Subacute Sclerosing Panencephalitis
By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
Dr. Deresinski reports no financial relationships relevant to this field of study.
SYNOPSIS: Subacute sclerosing panencephalitis is a lethal complication of measles that is not as rare as previously believed.
SOURCE: Wendorf K, Winter K, Harriman K, et al. Subacute sclerosing panencephalitis: The devastating measles complication is more common than we think. IDWeek, Oct. 28, 2016, New Orleans, LA. Abstract 916.
Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal illness that occurs as a complication of measles virus infection acquired years previously. While considered rare, Wendorf and colleagues recently presented data at IDWeek suggesting that it is not as rare a complication of measles as previously believed.
Wendorf et al identified 17 cases of SSPE that occurred in California from 1998-2016. Cases had a compatible clinical illness and at least one of the following: IgG antibody to measles virus in cerebrospinal fluid (CSF); characteristic electroencephalographic (EEG) findings; typical histologic findings in brain tissue; or medical record documentation of typical SSPE-related complications.
Males outnumbered females in the study. Twelve of the 17 (71%) cases had a history of an acute measles-compatible rash illness. In all 12 patients, this occurred before age 15 months and before any had received the measles vaccine. Eight of the 12 were residing in the United States at the time of the possible episode of acute measles infection.
The diagnosis of SSPE was made at a median age of 12 years (range 3-35 years), although many patients had a prolonged history of cognitive or motor abnormalities prior to diagnosis. The median latency period was 9.5 years (range 2.5-34 years). Using acute measles cases reported to the California Department of Public Health as the denominator, the incidence of SSPE in children younger than 5 years of age was 1:1,367, while for those younger than 12 months of age at the time, it was 1:609.
Previous estimates have varied, but one review recently indicated that the risk of development of SSPE after measles virus infection during childhood was approximately 1 in 25,000, although the review acknowledged that the estimate had a large margin for error because of the lack of reliable reporting.1 Schönberger and colleagues in Germany estimated the risk of SSPE in children whose infection occurred in the first five years of life was much more frequent, with an estimated incidence of 1 in 1,700 to 1 in 3,300, which they point out is similar to the risk of acute mortality from measles virus infection.2 Furthermore, the risk of this complication occurring when infection occurs in the first year of life has been estimated to be significantly more frequent: 1 in 550, which is remarkably comparable to the estimate by Wendorf et al of 1 in 609.1
The delay in diagnosis of SSPE is not surprising given the prolonged period of latency and gradual progression of the disease. The interval between infection and onset of symptoms is generally 1-10 years, but it can be more than 10 years in adults and as short as several months in infants. The initial symptoms generally include subtle alterations in cognition, behavior, and personality, and these eventually are followed by myoclonic jerking, seizure activity, and dementia.2 The development of extrapyramidal symptoms and progressive unresponsiveness finally evolves into coma and a vegetative state, with the entire illness culminating in death after one to three years.
The diagnosis may be confirmed by the identification of measles virus inclusion bodies in neuronal and glial cytoplasm or nuclei. In every case in which genetic investigations were performed, the virus was wild type — no cases associated with vaccine-type virus have been identified. CSF examination also is of value: The immunoglobulin index is elevated and oligoclonal bands targeting measles virus antigens are almost universally present; the presence of IgG antibody against the virus and elevated measles specific index are also diagnostic.1 MRI findings are nonspecific, but EEG may be helpful.
In the series from California reviewed here, the majority of cases occurred in children younger than 12 months of age who, as recommended, had not received measles vaccine (MMR) prior to their presumed measles virus infection. The Centers for Disease Control and Prevention recommends that all children receive two doses of MMR vaccine, starting with the first dose at 12 through 15 months of age, and the second dose at 4 through 6 years of age. In addition, they recommend that infants 6-11 months of age about to travel to any international destination receive a single dose of MMR, with two more subsequent doses, one at age 12-15 months and another 28 days later. Most infants younger than 6 months of age are presumed to be protected by maternal antibody, and available evidence indicates that MMR, which is comprised of live attenuated virus, is safe when administered at 6-12 months of age.3
As long as the recommendation in the United States is to administer the initial dose of MMR at 12-15 months except in cases of impending international travel, those 6-12 months of age remain at risk of acquiring infection with this highly contagious virus and, potentially, of suffering from its complications, including SSPE. Measles and SSPE are, however, preventable in this and other age groups via herd immunity — i.e., by maintenance of a greater than 90% immunization rate in the general population.
- Anlar B. Subacute sclerosing panencephalitis and chronic viral encephalitis. Handb Clin Neurol 2013;112:1183-1189.
- Schönberger K, Ludwig MS, Wildner M, Weissbrich B. Epidemiology of subacute sclerosing panencephalitis (SSPE) in Germany from 2003 to 2009: A risk estimation. PLoS One 2013;8:e68909.
- van der Maas NA, Woudenberg T, Hahne SJ, de Melker HE. Tolerability of early measles-mumps-rubella vaccination in infants aged 6-14 months during a measles outbreak in The Netherlands in 2013-2014. J Infect Dis 2016;213:1466-1471.
Subacute sclerosing panencephalitis is a lethal complication of measles that is not as rare as previously believed.
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