Gabriela Meade, Jennifer L Whitwell, Dennis W Dickson, Joseph R Duffy, Heather M Clark, J Eric Ahlskog, Mary M Machulda, Keith A Josephs, Rene L Utianski
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At subsequent visits, agrammatic aphasia and motor symptoms consistent with corticobasal syndrome were evident. Cognition and behavior remained relatively intact until advanced stages. FDG-PET revealed hypometabolism in the right temporoparietal cortex and left premotor and motor cortices. There was also low-level signal in the right temporoparietal cortex on tau-PET. A sequence variation in the progranulin gene was identified (GRN c.1A>C, p.Met1). Pathologic diagnosis was TDP-43 Type A with an atypical distribution of inclusions in premotor and motor cortices.</p><p><strong>Discussion: </strong>This case report demonstrates that TDP-43 Type A inclusions in an atypical distribution can present clinically as PPAOS. 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引用次数: 0
摘要
目的介绍首例原发性进行性语言障碍(PPAOS)与TAR DNA结合蛋白43(TDP-43)而非4-repeat tau有关的病例:该患者是通过尸检发现的。在初步诊断评估后,他参加了 3 次年度研究访问,访问期间进行了言语、语言、认知和神经评估。此外,还进行了神经影像学检查:结果:在首次就诊时,他被诊断为语言障碍,全面的神经系统检查进一步发现了右手的细微运动症状。在随后的就诊中,失语症和运动症状与皮质基底综合征一致。直到晚期,患者的认知和行为仍相对正常。FDG-PET 显示,右侧颞顶叶皮层、左侧运动前皮层和运动皮层代谢不足。在 tau-PET 上,右侧颞顶叶皮层也出现了低水平信号。原粒细胞蛋白基因序列变异已被确定(GRN c.1A>C,p.Met1)。病理诊断为 TDP-43 A 型,内含物在运动前皮层和运动皮层的分布不典型:本病例报告表明,TDP-43 A 型包涵体的非典型分布可在临床上表现为 PPAOS。原花青素基因的序列变异和颞顶叶皮层的非对称受累是尸检前异常神经病理生理学的最有力证据。
Primary Progressive Apraxia of Speech Caused by TDP-43: A Case Report.
Objectives: To introduce the first case in which primary progressive apraxia of speech (PPAOS) is associated with TAR DNA-binding protein 43 (TDP-43) instead of 4-repeat tau.
Methods: This patient was identified through a postmortem autopsy. Following an initial diagnostic evaluation, he participated in 3 annual research visits during which speech, language, cognitive, and neurologic assessments were administered. Neuroimaging was also acquired.
Results: Apraxia of speech was diagnosed at his initial visit with a comprehensive neurologic examination further revealing subtle motor findings in the right hand. At subsequent visits, agrammatic aphasia and motor symptoms consistent with corticobasal syndrome were evident. Cognition and behavior remained relatively intact until advanced stages. FDG-PET revealed hypometabolism in the right temporoparietal cortex and left premotor and motor cortices. There was also low-level signal in the right temporoparietal cortex on tau-PET. A sequence variation in the progranulin gene was identified (GRN c.1A>C, p.Met1). Pathologic diagnosis was TDP-43 Type A with an atypical distribution of inclusions in premotor and motor cortices.
Discussion: This case report demonstrates that TDP-43 Type A inclusions in an atypical distribution can present clinically as PPAOS. The sequence variation in the progranulin gene and asymmetric temporoparietal cortex involvement were the strongest indications of the unusual neuropathophysiology prior to autopsy.
期刊介绍:
Neurology: Genetics is an online open access journal publishing peer-reviewed reports in the field of neurogenetics. Original articles in all areas of neurogenetics will be published including rare and common genetic variation, genotype-phenotype correlations, outlier phenotypes as a result of mutations in known disease-genes, and genetic variations with a putative link to diseases. This will include studies reporting on genetic disease risk and pharmacogenomics. In addition, Neurology: Genetics will publish results of gene-based clinical trials (viral, ASO, etc.). Genetically engineered model systems are not a primary focus of Neurology: Genetics, but studies using model systems for treatment trials are welcome, including well-powered studies reporting negative results.