自身免疫性脑炎相关认知和癫痫精神障碍临床研究

目的评估自身免疫性脑炎(AE)患者相关临床疾病特点,增强对该病的认识。方法对2016年1月至2017年12月期间在佛山市第三人民医院诊断为AE患者的临床特点、实验室检查、影像学检查、脑电图检查、简明智能量表(MMSE)、简明精神病评定量表(BPRS)评分以及治疗和预后进行分析。结果抗NMDAR脑炎患者27例,抗LGI1脑炎患者1例,抗CASPR2脑炎患者2例。以癫痫为主要表现者2例(抗NMDAR脑炎患者),以精神障碍为主要表现者1例(抗NMDAR脑炎患者),以精神障碍/癫痫为主要表现者9例(抗NMDAR脑炎患者8例,抗CASPR2脑炎患者1例),以精神障碍/认知功能障碍为主要表现者13例(抗NMDAR脑炎患者),以精神障碍/癫痫/认知功能障碍为主要表现者5例(抗NMDAR脑炎患者3例,抗CASPR2脑炎患者1例,抗LGI1脑炎患者1例)。14例患者头颅MRI检查异常。24例脑电图检查异常。简明智能量表平均分为18.87±4.93,阳性率76.6%。简明精神病评定量表阳性率83.3%,单因素方差分析显示,BPRS各因子之间比较差异有统计学意义,而且以焦虑抑郁、思维障碍分值较高。24例患者使用AEDs联合免疫球蛋白治疗,6例患者合并免疫抑制剂治疗。治疗后症状明显缓解的患者28例,其中26例症状完全缓解,2例症状部分缓解。结论 AE以精神障碍、癫痫发作和认知功能障碍为主要特点,患者症状表现、头颅影像学、脑电图特点、简明智能量表和简明精神病评定量表评分都有独特的特点。对于该病,早期诊断并选择合适的药物及早治疗,可有效改善患者预后。     

正接触蛋白相关蛋白2抗体相关的慢性自身免疫性癫痫的临床特点分析

目的 探讨慢性病程的正接触蛋白相关蛋白2(contactin associated protein-like 2,CASPR2)抗体相关的自身免疫性癫痫的临床特点.方法 收集2018年1月-2020年1月就诊于首都医科大学宣武医院神经内科的3例CASPR2抗体阳性的慢性自身免疫性癫痫患者的一般资料、临床表现、实验室及影...     

自身免疫性痴呆的诊治进展

自身免疫性痴呆(AiD)是一种复杂的疾病，可导致免疫介导的认知障碍，临床表现为脑病和亚急性或慢性的认知功能下降。该病可能是特发性自身免疫病或副肿瘤综合征，通常具有共同的、可识别的临床特征，如炎性CSF、EEG慢波、内侧颞叶异常T₂高信号、自身抗体阳性、伴随肿瘤等。大剂量糖皮质激素治疗是多数患者的初始治疗。由于通过适当治疗可逆转和预防残疾，故早期识别AiD非常重要。本文总结了AiD的临床、实验室和神经影像特征及目前的治疗方式，以促进对AiD患者的快速评估和治疗。     

晚发性癫痫的临床研究进展

晚发性癫痫（LOE）是指65岁以上老年人新发的癫痫。LOE的患病率及发病率逐年升高,但相关临床研究较少,这为LOE患者临床管理带来了挑战。该综述回顾了近10年关于LOE研究的文献,总结了LOE的定义、流行病学资料、病因、临床表现、诊断、鉴别诊断及治疗,希望为LOE患者的临床规范化管理提供参考。 [国际神经病学神经外科学杂志, 2023, 50(6): 68-71]     

从病例看“自身免疫（相关）性癫痫”在临床诊治中的挑战

通过回顾性分析3例代表性临床病例的诊断、治疗及后期随访资料,以揭示目前有关“自身免疫（相关）性癫痫”在诊断和治疗方面存在的挑战和问题,并通过文献复习来探讨合理的应对策略。3例患者中,2例因反复癫痫发作就诊,在临床未明显提示免疫病因的情况下,多次送检相关抗体或启动免疫治疗。另1例患者临床除了癫痫发作,还有其他脑病表现,结合病史和影像所见高度提示免疫病因,最终经抗体检测阳性结果证实。3例患者的诊治经过提示,目前对“自身免疫（相关）性癫痫”诊断和治疗存在一定程度“过度化”情况。“自身免疫”和“癫痫”的关系较为复杂。自身免疫性脑炎中的癫痫发作和慢性自身免疫（相关）性癫痫之间的界限仍不清晰,缺乏可用于实际操作的标准（如生物标记物）是造成后者混乱临床诊疗现状的重要原因。现阶段,理清诸如“急性症状性发作”和“癫痫”等基本概念,仔细全面评估患者,尽早识别出自身免疫性脑炎中已经确定的、具有一定表型特征的综合征,以及使用可指导临床送检抗体或启动免疫治疗的相关评测量表,可帮助临床医生更加合理、有效地诊疗。     

抗amphiphysin抗体相关自身免疫性癫痫1例报告

癫痫发作是神经科常见的临床症状,是由中枢神经系统过度、同步化异常放电引起的症状,见于多种疾病的发病过程中,如脑炎、脑血管病和颅脑肿瘤等.在美国,每年约有1.5万成年人出现无明显诱发因素的首次癫痫发作[1].对于成年人癫痫发作,最重要的是尽可能寻找引起癫痫发作的病因,而引起癫痫发作的病因很多,越来越多的证据表明自身免疫机...     

自身免疫性癫痫早期诊断和治疗的研究进展

随着近十余年来对自身免疫性癫痫(AE)认识的不断加深,免疫已成为癫痫不可忽视的病因。越来越多的研究表明免疫治疗对AE效果十分显著,早期诊断和免疫治疗与其良好预后相关。神经特异性自身抗体检测是诊断AE的关键检查,但其较高的检测费用并不适合作为普查手段,因此明确具有何种特征的癫痫患者需要进行相关抗体检测,对于早期诊断和早期治疗AE具有重要意义。本文将围绕AE相关的临床线索、诊断原则、传统治疗和免疫治疗等方面进行综述,以供临床医生和今后研究参考。     

后头部癫痫的临床研究进展

后头部癫痫(posterior cortex epilepsies,PCEs)是顶叶癫痫、枕叶癫痫、颞顶枕交界区癫痫的总称,症状学不典型,由于复杂的纤维联系癫痫活动迅速扩散,表现为类似额叶癫痫和颞叶癫痫的发作形式.常规脑电图检查价值有限,结合影像学、神经电生理检查尤其是侵入性检查能提高致痫区定位的精确性.多数患者手术效...     

癫痫免疫性病因研究进展北大核心CSCD

免疫性癫痫在癫痫患者中占比不低,癫痫的免疫性病因应受到更多重视。自身免疫相关性癫痫(autoimmune-associated epilepsy,AAE)指自身免疫性脑炎(autoimmune encephalitis,AIE)后遗留的慢性癫痫发作,AIE患者神经特异性抗体(neural specific autoantibodies,NSAbs)类型不同,发生AAE的比例也不同,早期免疫治疗是预防AAE发生的重要预防措施。在不明原因癫痫患者中检出NSAbs同样提示病因为免疫性,这类患者常表现频繁发作、药物难治等特点。近期学者提出多种预测不明原因癫痫患者NSAbs阳性的评分系统,但其有效性仍需进一步研究证实。免疫是癫痫的重要病因,及早诊断和治疗能更好地改善患者的预后,临床医师应加强癫痫免疫性病因的筛查,务求早诊断、早治疗。     

正确认识自身免疫性癫痫与自身免疫性脑炎的关系

自身免疫性癫痫与自身免疫性脑炎均是近年来随着神经免疫学发展而提出的临床新概念。对于伴有癫痫样发作、抗神经元抗体阳性的患者,诊断为自身免疫性脑炎还是自身免疫性癫痫,目前还存在争议和误区。由于二者存在部分共同的抗神经元抗体,且临床表现有一定重叠性,如癫痫的耐药性、合并认知功能损害等,常被临床所混淆,造成了不必要的过度抗癫痫治疗。笔者从二者临床概念、流行病学、发病机制及相关危险因素、临床表现、辅助检查、治疗和预后对二者区别和联系进行了释义。     

Electroencephalography in clinical epilepsy research

Electroencephalography (EEG) remains central to the investigation of epilepsy. This review discusses two clinical problems at the temporal extremes of neurophysiologic recording: evaluation of the clinical significance of individual spike discharges in benign epilepsy of childhood with centrotemporal spikes (BECTS), and prolonged (several days) continuous EEG monitoring in the ICU. BECTS is misdiagnosed often, and probably mis-treated often as well. Though the long-term outcome is usually excellent, it remains unclear whether the individual epileptiform discharges have a clinical effect. Answering this question is difficult, in part because of the natural evolution of the epilepsy and its different appearance depending on wakefulness or sleep state, and also due to substantial methodologic problems in measuring short and long-term cognitive effects. Continuous EEG (CEEG) recording has grown remarkably over the last 10 years. It has proved crucial in the diagnosis of nonconvulsive status epilepticus (NCSE), especially in the ICU, given the usual lack of obvious clinical signs of seizures in most of these patients, many of whom are critically ill. Much progress has been made in agreeing on terminology for the EEG findings, but diagnosis is still complicated. More efficient and reliable technology is being developed to help process the massive amount of data captured by CEEG and make it more useful (and in a timely fashion) clinically. Still, it is not completely clear which patients should be monitored, for how long, and what is the best role for CEEG in assessing and adjusting treatment once the diagnosis has been made. Investigators are using CEEG to study “seizure burden,” to help determine what are the long-term effects of nonconvulsive seizures and NCSE, and to help guide treatment and improve outcome.     

卒中后癫痫发作的临床研究进展

卒中后癫痫发作和卒中后癫痫是常见的卒中并发症,给患者及其家属的身心健康带来巨大影响,但目前仍缺乏明确的预防和诊治指南。不同类型的卒中可引起不同类型的癫痫发作和癫痫,且其相应的危险因素亦不相同。脑出血是目前公认度较高的卒中后癫痫发作或卒中后癫痫的首要危险因素。鉴于相关的评估手段和干预策略尚处于研究阶段,因此针对主要危险因素的干预成为当前较为可行的应对选择。卒中后癫痫发作和卒中后癫痫的诊断和治疗同样面临着不少困难。目前,头颅磁共振成像(magnetm resonance imaging,MRI)动脉自旋标记(arterial spin labeling,ASL)序列和新一代抗癫痫药物左乙拉西坦已成为关注的焦点。本文对近年来有关卒中后癫痫发作和卒中后癫痫的危险因素及临床诊治的研究进展进行总结和讨论。     

论自身免疫性脑炎责任抗体的致病性

自身免疫性脑炎是一种中枢神经系统自身免疫性疾病,大量新抗体的发现扩增其临床疾病谱,但也为临床表型的精准识别带来一定困难.责任抗体系指同一例患者病程中与一个或多个临床表型有对应因果关系的致病性抗体,这一概念的提出,在自身抗体与临床表型之间建立联系,体现出现代精准医学的理念.明确责任抗体的致病性是理解抗体-临床表型因果关系...     

神经突触前膜胞内蛋白抗体致大鼠癫癎的机制

目的研究神经突触前膜胞内蛋白(Munc18)抗体致大鼠的机制。方法60只SD大鼠分为4组,在实验组大鼠的海马CA1区间断注射Munc18抗体,共9次。监测大鼠的脑电图和样行为。10周后全部大鼠处死取脑,切片做HE、尼氏和TUNEL染色后观察。结果实验组12只大鼠中,10只出现异常脑电,5只在6周之后仍然存在;9只出现1~4级不等的样行为,6周后仍有4只存在样行为;大鼠脑片显示海马区神经细胞数量明显减少(155±20,P<0·01),而凋亡细胞数量明显增多(16·80±3·32,P<0·01),伴有胶质细胞增生及细胞形态异常。结论Munc18抗体能慢性点燃致大鼠,其机制可能与其诱导整个海马区神经细胞的凋亡和丢失有关。     

基于“责任抗体”概念的自身免疫性脑炎诊断与治疗进展

自身免疫性脑炎是神经系统免疫性疾病的重要组成之一,存在靶向神经元表面蛋白、离子通道或突触表面受体的自身抗体,自身抗体检测对疾病的诊断、治疗及预后评估具有重要意义。确定责任抗体是解决同一例患者多种自身抗体共存的重要方法,本文基于新近提出的"责任抗体"概念对自身免疫性脑炎诊断与治疗进展进行综述。     

VGKC complex antibodies in epilepsy: Diagnostic yield and therapeutic implications

PurposeIn a significant number of patients developing epilepsy in adult life, the aetiology of their seizures remains unclear. Antibodies directed against the voltage gated potassium channel complex (VGKC Ab) have been identified in various cohorts of patients with epilepsy, although the role of these antibodies in epilepsy pathogenesis is not fully known.MethodWe reviewed the notes of 144 patients with unexplained adult onset epilepsy who had been tested for VGKC Abs. We collected data on their clinical syndrome, investigation results and response to treatment.ResultsWe identified 6 (4.2%) patients who had titres of >400 pM. One of the six patients was positive for LGI1 and another for CASPR2 subunit antibodies. All patients were given immunotherapy and experienced improvement in seizure control. No patient had the clinical syndrome of limbic encephalitis.ConclusionPatients with otherwise unexplained epilepsy and positive VGKC Abs are a heterogeneous group. In our cohort there was an overall favourable response to immunotherapy but further prospective studies are needed to determine the significance of these antibodies and the optimum treatment regimen for patients.     

Glutamic acid decarboxylase (GAD) antibodies in epilepsy: Diagnostic yield and therapeutic implications

PurposeThe aetiology of adult onset epilepsy remains unascertained in a significant proportion of patients. Antibodies directed against neuronal antigens have been suggested to have a potential pathogenic role in some cases of epilepsy. We describe a series of patients with adult onset epilepsy in whom antibodies to glutamic acid decarboxylase (GAD Abs) have been identified.MethodsAll patients attending a regional epilepsy service with unexplained adult onset epilepsy’ were tested for the presence of GAD Abs. Those with high serum titres underwent CSF analysis, and were offered additional treatment with immunotherapy. Those who underwent immunotherapy were monitored by monthly review. Clinical details and response to treatment was collated by review of notes.ResultsOf 112 patients tested, high serum titres were found in 6 (5.4%) patients. These patients had clinical and electroencephalographic evidence of focal epilepsy. CSF analysis revealed oligoclonal bands and intrathecal GAD Abs in all patients. Five patients received immunotherapy. No improvement in seizures was observed in any. One patient with equivocal MRI evidence of hippocampal sclerosis and concordant video EEG and PET scan, achieved 12 months seizure freedom following temporal lobectomy.ConclusionsThe relevance of GAD Abs to epilepsy remains uncertain. Our experience does not support the routine use of immunotherapy in patients with epilepsy and GAD Abs. Larger studies enrolling greater numbers of patients are required to identify sufficient numbers of patients for controlled treatment trials.     

Postencephalitic epilepsy and drug‐resistant epilepsy after infectious and antibody‐associated encephalitis in childhood: Clinical and etiologic risk factors

To define the risk factors for postencephalitic epilepsy (PE) and drug‐resistant epilepsy (DRE) in childhood following infectious and autoimmune encephalitis, we included 147 acute encephalitis patients with a median follow‐up of 7.3 years (range 2–15.8 years). PE was defined as the use of antiepileptic drugs (AEDs) for ≥24 months, and DRE was defined as the persistence of seizures despite ≥2 appropriate AEDs at final follow‐up. PE and DRE were diagnosed in 31 (21%) and 15 (10%) of patients, respectively. The features during acute encephalitis predictive of DRE (presented as odds ratio [OR] with confidence intervals [CIs]) were status epilepticus (OR 10.8, CI 3.4–34.3), visual disturbance (6.4, 1.4–29.9), focal seizures (6.2, 1.9–20.6), magnetic resonance imaging (MRI) hippocampal/amygdala involvement (5.0, 1.7–15.4), intensive care admission (4.7, 1.4–15.4), use of >3 AEDs (4.5, 1.2–16.1), MRI gadolinium enhancement (4.1, 1.2–14.2), any seizure (3.9, 1.1–14.4), and electroencephalography (EEG) epileptiform discharges (3.9, 1.3–12.0). On multivariable regression analysis, only status epilepticus remained predictive of DRE in all models. DRE was common in herpes simplex virus (3/9, 33%) and unknown (8/40, 20%) encephalitis, but absent in acute disseminated encephalomyelitis (ADEM) (0/32, 0%), enterovirus (0/18), and anti‐N‐methyl‐d ‐aspartate receptor–NMDAR encephalitis (0/9). We have identified risk factors for DRE and demonstrated “high‐risk,” and “low‐risk” etiologies.