Department of Neurology, Imari Arita Kyoritsu Hospital, Arita, Japan; Division of Neurology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan; Department of Neurology, Kouhoukai Takagi Hospital, Okawa, Japan.
Division of Neurology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
J Neurol Sci. 2024 Sep 15;464:123166. doi: 10.1016/j.jns.2024.123166. Epub 2024 Aug 6.
Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal-dominant inherited prion disease most often associated with the human prion protein gene (PRNP)-P102L mutation. Although patients manifest considerable phenotypic heterogeneity, the involvement of the nigrostriatal system has not been well-studied.
We performed dopamine transporter single-photon emission computed tomography (DAT-SPECT) using I-ioflupane to investigate the nigrostriatal system function in nine patients with the PRNP-P102L mutation. We also examined the pathological findings in another patient whose predominant feature was ataxia and who died 5 years after disease onset.
Striatum uptake of I-ioflupane indicated by specific binding ratio (SBR) values was significantly reduced in two patients. The DAT-SPECT examination was performed 6 months after disease onset in one of these patients who manifested rapidly developing cognitive decline mimicking Creutzfeldt-Jakob disease. DAT-SPECT was also performed 9 years after disease onset in another patient who manifested the conventional features of GSS involving ataxia and dementia in the initial phase but showed akinetic mutism at the examination time. Another patient examined 2 years after disease onset who predominantly manifested ataxia showed marginally abnormal SBR values. An autopsy case showed moderate neuronal loss in the substantia nigra, and the degree of neuronal loss was similar in most other parts of the brain.
Nigrostriatal system involvement may occur in patients with GSS associated with the PRNP-P102L mutation, even though parkinsonism is not the predominant feature.
Gerstmann-Straussler-Scheinker 病（GSS）是一种常染色体显性遗传朊病毒病，最常与人类朊病毒蛋白基因（PRNP）-P102L 突变有关。尽管患者表现出相当大的表型异质性，但黑质纹状体系统的受累情况尚未得到很好的研究。
我们使用 I-ioflupane 进行多巴胺转运体单光子发射计算机断层扫描（DAT-SPECT），以研究 9 名携带 PRNP-P102L 突变的患者的黑质纹状体系统功能。我们还检查了另一名患者的病理发现，该患者的主要特征是共济失调，并且在发病后 5 年死亡。
两名患者的纹状体摄取 I-ioflupane 的特异性结合比（SBR）值显著降低。其中一名患者在发病后 6 个月进行了 DAT-SPECT 检查，该患者表现出迅速发展的认知能力下降，类似于克雅氏病。另一名患者在发病 9 年后也进行了 DAT-SPECT 检查，该患者在初始阶段表现出常规的 GSS 特征，包括共济失调和痴呆，但在检查时表现出无动性缄默。另一名发病 2 年后主要表现为共济失调的患者的 SBR 值略有异常。尸检病例显示黑质中有中度神经元丧失，大脑其他部位的神经元丧失程度相似。
即使帕金森病不是主要特征，携带 PRNP-P102L 突变的 GSS 患者也可能存在黑质纹状体系统受累。
