Children and adolescents were affected for the most part, the disease rarely appearing beyond the age of 10 years. Typically, there is a history of primary measles infection at a very early age, often before 2 years, followed by a 6to 8-year asymptomatic period. The illness evolved in several stages. Initially there was a decline in proficiency at school, temper outbursts and other changes in personality, difficulty with language, and loss of interest in usual activities. These soon give way to a severe and progressive intellectual deterioration in association with focal or generalized seizures, widespread myoclonus, ataxia, and sometimes visual disturbances caused by progressive chorioretinitis. As the disease advances, rigidity, hyperactive reflexes, Babinski signs, progressive unresponsiveness, and signs of autonomic dysfunction appear. In the final stage, the child lies insensate, virtually “decorticated.”
The course is usually steadily progressive, death occurring within 1 to 3 years. A series of 39 such adult cases from India with mean age of 21 years was reported by Prashanth and coworkers, the oldest patient a 43-year-old. The main features were similar in most ways to childhood cases, except that several had visual disturbances and two had extrapyramidal features, raising the possibility of prion disease. Myoclonus was present early in the illness in 26 and developed later in all cases; the movements were described as “slow,” a characteristic alluded to in other series. In two cases that occurred in pregnant women, blurred vision and weakness of limbs was followed by akinetic mutism, without a trace of myoclonus or cerebellar ataxia. Nevertheless, the progressive ataxic-myoclonic chronic dementia in a child is so typical that bedside diagnosis was usually possible.
The EEG shows a characteristic abnormality consisting of periodic (every 5 to 8 s) bursts of 2 to 3/s high-voltage waves, followed by a relatively flat pattern. The CSF contains few or no cells, but the protein content is increased, particularly the gamma globulin fraction, and agarose gel electrophoresis discloses oligoclonal bands of IgG. These proteins have been shown to represent measles-virus-specific antibody (Mehta et al). MRI changes begin in the subcortical white matter and spread to the periventricular region (Anlar et al).
Histologically, the lesions involve the cerebral cortex and white matter of both hemispheres and the brainstem. The cerebellum is usually spared. Destruction of nerve cells, neuronophagia, and perivenous cuffing by lymphocytes and mononuclear cells indicate the viral nature of the infection. In the white matter there is degeneration of medullated fibers (both myelin and axons), accompanied by perivascular cuffing with mononuclear cells and fibrous gliosis (hence the term sclerosing encephalitis). Eosinophilic inclusions, the histopathologic hallmark of the disease, are found in the cytoplasm and nuclei of neurons and glia cells. Virions, thought to be measles nucleocapsids, have been observed in the inclusion-bearing cells examined electron microscopically.
How a ubiquitous and transient viral infection in a seemingly normal young child allows the development, many years later, of a rare encephalitis is a matter of speculation. Sever believes that there is a delay in the development of immune responses during the initial infection and a later inadequate immune response that is incapable of clearing the suppressed infection.
The differential diagnosis of SSPE includes the childhood and adolescent dementing diseases such as lipid storage diseases (see Chap. 36), prion disease (Creutzfeldt-Jakob), and Schilder-type demyelinative disease (see