Mitsuyama Yoshio
Daigo Hospital, Miyazaki, Japan.
Brain Nerve. 2011 Feb;63(2):109-18.
Frontotemporal dementia (FTD) is a clinical entity that comprises at least two distinct diseases: Pick's disease with Pick bodies and frontotemporal lobar degeneration with tau-negative and ubiquitin-positive inclusions (FTLD-U). FTLD-U is now usually referred to as FTLD-TAR DNA binding protein 43 (TDP-43). FTLD-TDP-43, but not Pick's disease with tau-positive Pick bodies, is often associated with motor neuron disease (MND). More than 200 cases of this combined form, i.e., FTD-MND, have been reported in Japan. The neuropathological characteristics of MND in patients with FTD are essentially similar to the MND in patients without dementia. However the other characteristics of the combination of FTD and MND are such that the author has considered this disease a unique clinicopathological entity. These characteristics are as follows: (1) frontotemporal lobe-type dementia with insidious onset, usually in the presenile period; (2) neurogenic muscular wasting during the course of the illness [amyotrophic lateral sclerosis (ALS)]-- or [spinal progressive muscular atrophy (SPMA)]-like symptoms); (3) duration from the onset of illness to death is 2-5 years (average duration, 30.6 months); (4) both extrapyramidal symptoms and definite sensory deficiency are less commonly observed; (5) no characteristic abnormalities in the cerebrospinal fluid (CSF) or on the electroencephalogram (EEG) in screening tests; (6) no known parental consanguinity or familial occurrence; and (7) nonspecific mild-to-slight degenerative changes in the frontotemporal cortex, hypoglossal nuclei, spinal cord, and frequently in the substantia nigra. FTD-MND is characterized by ubiquitin-immunoreactive intraneuronal inclusions in cortical layers II and III and the hippocampal dentate granule cells. The occurrence of ubiquitin-positive, tau-negative and ubiquitinated TDP-43 positive inclusions could be the key to determining the pathological background of this disease. Further studies are required clinicopathological differentiation between FTD-MND and ALS-dementia (ALS-D).
额颞叶痴呆（FTD）是一种临床实体，至少包括两种不同的疾病：伴有Pick小体的Pick病和伴有tau阴性及泛素阳性包涵体的额颞叶变性（FTLD-U）。FTLD-U现在通常被称为FTLD-TAR DNA结合蛋白43（TDP-43）。FTLD-TDP-43，而非伴有tau阳性Pick小体的Pick病，常与运动神经元病（MND）相关。在日本已报道了200多例这种联合形式，即FTD-MND。FTD患者中MND的神经病理学特征与无痴呆患者的MND基本相似。然而，FTD和MND联合的其他特征使作者认为这种疾病是一种独特的临床病理实体。这些特征如下：（1）隐匿起病的额颞叶型痴呆，通常在老年前期；（2）病程中出现神经源性肌肉萎缩[肌萎缩侧索硬化（ALS）]或[脊髓性进行性肌萎缩（SPMA）]样症状；（3）从发病到死亡的病程为2至5年（平均病程30.6个月）；（4）较少观察到锥体外系症状和明确的感觉缺陷；（5）筛查试验中脑脊液（CSF）或脑电图（EEG）无特征性异常；（6）无已知的近亲结婚或家族发病情况；（7）额颞叶皮质、舌下神经核、脊髓以及经常在黑质出现非特异性轻度至中度退行性改变。FTD-MND的特征是皮质II层和III层以及海马齿状颗粒细胞中有泛素免疫反应性神经元内包涵体。泛素阳性、tau阴性和泛素化TDP-43阳性包涵体的出现可能是确定这种疾病病理背景的关键。需要进一步研究以对FTD-MND和ALS痴呆（ALS-D）进行临床病理鉴别。
