Stiff person syndrome associated with lower motor neuron disease and infiltration of cytotoxic T cells in the spinal cord
Stiff person syndrome associated with lower motor neuron disease and infiltration of cytotoxic T cells in the spinal cord
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DOI：
10.1016/j.clineuro.2009.06.005
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发表时间：
2009-10-01
影响因子：
1.9
通讯作者：
Alvik, Kirsti
中科院分区：
文献类型：
--
作者：
Holmoy, Trygve;Skorstad, Gjertrud;Alvik, Kirsti
我们报告了一位67岁的非糖尿病男性患者，他表现为左腿肌肉痉挛、麻痹、萎缩和抽搐，随后出现快速进行性肌肉僵硬和叠加痉挛，随后也影响了右腿和躯干。血清和脑脊液中GAD65自身抗体升高，与全身和鞘内合成的寡克隆和高亲和力自身抗体兼容，并且GAD65特异性T细胞在脑脊液中克隆扩增。患者对gaba能和免疫调节治疗或血浆置换无反应，18个月后死于呼吸衰竭。尸检显示脊髓下段前角细胞单侧轴突肿胀、染色质溶解和空泡化，伴有小胶质细胞增生和CD8+细胞毒性T细胞的离散浸润。未检测到CD4+ T辅助细胞、B细胞及补体沉积。据我们所知，这是首次报道下肢下肢运动体征受限的僵硬者综合征，也是首次尝试表征浸润性T细胞。在没有B细胞的脊髓炎症区发现CD8+细胞毒性T细胞，提示鞘内GAD65自身抗体的合成发生在与临床相关病变不严格相关的中枢神经系统区域。(C) 2009 Elsevier B.V.版权所有
We present a 67-year-old non-diabetic male who presented with muscle cramps, paresis, atrophy and fasciculations in the left leg, followed by rapidly progressive muscle stiffness and superimposed spasms which subsequently also affected the right leg and the trunk. GAD65 autoantibodies were elevated in serum and CSF, compatible with systemic and intrathecal synthesis of oligoclonal and high-avidity autoantibodies, and GAD65 specific T cells were clonally expanded in the CSF. The patient did not respond to GABAergic and immunomodulatory treatment or plasma exchange, and died from respiratory failure after 18 months. Autopsy revealed unilateral axonal swelling, chromatolysis and vacuolisation of anterior horn cells of the lower spinal cord, accompanied by microglia proliferation and discrete infiltration of CD8+ cytotoxic T cells. No CD4+ T helper cells, B cells or complement deposition were detected. To our knowledge, this is the first report of stiff person syndrome with lower motor signs restricted to a lower limb, and also the first attempt to characterize the infiltrating T cells. The finding of CD8+ cytotoxic T cells in the absence of B cells in the inflamed area of the spinal cord suggests that the intrathecal synthesis of GAD65 autoantibodies takes place in areas of the CNS not strictly related to the clinically relevant lesions. (C) 2009 Elsevier B.V. All rights reserved.