Subacute Sclerosing Panencephalitis

In this issue of Neurology, Honarmand et al. remind us that subacute sclerosing panencephalitis (SSPE), a neurodegenerative complication of measles virus infection in young childhood, must not be forgotten.1 Through a passive surveillance of encephalitis cases in California, the authors identified five cases of SSPE between the middle of 1998 and the end of 2003, corresponding to approximately one case per year. In three cases SSPE was not considered strongly until the results of CSF measles antibody titers were known. Although rare in the United States (the overall annual incidence of measles is 1 case/million inhabitants), measles remains a major source of morbidity and mortality in many regions of the developing world. In 2002, the most recent year for which such data are available, the World Health Organization estimated that measles caused nearly 200,000 deaths in Southeast Asia.2 Prior to 1969, when the United States instituted widespread immunization for measles, the annual incidence of SSPE, the most serious complication of childhood measles virus infection, in the United States was approximately 1 case per million children. This contrasts with the current rate of 21 cases of SSPE per million persons in India3; in some regions, such as Papua New Guinea, rates have recently approached 100 cases of SSPE per million persons under age 20 years.4 These cases relate directly to infection with wild measles virus; there is no evidence currently to suggest that measles virus immunization causes SSPE. What do we learn from this report? Honarmand et al. remind us that although SSPE usually begins insidiously, the disorder can sometimes mimic an acute encephalopathy. Given the rarity of SSPE in the United States, it was not unanticipated that the clinicians investigating these cases thought first of acute disseminated encephalomyelitis, a condition that accounts for 10% to 15% of encephalitis cases in the United States, or of mitochondrial disorders. The white matter abnormalities observed in children with SSPE can suggest a subacute demyelinative process, and signature of magnetic resonance spectroscopy in SSPE, consisting of elevated myoinositol and reduced N-acetylaspartate peaks, can suggest an unspecified neurodegenerative disorder. The cases provide no new insights regarding the pathogenesis or treatment of SSPE. The pathogenesis of this disorder remains enigmatic, and treating SSPE continues to be a daunting task. Most investigators implicate the interplay of a defective measles virus, albeit a wild strain, and undefined defects in host cell mediated immune responses.5 Despite high levels of neutralizing anti-measles antibodies in serum and CSF, patients with SSPE do not eradicate the measles virus. Exposure to the virus at a young age contributes to the risk of acquiring SSPE, suggesting that immune immaturity participates in the pathogenesis of SSPE. Four of the five children in this report had illnesses compatible with measles before they were 1 year old. The authors postulated that these cases of SSPE were linked to a measles outbreak that began in California in the late 1980s and continued into the early 1990s. Many different regimens of antiviral and immunomodulating therapy in SSPE have been described, usually in small, uncontrolled case series. Most report variable outcomes. In a recent large trial reported by the International Consortium on Subacute Sclerosing Panencephalitis,6 patients with SSPE were randomized to either oral inosiplex (isoprinosine) or inosiplex and intraventricular interferon alpha 2b. Treatment lasted 6 months. The investigators observed no differences between the two regimens in rates of stabilization or improvement (34% vs 35%), but the Consortium concluded that the 34% to 35% rate of stabilization or improvement at 6 months was substantially greater than the spontane-