International Journal of Health Sciences and Pharmacy SRINIVAS

(IJHSP), ISSN: Applied, Vol. 2, No. 2, September 2018 PUBLICATION

Subacute Sclerosing Panencephalitis (SSPE) in

a 10 ½ Year Old Male Child
Edwin Dias
Professor and HOD,
Department of Pediatrics, Srinivas Institute of Medical Science and Research Center, Mangalore,
India
E-mail: [email protected]

Type of the Paper: Research Article.

Type of Review: Peer Reviewed.
Indexed In: OpenAIRE.
DOI: http://dx.doi.org/10.5281/
Google Scholar Citation: IJHSP

How to Cite this Paper:

Dias, Edwin. (2018). Subacute sclerosing panencephalitis (SSPE) in a 10 ½ Year Old Male
Child. International Journal of Health Sciences and Pharmacy (IJHSP), 2(2), 1-6.
DOI: http://dx.doi.org/

International Journal of Health Sciences and Pharmacy (IJHSP)

A Refereed International Journal of Srinivas University, India.

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 International Journal of Health Sciences and Pharmacy SRINIVAS
(IJHSP), ISSN: Applied, Vol. 2, No. 2, September 2018 PUBLICATION

Subacute Sclerosing Panencephalitis (SSPE) in a 10 ½

Year Old Male Child
Edwin Dias
Professor and HOD,
Department of Pediatrics, Srinivas Institute of Medical Science and Research Center, Mangalore,
India
E-mail: [email protected]

ABSTRACT
Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood
and early adolescence, caused by persistent defective measles virus. A 10 ½ year-old male
child with h/o having normal milestones till the age of 15 months had an episode of measles
for which child was hospitalized. After one year he showed gradual deterioration of already
attained milestones but continued regression of milestones noticed, presented to the department
at 10½ years with h/o not getting up from the bed. Patients usually have behavioural changes,
myoclonus, dementia, visual disturbances, and pyramidal and extrapyramidal signs and can
cause death within 1-3 years of presentations. 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 being researched. A combination of oral Isoprinosine and
intraventricular interferon alfa appears to be the best effective treatment. Patients responding
to treatment need to receive it lifelong. At present effective measles vaccination is the only
solution to SSPE.
Keywords: SSPE, Measles, Vaccination.
1. INTRODUCTION: virus in the brain [5]. In1969 measles virus
isolation was done from the brain of a patient
Subacute sclerosing panencephalitis (SSPE) is
with SSPE [6].
a disorder of the central nervous system, a slow
virus infection caused by defective measles 2. CASE REPORT:
virus. Greenfield suggested it in 1960 to
A 10 1/2 year old male child with h/o having
designate a condition due to a persistent
normal milestones till the age of 15 months had
infection by a virus involving both grey matter
an episode of measles. After one year he
and white matter [1]. Dawson, for the first time,
showed gradual deterioration of already
described a child with progressive mental
attained milestones, after one year presented to
deterioration and involuntary movements who,
the department with h/o not getting up from the
at a necropsy, was found to have a dominant
bed. His mother noted personality changes of
involvement of grey matter in which neuronal
irritability and worsened attention. Several
inclusion bodies were abundant [2] using the
months later, he developed intermittent,
term “subacute inclusion body encephalitis”.
random, low-amplitude, lightning-like jerking
Later Pette and Doring (1939) reported a single
movements of the extremities. During the next
case, called “nodular panencephalitis” having
several months, the boy became increasingly
equally severe lesions in both grey and white
withdrawn and emotionally weak. He was
matter [3]. Van Bogaert noticed the presence of
treated for depression, but fluoxetine induced a
dominant demyelination and glial proliferation
marked worsening of the movement disorder
in the white matter and coned it “subacute
and was discontinued. He was next treated with
sclerosing leukoencephalitis” [4]. Bouteille et
valproic acid, which worsened the movement
al, in 1965, on electron microscopy
disorder and no improvement in the psychiatric
demonstrated structures resembling measles
symptoms. Although the boy’s academic

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performance had previously been average, he G (IgG) was elevated at 16.5 mg/dL (normal,
began to fail academically. He lost previous 0.5–5.9 mg/dL).) Measurement of specific
mathematics and language skills, and his antibodies by enzyme-linked immunosorbent
teachers and parents noted progressive memory assay revealed that rubeola (measles) IgG
deficits. The movement disorder evolved from antibodies were markedly elevated in the CSF
random myoclonic jerks of all four extremities at 1:320 (normal, <1:5) and in the serum at
to drop attacks many times a day, during which, 1:5560. Both the EEG and CSF patterns were
while walking or standing, he would suddenly pathgnomic for SSPE and that diagnosis was
fall to the floor. Parents had consulted many made.
doctors for the treatment. But there was The child was given the following treatment,
continued regression of milestones. was subjected to multidisciplinary
No h/o altered sensorium, diplopia, vomiting. management, physiotherapy, neuro
Family history was unremarkable. rehabilitation and occupational therapy. The
General physical examination: The child was child was put on Isoprinosine 100mg/kg/day.
bedridden. Parental counselling was given. The child did
Anthropometry revealed not improve during hospitalisation.
Height: 154cms, Weight: 30Kg, HC: 50CMS
3. DISCUSSION:
CNS examination showed he was alert and
cooperative; posture restricted to the bed, but Epidemiology
produced little spontaneous or prompted The SSPE has declined because of effective
speech. He followed simple verbal commands, measles vaccination. Saha et al. reported an
but had difficulty with more complex ones and annual incidence rate of 21 per million
appeared confused by simple written population in India, in comparison to 2.4 per
commands. On Cranial nerve examination, million population in Middle East. Most patient
saccadic pursuit movements of gaze, give history of primary measles infection at an
hypometric saccades, and mild facial diplegia. early age (< 2 years), which is followed after a
Motor examination revealed cogwheeling in the latent period of 6 to 8 years by the onset of a
upper extremities bilaterally, especially on progressive neurological disorder. Children
pronation-supination. The posture and stance who get measles below age of 1 year carry a risk
were remarkable for intermittent shock like of 16 times more than those infected at 5 years
dipping of the head and shoulders with no or later. A higher incidence (male/female ratio
apparent change in level of consciousness or 3:1) has been noted in rural children than city
postictal state. Systemic examination revealed children, children with two or more siblings,
normal RS, CVS and PA. children of lower socio-economic status, and
Investigations revealed that CBC, chest x-ray, mentally retarded children. Neither the age of
serum electrolytes, CPK were all within normal exposure to measles, nor severity of infection
limits. Magnetic Resonance Imaging (MRI) seem to affect the age of onset of SSPE or
showed focally abnormal with a single patch of course of the disease. Universal measles
increased T2 signal intensity and decreased T1 vaccination has produced greater than
signal intensity in the subcortical white matter 90%reduction in the incidence of SSPE in
of the frontal lobe. The focal lesion did not developed nations. In vaccinated children
enhance with gadolinium. prolongation of age of onset and latency of
Electroencephalogram (EEG) revealed high- infection had been observed. There is no
amplitude bursts of periodic slow-wave revealed evidence to suggest that attenuated
complexes every 4–10 seconds, often vaccine virus is responsible for sporadic cases
accompanied by observable axial myoclonic of SSPE (Dawson’s disease).
spasms. The periodic slow-wave complexes Pathogenesis:
arose from background activity that was SSPE virus is distinguished from the wild type
essentially normal, except for some mild bi of measles virus in that there appears to be a
frontal dominant slowing. Burst suppression defect in assembly of the virus within the
was also seen. Cerebrospinal fluid (CSF) nervous system, and which is related to an
cytology, glucose, and total protein levels (15 abnormality of matrix of ‘M’ protein of the
mg/dL) were normal, but CSF immunoglobulin virus. Studies that show that the matrix protein

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 International Journal of Health Sciences and Pharmacy SRINIVAS
(IJHSP), ISSN: Applied, Vol. 2, No. 2, September 2018 PUBLICATION

is the only structural protein which is Convulsions.

undetected in brain cells from patients with Stage III. Rigidity, Progressive decerebration
SSPE, and on observation of a selective and coma.
decrease in antibodies to the matrix protein in Stage IV. Death
these patients. Electro-encephalogram characteristically
Studies on SSPE cell lines further suggest that shows high voltage slow wave complexes
the M protein may be synthesized but fails to across all leads. They occur regularly at 3.5 to
accumulate and there may be defective 20 sec intervals and are often synchronous with
translation of matrix messenger RNA. An the myoclonic jerks. Measles serology is an
immune response can be made against the viral essential diagnostic tool. The most important
hemagglutination resulting in very high levels single diagnostic criterion for SSPE is the
of neutralizing antibody, and yet the antibody is finding of a low CSF: serum ratio of measles
ineffective in eradicating the virus. So, M- antibody. In normal control patients this is
protein is necessary for correct assembly of between 1/200 and 1/500 (Clarke et al.).
progeny virus at the surface of infected cells, Although increased permeability of the
mutations in this protein lead to an antigenically blood/brain barrier occurs in some other
distinct form that can no longer bind to viral inflammatory conditions (Sherwin et al. [15])
nucleocapsid that initiate virus maturation. The the CSF antibody levels do not reach the values
absence of functionally intact, budding virus seen in SSPE, and the CSF: serum ratio remains
particle, results in intracellular accumulation of high. Brain histology is the least important
incomplete measles virus in brain cells (7-12)., criterion and it is unnecessary to perform a
Modulation of measles antigen on the surface of brain biopsy to make a diagnosis of SSPE.
infected cells by antimeasles antibody is seen, Treatment
and the modulation might make the cell No adequate therapy is currently available for
vulnerable to attack by the immune system and the patients of SSPE. Some non randomized
could alter expression of virus within the cells. studies revealed that certain immuno-
Antigenic challenge of a second infection may modulator anti-viral agents can prolong life if
alter the dormant state of SSPE virus and long-term treatment is continued. Extremely
manifest in disease expression. Sero- variable natural course of SSPE as few patients
epidemiological data suggest that an exposure may have spontaneous prolonged remission
to another virus, such as Epstein-Barr virus or (Risk and Haddad) [14].
influenza type I virus may transform the Treatment with isoprinosine (Inosiplex)
measles virus into a defective virus (Dawson) remains controversial but has been reported to
[9]. prolong survival and produce clinical
Diagnosis: improvement in some patients. This drug is
The clinical course has been arbitrarily divided recommended in a daily dose of 100 mg/kg/ day
into several stages. The first stage is and without major side effects. Nunes et al [13].
characterized by an insidious onset of dementia observed good results combining
and changes in behaviour, and the child often trihexyphenidyl and is oprinosine in controlling
presents because of a deteriorating school myoclonus refractory to sodium valproate.
performance. Progression to the second stage is Intravenous administration of a-interferon has
initiated by motor dysfunction with both not proved useful because of poor penetration
pyramidal and extrapyramidal signs. of blood brain barrier. The modest
Myoclonic jerks are usually present and improvement with intraventricular and
convulsions can occur. In the third stage the intrathecal routes (6 million unit/dose/week) of
patient shows progressively decerebration with administration have been observed in small
increasing rigidity and a declining level of number of patients (Steiner et al.) [16]. The
consciousness. Death usually within 1-3 years pathophysiology of natural remissions and
but may be delayed several months or even relapses in SSPE in unknown. CSF interferon
years. This is the fourth stage, a temporary levels are low in these patients. Exogenous
arrest in the continuous progress of the disease. interferons suppress replication of virus and
Stage I. Progressive mental changes. also influence immune system. There are early
Stage II. Motor dysfunction, Myoclonic jerks, relapses after discontinuing interferon therapy.

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A prolonged therapy is required for sustained encephalomyelitis in England and Wales during
response (Gascon et al.) [10]. last decade. Brain 1950;73:141–66. FREE Full
Combined use of alpha interferon plus Text Google Scholar
isoprinosine. Anlar et al [8]. observed a higher
[2] Dawson JR Jr. Cellular inclusions in
survival rate in the 22 patients after long term
cerebral lesions of epidemic encephalitis. Am J
(56-108 months) treatment with
Pathol1933;9:7–15. PubMedWeb of Science
intraventricular. alpha-interferon and inosiplex
Google Scholar
as compared to those who did not receive alpha-
interferon regimen. But, it did not affect [3] Pette H, Doring G. Uber
oligoclonal bands and intrathecal CSF einheimischepanencephalomyelitisvomcharakt
immunoglobulin (IgG) synthesis (Mehta et al.) er der encephalitis Japonica. Deutsche
[12]. Zeitschrift fur Nerven-heilk1939; 149:7–44.
In an isolated case report intravenous Google Scholar
immunoglobulin was found effective in SSPE [4] Van Bogaert L.
when administered along with a prolonged Uneleocoencephalitesclerosantesubaigue. J
therapy with inosiplex. Further evaluation is Neurol Neurosurg Psychiatry1945;8:101–20.
required to recommend it for regular Google Scholar
management of SSPE (Gurer et al.) [11].
Cimetidine, an H2-receptor antagonist, was [5] Bouteille M, Fontaine C, Vedrenne CL, et
used in SSPE due to its immunomodulatory al. Sur uncasd'encephalitesubaiguea inclusions.
effect. Anlar et al7, did not observe any Etudeanatomoclinique et ultra structurale. Rev
worsening in cimetidine-treated group during Neurol (Paris)1965; 113:454–8. Google
the study period. Scholar
Symptomatic Treatment is essential in SSPE. [6] Horta-Barbosa L, Fuccillo DA, Sever JL, et
The good general nursing care is the most al. Subacutesclerosingpanencephalitis:
important aspect in the management of SSPE. isolation of measles virus from a brain biopsy.
Anticonvulsants, sodium valproate and Nature1969; 221:974. CrossRef PubMed,
clonazepam, are helpful in controlling the Google Scholar
myoclonus. If spasticity is marked, baclofen
and other drugs are used to treat spasticity. [7] Anlar, B., Gucuyener, K., Imir, T., Yalaz,
K., Renda, Y., 1993, Cimetidine as an immuno-
4. CONCLUSION modulator in subacute sclerosing
SSPE is a slow virus infection caused by panencephalitis: A double blind placebo-
aberrant measles virus. One of the most controlled study. Pediatr Infect Dis J., 12: 578-
important limitations in treatment of SSPE is 581
difficulty in recognising early manifestations of [8] Anlar, B., Yalaz, K., Oktem, G., 1997,
disease, when the inflammatory changes are, Longterm follow- up of patients with subacute
possibly, still reversible. Treatments available sclerosing
are very costly in developing nations and are
available only at a few centres in the world. panencephalitis treated with intraventricular a
Moreover, these treatments are not curative and interferon. Neurology, 48: 526-528.
only help in prolonging life. The families of [9] Dawson, J. R., Jr. 1933. Cellular inclusions
patients with SSPE have a lot of physical, in cerebral lesions of lethargic encephalitis.
psychological, and economical stresses to Amer. J. Dawson, J. R., Jr. 1934. Cellular
endure. A great deal of external support is inclusions in cerebral lesions of epidemic
required for these suffering families to cope encephalitis. Arch. Neurol. Psychiat. 31:685-
with these stresses. At present effective measles 700.
vaccination seems to be the only solution to
problem of this dreaded neurological disorder. [10] Gascon, G., Yamani, S., Crowell, J.,
Effective measles vaccination decreased the Sligesby, B., Nester, M., Kanaan, I., 1993,
problem of SSPE. Combined oral isoprinosine-intraventricular
alphainterferon therapy for subacute sclerosing
REFERENCES panencephalitis. Brain Dev., 15: 346-355.
[1] Greenfield J. G. Encephalitis and
Architha Aithal et al, (2018); www.srinivaspublication.com PAGE 5
 International Journal of Health Sciences and Pharmacy SRINIVAS
(IJHSP), ISSN: Applied, Vol. 2, No. 2, September 2018 PUBLICATION

[11] Gurer, Y.K., Kukner, S., Sarica, B., 1996,

Intravenous gamma-globulin treatment in a
patient with subacute sclerosing
panencephalitis. Padiatr Neurol., 14: 72-74.
[12] Mehta, P.D., Kulczycki, J., Patrick, B.A.,
Sobcyzk, W., Wisiniewski, H.M., 1992, Effect
of
treatment on oligoclonal IgG bands and
intrathecal IgG synthesis in sequential
cerebrospinal fluid and serum from patients
with subacute sclerosing panencephalitis. J
Neurol Sci., 109: 64-68.
[13] Nunes, M.L., da-Costa, J.C., da-Silva,
L.F., 1995, Trihexyphenidyl and isoprinosine in
the treatment of subacute sclerosing
panencephalitis. Pediatr Neurol., 13:153-156.
[14] Risk, W.S., Haddad, F.S., 1979, The
variable natural history of subacute sclerosing
panencephalitis: A study of 118 cases from the
Middle East. Arch Neurol, 56: 610- 614.
[15] SHERWIN, A.L., RICHTER, M.,
COSGROVE, J.B.R. & ROSE, B., 1963,
Studies of blood cerebrospinal fluid barrier to
antibodies and other proteins. Neurology.
Minneapolis, 13:113.
[16] Steiner, T., Wirguin, I., Morag, A.,
Abramsky, O., Intraventricular interferon
treatment for subacute sclerosing
panencepahlitis. J. Child Neurol., 4: 20-24.

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