Five cases of subacute sclerosing panencephalitis (SSPE) are reported from the California Department of Health Services, Richmond, CA. 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 to 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 encephalopathy and one 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 is based on 1) elevated measles virus (MV) immunoglobulin (Ig) G antibody in CSF, and absent antibody to herpes simplex virus 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 antibody levels for MV [8.6 and <0.5; p=0.0004 and 0.0001] were reported in patients referred with alternative diagnoses [eg HSV, rabies]. The differential diagnoses on referral included mitochondrial disorder and ADEM, and a 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 time of hospital admission. The 2 survivors have severe neurologic impairments. [1]

COMMENT. The authors found 1 case per year of SSPE in California and they stress the need to include SSPE in the differential diagnosis of encephalitis, especially among pediatric patients. SSPE was suspected only after the results of measles testing were known. SSPE is rare in the United States and the diagnosis may be missed 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. Progression is variable, but the disease is usually fatal in 1 to 3 years. 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 brain biopsy). The course is usually progressive, but acute fulminant cases occur. The history of an illness with rash is usually obtained subsequent to SSPE diagnostic confirmation, in patients who have entered the US from developing countries. Treatment with oral inosiplex (isoprinosine) in a recent international multicenter study provided a 34% rate of stabilization or improvement at 6 months (better than the expected 5 to 10% remission rate in untreated patients); the addition of intraventricular interferon had no added benefit [2, 3]. Prevention by measles immunization is the only effective treatment. Some reports of SSPE related to measles vaccination are now considered doubtful, since the genome of wild MV has been identified rather than the vaccine strain. [4]

SSPE after intrauterine measles infection in the mother is reported in an infant infected shortly before delivery. The infant developed focal seizures at 5 months of age, and SSPE was diagnosed at 14 months by characteristic findings on EEG and MRI and confirmed by elevated CSF and serum MV IgG antibodies. Despite treatment with intraventricular interferon and oral isoprinosine, the child’s condition progressed to a vegetative state and he died at 3 years of age by aspiration pneumonia.[5]

Familial SSPE in two siblings who had not been immunized is reported from Germany [6]. A 7-year-old boy had behavioral problems and school difficulties for 1 year before referral and 2 years following measles, contracted at the same time as his father and younger brother. The diagnosis was confirmed in both children by CSF and serum measles specific immunoglobulin G synthesis and brain biopsy. Both children showed progressive myoclonic and partial complex seizures, and characteristic EEG and MRI findings.

Measles inclusion body encephalitis complicating stem cell transplantation is reported in a 13-year-old Mexican-American immunocompromised boy treated at Children’s Memorial Hospital, Chicago, for an X-linked chronic granulomatous disease [7]. Neither the patient nor the donor had known recent measles exposure or vaccination. Measles virus, genotype D3, was confirmed by reverse transcriptase-polymerase chain reaction and viral growth in brain biopsy. Early brain biopsy is recommended in cases of obscure encephalitis in afebrile immunocompromised patients who present with focal status epilepticus.