Saito Y, Kawai M, Inoue K, Sasaki R, Arai H, Nanba E, Kuzuhara S, Ihara Y, Kanazawa I, Murayama S
Department of Neurology, Division of Neuroscience, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
J Neurol Sci. 2000 Aug 1;177(1):48-59. doi: 10.1016/s0022-510x(00)00337-3.
Hallervorden-Spatz syndrome (HSS) is a rare autosomal recessive disorder clinically characterized by extrapyramidal signs and progressive dementia. In a typical case, the clinical symptoms become apparent during late childhood, and usually the course is protracted over a decade or more. We recently had an opportunity to study the brains of two cases of HSS with a clinical course of over 30 years. Case 1 was a 44-year-old female and case 2 was a 37-year-old male. Grossly, the brains showed severe fronto-temporal lobar atrophy with abundant spheroids and mild iron deposits in the globus pallidus, associated with features of motor neuron disease. In addition, there was diffuse sponginess in the atrophic cortex as well as widespread Alzheimer's neurofibrillary tangles (NFTs) and Lewy bodies (LBs) in the cortical and subcortical regions, including the spinal cord. Ultrastructurally, NFTs were composed of paired helical filaments, and LBs of central dense cores with radiating fibrils. Discrete immunostaining was demonstrated in NFTs and neuropil threads with various antibodies against phosphorylated tau, and in LBs with antibody against alpha-synuclein. In addition, diffuse, overlapping immunoreactivity of alpha-synuclein and phosphorylated tau was seen within the cytoplasm of many neurons. However, when LBs and NFTs coexisted within the same neurons, they were clearly segregated. The findings of our present cases as well as those reported in the literature may indicate that simultaneous and extensive occurrence of abnormal phosphorylation of tau and accumulation of alpha-synuclein may constitute cardinal pathological features of HSS with protracted clinical course.
哈勒沃登-施帕茨综合征（HSS）是一种罕见的常染色体隐性疾病，临床特征为锥体外系症状和进行性痴呆。在典型病例中，临床症状在儿童晚期显现，病程通常会持续十年或更长时间。我们最近有机会研究两例病程超过30年的HSS患者的大脑。病例1为一名44岁女性，病例2为一名37岁男性。大体上，大脑显示出严重的额颞叶萎缩，有大量球状体，苍白球有轻度铁沉积，伴有运动神经元病的特征。此外，萎缩的皮质有弥漫性海绵样变，皮质和皮质下区域包括脊髓有广泛的阿尔茨海默病神经原纤维缠结（NFTs）和路易小体（LBs）。超微结构上，NFTs由双螺旋丝组成，LBs由有放射状纤维的中央致密核心组成。用各种抗磷酸化tau抗体在NFTs和神经毡丝中以及用抗α-突触核蛋白抗体在LBs中显示出离散的免疫染色。此外，在许多神经元的细胞质中可见α-突触核蛋白和磷酸化tau的弥漫性、重叠性免疫反应。然而，当LBs和NFTs在同一神经元中共存时，它们明显分离。我们目前病例的发现以及文献报道的发现可能表明，tau异常磷酸化和α-突触核蛋白积累的同时广泛发生可能构成病程迁延的HSS的主要病理特征。
