The importance of early immunotherapy in patients with faciobrachial dystonic seizures.
The importance of early immunotherapy in patients with faciobrachial dystonic seizures.
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DOI：
10.1093/brain/awx323
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发表时间：
2018-02-01
期刊：
影响因子：
--
通讯作者：
Faciobrachial Dystonic Seizures Study Group
中科院分区：
文献类型：
--
作者：
Thompson J;Bi M;Murchison AG;Makuch M;Bien CG;Chu K;Farooque P;Gelfand JM;Geschwind MD;Hirsch LJ;Somerville E;Lang B;Vincent A;Leite MI;Waters P;Irani SR;Faciobrachial Dystonic Seizures Study Group
面臂张力障碍发作（FBDS）是成人首发的自身抗体介导的癫痫。Thompson等人描述了103例FBDS患者，并表明癫痫发作对免疫治疗有反应，早期癫痫发作停止可减少长期残疾并预防认知障碍。潜在的致病机制包括补体固定和LGI1-ADAM22复合体内化。面臂张力障碍发作和边缘脑炎与富含亮氨酸的胶质瘤失活1 （LGI1）抗体密切相关。在这里，我们描述了103例连续的脸臂肌张力障碍发作和LGI1抗体，以了解有和没有认知障碍的患者的临床、治疗和血清学差异，并确定停止脸臂肌张力障碍发作是否可以预防认知障碍。22/103无认知障碍的患者通常具有正常的脑MRI、脑电图和血清钠水平（P < 0.0001）。总的来说，仅9/89（10%）的患者使用抗癫痫药物停止面部肱肌张力障碍发作。相比之下，51%的患者在增加免疫治疗后30天停止了面部肱肌张力障碍发作（P < 0.0001），认知正常患者的停止时间更早（P = 0.038）。事实上，加速免疫治疗（P = 0.031）和正常认知（P = 0.0014）也预示着24个月时残疾的减少。此外，在80例以面部肱肌张力障碍发作为初始特征的患者中，56%的患者在活动性面部肱肌张力障碍发作90天后出现认知障碍。而只有1例患者在脸臂肌张力障碍发作停止后出现认知障碍（P < 0.0001）。所有患者均有IgG4-LGI1抗体，但认知障碍患者的补体固定IgG1抗体比例更高（P = 0.03）。这两种亚型均引起LGI1-ADAM22复合物内化，这是一种潜在的非炎症性致痫机制。综上所述，面臂肌张力障碍发作对免疫治疗表现出显著的时间敏感反应，其停止可以预防认知障碍的发展。
Faciobrachial dystonic seizures (FBDS) are the first adult-onset autoantibody-mediated epilepsy. Thompson et al. describe 103 patients with FBDS, and show that seizures are responsive to immunotherapy, with early seizure cessation reducing long-term disability and preventing cognitive impairment. Potential pathogenic mechanisms include complement fixation and LGI1-ADAM22 complex internalisation. Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.
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DOI：
10.1212/nxi.0000000000000161
发表时间：
2015-12
期刊：
Neurology(R) neuroimmunology & neuroinflammation
影响因子：
--
作者：
Flanagan EP;Kotsenas AL;Britton JW;McKeon A;Watson RE;Klein CJ;Boeve BF;Lowe V;Ahlskog JE;Shin C;Boes CJ;Crum BA;Laughlin RS;Pittock SJ
通讯作者：
Pittock SJ
影响因子：
11.2
作者：
Irani, Sarosh R.;Michell, Andrew W.;Vincent, Angela
通讯作者：
Vincent, Angela
影响因子：
14.5
作者：
Bien, Christian G.;Vincent, Angela;Bauer, Jan
通讯作者：
Bauer, Jan
影响因子：
11.2
作者：
Irani, Sarosh R.;Gelfand, Jeffrey M.;Al-Diwani, Adam;Vincent, Angela
通讯作者：
Vincent, Angela
影响因子：
9.9
作者：
Bien, C. G.;Urbach, H.;Elger, C. E.
通讯作者：
Elger, C. E.