Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150, Vienna, Austria.
J Neural Transm (Vienna). 2023 Dec;130(12):1509-1522. doi: 10.1007/s00702-023-02691-w. Epub 2023 Sep 2.
Corticobasal degeneration (CBD) is a rare, sporadic, late-onset progressive neurodegenerative disorder of unknown etiology, clinically characterized by an akinetic-rigid syndrome, behavior and personality disorders, language problems (aphasias), apraxia, executive and cognitive abnormalities and limb dystonia. The syndrome is not specific, as clinical features of pathologically proven CBD include several phenotypes. This 4-repeat (4R) tauopathy is morphologically featured by often asymmetric frontoparietal atrophy, ballooned/achromatic neurons containing filamentous 4R-tau aggregates in cortex and striatum, thread-like processes that are more widespread than in progressive supranuclear palsy (PSP), pathognomonic "astroglial plaques", and numerous inclusions in both astrocytes and oligodendroglia ("coiled bodies") in the white matter. Cognitive deficits in CBD are frequent initial presentations before onset of motor symptoms, depending on the phenotypic variant. They predominantly include executive and visuospatial dysfunction, sleep disorders and language deficits with usually preserved memory domains. Neuroimaging studies showed heterogenous locations of brain atrophy, particularly contralateral to the dominant symptoms, with disruption of striatal connections to prefrontal cortex and basal ganglia circuitry. Asymmetric hypometabolism, mainly involving frontal and parietal regions, is associated with brain cholinergic deficits, and dopaminergic nigrostriatal degeneration. Widespread alteration of cortical and subcortical structures causing heterogenous changes in various brain functional networks support the concept that CBD, similar to PSP, is a brain network disruption disorder. Putative pathogenic factors are hyperphosphorylated tau-pathology, neuroinflammation and oxidative injury, but the basic mechanisms of cognitive impairment in CBD, as in other degenerative movement disorders, are complex and deserve further elucidation as a basis for early diagnosis and adequate treatment of this fatal disorder.
皮质基底节变性（CBD）是一种罕见的、散发性的、晚发性进行性神经退行性疾病，病因不明，临床上以无动性僵硬综合征为特征，伴有行为和人格障碍、语言问题（失语症）、失用症、执行和认知功能异常以及肢体肌张力障碍。该综合征不具有特异性，因为经病理证实的 CBD 的临床特征包括几种表型。这种四重复（4R）tau 病在形态上的特征是常不对称的额顶叶萎缩，含有丝状 4R-tau 聚集物的气球样/无色神经元，在皮质和纹状体中，线状过程比进行性核上性麻痹（PSP）更广泛，特征性的“星形胶质斑块”，以及在星形胶质细胞和少突胶质细胞中都有大量包含物（“卷曲体”）在白质中。CBD 的认知缺陷在运动症状出现之前是常见的首发表现，具体取决于表型变体。它们主要包括执行和视空间功能障碍、睡眠障碍和语言缺陷，通常记忆域保留。神经影像学研究显示大脑萎缩的位置不同，特别是与优势症状相反，纹状体与前额叶皮质和基底节回路的连接中断。不对称的低代谢，主要涉及额区和顶区，与大脑胆碱能缺陷和多巴胺能黑质纹状体变性有关。皮质和皮质下结构的广泛改变导致各种大脑功能网络的异质性变化，支持 CBD 与 PSP 相似，是一种大脑网络中断障碍的概念。假定的致病因素是过度磷酸化的 tau 病理学、神经炎症和氧化损伤，但 CBD 中认知障碍的基本机制，与其他退行性运动障碍一样，是复杂的，值得进一步阐明，作为早期诊断和充分治疗这种致命疾病的基础。
