Stiff-person syndrome (SPS) is the prototypical and most common autoimmune neuronal hyperexcitability disorder. It presents with stiffness in the limbs and axial muscles, stiff gait with uncontrolled falls, and episodic painful muscle spasms triggered by anxiety, task-specific phobias and startle responses, collectively leading to disability. Increased awareness of SPS among patients and physicians has created concerns about diagnosis, misdiagnosis and treatment. This Review addresses the evolving diagnostic challenges in SPS and overlapping glutamic acid decarboxylase (GAD) antibody spectrum disorders, highlighting the growing number of overdiagnoses and focusing on the progress made in our understanding of SPS pathophysiology, antibodies against GAD and other inhibitory synaptic antigens, and the fundamentals of neuronal hyperexcitability. It considers the role of impaired GABAergic or glycinergic inhibition in the cortex and at multiple levels in the neuraxis; the underlying autoimmunity and involvement of GAD antibodies; immunopathogenic mechanisms beyond antibodies, including environmental triggers; familial and immunogenetic susceptibility; and potential T cell cytotoxicity. Finally, the mechanistic rationale for target-specific therapeutic interventions is presented along with the available therapeutic approaches, including enhancers of GABA signalling drugs and immunotherapies.

僵人综合征 （SPS） 是典型且最常见的自身免疫性神经元过度兴奋性疾病。它表现为四肢和中轴肌僵硬，步态僵硬且跌倒不受控制，以及由焦虑、任务特异性恐惧症和惊吓反应引发的阵发性疼痛性肌肉痉挛，共同导致残疾。患者和医生对 SPS 的认识不断提高，这引起了人们对诊断、误诊和治疗的担忧。本综述讨论了 SPS 和重叠谷氨酸脱羧酶 （GAD） 抗体谱系疾病中不断变化的诊断挑战，强调了越来越多的过度诊断，并侧重于我们对 SPS 病理生理学、抗 GAD 和其他抑制性突触抗原的抗体以及神经元过度兴奋的基本原理的理解所取得的进展。它考虑了受损的 GABA 能或甘氨酸能抑制在皮层和神经轴的多个水平上的作用;潜在的自身免疫和 GAD 抗体的参与;抗体以外的免疫致病机制，包括环境触发因素;家族性和免疫遗传学易感性;和潜在的 T 细胞毒性。最后，介绍了靶点特异性治疗干预的机制原理以及可用的治疗方法，包括 GABA 信号药物和免疫疗法的增强剂。