Polyneuropathy in neurofibromatosis 2: clinical findings, molecular genetics and neuropathological alterations in sural nerve biopsy specimens
Polyneuropathy in neurofibromatosis 2: clinical findings, molecular genetics and neuropathological alterations in sural nerve biopsy specimens
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DOI：
10.1007/s00401-002-0535-7
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发表时间：
2002-08-01
影响因子：
12.7
通讯作者：
Mautner, VF
中科院分区：
文献类型：
--
作者：
Hagel, C;Lindenau, M;Mautner, VF
神经纤维瘤病2(NF2)是一种常染色体显性遗传病，以中枢和外周神经系统肿瘤的发展为特征。一些NF2患者发展为远端感觉运动性多发性神经病，仅靠肿瘤负担很难解释。本研究对7例NF2多发性神经病患者的8例腓肠神经活检标本进行了研究，包括临床病程、电生理、纤维准备、组织病理学、形态计量学、免疫组织化学、电子显微镜和分子遗传学。所有患者均出现远端对称性反射丧失、对称性袜样痛觉减退和感觉减退及振动觉丧失，继而出现缓慢进行性远端肌肉萎缩和瘫痪。腓肠神经活检标本显示与年龄相关的神经纤维密度病理性降低。此外，8例活检组织中有5例雪旺细胞弥漫性增殖，8例神经鞘瘤和神经周围瘤中分别有2例和1例出现小的神经内膜瘤。Ki-67标记显示3例神经内膜有轻度增殖活性。2例可见有或无中央有髓轴突的雪旺细胞洋葱球。研究结果表明，这是一种多因素引起的轴索病变，不仅是由于大体肿瘤的生长，而且还与小的神经内肿瘤、雪旺细胞的弥漫性增殖和神经周围细胞的增殖有关。
Neurofibromatosis 2 (NF2) is an autosomal dominant disease characterised by development of tumours in the central and peripheral nervous system. Some NF2 patients develop acro-distal sensory motor polyneuropathy that can hardly be explained by the tumour burden alone. In the present study eight sural nerve biopsy specimens from seven NF2 patients suffering from polyneuropathy were investigated, data including clinical course of the disease, electrophysiological findings, teased fibre preparations, histopathological, morphometric, immunohistochemical, electron microscopic and molecular genetic findings. All patients suffered from distal symmetric reflex loss, symmetrical stocking-like hypalgesia and hypesthesia and loss of vibration sense later followed by a slowly progressive distal muscle atrophy and paresis. Sural nerve biopsy specimens revealed a pathological reduction of nerve fibre density correlating with age. In addition, diffuse proliferation of Schwann cells was observed in five of eight biopsies, and small endoneurial tumourlets of schwannomas and perineuriomas were found in two of eight and one of eight samples, respectively. Ki-67 labelling revealed a slight endoneurial proliferative activity in three cases. Schwann cell onion bulbs with or without central myelinated axon were seen in two cases. The findings suggest an axonopathy of multifactorial origin resulting not only from gross tumour growth but, in addition, from small endoneurial tumourlets, diffuse proliferation of Schwann cells and proliferation of perineurial cells.