Course Of Subacute Sclerosing Panencephalitis Research Articles

Subakutni sklerozirajući panencefalitis - promene fenotipa tokom poslednje decenije

Introduction: Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, neurodegenerative disease with poor outcome. Anti-measles vaccination contributed to a decreasing number of SSPE patients, but not to its eradication. The aim of our study is to evaluate the course of the disease in our SSPE patients with a focus on vaccinated children. The main goal is considering possibilities for improving prevention of the disease. Methods: A retrospective study included the patients with SSPE treated in the period from December 2010 to December 2020 at the Pediatric Clinic of the Institute. The inclusion criteria were the patients with the diagnosis of SSPE based on clinical presentation, neuroimaging, electroencephalography and positive IgG anti-measles antibodies, both in serum and CSF. Results: Five children with fulminant course of SSPE were included. All these patients were suffering from measles at an early age. Three of them had been vaccinated against measles and two had not. All of them had previously been healthy, immune-competent children, with normal general development. The course was extremely fulminant with lethal outcome within three months since the initial symptoms in four cases. Progressive motor and cognitive decline, behavior changes, movement disorders, myoclonic jerks and seizures were dominant in clinical presentation. Conclusion: Despite vaccination, SSPE has not been eradicated. An increasing number of vaccinated immune-competent children with fulminant form of SSPE and history of measles infection at an early age were treated at our Clinic. As a measure for improving prevention, we suggest considering weaning of vaccine-derived immunity, and re-vaccination of girls at reproductive period.

Short-term Outcomes of the Use of Intraventricular Ribavirin in Filipino Patients with Subacute Sclerosing Panencephalitis

Background. Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by prolonged persistent infection of the central nervous system with a measles virus mutant. Though various treatment modalities have been tried, there is no effective treatment to completely cure SSPE and new therapeutic strategies are needed.
 Objective. This is a prospective uncontrolled observational open label trial to describe the short-term outcomes and safety of intraventricular ribavirin in combination with oral isoprinosine in Filipino SSPE patients.
 Methods. Sixteen (16) unrelated SSPE patients between ages 3-26 years and in various clinical stages were included in this study. Demographic data were described. Intraventricular instillation of ribavirin (1-3 mg/kg/dose) through an Ommaya reservoir was given for a duration of 3-6 months in 13 patients. The duration of follow-up was 48 weeks. The clinical outcome was assessed before, during, and after treatment using the Neurological Disability Index (NDI), Brief Assessment Examination (BAE), and clinical staging using the Jabbour Classification. Adverse side effects from intraventricular ribavirin were enumerated.
 Results. Six of 13 (46.15%) patients mostly in Stage III illness had clinical improvement showing decreasing NDI and BAE scores during treatment and the clinical improvement was maintained or improved further during the 48-week follow-up period. Clinical improvement manifested as improved mental alertness, decrease in spasticity and reduction of seizures. The clinical staging of those who improved remained stable during and after treatment was discontinued. Five (38.46%) patients in Stage II disease worsened and progressed to Stage III despite ribavirin therapy including 1 (7.6%) patient who died after the treatment phase due to pneumonia and brainstem failure. The clinical course of two (15.38%) patients remained unchanged. Minor adverse side effects of ribavirin included transient fever, rash, oral sores, seizure episodes, drowsiness, bladder retention and mild increase in transaminases. Ommaya reservoir infection was a serious adverse event in 5 (31.25%) patients.
 Conclusion. There is still no definitive cure for SSPE. Although ribavirin may help alleviate some of the symptoms of SSPE and prolong life, it may not reverse or halt the progression of the disease. Long term follow-up of these patients and continuous use of intraventricular ribavirin will better clarify its role in modifying the fatal course of SSPE. The role of ribavirin in Stage I patients and a controlled clinical trial in Stage II SSPE needs further studies.

Predictors of clinical course of subacute sclerosing panencephalitis: experience at the Children's Hospital, Lahore.

To determine the clinical course of Subacute Sclerosing Panencephalitis (SSPE) and different factors affecting the clinical course. Descriptive study. The Children's Hospital, Lahore, from October 2005 to May 2008. All serologically confirmed patients of SSPE were registered and clinical staging of these patients were done from stage-I to stage-IV. Clinical course of these patients was classified by using neurological disability index as fulminant, acute, subacute, and chronic course. Clinical course was analyzed for any difference with age, gender, immunization for measles, measles infection, nutritional status and correlation with age of onset of SSPE, (Spearman's correlation), using statistic package for social science (SPSS) V. 14. A total of 57 cases (41 males, 16 females) with mean age of 7.45 years were studied. Forty (71.4%) of them were vaccinated with single dose at about 9 months of age, 41% (23/57) had measles infections ≤ 2 years of age. Using the Neurology Disability Index for these patients 10.5% had fulminant, 17.5% had acute, 49.2% subacute and 22.8% had chronic course. Age, gender, age at measles infection, SSPE onset age and nutritional status were poor predictors of clinical course of SSPE. Unvaccinated patients showed significantly more rapid course of disease (p = 0.04). Clinical course of SSPE cannot be predicted at the onset of this catastrophic disorder. Children not immunized against measles had a significant rapid course of disease.

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

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. 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. 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. 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.

Subacute sclerosing panencephalitis with prominent neuro-ophthalmological manifestation at onset

Subacute sclerosing panencephalitis (SSPE) is a rare disease caused by the measles virus, which gives rise to clinical symptoms between two and 20 years after the primary infection. The course of SSPE is generally fatal and includes progressive intellectual and behavioral decline followed by relentless neurological deterioration. No treatment is currently available.We report the case of a seven-year-old boy presenting with nausea and decreased visual acuity, showing a clinical evolution consistent with SSPE. The interval between the first symptoms and death was less than one year.At autopsy, findings consistent with viral encephalitis and the presence of intranuclear inclusion bodies in the brainstem ganglions supported the diagnosis of SSPE.

Paradoxical a Waves Seen in the Course of Subacute Sclerosing Panencephalitis

Paradoxical a Waves Seen in the Course of Subacute Sclerosing Panencephalitis

Electroencephalographic Changes during Interferon Therapy in a Case of Subacute Sclerosing Panencephalitis

We treated a case of subacute sclerosing panencephalitis (SSPE) with interferon and observed electroencephalographic (EEG) changes and the clinical condition during the treatment period. EEG studies were carried out more than 30 times over the period of 1 year. It was observed that, especially after the first intravenous injection of interferon, periodic synchronous discharges on EEG completely disappeared and the clinical condition improved, although transiently. We found that interferon has some temporary influence on the course of SSPE.

Measles IgM antibodies in cerebrospinal fluid and serum in subacute sclerosing panencephalitis

Using a direct enzyme-linked immunosorbent assay (ELISA), we examined serum and cerebrospinal fluid (CSF) from six patients with subacute sclerosing panencephalitis (SSPE) and control subjects for presence of measles-virus-specific IgM antibodies. All samples from the SSPE patients contained demonstrable titers of measles antibodies. The levels of measles IgM antibodies were higher in CSF diluted 1:5 than in serum diluted 1:50, reflecting a local production of IgM antibodies in the central nervous system. Antibody titers remained constant over the course of SSPE in three of the patients followed for three to six months. The IgM ELISA had high sensitivity as well as specificity and was not complicated by false-positive reactions owing to the presence of rheumatoid factor.

Natural history of restricted synthesis and expression of measles virus genes in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a slow infection caused by measles virus in which several years separate recovery from typical acute measles and the development of a slowly progressive neurological disease. We have investigated replication of measles virus in brain tissue obtained after the onset of neurological disease and in the terminal phase. With a hybridization tomographic technique that combines in situ hybridization with macroradioautographic screening of large areas of tissue, we analyzed the spatial and temporal distribution of virus genes in vivo, using region- and strand-specific probes for the nucleocapsid and matrix genes. We show that early in the course of SSPE there is a global repression in the synthesis and expression of the genome. In the final stage of SSPE most infected cells still have depressed levels of plus- and minus-strand viral RNA and contain nucleocapsid protein but lack matrix protein. These findings provide further evidence for a unified view of slow infections of the nervous system, where the general constraints on virus gene expression provide an explanation for persistence of virus in the face of the host's immune response, and the slow evolution of pathological change. In the final phases of SSPE the more specific block in virus replication accounts for the cell-associated state of the virus and the difficulty in virus isolation.