Department of Pediatric Neuropathology, Institute for Medical Research of Aging, Aichi Medical University, Aichi, Japan.
Department of Neuropathology, Institute for Medical Research of Aging, Aichi Medical University, Aichi, Japan.
Brain Pathol. 2022 Nov;32(6):e13069. doi: 10.1111/bpa.13069. Epub 2022 Apr 4.
Subacute sclerotic panencephalitis (SSPE) is a refractory neurological disorder after exposure to measles virus. Recently, SSPE cases have been treated with antiviral therapies, but data on the efficacy are inconclusive. Abnormal tau accumulation has been reported in the brain tissue of SSPE cases, but there are few reports in which this is amply discussed. Five autopsied cases diagnosed as definite SSPE were included in this study. The subject age or disease duration ranged from 7.6 to 40.9 years old or from 0.5 to 20.8 years, respectively. Cases 3 and 4 had been treated with antiviral therapies. All evaluated cases showed marked brain atrophy with cerebral ventricle dilatation; additionally, marked demyelination with fibrillary gliosis were observed in the cerebral white matter. The brainstem, cerebellum, and spinal cord were relatively preserved. Immunoreactivity (IR) against measles virus was seen in the brainstem tegmentum, neocortex, and/or limbic cortex of the untreated cases but was rarely seen in the two treated cases. Activated microglia were broadly observed from the cerebrum to the spinal cord and had no meaningful difference among cases. Neurofibrillary tangles characterized by a combination of 3- and 4-repeat tau were observed mainly in the oculomotor nuclei, locus coeruleus, and limbic cortex. IR against phosphorylated tau was seen mainly in the cingulate gyrus, oculomotor nuclei, and pontine tegmentum, and tended to be observed frequently in cases with long disease durations but also tended to decrease along with neuronal loss, as in Case 5, which had the longest disease duration. Since the distribution of phosphorylated tau was independent from that of measles virus, the tauopathy following SSPE was inferred to be the result of diffuse brain inflammation triggered by measles rather than a direct result of measles virus. Moreover, antiviral therapies seemed to suppress measles virus but not the progression of tauopathy.
亚急性硬化性全脑炎（SSPE）是麻疹病毒暴露后引起的难治性神经障碍。最近，SSPE 病例已接受抗病毒治疗，但疗效数据尚无定论。SSPE 病例的脑组织中已报道存在异常的 tau 积累，但对此充分讨论的报道很少。本研究纳入了 5 例经尸检证实的明确 SSPE 病例。病例年龄或疾病持续时间从 7.6 岁至 40.9 岁不等，或从 0.5 年至 20.8 年不等。病例 3 和 4 曾接受抗病毒治疗。所有评估病例均表现为明显的脑萎缩伴脑室扩张；此外，大脑白质中还观察到明显的脱髓鞘伴纤维状胶质增生。脑干、小脑和脊髓相对保存。未治疗病例的脑干被盖、大脑皮质和/或边缘皮质中可见麻疹病毒免疫反应性（IR），但在 2 例治疗病例中很少见。从大脑到脊髓广泛观察到活化的小胶质细胞，各病例之间无明显差异。以 3 重复和 4 重复 tau 组合为特征的神经原纤维缠结主要见于动眼神经核、蓝斑核和边缘皮质。磷酸化 tau 的 IR 主要见于扣带回、动眼神经核和脑桥被盖，并且在疾病持续时间较长的病例中观察到的频率更高，但也随着神经元丢失而减少，如疾病持续时间最长的病例 5 所示。由于磷酸化 tau 的分布独立于麻疹病毒，因此推测 SSPE 后的 tau 病是麻疹引起的弥漫性脑炎症的结果，而不是麻疹病毒的直接结果。此外，抗病毒治疗似乎抑制了麻疹病毒，但不能抑制 tau 病的进展。
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