■谷氨酸脱羧酶(GAD)是γ-氨基丁酸(GABA)合成的限速酶,中枢神经系统中主要的抑制性神经递质。抗谷氨酸脱羧酶(GAD)的抗体与患者中描述的各种神经系统疾病有关,包括僵硬的人综合征,小脑共济失调,难治性癫痫,和边缘性和边缘性脑炎。虽然成人抗GAD65抗体相关脑炎的病例报道和研究较少,这种情况在儿科病例中极为罕见。
■第一次,我们报告一例抗GAD65阳性自身免疫性脑炎与自身免疫性多内分泌综合征(APS)II型相关.我们回顾了以前发表的抗GAD65自身免疫性脑炎的儿科病例,以讨论其临床特征。实验室测试,影像学发现,脑电图模式,和预后。
■一个8岁的孩子,男性儿童在经历了20天的全身抽搐后出现在门诊部。该儿童因癫痫入院,并在另一个中心接受了口服丙戊酸钠(500毫克/天),USG腹部和MRI脑部等检查没有发现异常,然而,左前中前额颞区脑电图异常,弥漫性混合活动。在随访日,重复血液检查显示丙戊酸钠的血清药物浓度非常低,因此剂量增加至750mg/天。然后,孩子经历了不良影响,包括睡眠增加,口渴,食欲不振,促使父母停止服药。重复MRI显示右海马FLAIR序列上的信号增加,因此接受进一步处理。该患儿的既往病史包括4岁时诊断为甲状腺功能减退,并每天接受一次左甲状腺素75mcg。他的父母很健康,没有任何类似的神经病史,自身免疫,或遗传疾病,但他叔叔有癫痫病史.在介绍时,他的血糖水平不受控制,HbA1c水平升高.此外,血清和CSF自身抗体抗GAD65抗体阳性,滴度分别为1:100和1:32。患者接受混合类型的胰岛素治疗方案,并接受一线免疫疗法(静脉注射免疫球蛋白,IVIG)连续五天,随后口服泼尼松和丙戊酸钠作为抗癫痫药物。在取得良好的临床结果后,患者口服药物出院。
■在本文献报道的15名儿科患者中,九人出现边缘叶脑炎(LE),三个患有外系脑炎(ELE),还有三种是边缘性和外缘性脑炎。这些病例中的大多数在早期表现出主要位于颞叶的T2-WFLAIR高强度,在MRI的后期进展为海马硬化/萎缩。EEG通常在额颞叶上显示出缓慢或尖峰波,并伴有癫痫性放电。患者的预后因素各不相同,一些人经历了持续性的难治性癫痫发作,1型糖尿病(T1DM),持续性记忆障碍,持续残疾需要全面援助,and,在严重的情况下,死亡。
■我们的研究结果表明,抗GAD65抗体阳性自身免疫性脑炎患者可能与其他APS同时存在。我们的独特病例表现为多种内分泌综合征,是儿童中首次报告的病例。早期诊断和及时启动免疫疗法对于改善临床症状和减少复发或永久性残疾的可能性至关重要。因此,重点应放在及时诊断和适当的治疗实施,以实现更好的患者结果。
Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few
case reports and research on anti-GAD65 antibody-associated encephalitis in adults, such cases are extremely rare in pediatric cases.
For the first time, we report a
case of anti-GAD65-positive autoimmune encephalitis associated with autoimmune polyendocrine syndrome (APS) type II. We reviewed previously published pediatric cases of anti-GAD65 autoimmune encephalitis to discuss their clinical features, laboratory tests, imaging findings, EEG patterns, and prognosis.
An 8-year-old, male child presented to the outpatient department after experiencing generalized convulsions for twenty days. The child was admitted for epilepsy and had received oral sodium valproate (500 mg/day) in another center, where investigations such as USG abdomen and MRI brain revealed no abnormalities, however, had abnormal EEG with diffuse mixed activity in the left anterior middle prefrontal temporal region. On the follow-up day, a repeat blood test showed a very low serum drug concentration of sodium valproate hence the dose was increased to 750 mg/day. Then, the child experienced adverse effects including increased sleep, thirst, and poor appetite, prompting the parents to discontinue the medication. A repeat MRI showed increased signals on FLAIR sequences in the right hippocampus hence admitted for further management. The child\'s past history included a diagnosis of hypothyroidism at the age of 4, and receiving levothyroxine 75 mcg once daily. His parents are healthy with no history of any similar neurological, autoimmune, or genetic diseases, but his uncle had a history of epilepsy. At presentation, he had uncontrolled blood glucose levels with elevated HbA1c levels. Additionally, the serum and CSF autoantibodies were positive against the anti-GAD65 antibody with the titer of 1:100 and 1:32 respectively. The patient was managed with a mixed type of insulin regimen and received first-line immunotherapy (intravenous immunoglobulin, IVIG) for five consecutive days, followed by oral prednisone and sodium valproate as an antiepileptic drug. Upon achieving a favorable clinical outcome, the patient was discharged with oral medications.
Among the 15 pediatric patients reported in this literature, nine presented with limbic encephalitis (LE), three with extralimbic encephalitis (ELE), and three with a combination of limbic and extralimbic encephalitis. Most of these cases exhibited T2-W FLAIR hyperintensities primarily localized to the temporal lobes in the early phase, progressing to hippocampal sclerosis/atrophy in the later phase on MRI. EEG commonly showed slow or spike waves on frontotemporal lobes with epileptic discharges. Prognostic factors varied among patients, with some experiencing persistent refractory seizures, type-1 diabetes mellitus (T1DM), persistent memory impairment, persistent disability requiring full assistance, and, in severe cases, death.
Our findings suggest that anti-GAD65 antibody-positive autoimmune encephalitis patients may concurrently present with other APS. Our unique
case presented with multiple endocrine syndromes and represents the first reported occurrence in children. Early diagnosis and timely initiation of immunotherapy are crucial for improving clinical symptoms and reducing the likelihood of relapses or permanent disabilities. Therefore, emphasis should be placed on prompt diagnosis and appropriate treatment implementation to achieve better patient outcomes.