亜急性硬化性全脳炎

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a rare, fatal, late complication of measles that develops years after infection, particularly following measles in early childhood. In Japan, measles incidence has declined markedly after improved vaccination coverage and verification elimination; however, recent SSPE epidemiology remains poorly characterized. METHODS: SSPE cases were identified from the Intractable Disease Treatment Research Project, the Research Project on the Treatment of Children with Specified Chronic Diseases, and Okinawa-specific publications. Measles-related outpatient visits (1986-2007) were estimated by public health center jurisdiction using annual pediatric sentinel surveillance reports and outpatient visit volumes from the Static Survey of Medical Institutions. Ratio estimation with finite population correction was applied. RESULTS: Seventeen SSPE cases were identified, 71% in males. SSPE onset occurred during 1994-2009, at a mean age of 8.1 years. The year of measles infection was known for 14 cases, most frequently 1990. For risk estimation, 16 infections occurring during 1986-2007 were included. SSPE risk was estimated as one per 3944 estimated measles-related outpatient visits (95% CI: 1054-6995). In 1990, SSPE risk was one per 1828 outpatient visits (95% CI: 836-2820). Among infants aged < 1 year, SSPE risk was one per 910 outpatient visits (95% CI: 416-1403). CONCLUSIONS: Estimating denominators for medically attended measles cases from sentinel surveillance enabled quantification of SSPE risk during historical outbreaks in Okinawa. The higher risk during infancy emphasizes the long-term consequences of measles transmission and the need to maintain high measles vaccination coverage.

We report a case of subacute sclerosing panencephalitis in a 14-year-old boy who presented to specialized care 17 months after the onset of symptoms, at advanced disease stage with cognitive decline, seizures, myoclonus and dystonia. A history of infantile measles, combined with characteristic electroencephalography, neuroimaging, and elevated cerebrospinal fluid measles IgG levels, confirmed the diagnosis. The prolonged delay to presentation, driven by barriers to healthcare access, limited community and provider awareness of subacute sclerosing panencephalitis, and social stigma resulted in presentation at stage 3 disease and precluded any meaningful therapeutic interventions. Additionally, empirical antituberculosis therapy was initiated despite negative cerebrospinal and stool GeneXpert MTB/RIF results, illustrating the diagnostic anchoring that occurs in tuberculosis endemic settings. This case highlights the critical importance of early recognition of subacute sclerosing panencephalitis, the need to strengthen healthcare access and neurological diagnostic capacity in resource limited settings and the risk of empiric treatment practices that may delay appropriate diagnosis and management. With the global resurgence of measles, increased awareness and surveillance for subacute sclerosing panencephalitis in high-burden settings are essential.

Long-term persistent measles virus (MeV) infection of the central nervous system (CNS) can result in subacute sclerosing panencephalitis (SSPE), an invariably fatal late neurological complication of measles. Analogous SSPE-like chronic diseases have also been reported in adult dogs, cetaceans, and more recently harbor seals following infection by canine distemper virus (CDV), dolphin morbillivirus (DMV), and phocine distemper virus (PDV), respectively. Here, we characterize different animal morbilliviruses (CDVlynx, PDV2001, PDV2014, and DMV232-18) that persisted in the CNS of their respective host species for several years after the initial infections. The CDVlynx and DMV232-18 strains encode nonfunctional matrix proteins and hyperfusogenic fusion proteins which are hallmark features of SSPE MeV strains. The complex mutational profile apparent in the PDV2001 strain also has parallels with MeV strains from SSPE cases. In contrast, the PDV2014 strain encodes for a nonfunctional matrix protein but an unmodified F protein supporting the evolutionary precedence of M protein changes in facilitating long-term morbillivirus infections of the CNS. Consequently, our findings show that similar evolutionary pathways across different animal species drive morbilliviruses to evolve analogous mechanisms favoring virus persistence in the CNS and the development of chronic neurological disease. Such naturally occurring chronic animal morbillivirus infections of the CNS provide natural analogues for studying the evolutionary trajectory and molecular basis of the pathogenesis of SSPE in humans. This may pave the way for developing early diagnostics and intervention strategies.

BACKGROUND AND PURPOSE: Subacute sclerosing panencephalitis (SSPE) is a progressive, uniformly fatal neuroinflammatory disease caused by persistent measles virus encephalitis, characterised by chronic T-cell-mediated inflammation, progressive demyelination, and cortico-striatal-thalamic network dysfunction. Conventional MRI characterises established structural disease but does not capture early haemodynamic alterations. We aimed to characterise regional perfusion patterns using cerebellar-normalised arterial spin labeling (ASL) ratios, define qualitative perfusion phenotypes, and examine their association with clinical severity and disease staging in a cohort of patients with confirmed SSPE. MATERIALS AND METHODS: 33 patients with confirmed SSPE (mean age 13.9 ± 6.7 years; 23 male) and 8 age-matched controls underwent 3T MRI including ASL in this retrospective case-control study. Cerebellar-normalised perfusion ratios (CNRs) were computed across 8 bilateral cortical and subcortical regions of interest. Group comparisons used Mann-Whitney U testing; Spearman correlations assessed the Neurological Disability Index (NDI), Barthel Index and illness duration. Jabbour stage comparisons used Kruskal-Wallis testing with post-hoc pairwise comparisons. RESULTS: CNRs were significantly elevated in SSPE versus controls in 6/8 bilateral regions. The strongest discriminators were the lentiform nucleus, occipital cortex, and caudate nucleus. Basal ganglia hyperperfusion was the dominant ASL pattern (18/33, 54.5%), whereas structural basal ganglia abnormalities were present in only 5/33 patients (15.2%), demonstrating a marked perfusion-structure dissociation. A four-region composite achieved an AUC of 0.9 with 100% specificity. Deep grey matter CNRs correlated significantly with NDI across five subcortical regions but showed no correlation with illness duration. CONCLUSIONS: ASL-derived cerebellar-normalised perfusion ratios demonstrate regionally specific hyperperfusion in SSPE, likely reflecting the haemodynamic consequences of active neuroinflammation and cortico-striatal-thalamic network dysfunction. The marked dissociation between ASL-detected basal ganglia hyperperfusion and structural MRI signal change suggests that perfusion imaging may detect disease-related haemodynamic alterations before structural injury becomes radiologically evident. Correlation of deep grey matter CNRs with neurological severity, but not disease duration suggests that ASL may track the biological intensity of disease activity rather than its chronological extent. These findings warrant prospective validation in larger cohorts before CNRs can be recommended as routine biomarkers in SSPE.