Kiuru S, Salonen O, Haltia M
Department of Clinical Neurosciences, Helsinki University Central Hospital, Finland.
Ann Neurol. 1999 Mar;45(3):305-11. doi: 10.1002/1531-8249(199903)45:3<305::aid-ana5>3.0.co;2-e.
Gelsolin-related amyloidosis (familial amyloidosis, Finnish type) is a rare disorder, reported worldwide in kindreds carrying a G654A or G654T gelsolin gene mutation. Facial palsy, mild peripheral neuropathy, and corneal lattice dystrophy are characteristic, but atrophic bulbar palsy, ataxia of gait, and minor cognitive impairment may occur. In histological and immunohistochemical studies of the central nervous system in 4 patients with a G654A gelsolin mutation, we found widespread spinal, cerebral, and meningeal amyloid angiopathy, with deposition of gelsolin-related amyloid (AGel). Marked extravascular deposits occurred in the dura, spinal nerve roots, and sensory ganglia. The amyloid deposits were also variably immunoreactive for apolipoprotein E (ApoE), alpha1-antichymotrypsin (alpha1-ACT), and cystatin C (Cys C). Cerebral perivascular fibrinogen immunoreactivity was occasionally noted. The patients showed posterior column degeneration and diffuse loss of myelin in the centrum semiovale with perivascular accentuation. Postmortem magnetic resonance imaging, performed on 1 patient, showed white matter lesions, colocalizing with the histological abnormalities. Our study shows that deposition of AGel in the spinal and cerebral blood vessel walls, meninges, as well as spinal nerve roots and sensory ganglia is an essential feature of this form of systemic amyloidosis and may contribute to the central nervous system symptoms.
凝溶胶蛋白相关淀粉样变性（家族性淀粉样变性，芬兰型）是一种罕见疾病，在携带G654A或G654T凝溶胶蛋白基因突变的家族中，全球均有报道。面瘫、轻度周围神经病变和角膜格子状营养不良是其特征表现，但也可能出现延髓性麻痹、步态共济失调和轻度认知障碍。在对4例携带G654A凝溶胶蛋白突变患者的中枢神经系统进行组织学和免疫组织化学研究时，我们发现脊髓、脑和脑膜存在广泛的淀粉样血管病，伴有凝溶胶蛋白相关淀粉样蛋白（AGel）沉积。硬脑膜、脊神经根和感觉神经节出现明显的血管外沉积。淀粉样沉积物对载脂蛋白E（ApoE）、α1-抗糜蛋白酶（α1-ACT）和胱抑素C（Cys C）也有不同程度的免疫反应性。偶尔可见脑周血管纤维蛋白原免疫反应性。患者表现为后柱变性，半卵圆中心髓鞘弥漫性丢失，血管周围更为明显。对1例患者进行的死后磁共振成像显示白质病变，与组织学异常部位一致。我们的研究表明，AGel在脊髓和脑的血管壁、脑膜以及脊神经根和感觉神经节中的沉积是这种全身性淀粉样变性的一个基本特征，可能导致中枢神经系统症状。
