Meguro,Tokyo, Japan

Abstract

Multiple sclerosis (MS) is usually diagnosed on the basis of the typical clinical course, with
remission and exacerbation in multiple parts of the central nervous system (CNS). Recently,
magnetic resonance imaging (MRI) has made a large contribution to the diagnosis of patients
with MS. But it is difficult to make a definite diagnosis due to clinical variability of the disease
and variable MRI findings. We report the case of a 26-year-old woman who developed progressive left hemiplegia, mental dysfunction, and had extensive bilateral cerebral white matter
lesions diagnosed by brain MRI. Complete recovery from the left hemiplegia followed the use of
corticosteroid, and her brain MRI findings also improved after medication. Early in the clinical
course it was difficult to differentiate between multiple sclerosis and granulomatous angiitis of
the CNS. After recovery from the first episode of left hemiplegia and mental dysfunction, she
developed acute visual disturbance five months after her first admission. Readmission followed
and her retrobulbar neuritis was successfully treated by methylpredonisolone pulse therapy. In
summary, she experienced two episodes of neurological deficit, had left hemiplegia and mental
dysfunction associated with multiple lesions in bilateral cerebral white matter in brain MRI, and
the left retrobulbar neuritis with delay of P100 by visual evoked potential study. Due to these
two episodes we concluded that she had multiple sclerosis. Though the initial diagnosis was
difficult, prompt treatment and close follow-up was important, since multiple sclerosis and
granulomatous angiitis of the CNS can both recur.

Key words

isolated angiitis of the central nervous system, large demyelinating lesions, magnetic resonance
imaging, multiple sclerosis.

INTRODUCTION
We report the case of a 26-year-old Japanese female
who developed acute left hemiplegia and mental
confusion and had very extensive white matter lesions
shown by magnetic resonance imaging (MRI) studies.
Five months later she developed left retrobulbar
neuritis. It was difficult to make a definite diagnosis
before the second episode.
Since granulomatous angiitis of the central nervous
system (CNS) and multiple sclerosis (MS) can both
Correspondence address: Kana Ogawa, Fourth Department of
Medicine, Toho University School of Medicine, 2–17–6 Ohashi,
Meguro, Tokyo 153–0044, Japan
Received 24 August 1998; revised 4 December 1998; accepted 13
December 1998.

recur and can respond to corticosteroid therapy, it is
difficult to make a definite diagnosis by the first
episode of neurological illness, but close follow-up
and prompt therapy at each episode may eventually
provide a correct diagnosis.
The patient showed symptoms in late 1997 when
she suddenly ceased her long-standing use of the
Internet because she kept forgetting her password
and made continual typing errors. The following day
her speech reduced and very soon she was saying
nothing at all to her family. She became silent and did
not use her left hand. One week after her speech
reduction she visited the bathroom and had a bowel
movement fully dressed. The following day her
mother noted a limp in her left leg. One day later she
experienced urinary incontinence and would not eat.
The next day she attended a nearby hospital and

underwent neuroradiological examinations including
brain computed tomography (CT) and MRI and
was noted as having an unusually diffuse brain
disorder, though a definite diagnosis was not made.
Subsequently, she became unable to walk and her
general condition deteriorated.
Admitted to our neurosurgery department, she had
brain MRI studies which revealed diffuse brain white
matter disorder. Past history revealed fibrile convulsions at the age of one year and otitis media at the
age of 10 years. There was no history of allergies or of
surgery. She did not use alcohol or tobacco and had
no history of oral contraceptive use or any regular
medication. The family history was unremarkable.
The patient was physically mature but obese. On
general physical examination her blood pressure (BP)
was 136/92 mmHg and her pulse rate was 78 b.p.m.
and steady. Her temperature was 36.5 °C and respiration was 18/min. She had no skin eruptions or
evidence of lymphadenopathy.

Neurological examinations
At neurological examination the patient was awake
and lying quietly. She did not initiate any conversation. Her left leg was abducted due to the left
hemiplegia, and there was no spontaneous movement of her left arm and hand and no involuntary
movement otherwise. When questioned she answered
with one or two words. She was able to perform
simple addition and could follow simple instructions
appropriately. Her orientation to time and place was
preserved, though she had retrograde amnesia covering the previous two weeks. Judgement was poor,
but she displayed insight. She did not experience
hallucinations or delusions. She had normal vision
and the optic fundi were normal. The pupils were
round, equal in size, and reacted to light and accommodation. The extraocular movements were full. She
had central facial palsy on the left side, and her neck
was supple. The deep tendon reflexes were increased
to 2 + bilaterally and the extensor toe signs were
positive bilaterally. She had left hemiplegia. Pain
and temperature sense was decreased to 5/10 on the
left upper and lower extremities. Coordination was
normal on the right side. She was unable to perform a
finger-to-nose test on the left side, nor heel-to-shin
test, due to left hemiparesis. No tremors or seizures
were noted.
The impression upon admission was that of
extensive and acute demyelinating disorder involving
cerebral white matter bilaterally but more extensively on the right brain. She had left hemiparesis
and increased deep tendon reflexes, with positive
extensor toe signs bilaterally. The differential diag-

K. Ogawa et al.

nosis included acute multiple sclerosis, progressive
multifocal leukoencephalopathy, acute disseminated
encephalomyelopathy, primary lymphoma of the
brain, neoplastic angioendotheliosis, mitochondrial
myopathy, encephalopathy, lacticacidosis, and strokelike episodes (MELAS), and cerebral granulomatous
angiitis.

Laboratory examinations
Complete blood cell count, serum electrolytes, renal
and liver function tests, and urinalysis were normal;
the erythrocyte sedimentation rate was 12 mm/h.
Cholesterol was 163 mg/100 mL and glucose was
98 mg/100 mL. The lactic dehydrogenase (LDH) was
380 U and the creatine kinase (CK) 79 U. The following laboratory tests were negative or normal: HIV,
HTLV-1, cortisol at 06.00 h, angiotensin-converting
enzyme and very long-chain fatty acids. Serum
immuno-electrophoresis and agarose-gel electrophoresis gave normal patterns; tests for rheumatoid factor, antinuclear antibodies. The CH50 was
45.5 U/mL (normal range is 30–40).
Concerning cerebrospinal fluid (CSF), the lumbar
puncture yielded clear, colourless CSF that contained
2 cells/mm3, of which 82% were mononuclear cells
and 18% polymorphonuclear cells. The CSF glucose
was 86 mg/100 mL, and the protein 36 mg/100 mL.
Oligoclonal IgG band was absent, total IgG was
2 mg/100 mL, and myelin basic protein was 1.7 ng/mL.
Culture of CSF was negative for fungi, mycobacteria
and other micro-organisms. Cytologic examination of
CSF was negative for tumour cells. Virus antibody
screening, hepatitis B and C antibodies, antigen tests,
Waaler–Rose and Epstein–Barr (EB) viral antibodies
were normal or of non-diagnostic finding. Chest
radiograph and ECG were normal. An electroencephalogram was abnormal because of right-sided delta
and theta slowing.
Concerning neuroradiological studies, a resonance
MRI scan of the brain, performed on the first day of
hospitalization, revealed predominantly white matter
abnormality, characterized by diffuse, hypointense
T1-weighted and hyperintense T2-weighted signal
abnormality of the deep white matter of the bilateral
cerebral hemispheres. The lesions were mainly in the
white matter, but the right white matter lesion was so
extensive that the high intensity area partially spread
to the right parietal cortical grey matter, which could
indicate brain oedema (Figs 1,2). On the T1-weighted
images, the white matter lesions were well-enhanced
with gadolinium (Fig. 1).201 TlCl scintigraphy of the
brain showed no remarkable enhancement, rCBF
SPECT with 123I-IMP showed low perfusion in the
right parietal, frontal and posterior temporal region.

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486

487

Figure 1. T1-weighted (TR 500/
TE 15) brain magnetic resonance
imaging (MRI) after gadolinium
administration demonstrates diffuse irregular enhancement in the
lesions of bilateral white matter.

Figure 2. T2-weighted (TR 4000/
TE 15) brain magnetic resonance
imaging (MRI) on 21 November
shows high signal areas in the
frontal and parietal white matter
bilaterally. The right white matter
lesion was so extensive that
the high intensity area partially
spread to the right parietal cortical grey matter, which could
indicate brain oedema. Follow-up
studies two and four weeks later
show marked improvement in the
white matter lesions. Brain MRI
two and five weeks after this show
further improvement.

rCBF SPECT with 99mTc-ECD revealed that bilateral
brain blood flow was not low, but low perfusion was
seen in the right parietal, temporal and frontal base.
Cerebral angiogram was normal.

Clinical course
The patient was transferred to the neurology
department and treated with a 2-day course of intra-

venous (i.v.) methylpredonisolone of 500 mg/day
followed by 5-day course of i.v. predonisolone (as
much as 60 mg/day). Following this, her clinical status
improved. On the third day she was able to move her
fingers, and on the seventh day she could walk by
herself. On the fourteenth day her left hemiparesis
completely improved. Mental dysfunction gradually
improved and she became able to communicate with
people using complete sentences. She began to talk to

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Acute multiple sclerosis

K. Ogawa et al.

Figure 3. Serial studies of T1weighted (TR 500/TE 15) brain
magnetic resonance imaging with
gadolinium enhancement also
showed improvement in the
course of the illness.

Figure 4. T1-weighted (TR 500/
TE 15) brain magnetic brain
imaging after gadolinium administration demonstrates enhancement in the left optic nerve
(arrow) directly behind the left
eye,
indicating
retrobulbar
neuritis.

her mother more spontaneously and her mathematical ability improved to two-digit simple addition
and subtraction. Her short-term memory improved to
a level that was almost normal and she became able
to carry out the activities of daily living. The large
white matter lesions observed by the initial brain
MRI had decreased in size by the twenty-fourth
day and her condition was almost normal condition in
two months (Figs 2,3). As she clinically improved,
predonisolone was reduced to 20 mg/day. She was
discharged after fifty days. By then she could walk
by herself, carry out daily activities independently,
and communicate without assistance. Her Wechsler
Adult Intelligence Scale, Revised (WAIS-R) score at
the time of discharge was 70 points. This result is

borderline, and indicated some persisting cognitive
dysfunction.
Upon the second admission 5 months later the patient was monitored at the outpatient clinic and did
well until mid-April 1998, when she developed acute
left visual disturbance. She was readmitted and visual
evoked potential (VEP) revealed delayed P100 on left
side. She was treated with intravenous methylpredonisolone for 3 days and thereafter oral predonisolone
(100 mg/day), after which her vision rapidly improved.
Oral predonisolone was reduced and she was discharged in late May 1998. Magnetic resonance imaging
of the brain demonstrated lesion in the left optic nerve
(Fig. 4). The VEP (P100) was 119 msec on the right side
but was prolonged to 148 msec on the left side.

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488

DISCUSSION
The case began with progressive mental dysfunction
and left hemiplegia, showing marked improvement
with steroid pulse therapy followed by oral steroids.
Brain MRI indicated extensive white matter lesions
in the bilateral cerebral hemispheres. The clinical,
neuroimaging features, and the clinical response to
steroids suggested several differential diagnoses,
including myelinoclastic diffuse sclerosis (a variant
type of multiple sclerosis), adrenoleukodystrophy,
various leukoencephalopathies, and atypical primary
CNS lymphoma, all excluded by cerebrospinal fluid
findings, cerebral angiography and thalium scintigraphy. Acute disseminated encephalomyelopathy
was another possible differential diagnosis. Another
possibility was idiopathic granulomatous angiitis of
the CNS (IGANS), which predominantly involves the
small and medium-sized arteries and veins of the
leptomeninges and brain parenchyma. In the previous
reports they demonstrated granulomatous, lymphocytic, or necrotizing inflammation with granulomas
present in less than half the cases.1 However,
pre-mortem diagnosis is difficult and in most cases
correct diagnosis occurs by autopsy. Moreover, even
brain biopsy results are not always satisfactory,
and correct diagnosis can not be made in 8–18% of
cases.2–5 For these reasons, open brain biopsy is
recommended, though this cannot be done easily
when we consider the invasiveness of open biopsy
and the unsatisfactory diagnostic rate. It is also
necessary to start therapy as soon as possible without
spending too much time on investigations, since the
neurological manifestations, including disturbance
of consciousness, and the progressive nature of the
disorder, require that the patient be treated quickly.
In our case the patient and the family refused to
allow brain biopsy and a pathologically definite
diagnosis could not be obtained. Although MRI
features resembling demyelinating disease have been
reported with IGANS, bilateral, diffuse, relatively
symmetric white matter changes mimicking leukoencephalopathies and leukodystrophies are limited to
several case reports.1,6,7 Recently, Pasquale et al.
reported a case of IGANS with widespread cerebral
white matters, as reported here.8 In our case the
widespread white matter lesions were unique and
strongly enhanced by gadolinium, and improved with
steroid therapy. Although IGANS is a rare disorder,
it is important to think of the disease as described
by Launess when we see a patient with undiagnosed
fluctuating neurological symptoms, with progressive
disturbance of consciousness, cognitive dysfunctions,
and focal neurological signs.9 Although we could not

489

get the typical findings of CFS, the possibility of MS
had remained from the first admission because of the
multiple clinical features. Some patients with MS may
have cognitive and emotional defects that correspond
to degenerative brain changes. In some instances,
neuropsychological impairment may be the initial or
predominant symptom of MS.10 The characteristic
brain MRI findings of MS are multiple white matter
lesions seen as high signal areas on T2-weighted
sequences, and these are predominantly located
around the lateral ventricles in irregular and asymmetrical patterns.11
While monitoring this case in the out-patient clinic,
the patient suddenly developed left visual disturbance. She was readmitted and VEP studies and MRI
of the optic nerve revealed retrobulbar neuritis, a
very common lesion in multiple sclerosis. At this point
the most probable diagnosis is multiple sclerosis
rather than IGANS. With these two episodes of
exacerbation, the patient fulfilled the diagnostic
criteria of multiple sclerosis. Although the diagnosis
was not conclusive at the first admission, close followup and prompt treatment with steroid pulse and oral
corticosteroid during exacerbations quickly resolved
the neurological symptoms, and lead to the diagnosis
of acute MS with bilateral extensive cerebral white
matter lesions in MRI, followed by the left optic
nerve involvement five months later. Additionally,
multifocal MRI white matter lesions are seen in many
disorders other than multiple sclerosis, but Fazekas
et al. have applied the rule that two of the following
three findings are required: a lesion abutting the body
of the lateral ventricles; an infratentorial lesion, and
a lesion > 5 mm in diameter. An evaluation of 1500
consecutive patients using these criteria yielded a
sensitivity of 81% and specificity of 96% for the
diagnosis of MS.11,12 However, MRI findings should
never be used in isolation to establish a diagnosis of
MS. The clinical findings and age of the patient must
be carefully considered.

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