Prospects of measles and subacute sclerosing panencephalitis (SSPE) elimination in Poland]

Following the introduction of vaccinations against measles in 1975 supplemented in recent years with booster vaccinations at the age of 6 years the epidemiological situation with respect to measles and SSPE has been gradually improving, particularly recently. In the paper discussion is presented on the question in what degree the present epidemiological situation of measles, the epidemiological supervision and vaccinations against measles in Poland meet the operative aim of measles and, consequently, SSPE elimination, as recommended by the WHO Regional Bureau. Attention is called to incomplete reliability of measles diagnosis based on clinical manifestations, economic difficulties in conducting serological investigations (detection of IgM antibodies to measles) necessary for measles confirmation, and shortcomings in vaccination organization.     

Subacute sclerosing panencephalitis

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. Electronic Supplementary Material  The online version of this article DOI contains supplementary material, which is available to authorized users.     

SSPE-epidemiology and measles vaccination: our cases

We are discussing the results of an epidemiologic prospective study of 194 children with SSPE. We analyzed, registered and treated these SSPE patients in the period from 1952 to 1983 at the Department for Child Neurology and Psychiatry in Belgrade. There were 140 boys and 54 girls with SSPE. The male to female ratio was 2.6:1. The average age of onset was 8.3 years for boys and 7.2 years for girls, the overall average being 7.7 years. The average duration of illness was 10 months for boys and 8 months for girls; the overall average duration of SSPE was 9 months. The average age for measles infection was 2.4 years. The interval between measles infection and clinical manifestation of SSPE was 5.5 years. The patients came from different parts of Yugoslavia. Most of them were from SR Serbia (95 patients or 49%), AP Vojvodina (39 patients or 20%), SR Bosnia and Herzegovina (22 patients or 11%), AP Kosovo (14 patients or 7.2%), SR Macedonia (14 patients or 7.2%), SR Croatia (6 patients or 3%), and SR Montenegro (4 patients or 2.5%). Mass measles vaccination started in SR Serbia in 1972. In the period 1952-1983 there was an average of six registered patients with SSPE per year. In the same period, there were four peaks of illness: 20 patients in 1957, 15 patients in 1958, 12 patients in 1961, and 9 patients in 1977. The average number of SSPE per year in the period 1952-1972 was 7.2 patients before mass vaccination. The average number of SSPE per year in the period 1973-1983 was 3.3 patients after mass vaccination.     

Subacute sclerosing panencephalitis: A clinical appraisal

Introduction:

Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis affecting primarily children and young adults, caused by a persistent infection of immune resistant measles virus. The aim of the present study is to describe the clinical profile and natural history of patients with SSPE.

Methods:

We collected data of patients with SSPE during 2004-2010 who fulfilled Dyken''s criteria. We analyzed demographical, clinical, electrophysiological, and imaging features.

Results:

Study included 34 patients, 26 (76.5%) males with age of onset from 3 to 31 years. Twenty one patients were below 15 years of age formed childhood SSPE and 13 above 15 years of age constituted adult onset group. 85.3% had low-socioeconomic status. Eleven received measles vaccination and seven were unvaccinated. 59.9% patients had measles history. Most common presenting symptom was scholastic backwardness (52.5%) followed by seizures (23.5%). Three patients each had cortical blindness, macular degeneration, decreased visual acuity, and optic atrophy. Electroencephalographic (EEG) showed long interval periodic complexes and cerebrospinal fluid anti-measles antibody was positive in all. Magnetic resonance imaging was done in 70.5% with was abnormal in 52.5%. Mean incubation period of SSPE after measles was 9.6 years. The follow-up duration was 1-10 years, (average of 2 years). Only one patient died from available data of follow-up, 9 were stable and 10 deteriorated in the form of progression of staging.

Conclusion:

SSPE is common in low-socioeconomic status. The profile of adult onset did not differ from childhood onset SSPE, except for a longer interval between measles infection and presence of the ophthalmic symptom as presenting feature in adult onset group.Key Words: Measles, myoclonus, subacute sclerosing panencephalitis     

Changing character of subacute sclerosing panencephalitis in the United States

We analyzed National Registry data from 575 patients with subacute sclerosing panencephalitis (SSPE) in the United States to assess changes in patient characteristics and SSPE epidemiology. Racial proportions have changed in recent years with an increasing number of Hispanic patients reported in relation to a constant black:white ratio; however, the male:female ratio of approximately 2:1 has remained. The most striking feature of the data is the rapid decline in SSPE incidence. Corresponding to this decrease is an increase in the proportion of cases following measles vaccination. There also is a shorter incubation period for SSPE following vaccination than after measles infection.     

Subacute sclerosing panencephalitis in only one member of a monozygotic twin pair. Clinical, laboratory, electroencephalographic, and immunological study of both twins

Male monozygotic twins, one of whom developed subacute sclerosing panencephalitis (SSPE) are reported in detail. Both patients had measles at the age of 4 years and 6 months. The diagnosis of SSPE was based on clinical, electroencephalographic and laboratory findings. Titration of antibodies against measles was carried out in both cases. The healthy twin, who had been admitted with a clinical picture initially similar to that displayed by his brother, showed clinical manifestations mimicking those of the affected sib, but these vanished 4 days after his admission and were attributed to transient conversion hysteria.The genetic factors involved and the biological response of the antibodies against measles are discussed.     

A case of subacute sclerosing panencephalitis developing 8 years after immunosuppressive treatment for acute lymphocytic leukemia]

A 13-year-old girl developed subacute sclerosing panencephalitis (SSPE) with atypical absence attacks as an initial symptom. Eight years earlier she had been treated for acute lymphocytic leukemia with cytotoxic treatment and radiotherapy, which had resulted in complete remission. She was first treated with an anticonvulsant because the atypical absence attacks and the presence of epileptic discharges on an EEG suggested epilepsy. However, with this mode of treatment the epileptic discharges did not disappear, but periodic high-voltage slow-wave complex discharges were revealed on subsequent EEGs. The antibody titer for measles virus in the cerebrospinal fluid and serum was elevated, confirming the diagnosis of SSPE. SSPE may arise, though rarely, in an individual in an immunosuppressive state due to congenital immunodeficiency or various kinds of malignancies, and also may arise several years after the contraction of measles infection. Our patient, however, lacked a past history of measles infection or immunization, suggesting the possibility that she had contracted measles during or shortly after the course of treatment for ALL.     

Epidemiology of subacute sclerosing panencephalitis in Okinawa, Japan (1977-2005)

The epidemiology of subacute sclerosing panencephalitis (SSPE) has changed since the introduction of measles immunization in 1970's. We studied the incidence of SSPE in Okinawa. There were 22 cases (16 males and 6 females) of SSPE from 1977 to 2005 in Okinawa. The incidence was 0.63 per million population per year from 1977 to 1986, 0 from 1987 to 1993, 1.17 from 1994 to 1999 and 0.75 from 2000 to 2005. Twenty-one SSPE patients had a history of non-immunized measles and 19 of them (90%) had measles infection under 2 years of age. There were measles epidemic every 2-5 years in Okinawa. Ten of 21 cases contracted measles in 1990-1991. The percentage of patients with measles infection under 2 years of age during measles epidemics ranged from 46% to 56%. Early measles infection (under 2 years of age) is a risk factor for SSPE. Routine measles immunization to prevent measles infection is very important for the prevention of SSPE.     

Subacute sclerosing panencephalitis in two brothers

We report the occurrence of subacute sclerosing panencephalitis (SSPE) in two brothers two years after measles infection. The diagnosis was confirmed by compatible data from medical history, occurrence of autochthonic measles virus (MV) IgG production in the central nervous system (CNS), and pathognomonic EEG changes. Pathogenetically, SSPE is caused by a genome mutation of intracellularly persisting MV, causing viral nucleocapsides to accumulate in the brain cells. A specific predisposing immune defect is not known. The occurrence of two cases in one family is suggestive of a genetic predisposing factor.     

Subacute sclerosing panencephalitis in a child with human immunodeficiency virus (HIV) infection on antiretroviral therapy

Subacute Sclerosing Panencephalitis (SSPE) in HIV-infected children is a scarcely reported entity with previous reports describing fulminant course. The impact of highly active antiretroviral therapy (HAART) in altering its course remains unknown. We describe a child with HIV infection, who developed measles at 5 months of age and later developed SSPE at 14 years of age, remaining stable at 7 month follow-up, while on HAART for WHO (World Health Organisation) stage IV disease. The dynamics of HIV-related immunosuppression has an impact on the clinical course of SSPE. Contrary to reported cases of fulminant progression, a classic presentation with slow progression can be expected in children on HAART. We reemphasize the recommendation of “early measles vaccination” to prevent measles infection and subsequent SSPE in these children with an increasingly good life expectancy in the era of HAART.     

Epidemiologic features of subacute sclerosing panencephalitis from clinical data of patients receiving a public aid for treatment

In 1999, clinical data of 125 patients with subacute sclerosing panencephalitis (SSPE) were obtained by the Research Committee from local prefectural governments. The data were made by physicians treating the patients, and were submitted to the governments when the patients applied for the aid. By analyzing the data, we observed the epidemiologic features of the disease in Japan, and discussed the availability of the data as the source of epidemiologic researches. Of the 125 patients, 66 were males and 59 were females. The distribution of age at onset had a peak in 5-14 years of age with the average of 10.3 years. Among the 109 cases in which the time of infection was obvious, more than 80% suffered from measles before 2 years of age, in agreement with the hypothesis that measles infection in young age is a risk factor of SSPE. The interval between measles and the onset of SSPE was between 5 and 10 years in most cases, with average of 8.8 years, median of 4.3 years, ranging from 2 months to 23.6 years. Because the data contain some problems, we have to observe the epidemiologic features of SSPE in Japan based on multiple data sources including this one, considering their advantages and disadvantages.     

Subacute Sclerosing Panencephalitis and Acquired Immunodeficiency Syndrome: Role of Electroencephalography and Magnetic Resonance Imaging

Subacute sclerosing panencephalitis (SSPE) had largely disappeared from the United States because of nearly universal measles vaccination, but it has reemerged in children infected with human immunodeficiency virus (HIV) . Two children with SSPE are described . The first was HIV positive and presented with seizures and encephalopathy at the age of 21 months. The second developed myoclonus and dementia at age 4 years; she was not infected with HIV, but her mother had acquired immunodeficiency syndrom. Magnetic resonance imaging findings were nonspecific and could have been compatible with HIV encephalopathy. Electroencephalography was characteristic of SSPE, showing high-voltage, periodic slow-wave complexes and background slowing . The diagnosis of SSPE was confirmed by brain biopsy or high measles antibody titers in the cerebrospinal fluid.     

Subacute sclerosing panencephalitis (SSPE) the story of a vanishing disease

Subacute sclerosing panencephalitis (SSPE), is a devastating "slow virus" brain disease which affects young children who had measles some 6-7years earlier. Although, the pandemic of SSPE during 1960-1980's was almost eradicated due to mass immunization, the disease is still taking the life of young children in countries where measles immunization is incomplete and in world regions where genetic polymorphism to this particular infection is present. The present review was written for the fortunate young generation of pediatricians and pediatric neurologists who probably have not seen a case of SSPE during their career, and for those who work in counties where the disease has not been eradicated. It is also a reminder that with full coverage of measles immunization this devastating disease can be fully eradicated.     

Subacute sclerosing panencephalitis in Bulgaria (1978-2002)

The epidemiology of subacute sclerosing panencephalitis (SSPE) has changed substantially since the introduction of measles vaccine. We studied the incidence of SSPE in Bulgaria based on cases admitted to the Child Neurology Clinic, University Hospital of Neurology and Psychiatry, Sofia, for a 25-year period (1978-2002). The SSPE incidence prior to and during the period of routine measles immunization was analyzed. SSPE was diagnosed in 40 children (29 males and 11 females, mean age 8.5 years), 28 from 1978 to 1984 (average 4 patients/year), and 12 from 1995 to 2002 (average 1.7 patients/year). Thirty-eight cases (95%) were non-immunized and had early measles infection. Age at onset of SSPE ranged from 8 to 11 years (52.5%) with a mean latent period of 7 years following measles infection. The increase in SSPE incidence (1995-2002) following a 10-year disease-free period (1985-1994) appears to be related to early measles infection (mean age 11 months) during the measles epidemic of 1991-1992. During the period 1995-2002, children had earlier measles infection (average 11 months) and earlier onset of SSPE (mean age 8.4 years) than in the period 1978-1984 (mean age at measles infection 18 months, and of SSPE onset 11.2 years). The SSPE incidence in Bulgaria during the 25-year period from 1978 to 2002 confirms the importance of early measles infection as a risk factor for SSPE, and the role of routine measles immunization in SSPE prevention.     

Subacute sclerosing panencephalitis: Is there something different in the younger children?

Subacute sclerosing panencephalitis is a rare, slow viral infection caused by a defective measles virus. Although it is a rare disease, it is still important in developing countries. The onset is generally between the ages of 5–15 years. We reported the clinical and laboratory profile and nature of 9 patients under the age of 4 years with SSPE. Although it is known that a few patients with SSPE have an acute and rapidly fulminating course, in this study rate of progression was rapidly progressive in 6 patients and progressive in 3 of them on admission. Unfortunately, 4 of them were lost to follow up because of address and/or telephone number alterations. Although the number of patients in this study is not sufficient, we suggest that SSPE patients under the age of 4 years have a poor prognosis as a result of progressive or rapidly progressive course despite medical treatment.     

Genetic characterization of measles virus genotype D6 subacute sclerosing panencephalitis case,Alberta, Canada

Subacute sclerosing panencephalitis (SSPE) is a progressive and eventually fatal neurological disease arising from a persistent infection with measles virus (MV) acquired at a young age. SSPE measles virus strains are defective and unable to produce progeny virions, due to multiple and extensive mutations in a number of key genes. We sequenced the full MV genome from our recently reported SSPE case, which typed as genotype D6, and compared it with other genotype D6 wild type and SSPE sequences. The Alberta D6 strain was significantly different from other reported SSPE D6 sequences. Mutations were observed in all the genes of the Alberta strain, with the greatest sequence divergence noted in the M gene with 17.6% nucleotide and 31% amino acid variation. The L gene showed the least variation with 1.3% nucleotide and 0.7% amino acid differences respectively. The nucleotide variability for 15,672 bases of the complete genome compared to the wild type and other SSPE D6 strains was around 3%.     

Adult onset subacute sclerosing panencephalitis: clinical profile of 39 patients from a tertiary care centre

Clinical and laboratory characteristics of 39 patients with adult onset subacute sclerosing panencephalitis (SSPE) are described and compared to those of juvenile onset patients regarding preceding measles, age at onset, gender, interval between onset and diagnosis, clinical profile, and course during follow up. Diagnosis was based on clinical and electroencephalographic findings and raised anti-measles antibody titres in cerebrospinal fluid. Mean age at SSPE symptom onset was 20.9+/-4.9 years and mean interval from onset to diagnosis was 6.3+/-9.6 months. Referral diagnosis was accurate in only 12 patients. Presenting symptoms included myoclonus, behavioural changes, seizures, and cognitive, visual, and extrapyramidal disturbance. All patients received symptomatic therapy; 19 also received disease modifying agents. Five of seven pregnant women had successful deliveries. The follow-up period varied widely (maximum 60 months, median 9 months). The profile of adult onset SSPE did not differ from the rest of the cohort, except for a longer interval between measles infection and symptom onset (p<0.0001). SSPE in adults poses diagnostic challenges for clinicians. A high index of suspicion and appropriate investigations are necessary for early diagnosis and counselling.     

Combination therapy with intraventricular interferon-alpha and ribavirin for subacute sclerosing panencephalitis and monitoring measles virus RNA by quantitative PCR assay

Subacute sclerosing panencephalitis (SSPE) is a degenerative disease of the central nervous system that leads to death within a few years. Recently, it has been reported that combination therapy with intraparenchymal interferon-alpha (INF-alpha) and intraventricular ribavirin is effective. An 11-year-old SSPE patient whose clinical symptoms progressed rapidly, was treated first with intraventricular INF-alpha and then with combined intraventricular INF-alpha and ribavirin therapy. To monitor viral load over the course of the therapy, measles virus RNA was quantified using a real-time polymerase chain reaction assay. Measles virus RNA decreased rapidly after the INF-alpha therapy was started, paralleling the decrease in the measles antibody titer in the cerebrospinal fluid and the improvement in the neurological disability. After intraventricular ribavirin was combined with INF-alpha therapy, no further improvement was observed. The neurological disability gradually progressed, although the amount of virus RNA remained low.     

Adult-onset subacute sclerosing panencephalitis: clinico-pathological findings in 2 new cases

Subacute sclerosing panencephalitis (SSPE), an uncommon disease usually affecting children and adolescents, is caused by persistent measles infection that progresses to chronic infection with fatal outcome. The debut of this disease in adults is rare, with a small number of cases in the medical literature. This article presents the clinical, radiologic and post-mortem neuropathologic findings in 2 new cases of women with SSPE (1 of them during pregnancy), which showed very atypical clinical characteristics, presentation and evolution. The influence of pregnancy on the course of the disease was unfavorable, in keeping with earlier reports. Our patients showed a very prolonged biphasal clinical course, with a period of disease-free remission that lasted several years. Histological study disclosed features of inflammatory disease associated with others of a neurodegenerative nature, such as the formation of neurofibrillary tangles, which would relate SSPE with other tauopathies.