遗传性痉挛性截瘫伴有胼胝体变薄和 SPG11 基因突变:神经病理学评估

IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY Neuropathology Pub Date : 2024-10-11 DOI:10.1111/neup.13007
Kathryn P Scherpelz, Rebecca A Yoda, Suman Jayadev, Marie Y Davis, Joshua C Hincks, Nicole F Liachko, Robert M Bragg, Alexa Cochoit, Christine L MacDonald, C Dirk Keene, Thomas D Bird, Caitlin S Latimer
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引用次数: 0

摘要

遗传性痉挛性截瘫(HSP)伴薄胼胝体可由多种遗传原因引起,其中最常见的是 SPG11(HSP11)的双偶变异。目前仅有六例 HSP11 神经病理学检查病例的报道。在此,我们介绍了另一例 HSP11 新型变异(同基因 c.6439_6442del)患者的神经病理学检查结果,以及另外三例 HSP11 患者的临床特征。这四例HSP11病例的病程相似,都有明显的下肢无力和痉挛症状,但认知症状和脑磁共振成像(MRI)结果却各不相同。其中一个病例的神经病理学检查包括脑部体外磁共振成像、组织学和免疫组化评估以及SPG11的Western印迹。该病例的显著特点是大脑小,皮质、白质和深灰色核体积减少。胼胝体变薄,黑质明显苍白。显微镜下,大脑皮层分层正常,神经元轻度缺失,伴有轻度胶质增生;胼胝体变薄,伴有局限性胶质增生;黑质的神经元和色素明显减少,胶质增生极少。与此相反,基底节、丘脑和脊髓(前角、皮质脊髓和脊髓小脑束)的神经元丢失和胶质增生非常明显。在多个部位发现了髓鞘巨噬细胞,但以胼胝体最为常见。未发现高磷酸化tau或TDP-43聚集体、路易体或淀粉样β斑块。与对照组相比,HSP11大脑中没有SPG11,Western印迹显示自噬标记物升高。与之前关于胼胝体变薄的 HSP 和 HSP11 的报道相比,该病表现出广泛的大脑结构变化,包括发育异常和退化的特征。
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Hereditary spastic paraplegia with thin corpus callosum and SPG11 mutation: A neuropathological evaluation.

Hereditary spastic paraplegia (HSP) with thin corpus callosum can be due to a variety of genetic causes, the most common of which are biallelic variants in SPG11 (HSP11). Only six cases of neuropathologic examination of HSP11 have been reported. Here we present neuropathological findings in another case of HSP11 with novel mutation (homozygous c.6439_6442del) and clinical features of three additional cases of HSP11. These four cases of HSP11 had similar disease courses with prominent lower extremity weakness and spasticity but varied cognitive symptoms and brain magnetic resonance imaging (MRI) findings. Neuropathological examination of one case included ex vivo MRI of the cerebrum, histologic and immunohistochemical evaluation, and Western blot for SPG11. The case was notable for a small cerebrum with decreased volume of cortex, white matter, and deep gray nuclei. The corpus callosum was thin, and the substantia nigra showed marked pallor. Microscopically, the cortex had normal lamination and mild loss of neurons with mild gliosis, the corpus callosum was thin with limited gliosis, and the substantia nigra had marked decrease in neurons and pigment, with minimal gliosis. In contrast, the basal ganglia, thalamus, and spinal cord (anterior horns, corticospinal, and spinocerebellar tracts) had prominent neuron loss and gliosis. Myelin-laden macrophages were found in multiple sites but were most common in the corpus callosum. No hyperphosphorylated tau or TDP-43 aggregates, Lewy bodies, or amyloid β plaques were found. Compared to control, SPG11 was absent in HSP11 brain and markers of autophagy were elevated by Western blot. Comparison with prior reports of HSP with thin corpus callosum and HSP11 demonstrates a disease with a broad range of structural changes of the brain, including features of abnormal development and degeneration.

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来源期刊
Neuropathology
Neuropathology 医学-病理学
CiteScore
4.10
自引率
4.30%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
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