Irie Ken-Ichi, Honda Hiroyuki, Tateishi Takahisa, Mori Shinichiro, Yamamoto Akifumi, Morimitsu Makoto, Shinsuke Kikuchi, Moritaka Taiga, Kurata Seiji, Kumazoe Hiroyuki, Shijo Masahiro, Sasagasako Naokazu, Taniwaki Takayuki
Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Neuropathology Center, NHO Omuta Hospital, Fukuoka, Japan.
Front Neurol. 2024 Sep 23;15:1452709. doi: 10.3389/fneur.2024.1452709. eCollection 2024.
Gerstmann-Sträussler-Scheinker (GSS) disease is an inherited prion disease characterized by dementia, cerebellar ataxia, and painful sensory disturbances. GSS is pathologically defined by the presence of amyloid plaques comprised of prion protein predominantly localized in the cerebral cortex, cerebellar cortex, and basal ganglia, resulting from mutations in the prion protein gene. This study investigated five cases of GSS P102L [GSS caused by a leucine (L) substitution of proline (P) at position 102 of the prion protein gene] with L-dopa-resistant extrapyramidal symptoms and reduced dopamine transporter single-photon emission computed tomography (DAT-SPECT) uptake. Clinical findings revealed diverse manifestations, with all cases exhibiting parkinsonism, and four patients had a vertical gaze palsy. Notably, all patients showed reduced striatal DAT-SPECT uptake, indicating neurodegeneration of the nigrostriatal system. Autopsy findings in one case confirmed prion protein plaques and dopaminergic neuron loss in the substantia nigra of a patient with GSS P102L. Additionally, reduced DAT immunostaining was observed in the putamen compared with a control. While previous studies have identified reduced DAT-SPECT and positron emission tomography uptake in Creutzfeldt-Jakob disease and fatal familial insomnia owing to nigrostriatal neurodegeneration induced by abnormal prion protein deposition, similar phenomena in GSS P102L have not been reported. This study provides support for a correlation between abnormal prion protein deposition and nigrostriatal system degeneration in GSS P102L. Our results reveal the importance of considering GSS P102L in cases of atypical Parkinsonism and abnormal DAT-SPECT results, which would serve as a valuable indicator for subsequent prion genetic testing.
格斯特曼-施特劳斯勒-申克综合征（GSS）是一种遗传性朊病毒病，其特征为痴呆、小脑共济失调和疼痛性感觉障碍。GSS在病理上的定义是存在由朊病毒蛋白组成的淀粉样斑块，主要定位于大脑皮质、小脑皮质和基底神经节，这是由朊病毒蛋白基因突变所致。本研究调查了5例GSS P102L型病例（由朊病毒蛋白基因第102位的脯氨酸（P）被亮氨酸（L）取代引起的GSS），这些病例存在左旋多巴抵抗性锥体外系症状且多巴胺转运体单光子发射计算机断层扫描（DAT-SPECT）摄取减少。临床发现显示出多样的表现，所有病例均表现为帕金森综合征，4例患者有垂直凝视麻痹。值得注意的是，所有患者的纹状体DAT-SPECT摄取均减少，表明黑质纹状体系统发生神经变性。1例尸检结果证实GSS P102L型患者的黑质存在朊病毒蛋白斑块和多巴胺能神经元丢失。此外，与对照组相比，壳核中观察到DAT免疫染色减少。虽然先前的研究已发现，由于异常朊病毒蛋白沉积导致黑质纹状体神经变性，克雅氏病和致死性家族性失眠症患者的DAT-SPECT和正电子发射断层扫描摄取减少，但GSS P102L型中的类似现象尚未见报道。本研究为GSS P102L型中异常朊病毒蛋白沉积与黑质纹状体系统变性之间的相关性提供了支持。我们的结果揭示了在非典型帕金森综合征病例和异常DAT-SPECT结果中考虑GSS P102L型的重要性，这将作为后续朊病毒基因检测的一个有价值指标。
