Source: Honarmand S, Glaser CA, Chow E, et al. Subacute sclerosing panencephalitis in the differential diagnosis of encephalitis. Neurology. 2004;63:1489–1493.Five cases of subacute sclerosing panencephalitis (SSPE) are reported from the California Department of Health Services. They were identified among 1000 cases of encephalitis referred by physicians and enrolled in the California Encephalitis Project (CEP) from June 1998 to December 2003. Median age was 12 years (range 9–13 years). Time from onset of behavioral and neurologic manifestations to first hospital admission ranged from 1 day to 2.5 years. The CEP was designed to identify the causes and clinical features of encephalitis in California. Case selection included patients older than 6 months, immunocompetent, with encephalitis and with 1 or more of the following: fever, seizure, focal neurologic signs, and EEG or neuroimaging findings consistent with encephalitis or CSF pleocytosis. The diagnosis of SSPE was based on 1) elevated measles virus (MV) immunoglobulin G (IgG) antibody in CSF, and absent antibody to herpes simplex virus (HSV) and varicella zoster virus, and 2) clinical or neurodiagnostic manifestations of SSPE. Patients diagnosed with SSPE had a median MV IgG antibody level of 22.5 in serum and 18.2 in CSF; significantly lower MV antibody levels (8.6 and <0.5; P=.0004 and P=.0001) were reported in patients referred P with alternative diagnoses (eg, HSV, rabies). The differential diagnoses on referral included mitochondrial disorder and acute disseminated encephalomyelitis. The history of an illness compatible with measles was obtained only after positive antibody tests were reported. As of January 2004, 3 patients had died after intervals of 20, 40, and 96 days from the time of hospital admission. The 2 survivors have severe neurologic impairments.Dr. Millichap has not disclosed any financial relationships relevant to this commentary.The resurgence and changing character of SSPE in the United States has been stressed previously,1 and the diagnosis may be overlooked or delayed because of nonspecific clinical manifestations at onset. Early signs include behavioral changes, deteriorating school performance, slurred speech, and hyperactivity. These are followed by aphasia, ataxia, tremors, myoclonic jerks, or choreoathetosis. Examination of the retina may show chorioretinitis and optic atrophy even prior to the onset of clinical symptoms. Papilledema and symptoms of increased intracranial pressure can be the earliest presentation of SSPE. The risk of SSPE is highest in patients with measles contracted in the first 2 years of life. The EEG characteristically shows periodic high amplitude sharp and slow-wave bursts, associated with myoclonic jerks. The MRI may show increased T2 signal in cerebral white matter and brainstem. Laboratory testing is necessary for diagnostic confirmation (elevated MV IgG antibody in CSF; or MV protein or RNA in a brain biopsy). The course is usually subacute progressive, but acute fulminant and chronic atypical cases may occur.Comparing a study in India completed in 1974 and another in the same institution in 2004, the later series had a later mean age of onset, particularly in patients who had received vaccination.2 SSPE has been reported in vaccinated patients but the causal relationship is controversial. SSPE is caused by a wild measles virus, and in some vaccine-related cases, the genome of wild measles virus has been isolated and not the vaccine strain.3 In patients who have entered the US from developing countries, the history of an illness with rash is usually obtained subsequent to SSPE diagnostic confirmation. Prevention by measles immunization is the only effective treatment. Treatment with oral inosiplex (isoprinosine) provides a 34% rate of stabilization or improvement at 6 months, which is better than the expected 5 to 10% remission rate in untreated patients; the addition of intraventricular interferon has no added benefit.4 Progression is variable, but the disease is usually fatal in 1 to 3 years.The best shot we have at preventing this debilitating and usually fatal illness is vaccination. So long as some parents refuse to get their children immunized, SSPE will remain part of the differential diagnosis of encephalitis.