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.

https://pmj.bmj.com/content/postgradmedj/78/916/63.full.pdf

Subacute sclerosing panencephalitis

Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis occurring after infection with measles virus. The prevalence of the disease varies depending on uptake of measles vaccination, with the virus disproportionally affecting regions with low vaccination rates. The physiopathology of the disease is not fully understood; however, there is evidence that it involves factors that favour humoral over cellular immune response against the virus. As a result, the virus is able to infect the neurons and to survive in a latent form for years. The clinical manifestations occur, on average, 6 years after measles virus infection. The onset of SSPE is insidious, and psychiatric manifestations are prominent. Subsequently, myoclonic seizures usually lead to a final stage of akinetic mutism. The diagnosis is clinical, supported by periodic complexes on electroencephalography, brain imaging suggestive of demyelination, and immunological evidence of measles infection. Management of the disease includes seizure control and avoidance of secondary complications associated with the progressive disability. Trials of treatment with interferon, ribavirin, and isoprinosine using different methodologies have reported beneficial results. However, the disease shows relentless progression; only 5% of individuals with SSPE undergo spontaneous remission, with the remaining 95% dying within 5 years of diagnosis.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-8749.2010.03717.x

Subacute sclerosing panencephalitis: an update.

Background When measles vaccines were widely introduced in the 1970s, there were concerns that they might cause subacute sclerosing panencephalitis (SSPE): a very rare, late-onset, neurological complication of natural measles infection. Therefore, SSPE registries and routine measles immunization were established in many countries concurrently. We conducted a comprehensive review of the impact of measles immunization on the epidemiology of SSPE and examined epidemiological evidence on whether there was any vaccine-associated risk. Methods Published epidemiological data on SSPE, national SSPE incidence, measles incidence and vaccine coverage, reports of SSPE in pregnancy or shortly post partum were reviewed. Potential adverse relationships between measles vaccines and SSPE were examined using available data. Results Epidemiological data showed that successful measles immunization programmes protect against SSPE and, consistent with virological data, that measles vaccine virus does not cause SSPE. Measles vaccine does not: accelerate the course of SSPE; trigger SSPE or cause SSPE in those with an established benign persistent wild measles infection. Evidence points to wild virus causing SSPE in cases which have been immunized and have had no known natural measles infection. Perinatal measles infection may result in SSPE with a short onset latency and fulminant course. Such cases are very rare. SSPE during pregnancy appears to be fulminant. Infants born to mothers with SSPE have not been subsequently diagnosed with SSPE themselves. Conclusions Successful measles vaccination programmes directly and indirectly protect the population against SSPE and have the potential to eliminate SSPE through the elimination of measles. Epidemiological and virological data suggest that measles vaccine does not cause SSPE.

/pdf/review-of-the-effect-of-measles-vaccination-on-the-2ff0bo0oko.pdf

Review of the effect of measles vaccination on the epidemiology of SSPE

Subacute sclerosing panencephalitis (SSPE) is a subacute encephalopathy of childhood and young adolescence. Infrequently, SSPE can occur in adults and pregnant women. It is caused by an aberrant measles virus, known as the SSPE virus. SSPE virus differs from wild-type measles viruses in the form of several mutations affecting the viral genome. The matrix gene is most commonly affected by these mutations. The characteristic clinical manifestations of SSPE include behavioral changes, cognitive decline, myoclonic jerks, seizures, abnormalities in vision, bilateral pyramidal signs and coma. Ocular changes may occur in up to 50% of patients. The most characteristic ophthalmological lesion is necrotizing retinitis. Cortical blindness can be the early feature of SSPE. The diagnosis of SSPE is often difficult in the early stages. In a typical case diagnosis is based on clinical, electroencephalographic, and cerebrospinal fluid findings. At present, there is no effective treatment to completely cure SSPE. Oral isoprinosine and intrathecal or intraventricular alpha-interferon may prolong survival to some extent. Immunization against measles is currently the most effective strategy against SSPE.

Subacute sclerosing panencephalitis.

Acute infection of the central nervous system by the neurotropic JHM strain of mouse hepatitis virus (JHMV) induces nucleocapsid protein specific cytotoxic T lymphocytes (CTL) not found in the periphery (S. Stohlman, S. Kyuwa, J. Polo, D. Brady, M. Lai, and C. Bergmann, J. Virol. 67:7050-7059, 1993). Peripheral induction of CTL specific for the nucleocapsid protein of JHMV by vaccination with recombinant vaccinia viruses was unable to provide significant protection to a subsequent lethal virus challenge. By contrast, the transfer of nucleoprotein-specific CTL protected mice from a subsequent lethal challenge by reducing virus replication within the central nervous system, demonstrating the importance of the CTL response to this epitope in JHMV infection. Transfer of these CTL directly into the central nervous system was at least 10-fold more effective than peripheral transfer. Histological analysis indicated that the CTL reduced virus replication in ependymal cells, astrocytes, and microglia. Although the CTL were relatively ineffective at reducing virus replication in oligodendroglia, survivors showed minimal evidence of virus persistence within the central nervous system and no evidence of chronic ongoing demyelination.

Paul R. Dyken

Papers

Subacute Sclerosing Panencephalitis: Current Status