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Journal ArticleDOI

A study of SSPE: early clinical features

29 Jul 2015-Journal of pediatric neurology (IOS Press)-Vol. 02, Iss: 02, pp 073-077

TL;DR: With progressive increase in age of presentation, in patients with features like loss of vision, seizures and behavioral changes, SSPE should be carefully considered.

AbstractThirty two patients with subacute sclerosing panencephalitis (SSPE) admitted under the care of Department of Neurology at JJ Hospital and Grant Medical College, Mumbai during the period 1998-2003 were analyzed. All patients were evaluated clinically, with relevant investigations and neuroimaging wherever possible. Particular attention was given to early clinical features. Diagnosis was confirmed by cerebrospinal fluid study for measles antibody and by electroencephalography. The mean age of our patients was 13.4 years and the vaccinated patients tended to be older. Nine patients had received measles vaccination. Twelve percent of patients were older than the age of 20 years at the onset of symptoms. Approximately 40.6% of patients presented with symptoms of loss of vision, seizures and behavioral change. At this stage myoclonus and cognitive decline were conspicuous by their absence. Eventually typical features like myoclonus and cognitive decline evolved after a mean period of 8 months. Even in the present era, SSPE continues to remain the most important cause of progressive myoclonic epilepsy. With progressive increase in age of presentation, in patients with features like loss of vision, seizures and behavioral changes, SSPE should be carefully considered. (J Pediatr Neurol 2004; 2(2): 73–77).

Summary (2 min read)

Introduction

  • Subacute sclerosing panencephalitis (SSPE) is a slowly progressive fatal inflammatory disease of the central nervous system, developing as a sequel to childhood measles infection (1,2).
  • Typically it presents with myoclonus and dementia progressing to a mute, bed-ridden and incontinent state finally leading to death.
  • It has been brought down following implementation of measles vaccination in the developed countries (4).
  • SSPE still continues to take lives of children in developing countries (6); the uncommon modes of presentation of SSPE pose diagnostic difficulties and hence are being highlighted in this study.

Materials and Methods

  • This study was carried out in the department of neurology of a tertiary care hospital during the period of five years from 1998 to 2003.
  • Those patients fulfilling the above criteria were selected and enrolled for the study.
  • These patients were then evaluated clinically to look for abnormalities of higher mental functions, visual acuity, presence of chorioretinitis on fundus examination, presence of long tract signs and motor or sensory deficit.
  • Clinical examination was followed by investigations including EEG, cerebrospinal fluid and serum examination to look for measles antibody titers.

Results

  • Twenty four of these patients were males and eight were females.
  • In their series 26 patients presented with cognitive decline, while myoclonus was seen in 27 patients .
  • Out of the four patients with onset of illness after the age of 20 years three were vaccinated and, the single unvaccinated patient had suffered from measles at the age of 5 years.
  • Thirteen out of the 32 patients showed uncommon features at the onset of the disease .
  • Out of these seven, visual loss was the first symptom in six patients.

Features Number of Cases

  • Presenting with seizures had a prolonged history of seizures, with average duration of 15 months before cognitive decline set in.
  • Twenty one patients were imaged in their series.
  • Changes were seen in parieto-occipital cortical and subcortical areas with symmetric involvement of the periventricular white matter in 10 out of 13 patients.
  • Three patients had involvement of white and grey matter together while isolated involvement of basal ganglia was seen in a single patient .

Discussion

  • SSPE is a chronic inflammatory disease of the central nervous system following childhood measles infection which is invariably fatal.
  • The authors observation of rapid evolution of SSPE in vaccinated patients will need further scrutiny with larger number of patients.
  • Visual loss was seen as frequently with the young as with the older patients.
  • All six patients experienced generalized seizures, out of which four patients began their illness with seizures alone and in the other two such seizures were either along with or following other symptoms respectively.
  • Those social issues have much changed over the past 30 years and this observation is difficult to explain and may be related to hormonal influence as suggested by Dyken et al (4).

Conclusions

  • The mean age of presentation has increased to 13.4 years, over the past 30 years.
  • Almost 40% of their patients presented with one or more of uncommon features like vision loss, seizures, and behavioral disturbances.
  • These presentations need emphasis in the early diagnosis of this devastating condition.

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Journal of Pediatric Neurology 2004; 2(2): 73-77
www.jpneurology.org
Abstract
Thirty two patients with subacute sclerosing
panencephalitis (SSPE) admitted under the
care of Department of Neurology at JJ Hospital
and Grant Medical College, Mumbai during
the period 1998-2003 were analyzed. All
patients were evaluated clinically, with relevant
investigations and neuroimaging wherever
possible. Particular attention was given to early
clinical features. Diagnosis was conrmed by
cerebrospinal uid study for measles antibody
and by electroencephalography. The mean age
of our patients was 13.4 years and the vaccinated
patients tended to be older. Nine patients had
received measles vaccination. Twelve percent of
patients were older than the age of 20 years at
the onset of symptoms. Approximately 40.6%
of patients presented with symptoms of loss of
vision, seizures and behavioral change. At this
stage myoclonus and cognitive decline were
conspicuous by their absence. Eventually typical
features like myoclonus and cognitive decline
evolved after a mean period of 8 months. Even
in the present era, SSPE continues to remain the
most important cause of progressive myoclonic
epilepsy. With progressive increase in age of
presentation, in patients with features like loss
of vision, seizures and behavioral changes, SSPE
should be carefully considered. (J Pediatr Neurol
2004; 2(2): 73-77).
Key words: early clinical features, SSPE, vision loss,
seizures.
Introduction
Subacute sclerosing panencephalitis (SSPE) is
a slowly progressive fatal inammatory disease of
the central nervous system, developing as a sequel
to childhood measles infection (1,2). Typically it
presents with myoclonus and dementia progressing
to a mute, bed-ridden and incontinent state nally
leading to death. The best accepted postulation is
that during the measles infection there is incomplete
clearance of the measles virus by the patients
immune system leading to persistence of incomplete
forms of the virus with aberrant M protein in the
central nervous system. This results in cell death,
inammation and gliosis (1).
The worldwide prevalence of SSPE is 0.04-2
cases per million (1,3). It has been brought down
following implementation of measles vaccination
in the developed countries (4). SSPE still exists in
the developing nations, with high incidence amongst
some ethnic groups (3,6). The pattern of clinical
presentation of SSPE has been noticed to change to
an extent over the years, while some changes have
also been noted in the laboratory features of SSPE
(1,2). SSPE still continues to take lives of children
in developing countries (6); the uncommon modes
of presentation of SSPE pose diagnostic difculties
and hence are being highlighted in this study. We
have also compared the present results with a
similar study carried out in the same department of
neurology in 1974 (7).
Materials and Methods
This study was carried out in the department
of neurology of a tertiary care hospital during the
period of ve years from 1998 to 2003.
Inclusion criteria given by Dyken (1) were
followed, namely:
1. Progressive cognitive decline with stereotyped
myoclonic jerks.
2. Generalized long-interval periodic complexes in
the electroencephalography (EEG).
3. Elevated cerebrospinal uid globulin levels.
4. Elevated cerebrospinal uid measles antibody
titers.
5. Typical histological ndings in brain biopsy or
Correspondence: Dr. Satish V Khadilkar
Room no 110, First Floor,
MRC Bulding,
Bombay Hospital, Mumbai, India.
E-mail: khadilkar@vsnl.com
Received: November 02, 2003.
Revised: December 24, 2003.
Accepted: January 16, 2004.
ORIGINAL ARTICLE
A study of SSPE: early clinical features
Satish V. Khadilkar, Shekhar G. Patil, Kedar S. Kulkarni
Department of Neurology, Grant Medical College and Sir JJ Group of Hospitals, Mumbai, India

autopsy.
The diagnosis was established if three out the
ve criteria were fullled. Those patients fullling
the above criteria were selected and enrolled for the
study. Their data was obtained under the following
headings.
a. Preliminary data: name, age, sex, duration of
symptoms, history of measles, history of measles
vaccination.
b. Presence of symptoms like cognitive decline,
myoclonic jerks, seizures, loss of vision, behavioral
change, and sphincter dysfunction.
These patients were then evaluated clinically to
look for abnormalities of higher mental functions,
visual acuity, presence of chorioretinitis on fundus
examination, presence of long tract signs and motor
or sensory decit. Clinical examination was followed
by investigations including EEG, cerebrospinal uid
and serum examination to look for measles antibody
titers. Neuroimaging, wherever possible, was carried
out.
Results
A total of 32 cases were included in the study.
Twenty four of these patients were males and eight
were females. The age at presentation varied from 4
years to 21 years with a mean age of 13.4 years.
In our series 26 patients presented with cognitive
decline, while myoclonus was seen in 27 patients
(Figure 1). Almost 90% of the patients had at least
one of these two symptoms. In the remainder,
predominant seizures, loss of vision or behavioral
change were the presenting symptoms. Six patients
were incontinent by the time medical attention was
obtained. It can thus be seen that cognitive decline
and myoclonus were the essential features of the
clinical symptomatology at the initial examination.
Figure 1 also depicts the symptoms at the onset
of the disease. Relatives of two of our patients were
unable to pinpoint the exact symptom amongst
myoclonus and cognitive decline at the onset hence
in these patients we considered that both symptoms
began at the same time. Out of the 32 patients,
features like vision loss, seizures, and behavioral
changes were seen in 13 patients with one patient
having a simultaneous onset of seizures with
behavioral change (Table 1). Typical features like
myoclonus and/or cognitive decline were seen in the
remaining 19 patients. Thus in approximately 40.6%
of patients uncommon features marked the onset of
disease.
In our study nine patients were vaccinated for
measles at nine months of age. The mean age at
onset of the disease in the vaccinated group was 15.7
years as compared to 12.4 years in the unvaccinated
group. The vaccinated group had a rapid clinical
worsening as compared to the non-vaccinated group.
The average duration of illness from the onset of
rst symptom to seeking medical attention was 3.2
months in the vaccinated group while it was 6.6
months in the non-vaccinated group. By using the
Neurologic Disability Index, all the unvaccinated
and six vaccinated patients were found to have
subacute speed of progression, while three patients
in the vaccinated group had acute evolution. 23
patients were unvaccinated. Relatives of 15 patients
(65.2%) could remember the presence of measles
infection in the childhood, prior to the age of 4
years. The mean incubation period in these patients
was at least 8.13 years. Out of the four patients with
onset of illness after the age of 20 years three were
vaccinated and, the single unvaccinated patient had
suffered from measles at the age of 5 years.
Thirteen out of the 32 patients showed uncommon
features at the onset of the disease (Figure 1).
Amongst our series of 32 patients, seven patients
presented with vision loss which was attributed
to white matter lesions in the parieto-occipital
region. Out of these seven, visual loss was the rst
symptom in six patients. Three other patients had
signs of early optic atrophy but had no symptoms
of loss of vision. Thus all patients in our series had
cortical type of vision loss. Five (15.7%) patients
had onset with seizure disorder, while long tract
signs in the form of spasticity which manifested as
either hemiparesis or quadriparesis was seen in ve
(15.7%) patients. The pyramidal tract signs were
seen in later stages of the disease. The six patients
Figure 1. Clinical symptomatology.
Table 1. Uncommon clinical features at initial
examination
Features Number of Cases
Vision loss 7
Seizures 6
Behavioral change 7
Catatonia 1
Early clinical features in SSPE
S V Khadilkar et al
74

presenting with seizures had a prolonged history
of seizures, with average duration of 15 months
before cognitive decline set in. Seven patients had
behavioural changes. It was the presenting symptom
in three of them.
Twenty one patients were imaged in our
series. Eighteen magnetic resonance imaging
(MRI) and three computed tomography (CT)
examinations were performed. Eight patients had
normal imaging ndings. Out of the remaining 13
patients abnormalities were seen in white matter,
grey matter and basal ganglia. Changes were seen
in parieto-occipital cortical and subcortical areas
with symmetric involvement of the periventricular
white matter in 10 out of 13 patients. Seven patients
in this group of white matter lesions presented with
vision loss. Three patients had involvement of white
and grey matter together while isolated involvement
of basal ganglia was seen in a single patient (Figure 2).
Discussion
SSPE is a chronic inammatory disease of the
central nervous system following childhood measles
infection which is invariably fatal. The average
age of presentation worldwide is between 5 and 15
years with the mean age being 9-10 years (1,2). The
average age of patients in our study was 13.4 years,
which is higher than other studies. This nding is
in keeping with the fact that globally the average
age of SSPE is increasing, which can be attributed
to better vaccination coverage. In the present study,
the vaccinated patients presented later than the
unvaccinated ones by 3.3 years. There are some
reports in which the average age has been shown to
have decreased following vaccination; however the
importance of this observation is unclear at present
(4,6).
In our study, patients who had been vaccinated
had more rapid course of disease, from the onset
till the diagnosis, being 3.2 months as compared to
6.6 months in the unvaccinated group. Also, acute
progression was seen only in the vaccinated patients,
but we could not nd any study to corroborate this
nding. The association of measles vaccine and
SSPE has been an issue of much importance. In
patients of SSPE who had been vaccinated, It has
been documented that the genomic structure of
the measles virus from the vaccine did not match
the virus obtained from the specimens of brain
biopsy as reported by Jin et al. (8), and measles
vaccination has not been causally associated with
the development of SSPE. Our observation of rapid
evolution of SSPE in vaccinated patients will need
further scrutiny with larger number of patients.
The higher percentage of cases of SSPE amongst
the vaccinees may be due to poor nutritional status
of children in the developing countries resulting in
poor uptake, or due to a different type of strain in
the environment, subclinical measles infection prior
to measles vaccination or due to faulty storage (cold
chain) of the vaccine. We believe that one or more
of these factors were operating in our vaccinated
children who had SSPE.
Thirteen patients presented with unusual
symptoms like loss of vision, seizures, or behavioral
changes. Though loss of vision is a well documented
symptom, studies have reported a higher incidence
of visual loss amongst patients with adult onset
SSPE with age ranging from 20-35 years (2,9,10).
However, in our study, the mean age of patients
presenting with loss of vision was 14.8 years with
Figure 2. Imaging ndings.
Figure 3. T2 weighted MRI showing increased signal in
the parieto-occipital white matter and grey matter.
Early clinical features in SSPE
S V Khadilkar et al
75

age range of 12-20 years. Visual loss was seen as
frequently with the young as with the older patients.
The vision loss in these patients was of the posterior
type with neuroimaging features suggestive of
diffuse white matter lesions in the parieto-occipital
lobes which are best seen on the T2 weighted MRI
images (Figure 3 and 4). Features suggestive of
chorioretinitis were seen in four patients, out of
which three patients also had early optic atrophy,
however loss of vision was neither reported nor found
in these four patients. Thus, at all ages, visual loss of
the occipital type formed an important feature in the
early phases of SSPE.
Those patients who presented with seizures
had a longer duration of symptomatology till the
diagnosis of SSPE. Most of these patients continued
to experience seizures in spite of anti-epileptic
medications and then they progressed slowly with
evolution of myoclonus and cognitive decline as
the time elapsed. All six patients experienced
generalized seizures, out of which four patients
began their illness with seizures alone and in the
other two such seizures were either along with or
following other symptoms respectively. Patients with
“disease revealing seizures, as seen in ve of our
patients, had a prolonged course of symptomatology,
before cognitive decline set in. Kissani et al. (11)
documented epilepsy in 30 (42%) of their patients
in a series of 70 patients. Among these 30 patients,
“disease revealing seizures were seen in 23%
of patients. Özturk et al. (12) had seven (19.4%)
patients with seizures in their series of 36 patients.
The incidence of seizures in our study is less as
compared to studies mentioned in literature.
Wandering behavior was noted in four patients
and it was the rst symptom in two of them. These
patients had uncontrolled urge to leave home
and would wander for hours before returning.
Irritability and adamant behavior was seen in all
the seven patients. Hyper religiosity was seen in one
patient. He used to spend most of his awake hours in
praying and worshipping. All the seven patients
gradually developed more obvious cognitive decline
and myoclonus over an average period of 5.9
months.
Out of 21 patients who underwent neuroimaging
approximately one-third of patients had normal
imaging. The most striking feature of neuroimaging
was abnormalities in the white matter mainly
involving the parieto-occipital cortical and
subcortical regions. Changes were also detected
in the grey matter and the basal ganglia but these
changes were far and few as compared to the
white matter changes. Early stages of SSPE shows
edematous change or normal imaging while later
stage of the disease shows marked atrophy of the
brain which was seen in three of our patients (13).
In our study there was no enhancement of lesions on
CT scans, but Brismar et al. (14) have reported a case
with rapid clinical deterioration and multiple areas
of enhancement on neuroimaging.
A similar study regarding clinical aspects of
SSPE was published from our department in 1974
(7). We compared the ndings of our present study
with the study done at our institution 30 years ago.
As can be seen from Table 2, there has been no
signicant change in the mean age of patients. The
striking preponderance of male patients continues,
though less prominent. This is curious. Earlier it was
believed that the social circumstances were related
to this disparity. Those social issues have much
changed over the past 30 years and this observation
is difcult to explain and may be related to hormonal
inuence as suggested by Dyken et al (4). Zeman
and Kolar (15) mention a male to female affection
as 2.5:1 which is comparable to our study ratio of
3:1 (15). The majority of patients had myoclonus
and cognitive decline. No case of vision loss
was reported in the previous study. Hemiparesis,
Figure 4. T2 weighted MRI showing increased signal in
the parieto-occipital white matter and grey matter.
Table 2. Comparison of present and past study from
our department
Present study Singhal et al
2003 (n=32) 1974 (n=39)
n (%) n (%)
Mean age (years) 13.4 11.2
Sex (male:female) 24:8 36:3
Myoclonus 27 (84.3) 37 (94.8)
Cognitive decline 26 (81.2) 38 (97.4)
Seizures 6 (18.7) 13 (33.3)
Hemiparesis 5 (15.7) 2 (5.1)
Chorioretinitis 4 (12.5) 1 (2.5)
Vision loss 7 (21.8) 0 (0)
Early clinical features in SSPE
S V Khadilkar et al
76

choreoathetosis, tremors, and generalized seizures
were the other prominent features in the previous
study out of which choreoathetosis and tremors were
not seen in any of our patients.
Conclusions
SSPE is still an important cause of mental
decline at young ages in our set up. The mean age
of presentation has increased to 13.4 years, over
the past 30 years. A proportion of patients had
developed SSPE in spite of being vaccinated. Almost
40% of our patients presented with one or more of
uncommon features like vision loss, seizures, and
behavioral disturbances. These presentations need
emphasis in the early diagnosis of this devastating
condition.
Acknowledgements
We thank Dr. N.A. Mehta Shah, Professor and
Head, Department of Neurology and Dr. G.B. Daver,
Dean, Grant Medical College and Sir JJ group of
Hospitals, Mumbai for their support and allowing us
to present this work.
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77
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Abstract: Two members of the morbillivirus genus of the family Paramyxoviridae, canine distemper virus (CDV) and measles virus (MV), are well-known for their ability to cause a chronic demyelinating disease of the CNS in their natural hosts, dogs and humans, respectively. Both viruses have been studied for their potential involvement in the neuropathogenesis of the human demyelinating disease multiple sclerosis (MS). Recently, three new members of the morbillivirus genus, phocine distemper virus (PDV), porpoise morbillivirus (PMV) and dolphin morbillivirus (DMV), have been discovered. These viruses have also been shown to induce multifocal demyelinating disease in infected animals. This review focuses on morbillivirus-induced neuropathologies with emphasis on aetiopathogenesis of CNS demyelination. The possible involvement of a morbillivirus in the pathogenesis of multiple sclerosis is discussed.

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TL;DR: Subacute sclerosing panencephalitis (SSPE) is a slowly progressive brain disorder caused by mutant measles virus that affects younger age groups and a universal vaccination against measles is the only proven way to tackle this menace currently.
Abstract: Subacute sclerosing panencephalitis (SSPE) is a slowly progressive brain disorder caused by mutant measles virus. SSPE affects younger age groups. SSPE incidence is proportional to that of measles. High-income countries have seen substantial decline in SSPE incidence following universal vaccination against measles. SSPE virus differs from wild measles virus. Measles virus genome recovered from the autopsied brain tissues demonstrates clustered mutations in virus genome particularly in the M gene. These mutations destroy the structure and functioning of the encoded proteins. Complete infectious virus particle has rarely been recovered from the brain. Human neurons lack required receptor for entry of measles virus inside the neurons. Recent in vitro studies suggest that mutations in F protein confer hyperfusogenic properties to measles virus facilitating transneuronal viral spread. The inflammatory response in the brain leads to extensive tissue damage. Clinically, SSPE is characterized by florid panencephalitis. Clinically, SSPE is characterized by cognitive decline, periodic myoclonus, gait abnormalities, vision loss, and ultimately to a vegetative state. Chorioretinitis is a common ocular abnormality. Electroencephalography (EEG) shows characteristic periodic discharges. Neuroimaging demonstrates periventricular white matter signal abnormalities. In advanced stages, there is marked cerebral atrophy. Definitive diagnosis requires demonstration of elevated measles antibody titers in cerebrospinal fluid (CSF). Many drugs have been used to stabilize the course of the disease but without evidence from randomized clinical trials. Six percent of patients may experience prolonged spontaneous remission. Fusion inhibitor peptide may, in the future, be exploited to treat SSPE. A universal vaccination against measles is the only proven way to tackle this menace currently.

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Hasan Cece1, L Tokay1, Sema Yildiz1, Omer Karakas, Ekrem Karakas, Akin Iscan1 
TL;DR: A normal initial cranial MRI does not exclude subacute sclerosing panencephalitis, which should be kept in mind in childhood demyelinating diseases even when the presentation is unusual, according to a retrospective review of 76 cases.
Abstract: Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, inflammatory neurodegenerative disease. This study investigated the relationships of clinical stage with epidemiological and magnetic resonance imaging (MRI) findings in SSPE by retrospective review of 76 cases (57 male) diagnosed by typical periodic electroencephalographic features, clinical symptoms and elevated measles antibody titre in cerebrospinal fluid. Clinical stage at diagnosis was I or II in 48 patients, III in 25 and IV in three. Prominent findings at presentation were atonic/myoclonic seizures (57.9%) and mental deterioration with behaviour alteration (30.3%). Frequent MRI findings (13 – 32 patients) were subcortical, periventricular and cortical involvement and brain atrophy; the corpus callosum, basal ganglia, cerebellum and brainstem were less frequently involved. Five patients had pseudotumour cerebri. Cranial MRI at initial diagnosis was normal in 21 patients (19 stage I/II, two stage III/IV). Abnormal MRI findings were s...

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TL;DR: Measles antibody in the CSF is diagnostic for SSPE and is helpful in early diagnosis and can be prevented by timely immunization against measles.
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Journal ArticleDOI
TL;DR: Atypical SSPE presentation can include mainly focal intractable seizures, and no significant influence was found of the history of epilepsy on the type of S SPE progression.
Abstract: Introduction. Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, fatal neurodegenerative disease of childhood and early adolescence caused by defective measles virus. The initial symptoms of SSPE usually involve regression in cognitive functioning and behavior or recurrent myoclonic jerks. Seizures revealing SSPE and epilepsy during the clinical course can occur. Objective. The aim of the study was to analyze clinical and EEG characteristics of both initially occurred seizures and epilepsy which developed in the course of the disease. Methods. Retrospective study was carried out on 19 children (14 boys, 5 girls) with SSPE diagnosed and treated at our Clinic from 1995 to 2010. Seizures revealed SSPE in our patients aged from 6.5 to 11.5 years (mean 8.6 years). Results. SSPE onset ranged from 4.5 to 16.5 years (mean 10.05). Complete vaccination was performed in nine patients. Cognitive and behavioral decline was preceeded by 6-18 months in two children with intractable focal motor seizures with secondary generalization, one child with complex partial seizures and one with atypical absences. During the clinical course of the disease epilepsy developed in 10 (52.6%) cases, including four patients with seizures as the initial SSPE sign. It occurred mainly in the first year, while in three cases seizures appeared between 1 and 5 years of the disease evolution. Myoclonus was present independently from seizures. No significant inter-group differences were found relating to the type of SSPE progression and history of epilepsy. The only child with fulminant SSPE presented with initial seizures. Favorable seizure control was achieved in 60.0% patients. Intractable epilepsy developed in four patients. Conclusion. Atypical SSPE presentation can include mainly focal intractable seizures. Epilepsy developed during clinical course in 52.6% cases. No significant influence was found of the history of epilepsy on the type of SSPE progression.

7 citations


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Journal ArticleDOI
TL;DR: A combination of oral isoprinosine (Inosiplex) and intraventricular interferon alfa appears to be the best effective treatment for subacute sclerosing panencephalitis.
Abstract: Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence. It is caused by persistent defective measles virus. Brain biopsies or postmortem histopathological examination show evidence of astrogliosis, neuronal loss, degeneration of dendrites, demyelination, neurofibrillary tangles, and infiltration of inflammatory cells. Patients usually have behavioral changes, myoclonus, dementia, visual disturbances, and pyramidal and extrapyramidal signs. The disease has a gradual progressive course leading to death within 1-3 years. The diagnosis is based upon characteristic clinical manifestations, the presence of characteristic periodic EEG discharges, and demonstration of raised antibody titre against measles in the plasma and cerebrospinal fluid. Treatment for SSPE is still undetermined. A combination of oral isoprinosine (Inosiplex) and intraventricular interferon alfa appears to be the best effective treatment. Patients responding to treatment need to receive it life long. Effective immunisation against measles is the only solution presently available to the problem of this dreaded disease.

292 citations


"A study of SSPE: early clinical fea..." refers background in this paper

  • ...Though loss of vision is a well documented symptom, studies have reported a higher incidence of visual loss amongst patients with adult onset SSPE with age ranging from 20-35 years (2,9,10)....

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  • ...The pattern of clinical presentation of SSPE has been noticed to change to an extent over the years, while some changes have also been noted in the laboratory features of SSPE (1,2)....

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  • ...Subacute sclerosing panencephalitis (SSPE) is a slowly progressive fatal inflammatory disease of the central nervous system, developing as a sequel to childhood measles infection (1,2)....

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  • ...The average age of presentation worldwide is between 5 and 15 years with the mean age being 9-10 years (1,2)....

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  • ...Journal of Pediatric Neurology 2004; 2(2): 73-77...

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Journal ArticleDOI
TL;DR: Subacute sclerosing panencephalitis is a neurodegenerative disease of childhood that is due to a persistent measles infection that is coexistent with the decline in natural measles infection.
Abstract: Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease of childhood that is due to a persistent measles infection. Owing to a nationwide immunization program in the United States, the incidence has decreased considerable, coexistent with the decline in natural measles infection. The disease, now fully understood, still represents a great international problem. Clinical presentation, etiology, pathogenesis, prevention, and treatment are updated in this article.

125 citations


Journal ArticleDOI
TL;DR: Although the long-term pattern of incidence is unknown, the incidence of reported SSPE declined dramatically from 1970 to 1976, and available epidemiologic evidence suggests that some extrinsic factor, unrelated to measles or measles vaccine, is important in the pathogenesis of the disease.
Abstract: The Subacute Sclerosing Panencephalitis Registry has compiled data from 453 instances of SSPE occurring in the United States from 1960 through 1976. The mean annual incidence during this period was 3.5 per 10 million persons under 20 years of age, 2.3 times higher for males than females, and 4.0 times higher for whites than blacks. Although the long-term pattern of incidence is unknown, the incidence of reported SSPE declined dramatically from 1970 to 1976. There are marked geographic variations of SSPE activity within the United States and also a higher incidence for children from farms (9.4 per 10 million persons under 20) compared with children from other rural domiciles (3.7 per 10 million), suburban children (2.9 per 10 million), and inner-city children (1.6 per 10 million). Available epidemiologic evidence suggests that some extrinsic factor, unrelated to measles or measles vaccine, is important in the pathogenesis of the disease.

104 citations


"A study of SSPE: early clinical fea..." refers background in this paper

  • ...Though loss of vision is a well documented symptom, studies have reported a higher incidence of visual loss amongst patients with adult onset SSPE with age ranging from 20-35 years (2,9,10)....

    [...]


Journal Article
TL;DR: The progress of MR abnormalities seen in patients with SSPE seems to follow a constant pattern, but the severity of MR changes does not always correlate well with the clinical findings, so caution must be used when evaluating the effects of therapy.
Abstract: PURPOSE: To evaluate the progression of CT and MR changes of the brain in subacute sclerosing panencephalitis (SSPE) as a basis for assessing the effects of different types of therapy. METHODS:Fifty-two patients with SSPE were examined, 44 with MR imaging and 42 with CT of the brain on one or more occasions. A total of 92 MR and 67 CT studies were performed. RESULTS: Correlation between the clinical status and the MR findings on admission was poor. Of 20 patients with clinically advanced disease, only 8 had marked MR abnormalities; 6 had normal or almost normal findings on MR examinations. Two of 4 patients with clinically mild disease had advanced MR changes. The progression of the MR findings appeared to follow a constant pattern. The earliest pathologic finding was focal, high-T2-intensity white matter changes; later atrophic changes followed. The atrophy lagged behind the white matter changes and was thus mild when white matter changes were moderate or severe. In the most advanced stage, when the patient was in a neurovegetative state, an almost total loss of white matter had usually taken place. At this stage, the corpus callosum was also thin. Basal ganglia changes, usually involving the putamina, were seen in one third of patients and cortical gray matter changes were seen in one fourth of patients examined with MR imaging. In 2 of 20 patients, MR changes regressed in parallel with clinical improvement following therapy, but in 5 patients clinical improvement was accompanied by progression of MR changes.CONCLUSION:The progress of MR abnormalities seen in patients with SSPE seems to follow a constant pattern, but the severity of MR changes does not always correlate well with the clinical findings. Caution must therefore be used when evaluating the effects of therapy.

80 citations


"A study of SSPE: early clinical fea..." refers background in this paper

  • ...(14) have reported a case with rapid clinical deterioration and multiple areas of enhancement on neuroimaging....

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Journal ArticleDOI
TL;DR: Mice, hamsters, and rats have been used as model systems to study MV-induced CNS infections, and revealed interesting aspects of virulence, persistence, the immune response, and prerequisites of protection.
Abstract: Central nervous system (CNS) complications occuring early and late after acute measles are serious and often fatal. In spite of functional cell-mediated immunity and high antiviral antibody titers, an immunological control of the CNS infection is not achieved in patients suffering from subacute sclerosing panencephalitis (SSPE). The known cellular receptors for measle virus (MV) in humans, CD46 and CD150 (signaling lymphocyte activation molecule, SLAM), are important components of the viral tropism by mediating binding and entry to peripheral cells. Because neural cells do not express SLAM and only sporadically CD46, virus entry to neural cells, and spread within the CNS, remain mechanistically unclear. Mice, hamsters, and rats have been used as model systems to study MV-induced CNS infections, and revealed interesting aspects of virulence, persistence, the immune response, and prerequisites of protection. With the help of recombinant MV and mice expressing transgenic receptors, questions such as receptor-dependent viral spread, or viral determinants of virulence, have been investigated. However, many questions concerning the human MV-induced CNS diseases are still open.

79 citations