The Turkish Journal of Pediatrics
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Patients with acute, fulminant form of SSPE
M. Özlem Hergüner, Şakir Altunbaşak, Vildan Baytok
Department of Pediatric Neurology, Çukurova University Faculty of Medicine, Adana, Turkey
|Hergüner MÖ, Altunbaşak Ş, Baytok V. Patients with acute,
fulminant form of SSPE. Turk J Pediatr 2007; 49: 422-425.|
Subacute sclerosing panencephalitis (SSPE) usually begins insidiously and
follows a subacute course with relentless but slow progression to death. In
recent years, however, patients with acute or fulminant course were reported.
In this article, we report on three patients (2 girls, 1 boy) with SSPE who
developed an acute and fulminant course.
Subacute sclerosing panencephalitis may be seen with more atypical symptoms
and more acute and fulminant courses due to various undetermined reasons.
Early diagnosis is very important for the effectiveness of treatment. Children
presenting with acute or subacute neurologic symptoms should be examined for
SSPE, especially if they have no risk factors for hereditary neurodegenerative/
neurometabolic diseases, and it is more important if those children were not
vaccinated or were infected with measles.
SSPE, acute-fulminant course, atypical findings.
|Subacute sclerosing panencephalitis (SSPE)
is a progressive inflammatory disease of the
central nervous system caused by a persistent
measles virus. It usually begins insidiously
and follows a subacute course with relentless
but slow progression to death. In the typical
course of the disease, further clinical stages
include stereotypic attacks (myoclonia/atonia),
worsening dementia, long tract involvement,
autonomic failure, mutism, and decerebrated,
decorticated rigidity. Clinically, SSPE has a
four-stage course over many months to two or
more years. However, in about 10% of patients,
clinical manifestations of SSPE were not typical,
and patients with acute or fulminant course
were reported[3-6]. Acute, fulminant course is
diagnosed as the patient develops at least
66% neurologic disability (as measured by the
neurologic disability index) in the first three
months or death within six months.|
Here, we report on three patients with SSPE
who developed an acute, fulminant course.
|Case Presentation |
A 14-year-old-girl was admitted with acute
dysarthria for the last four days. Her past
medical history was unremarkable. No record of measles immunization or infection was found.
She had been attending a school for normal
children and had received good results from an
examination a week previously. Family history
was negative for neurologic disorders.
Her mental and motor development and physical
examination were normal. During neurologic
examination, she was conscious. It was found
that she had dysarthria, auditory agnosia, and
also increased tonus on her left side. The rest of
the neurologic examination was found normal.
Blood biochemistry, metabolic screening, blood
lactic/pyruvic acid levels, and cerebral magnetic
resonance imaging (MRI) were normal. An
electroencephalogram (EEG) showed spike and
wave, and sharp wave paroxysms especially
on right frontal and central zones. Ten days
after admission, she presented head drop
attacks. Analysis of cerebrospinal fluid (CSF)
was performed. The biochemistry of CSF was
normal, but increased titers of anti-measles
antibodies in CSF were measured by enzymelinked
fluorescent assay (ELFA) as 1:320. She
was treated with intravenous immunoglobulin,
carbamazepine, isoprinosine (100 mg/kg/d)
plus subcutaneous beta-interferon 1a. Her
neurological disability index (NDI) deteriorated
from 13 to 62 in two months. She died at home
four months after her first symptoms.
A three-year-old girl presented with poor
coordination, inability to walk, and head
nodding for the last 15 days. Mental and motor
status was normal. In her medical records, there
was no data about immunization or infection
with measles. Family history was unremarkable,
except for parental consanguinity. Her physical
examination was also normal. During the
neurological examination, she was confused,
slowed in her responses. She had dysarthria
and cerebellar signs on her left side.
In laboratory examination, blood chemistry,
metabolic screening and cerebral MRI were
found normal. EEG showed suppressionburst
pattern. CSF biochemistry was normal;
however, anti-measles antibody titers in
CSF were elevated (1:320). She was put on
carbamazepine, isoprinosine and beta-interferon
1a therapy. In spite of treatment, her NDI
score was deteriorated in one month (from 20
to 65), and she died after two months.
A 5.5-year-old boy presented with inability
to walk in the last four days. Six days before
admission, he had upper respiratory tract
infection, but no medical therapy was given.
His past medical history revealed measles virus
infection at the age of 10 months. His physical
and mental development were normal. During
neurologic examination, he was conscious, but
had slurred speech, mild truncal ataxia, and
mild pyramidal signs. His NDI score was 16.
Cranial nerve examination and funduscopic
examination were normal. During the course of
hospitalization, he exhibited head drop attacks.
Cerebral MRI was normal. EEG showed periodic,
paroxysmal sharp and slow wave discharges on a
diffusely slow background. SSPE was diagnosed
on the basis of abnormally elevated anti-measles
antibodies both in serum and CSF (1/640). He was treated with carbamazepine, beta-interferon
1a and isoprinosine. In spite of the therapy, his
neurologic status worsened progressively. The
clinical stage of disease progressed to vegetative
form in two months. The NDI score was 64
two months after his first admission.
|In the classical form of SSPE, slow progression
of neurologic symptoms goes through four
characteristic stages: (I) slowly evolving behavioral and intellectual deterioration; (II)
various types of involuntary movements; (III)
severe pyramidal and extrapyramidal hypertonus
and disappearance of hyperkinesias; and (IV)
chronic vegetative state and death. Stage I may
last from several weeks to several years, stage
II typically lasts from three months to one year.
Stages III and IV often last from six months to
one year[8,9]. The rate of progression is variable.
In the majority, death occurs within 1-3 years
after onset of symptoms. In the series of Risk
and Haddad10, approximately 10% of patients
had a fulminant course. PeBenito et al. reported
25 cases with acute, fulminant form of SSPE
between 1953 and 1997. Marjanovic et al. reported two patients with acute presentation of
SSPE. One of them presented with episodes of
night terror. He died 2.5 months after the onset
of the night terror attacks. The second patient
was admitted to hospital with sudden onset
of partial seizures, and he died four months
after the onset of the first partial seizure. In
another report, a girl aged 15 years 9 months
presented with drop attacks and died less than
three months after the initial presentation.
Chung et al. reported a 14-year-old boy who
manifested the acute fulminant form of the
disease and presented a month before with
transient visual agnosia. Takayama et al. also
reported a 12-year-old child with fulminant SSPE
who died within four months. They reviewed
the cases of fulminant SSPE in the literature
and reported that half of the cases involved
visual agnosia as an initial symptom. We did
not find this symptom in our patients. Our
patients presented acute neurological findings
during the first examination but did not have
the symptoms or evidence of behavioral and
intellectual deterioration at the beginning of the
disease. In spite of the therapy, the neurologic
status of all patients worsened progressively.
In rapidly progressive SSPE, various stages
of disease cannot be recognized. The exact
mechanism producing an acute fulminant course
is not known. Several factors such as exposure to
measles at an early age, viral virulence, impaired
host defense mechanisms, and concurrent
infections with other viruses have been
suggested as responsible for producing a rapid
course of the disease. Probable derangement of
T-cell subsets and alterations of T-lymphocyte
functions in patients with SSPE is thought to
be one of the causative factors.|
Most patients with SSPE have a history of
primary measles infection at an early age
(<2 years), and present after a latent period
of 6-8 years. Measles infection under one year
of age carries a risk of SSPE 16 times greater
than that in children over five years of age.
Widespread immunization has produced greater
than 90% reduction in the incidence of disease
in the developing countries. When the disease
occurs in vaccinated children, it is thought to
result from a subclinical measles infection. In
the history of the first two patients, no data
was found regarding measles infection or
immunization. This would indicate that they
had subclinical infection. For the diagnosis of
SSPE, subclinical infection cannot be ruled out
even in patients with no history of measles.
Diagnosis of SSPE is based on a positive history
of measles infection, clinical picture, typical
electroencephalographic finding (suppressionburst
pattern), and elevated serum and CSF antimeasles
antibody titer[1,2]. Reverse transcriptase
polymerase chain reaction technique and
brain biopsy may be useful in confirming the
diagnosis in SSPE with negative CSF findings.
MRI is more sensitive in detecting whitematter
abnormalities. In the early stages of
the disease, cerebral MRI shows lesions usually
involving parieto-occipital cortico-subcortical
regions asymmetrically. In time, symmetric
periventricular white matter changes become
more prominent. However, MRI findings can
be normal, especially in the early stages of
the disease, as seen in our patients. Öztürk
et al. concluded that there seems to be no
correlation between the clinical stages and
either the duration from the onset of SSPE or
the MRI findings. Rarely, atypical MRI findings
such as brain stem involvement and cerebellar
atrophy have also been reported[15-17].
The clinical profiles of SSPE have revealed
varied presentations. Some signs and symptoms
of SSPE at an early stage such as hemiparesis,
papilledema, headaches, generalized tonic-clonic
seizures, nausea, and vomiting can lead to an
erroneous diagnosis such as acute encephalitis,
acute disseminated encephalomyelitis or some
intoxications[5,6,18-21], but typical drop attacks,
and EEG, CSF and MRI findings can lead to the
SSPE diagnosis. At times, SSPE may need to be
distinguished from various neurodegenerative
conditions characterized by myoclonus,
ocular findings, and progressive dementia and from some other progressive neurological
disorders, such as Unverricht-Lundborg disease,
Lafora disease, juvenile ceroid lipofuscinosis,
myoclonic epilepsy with ragged red fibers
and neuraminidase deficiency. The action
myoclonus, ataxia, predominant generalized
tonic-clonic seizures, marked clinical and EEG
photosensitivity, slight mental retardation, and
trend toward stabilization of the condition
are typical for Unverricht-Lundborg disease;
ataxia, severe action and resting myoclonus,
predominant occipital abnormalities, and
constant photosensitivity in the EEG are characteristic of Lafora disease; retinitis
pigmentosa, slow evaluation of neurologic
deficits, and delayed seizure manifestation
are typical for juvenile ceroid lipofuscinosis;
deafness, myopathic or neuropathic signs,
ataxia, and polymorphic neuroimaging
abnormalities are consistent with myoclonic
epilepsy with ragged red fibers; and burning
hands and feet and prominent facial myoclonus
are typical of neuraminidase deficiency5. The
SSPE diagnosis may also be confirmed by the
typical CSF findings. Occasionally, patients with
SSPE can present with lateralizing neurological
signs, partial seizures, or papilledema; these findings can lead to an erroneous diagnosis
of an intracranial space occupying lesion. The
diagnosis is based upon typical CSF changes
and a characteristic electroencephalography
pattern. The diagnosis of SSPE can be reliably
established if the patient fulfils three of the
five criteria given by Dyken.
Treatment for SSPE is still undetermined.
Antiviral agents, such as amantadine and
ribavirin or immunomodulators, such as
isoprinosine, interferon, immunoglobulin and
corticosteroids, have been used[22-24]. Although
Cases 2 and 3 were younger than six years, we
administered beta-interferon therapy because of
progressive disease; however, we found no effect
on the progression. It is known that the sooner
the disease is diagnosed, the better the results
of treatment[25-27]. However, the results of the
treatment of SSPE are not yet totally satisfactory.
Since the treatment of SSPE is only partially
effective in some patients, immunization against
measles remains the only preventive intervention
against this fatal disease.
In conclusion, SSPE has recently been seen with
more atypical symptoms and more acute and
fulminant courses due to various undetermined reasons. SSPE must be considered also in
patients with acute neurologic presentation
such as ataxia, dysarthria, and inability to
walk. Early diagnosis is very important for
the effectiveness of treatment[15,18]. Children
presenting with acute and/or subacute
neurologic symptoms should be examined for
SSPE, especially if they have no risk factors for
diseases, and it is more important if those
children were not vaccinated and/or were
infected with measles.
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