Steriade Claude, Bauer Jan, Bien Christian G
New York University Comprehensive Epilepsy Center, New York, NY, USA.
NYU Neuroscience Institute, NYU Langone Medical Center, New York, NY, USA.
Nat Rev Neurol. 2025 May 2. doi: 10.1038/s41582-025-01089-4.
Autoimmune encephalitis (AE), defined by clinical criteria and its frequent association with neural autoantibodies, often manifests with seizures, which usually stop with immunotherapy. However, a subset of encephalitic conditions present with recurrent seizures that are resistant to immunotherapy. Three primary neurological constellations that fall within this subset are discussed in this Perspective: temporal lobe epilepsy with antibodies against glutamic acid decarboxylase, epilepsy in the context of high-risk paraneoplastic antibodies, and epilepsy following adequately treated surface antibody-mediated AE. These entities all share a common mechanism of structural injury and potentially epileptogenic focal neural loss, often induced by cytotoxic T cells. Recently, we have proposed conceptualizing these conditions under the term autoimmune encephalitis-associated epilepsy (AEAE). Here, we discuss the new concept of AEAE as an emerging field of study. We consider the clinical characteristics of patients who should be investigated for AEAE and highlight the need for judicious use of traditional epilepsy therapeutics alongside immunotherapeutic considerations that are of uncertain and incomplete efficacy for this group of disorders. Last, we discuss future efforts needed to diagnose individuals before structural epileptogenesis has superseded inflammation and to develop improved therapeutics that target the specific immunological or functional disturbances in this entity.
自身免疫性脑炎(AE),由临床标准及其与神经自身抗体的频繁关联所定义,常表现为癫痫发作,免疫治疗通常可使其停止。然而,一部分脑炎病症会出现对免疫治疗耐药的反复癫痫发作。本观点文章讨论了属于这一亚组的三种主要神经综合征:伴有谷氨酸脱羧酶抗体的颞叶癫痫、高危副肿瘤抗体背景下的癫痫,以及经充分治疗的表面抗体介导的AE后的癫痫。这些病症都具有共同的结构损伤机制以及潜在的致痫性局灶性神经损伤,通常由细胞毒性T细胞诱导。最近,我们提议将这些病症概念化为自身免疫性脑炎相关癫痫(AEAE)。在此,我们讨论AEAE这一新兴研究领域的新概念。我们考虑了应针对AEAE进行调查的患者的临床特征,并强调在免疫治疗的同时明智使用传统癫痫治疗方法的必要性,对于这组疾病,免疫治疗的疗效尚不确定且不完整。最后,我们讨论了在结构性癫痫发生取代炎症之前诊断个体以及开发针对该病症特定免疫或功能紊乱的改进治疗方法所需的未来努力。