The neurological syndromes associated with glutamic acid decarboxylase antibodies
The neurological syndromes associated with glutamic acid decarboxylase antibodies
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DOI：
10.1016/j.jaut.2019.04.007
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发表时间：
2019-07-01
影响因子：
12.8
通讯作者：
Fidel Baizabal-Carvallo, Jose
中科院分区：
文献类型：
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作者：
Fidel Baizabal-Carvallo, Jose
针对谷氨酸脱羧酶(GAD)的血清抗体(Abs)阳性的患者已描述了许多神经综合征，GAD是GABA(伽马氨基丁酸)合成的限速步骤。这些疾病包括：典型僵人综合征及其变异体、小脑性共济失调、边缘和边缘外脑炎、眼球震颤/动眼功能障碍、耐药癫痫、副肿瘤性僵尸综合征和进行性强直和肌阵挛(PERM)脑病，后两者分别主要与双体素和甘氨酸受体抗体有关，但患者也可能有GAD-抗体阳性。虽然观察结果与这些患者的自身免疫反应一致，并且在某些情况下有证据表明GABA能功能障碍，但GAD-Abs在神经系统中的致病作用尚未阐明，这是一个有争议的问题。这些综合征的诊断是基于临床依据，加上血清和脑脊液中GAD-Abs的存在，并显示鞘内分泌物。虽然有些临床表现可能是GAD-Abs阴性，如僵人综合征；但小脑性共济失调、脑炎和癫痫患者的诊断需要GAD-Abs阳性。大多数患者都需要进行免疫治疗。静脉注射免疫球蛋白、口服或静脉注射类固醇和血浆置换被认为是诱导缓解的一线选择，但通常需要慢性免疫抑制。还应提供对症治疗，以控制肌肉痉挛、癫痫发作、精神错乱等。不同患者的预后不同；但它被认为介于与抗膜抗原神经抗体相关的神经综合征患者和与肿瘤抗体相关的神经综合征患者之间。
A number of neurological syndromes have been described in patients with positive serum antibodies (Abs) against the enzyme glutamic acid decarboxylase (GAD), the rate limiting step in the synthesis of GABA (gamma-aminobutyric acid). These disorders include: classical stiff-person syndrome and variants, cerebellar ataxia, limbic and extra-limbic encephalitis, nystagmus/oculomotor dysfunction, drug-resistant epilepsy, paraneoplastic stiff-person syndrome and progressive encephalopathy with rigidity and myoclonus (PERM), the latter two are mainly related to amphiphysin and the glycine receptor Abs respectively; but patients may also have positive GAD-Abs. Although observations are consistent with an autoimmune response in these patients and there is evidence of GABAergic dysfunction in some cases; the pathogenic role of GAD-Abs in the nervous system has not been clarified and it is a matter of debate. The diagnosis of these syndromes is based on clinical grounds plus the presence of GAD-Abs in serum and CSF with demonstration of intrathecal secretion. Although some presentations may be negative for GAD-Abs, such as stiff-person syndrome; positive GAD-Abs are required for the diagnosis in patients with cerebellar ataxia, encephalitis, and epilepsy. Immunotherapy is required for most patients. Intravenous immunoglobulins, oral or IV steroids and plasma exchange are considered the first line options, aimed to induce remission, but chronic immunosuppression is usually required. Symptomatic therapy should also be provided, aimed to control muscle spasms, seizures, delirium, etc. Prognosis varies among patients; but it is considered intermediate between that of patients with neurological syndromes associated with neural Abs against membrane antigens and those with onconeural Abs.