Koga Shunsuke, Eric Ahlskog J, DeTure Michael A, Baker Matt, Roemer Shanu F, Konno Takuya, Rademakers Rosa, Ross Owen A, Dickson Dennis W
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida.
Department of Neurology, Mayo Clinic, Rochester, Minnesota.
J Neuropathol Exp Neurol. 2019 Aug 1;78(8):756-762. doi: 10.1093/jnen/nlz048.
Progressive supranuclear palsy with predominant cerebellar ataxia (PSP-C) has been reported as a rare clinical subtype, but the underlying pathology of its cerebellar ataxia remains unclear. Here, we report a patient with the coexistence of PSP with pontocerebellar atrophy and myotonic dystrophy type 1 (DM1). A 73-year-old man who was an asymptomatic carrier of DM1 (66 CTG repeats) started developing ataxic gait with multiple falls, visual blurring, double vision, and word finding difficulty at age 62 and was initially diagnosed with multiple system atrophy (MSA). Subsequently, the diagnosis was changed to PSP due to hypometric downward gaze, reduced blink frequency, symmetric bradykinesia, rigidity, and the absence of autonomic dysfunction. He eventually developed delayed grip opening with percussion myotonia at age 72. At autopsy, severe neuronal degeneration and astrogliosis in the pontocerebellar structures suggested MSA, but immunohistochemistry for α-synuclein did not reveal neuronal or glial cytoplasmic inclusions. Immunohistochemistry for phospho-tau and 4-repeat tau confirmed a neuropathological diagnosis of PSP with exceptionally numerous coiled bodies and threads in the pontine base and cerebellar white matter. This unusual distribution of 4-repeat tau pathology and neuronal degeneration with astrogliosis is a plausible clinicopathological substrate of PSP-C.
以小脑性共济失调为主的进行性核上性麻痹(PSP-C)已被报道为一种罕见的临床亚型,但其小脑性共济失调的潜在病理机制仍不清楚。在此,我们报告一例同时存在PSP与桥小脑萎缩及1型强直性肌营养不良(DM1)的患者。一名73岁男性,为DM1的无症状携带者(66个CTG重复序列),62岁时开始出现共济失调步态、多次跌倒、视力模糊、复视及找词困难,最初被诊断为多系统萎缩(MSA)。随后,由于向下凝视幅度减小、眨眼频率降低、对称性运动迟缓、僵硬且无自主神经功能障碍,诊断改为PSP。他最终在72岁时出现叩击性肌强直导致的抓握松开延迟。尸检时,桥小脑结构中严重的神经元变性和星形胶质细胞增生提示MSA,但α-突触核蛋白免疫组化未发现神经元或胶质细胞质内包涵体。磷酸化tau蛋白和4重复tau蛋白免疫组化证实为PSP的神经病理学诊断,桥脑基底部和小脑白质中存在异常大量的卷曲小体和细丝。4重复tau蛋白病理学的这种不寻常分布以及伴有星形胶质细胞增生的神经元变性是PSP-C合理的临床病理基础。