Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.
J Neurol Neurosurg Psychiatry. 2014 Sep;85(9):1016-23. doi: 10.1136/jnnp-2013-306995. Epub 2014 Feb 12.
Mutations in C9ORF72 are an important cause of frontotemporal dementia (FTD) and motor neuron disease. Accumulating evidence suggests that FTD associated with C9ORF72 mutations (C9ORF72-FTD) is distinguished clinically by early prominent neuropsychiatric features that might collectively reflect deranged body schema processing. However, the pathophysiology of C9ORF72-FTD has not been elucidated.
We undertook a detailed neurophysiological investigation of five patients with C9ORF72-FTD, in relation to patients with FTD occurring sporadically and on the basis of mutations in the microtubule-associated protein tau gene and healthy older individuals. We designed or adapted behavioural tasks systematically to assess aspects of somatosensory body schema processing (tactile discrimination, proprioceptive and body part illusions and self/non-self differentiation).
Patients with C9ORF72-FTD selectively exhibited deficits at these levels of body schema processing in relation to healthy individuals and other patients with FTD.
Altered body schema processing is a novel, generic pathophysiological mechanism that may link the distributed cortico-subcortical network previously implicated in C9ORF72-FTD with a wide range of neuropsychiatric and behavioural symptoms, and constitute a physiological marker of this neurodegenerative proteinopathy.
C9ORF72 基因突变是额颞叶痴呆（FTD）和运动神经元病的重要病因。越来越多的证据表明，C9ORF72 基因突变相关的 FTD（C9ORF72-FTD）在临床上以早期突出的神经精神特征为特征，这些特征可能共同反映了身体图式处理的紊乱。然而，C9ORF72-FTD 的病理生理学尚未阐明。
我们对 5 例 C9ORF72-FTD 患者进行了详细的神经生理学研究，这些患者与散发性 FTD 患者以及微管相关蛋白 tau 基因突变患者和健康老年人进行了比较。我们设计或系统地改编了行为任务，以评估躯体感觉身体图式处理的各个方面（触觉辨别、本体感觉和身体部位错觉以及自我/非自我区分）。
与健康个体和其他 FTD 患者相比，C9ORF72-FTD 患者在这些身体图式处理水平上选择性地表现出缺陷。
身体图式处理的改变是一种新的、通用的病理生理学机制，可能将以前与 C9ORF72-FTD 相关的皮质下网络与广泛的神经精神和行为症状联系起来，并构成这种神经退行性蛋白病的生理标志物。
