Chai Shuting, Liu Gang, Zhang Yan
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
BMC Neurol. 2025 Jul 17;25(1):297. doi: 10.1186/s12883-025-04308-z.
Anti-kelch-like protein 11 (KLHL11) antibody-associated encephalitis is a rare autoimmune neurological disorder, typically presenting with cerebellar syndrome and brainstem involvement. Diagnosis relies on the detection of anti-KLHL11 antibodies in serum and/or cerebrospinal fluid (CSF). Immunotherapy remains the cornerstone of treatment.
Patient 1 presented with an acute onset of dizziness, limb weakness, and slowed responses, with rapid symptom progression. Despite receiving immunotherapy-including intravenous corticosteroids, immunoglobulin, plasma exchange, and efgartigimod-which resulted in partial improvement, the patient experienced a rapid relapse and further clinical deterioration. He ultimately succumbed to central circulatory failure. Patient 2 exhibited a relatively slow disease course, primarily characterized by gait disturbances, slurred speech, and memory decline. He received only symptomatic treatment without immunotherapy. Follow-up assessments indicated slight symptomatic improvement. Brain magnetic resonance imaging (MRI) showed multiple hyperintense lesions on T2-weighted fluid-attenuated inversion recovery (T2/FLAIR) in the bilateral subcortical cerebral hemispheres and pons in patient 1. However, dominant pontine and cerebellar atrophy were noted in patient 2. Initial serum cell-based assay (CBA) testing detected anti-KLHL11 antibody titers of 1:30 in patient 1 and 1:100 in patient 2.
This study indicates that patients with KLHL11-IgG encephalitis may present not only with typical cerebellar symptoms, such as ataxia, and brainstem signs, such as dysarthria, but also with rapidly progressive impairment of consciousness accompanied by seizures. The differences in disease course and MRI findings observed between the two patients further suggest that clinical and imaging heterogeneity may be related to disease chronicity. Therefore, it is essential to recognize the diverse clinical presentations and varying stages when diagnosing KLHL11-IgG encephalitis. For patients exhibiting such symptoms, after exclusion of other potential causes, timely KLHL11-IgG antibody testing and tumor screening are recommended to facilitate early diagnosis and prompt treatment, thereby improving prognosis.
抗 kelch 样蛋白 11（KLHL11）抗体相关脑炎是一种罕见的自身免疫性神经系统疾病，通常表现为小脑综合征和脑干受累。诊断依赖于血清和/或脑脊液（CSF）中抗 KLHL11 抗体的检测。免疫治疗仍然是治疗的基石。
患者 1 急性起病，出现头晕、肢体无力和反应迟缓，症状进展迅速。尽管接受了免疫治疗，包括静脉注射皮质类固醇、免疫球蛋白、血浆置换和艾加莫德，症状有部分改善，但患者迅速复发并出现进一步的临床恶化。他最终死于中枢循环衰竭。患者 2 的病程相对较慢，主要表现为步态障碍、言语含糊和记忆力下降。他仅接受了对症治疗，未进行免疫治疗。随访评估显示症状略有改善。患者 1 的脑磁共振成像（MRI）在 T2 加权液体衰减反转恢复序列（T2/FLAIR）上显示双侧皮质下脑半球和脑桥有多个高信号病变。然而，患者 2 可见明显的脑桥和小脑萎缩。初始血清细胞检测（CBA）在患者 1 中检测到抗 KLHL11 抗体滴度为 1:30，在患者 2 中为 1:100。
本研究表明，KLHL11-IgG 脑炎患者不仅可能出现典型的小脑症状，如共济失调，和脑干体征，如构音障碍，还可能出现伴有癫痫发作的意识快速进行性损害。两名患者观察到的病程和 MRI 表现差异进一步表明，临床和影像学异质性可能与疾病慢性化有关。因此，在诊断 KLHL11-IgG 脑炎时，认识到其多样的临床表现和不同阶段至关重要。对于出现此类症状的患者，在排除其他潜在病因后，建议及时进行 KLHL11-IgG 抗体检测和肿瘤筛查，以促进早期诊断和及时治疗，从而改善预后。
