Josephs Keith A, Holton Janice L, Rossor Martin N, Braendgaard Hans, Ozawa Tetsutaro, Fox Nick C, Petersen Ronald C, Pearl Gary S, Ganguly Milan, Rosa Pedro, Laursen Henning, Parisi Joseph E, Waldemar Gunhild, Quinn Niall P, Dickson Dennis W, Revesz Tamas
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Brain. 2003 Oct;126(Pt 10):2291-303. doi: 10.1093/brain/awg231. Epub 2003 Jul 22.
We describe four cases of a new clinicopathological entity presenting with either a frontotemporal dementia or corticobasal degeneration syndrome with a mean age of onset of 45 years (range 41-50) characterized pathologically by deposition of neurofilament proteins. All four patients had a rapidly progressive course and have become mute and non-ambulatory, and three have died after mean illness duration of only 3 years (range 2 1/2 -4). Both structural (MRI) and functional (PET and SPECT) imaging demonstrated frontal and temporal lobe and basal ganglia involvement. Gross neuropathological examination in the three deceased patients (the fourth patient, still alive, was diagnosed by brain biopsy) revealed changes affecting predominantly the frontal and temporal cortices, basal ganglia and brainstem. There was superficial linear spongiosis affecting the frontal lobes in all three autopsied patients, and severe caudate atrophy was noted in two of them and demonstrated on MRI in the living patient. On routine staining, there were numerous intracytoplasmic inclusions, which ranged from eosinophilic to basophilic. Some had a clearly defined basophilic margin, while others were granular with a hyaline core. With modified Bielschowsky silver technique, a small number of the inclusions were intensely stained. Inclusions were not labelled with other silver stains. Immuno histochemistry revealed that the inclusions were immunoreactive with antibodies to neurofilament heavy and light chain subunits and to ubiquitin, but not with antibodies to tau and alpha-synuclein. These neurofilament- and ubiquitin-positive inclusions were widespread, specific to neurons and occasionally intranuclear. The frequency and distribution of the inclusions and the silver and immunohistochemical profiles in these four cases is novel and has not been described in detail before. We propose the term neurofilament inclusion body disease for this entity.
我们描述了4例新的临床病理实体病例，这些病例表现为额颞叶痴呆或皮质基底节变性综合征，平均发病年龄为45岁（范围41 - 50岁），病理特征为神经丝蛋白沉积。所有4例患者病程进展迅速，均已丧失语言能力且无法行走，3例患者在平均患病仅3年（范围2.5 - 4年）后死亡。结构成像（MRI）和功能成像（PET和SPECT）均显示额叶、颞叶及基底节受累。对3例死亡患者（第4例患者仍存活，通过脑活检确诊）进行大体神经病理学检查发现，主要病变累及额叶和颞叶皮质、基底节及脑干。所有3例尸检患者的额叶均有浅层线性海绵状变性，其中2例出现严重的尾状核萎缩，在存活患者的MRI检查中也有显示。常规染色可见大量胞质内包涵体，从嗜酸性到嗜碱性不等。有些包涵体有明确的嗜碱性边缘，而另一些则为颗粒状，有透明核心。改良的Bielschowsky银染技术显示，少数包涵体被强烈染色。其他银染法未标记出包涵体。免疫组化显示，这些包涵体对神经丝重链和轻链亚基以及泛素抗体呈免疫反应，但对tau蛋白和α-突触核蛋白抗体无反应。这些神经丝和泛素阳性包涵体广泛存在，对神经元具有特异性，偶尔位于细胞核内。这4例病例中包涵体的频率和分布以及银染和免疫组化特征是新颖的，此前尚未有详细描述。我们为此实体提出“神经丝包涵体病”这一术语。
