OBJECTIVE:CDKL5 deficiency disorder (CDD) is a rare, severe developmental and epileptic encephalopathy. There is a pressing need to develop effective and sustainable therapeutic strategies. We aimed to investigate the causal association between febrile episodes and epileptic seizures for therapeutic implications in CDD patients. METHODS:The study was a nationwide, cross-sectional survey on CDD patients in China (ClinicalTrials.gov, NCT06663163). Detailed phenotypic and genotypic data were collected through an online questionnaire with uploaded original medical records, genetic testing results, and peri-fever seizure diaries. The primary outcome was changes in epileptic seizure frequency during and post-fever phases compared to a 1-month pre-fever phase based on seizure diaries. RESULTS:Between October 2024 and December 2024, we received 131 questionnaires. Forty-seven questionnaires were removed after excluding duplicates and missing data. Ultimately, 84 eligible participants with complete uploads were included, from 26 of 34 (76.5%) province-level regions in China. Among these, 47 (56.0%) patients had significant decreased seizure frequency only during febrile episodes, and 27 (32.1%) patients with daily seizures achieved at least a seizure-free day. Notably, 20 patients (23.8%) exhibited post-fever seizure reduction: 12 (25.5%) for 3 days to 1 week, and 6 (12.8%) for more than 2 weeks (maximum > 40 days). The effect was independent of patients' clinical and genetic characteristics. INTERPRETATION:Our findings, for the first time, revealed that fever-related seizure reduction is a distinctive and prevalent genotype-phenotype for CDD, thereby providing evidence for further fundamental research into the underlying mechanisms and offering potential clinical implications for seizure control in CDD.

Objective Epilepsy-aphasia spectrum (EAS) represents the most common group of childhood epilepsy syndromes, however, the precise source localization of epileptiform discharges remains undetermined. This study aimed to localize and compare the sources of epileptiform discharges across different EAS subtypes using magnetoencephalography (MEG). Methods In this prospective MEG-based study, we recruited 70 patients with EAS, including 52 with self-limited epilepsy with centrotemporal spikes (SeLECTS), 12 with atypical benign partial epilepsy (ABPE), 3 with Landau-Kleffner syndrome (LKS), and 3 with Epileptic Encephalopathy with continuous Spike-and-Waves during sleep (EE-SWAS). Ten independent epileptiform discharges per patient were analyzed using distributed source modeling with standardized low-resolution electromagnetic brain tomography (sLORETA). The spike source density was quantified as current amplitude, and source locations were mapped according to the Desikan-Killiany atlas. Results The source locations of epileptiform discharges differed significantly across EAS subtypes. EE-SWAS exhibited the highest overall current source density, followed by ABPE, whereas SeLECTS and LKS showed the lowest values. Lobar analysis revealed frontal-predominant discharges in EE-SWAS and ABPE, contrasting with temporal-predominant discharges in SeLECTS and LKS. Moreover, patients with secondary generalized tonic‑clonic seizures exhibited higher current source densities than those with only focal seizures, consistent with broader EEG discharge spread. Conclusions This first systematic MEG source analysis across the full EAS reveals a hierarchical gradient from temporo-centric to fronto-centric distribution, paralleling the clinical severity gradient. Our findings highlight the potential of MEG source imaging for phenotyping and pathophysiological stratification in EAS.

ABSTRACT Objective To explore the clinical phenotypes, characteristics, immunotherapy response, and outcomes of glutamic acid decarboxylase‐65 (GAD65) neurological autoimmunity. Methods We performed a retrospective review of patients diagnosed with GAD65 neurological autoimmunity in the Department of Neurology at Xuanwu Hospital over the past 6 years (2017–2023). The clinical and laboratory data, imaging, therapeutic response, and long‐term prognosis of those patients were collected and analyzed. Results Among the 37 patients displaying significant neurological impairment, there were 14 males (37.8%) and 23 females (62.2%), with a median age of onset of 41.5 (25–59) years and a median interval of 9 (1.5–36) months from onset to a definitive diagnosis. Clinical phenotypes included epilepsy (15, 40.5%), limbic encephalitis (7, 18.9%), brainstem dysfunction (2, 5.4%), parkinsonism (2, 5.4%), peripheral neuropathy (3, 8.1%), cerebellar ataxia (1, 2.7%), and overlap syndromes (7, 18.9%). Out of 36 patients who received immunotherapy, the median time from onset to initiation of immunotherapy was 8.5 (1.5–37.5) months. Four cases were lost to follow‐up, leaving a median follow‐up period of 20.5 (16–37.25) months among the remaining 32 patients. Most patients (26, 81.3%) responded positively to immunotherapy, with some showing mild improvement or no response. Some patients showed inadequate responses to treatments such as mycophenolate mofetil (MMF), but significant improvement is observed after switching to rituximab (RTX). The relationship between the timing of initiating immunotherapy and prognosis by Spearman's rank correlation only showed weak correlation. Conclusion The clinical spectrum of GAD65 neurological autoimmunity appeared highly diverse. Immunotherapy can benefit the majority of patients, and early treatment appeared to be associated with good prognosis. RTX may be more effective than MMF; however, this requires more rigorous prospective studies to explore.

OBJECTIVE:The identification of epileptic lesions is crucial for improving surgical outcomes. Nevertheless, substantial focal cortical dysplasia (FCD) may be invisible on magnetic resonance imaging (MRI). We aimed to characterize the expression pattern of 18-kDa translocator protein (TSPO) in FCD and to evaluate the effectiveness of this inflammation-reflective molecular imaging technique for detecting FCD. METHODS:Patients clinically diagnosed with FCD, based on clinical features, interictal electroencephalographic (EEG) findings, and MRI characteristics, underwent positron emission tomography (PET) imaging using 18F-DPA714 and 18F-fluorodeoxyglucose (FDG) tracers. TSPO-PET activation patterns were qualitatively evaluated. Semiquantitative analysis using the Highlight Index (HI) was further performed to investigate its correlation with clinical characteristics. For patients who underwent stereo-EEG (SEEG) monitoring, the site of high-level TSPO-PET activation was compared with the seizure onset zone identified by SEEG. For patients who underwent resection surgery, the relationship between TSPO-PET uptake and histopathological findings was studied. RESULTS:Twenty-four patients were enrolled. Three groups were identified: MRI-positive with visible high-level TSPO-PET activation (six patients), MRI-negative with visible high-level TSPO-PET activation (thirteen patients), and MRI-positive with invisible low-level TSPO-PET activation (five patients). Regions of high-level TSPO-PET activation showed concordance with ictal discharges in five patients who underwent SEEG. Compared with FDG-PET, TSPO-PET exhibited a more prominent signal against the background (p = .0158). HI was correlated with seizure frequency (p = .0362) and the occurrence of focal to bilateral tonic-clonic seizures (p = .0294), and shorter interval between the TSPO-PET scan and the last seizure was associated with higher TSPO-PET HI (R = -.4323, p = .0349). Postoperative histopathological examination confirmed high-level TSPO-PET activation rates of 3/3 for FCD type IIb and 1/3 for FCD type IIa. SIGNIFICANCE:TSPO-PET activation patterns offer clinical significance for improving surgical outcomes by enhancing FCD detection during presurgical evaluation. Also, our observations offer new insights into the histopathological basis for increased TSPO uptake in humans.

AbstractObjectiveN‐methyl‐D‐aspartate receptors are glutamate‐gated ion channels that play a crucial role in brain function. Numerous inherited or de novo variants in the GRIN2A gene, encoding the GluN2A subunit of the receptor, have been identified in patients with epilepsy. In addition, it is worth noting that GRIN2A variants exhibit a strong correlation with epilepsy‐aphasia syndromes, a group of age‐dependent epileptic, cognitive, and language disorders with a characteristic electroencephalographic pattern.MethodsWhole exome sequencing was conducted in enrolled patients with epilepsy‐aphasia syndromes, and GRIN2A variants were screened. The conservation of substituted residues, conformational changes of mutant subunits, and in silico predictions of pathogenicity were thoroughly assessed in our study. Functional alterations of the variants were examined using whole‐cell voltage‐clamp current recordings while the relative surface expression levels of subunit proteins were assessed via immunofluorescence assays. A summary of previously published GRIN2A missense variants was conducted to investigate the genotypic‐phenotypic‐functional correlations.ResultsTwo missense GRIN2A variants (c. 2482A >G/p. M828V, c. 2627 T >C/p. I876T) were identified, which are located in the transmembrane helix M4 and C‐terminus domain of the GluN2A subunit, respectively. Both variants exhibited reduced current density of NMDARs and surface/total expression levels of GluN2A subunits, while M828V showed a decreased extent of desensitization as well. A further summary of the previously reported GRIN2A variants demonstrated that more variable phenotypes were observed for variants situated in the C‐terminus domain or those with loss‐of‐function effects.SignificanceOur study expands the phenotypic and functional range of GRIN2A‐related disorders. In order to optimally establish the domain‐function‐phenotype correlations in GRIN2A variants, it is imperative to gather a more extensive set of clinical and functional data.Plain Language SummaryThis study has identified two genetic variants of the GRIN2A gene in patients with epilepsy‐aphasia syndrome. We assess the variants' harmfulness through a variety of functional experiments, including evaluating the expression level of the mutated protein and the resulting changes in electrophysiological activities. Also, we reviewed previously published papers about GRIN2A variants in epilepsy to learn more about the correlations between their locations, functional changes, and clinical manifestations.

BackgroundEpilepsy (EP) is a common neurological disease in which 70-80% are thought to have a genetic cause. In patients with epilepsy, neurodevelopmental delay (NDD) was prevalent. Next generation of sequencing has been widely used in diagnosing EP/NDD. However, the diagnostic yield remains to be 40%-50%. Many reanalysis pipelines and software have been developed for automated reanalysis and decision making for the diseases. Nevertheless, it is a highly challenging task for smaller genetic centers or a routine pediatric practice. To address the clinical and genetic "diagnostic odyssey," we organized a Multidisciplinary Molecular Consultation (MMC) team for molecular consultation for 202 children with EP/NDD patients referred by lower level hospitals. MethodsAll the patients had undergone an aligned and sequential consultations and discussions by a "triple reanalysis" procedure by clinical, genetic specialists, and researchers. ResultsAmong the 202 cases for MMC, we totally identified 47 cases (23%) harboring causative variants in 24 genes and 15 chromosomal regions after the MMC. In the 15 cases with positive CNVs, 3 cases harbor the deletions or duplications in 16p11.2, and 2 cases for 1p36. The bioinformatical reanalysis revealed 47 positive cases, in which 12 (26%) were reported to be negative, VUS or incorrectly positive in pre-MMC reports. Additionally, among 87 cases with negative cases, 4 (5%) were reported to be positive in pre-MMC reports. ConclusionWe established a workflow allowing for a "one-stop" collaborative assessments by experts of multiple fields and helps for correct the diagnosis of cases with falsenegative and -positive and VUS genetic reports and may have significant influences for intervention, prevention and genetic counseling of pediatric epilepsy and neurodevelopmental disorders.

Background:No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study on perampanel early add-on therapy in China. This interventional study aimed to assess efficacy and safety of perampanel as an early add-on treatment of focal-onset seizures (FOS) with or without focal-to-bilateral tonic-clonic seizures (FBTCS) in Chinese patients. Methods:In this multicenter, open-label, single-arm, phase 4 interventional study, Chinese patients ≥ 12 years old with FOS with or without FBTCS who failed anti-seizure medication (ASM) monotherapy from 15 hospitals in China were enrolled and treated with perampanel add-on therapy (8-week titration followed by 24-week maintenance). The primary endpoint was 50% responder rate. Secondary endpoints included seizure-freedom rate and changes in seizure frequency from baseline. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were recorded. Results:The full analysis set included 150 patients. The mean maintenance perampanel dose was 5.9 ± 1.5 mg/day and the 8-month retention rate was 72%. The 50% responder rate and seizure-freedom rate for all patients during maintenance were 67.9 and 30.5%, respectively. Patients with FBTCS had higher 50% responder rate (96.0%) and seizure-freedom rate (76.0%) during maintenance. Patients on concomitant sodium valproate had a significantly higher seizure-freedom rate than those on concomitant oxcarbazepine. Eight-six (55.1%) patients experienced treatment-related TEAEs, and the most common TEAEs were dizziness (36.5%), hypersomnia (11.5%), headache (3.9%), somnolence (3.2%), and irritability (3.2%). Withdrawal due to TEAEs occurred to 14.7% of the patients. Conclusion:Perampanel early add-on was effective and safe in treating Chinese patients≥12 years old with FOS with or without FBTCS.Clinical trial registrationwww.chictr.org.cn, Identifier ChiCTR2000039510.

•Half patients with anti-mGluR5 encephalitis from publications developed seizures.•We report a case of anti-mGluR5 encephalitis presenting with focal motor seizures.•Isolated focal seizure highlights an unusual feature of anti-mGluR5 encephalitis.

Objectives To provide reference values of trans-laminar cribrosa pressure difference (TLCPD) and reveal the association of TLCPD with systemic biometric factors. Methods In this cross-sectional study, 526 quasi-healthy subjects (including 776 eyes) who required lumbar puncture for medical reasons were selected from 4915 neurology inpatients from 2019 to 2022. Patients with any diseases affecting intraocular pressure (IOP) or intracranial pressure (ICP) were excluded. The ICPs of all subjects were obtained by lumbar puncture in the left lateral decubitus position. IOP was measured in the seated position by a handheld iCare tonometer prior to lumbar puncture. TLCPD was calculated by subtracting ICP from IOP. Systemic biometric factors were assessed within 1 h prior to TLCPD measurement. Results The TLCPD (mean ± standard deviation) was 4.4 ± 3.6 mmHg, and the 95% reference interval (defined as the 2.5th–97.5th percentiles) of TLCPD was −2.27 to 11.94 mmHg. The 95% reference intervals for IOP and ICP were 10–21 and 6.25–15.44 mmHg, respectively. IOP was correlated with ICP ( r = 0.126, p < 0.001). TLCPD was significantly negatively correlated with body mass index ( r = −0.086, p = 0.049), whereas it was not associated with age, gender, height, weight, blood pressure, pulse, or waist and hip circumference. Conclusions This study provides reference values of TLCPD and establishes clinically applicable reference intervals for normal TLCPD. Based on association analysis, TLCPD is higher in people with lower BMI.

Objectives To expand the genotypes and phenotypes of sodium voltage-gated channel alpha subunit 1 (SCN1A)-related epilepsy. Methods We retrospectively collected the clinical and genetic information of 22 epilepsy patients (10 males, 12 females; mean: 9.2 ± 3.9 years; 3.9–20.3 years) carrying 22 variants of SCN1A. SCN1A mutations were identified by next-generation sequencing. Results Twenty-two variants were identified, among which 12 have not yet been reported. The median age at seizure onset was 6 months. Sixteen patients were diagnosed with Dravet syndrome (DS), two with genetic epilepsy with febrile seizures plus [one evolved into benign epilepsy with centrotemporal spikes (BECTS)], one with focal epilepsy, one with atypical childhood epilepsy with centrotemporal spikes (ABECTS) and two with unclassified epilepsy. Fourteen patients showed a global developmental delay/intellectual disability (GDD/ID). Slow background activities were observed in one patient and epileptiform discharges were observed in 11 patients during the interictal phase. Significance This study enriches the genotypes and phenotypes of SCN1A-related epilepsy. The clinical characteristics of patients with 12 previously unreported variants were described.

Objective:To evaluate neurological function and its influencing factors in patients with anti-γ -aminobutyric acid B receptor (GABABR) encephalitis.Methods:This was a clinical cohort study of patients diagnosed with anti-GABABR encephalitis; long-term follow-up was performed by telephone. Clinical factors associated with prognosis were analyzed, including clinical manifestations, laboratory examinations, imaging features, tumor comorbidities and therapeutic responses.Results:Twenty-two patients with anti-GABABR encephalitis were evaluated (median age: 55 years). Lung cancer was detected in eight patients. All were with serum tumor markers (mainly NSE), and three of them had additional onconeuronal antibodies. The patients with tumors were older than the patients without tumors and more likely to develop status epilepticus (62.5% vs. 14.3%; p = 0.052), central hypoventilation (50% vs. 7.1%; p = 0.039), and hyponatremia (87.5% vs. 14.3%; p = 0.001). The patients with tumors had higher mortality (87.5% vs. 0%; p < 0.05). Although 92.9% of the patients without tumors became functionally independent (mRS ≤2), sequelae of symptomatic seizures, neuropsychiatric symptoms, and cognitive impairment were still observed in 14.3%, 21.4%, and 21.4% of patients, respectively.Conclusions:(1) Elderly patients with anti-GABABR antibodies, especially those with severe symptoms, serum tumor markers, and additional onconeuronal antibodies, should be screened for lung cancer. (2) Anti-GABABR encephalitis with tumors has a poor prognosis. (3) Most patients without tumors achieve self-care, but some still experience remaining neurological deficits.

OBJECTIVE The investigators aimed to explore the clinical characteristics, immunotherapy, and outcomes of patients with antileucine-rich glioma-inactivated-1 (anti-LGI1) encephalitis. METHODS Data on participants' clinical characteristics, laboratory findings, radiological and electroencephalogram (EEG) features, treatment, and outcomes from January 2012 to December 2016 were collected. Statistical analysis was conducted to assess the factors associated with patient functional outcome. Forty-three patients were enrolled in the study, with a predominance of males (65.1%). The median age at onset was 57 years (interquartile range [IQR]: 44.0-65.0). The median time from onset to diagnosis was 60 days (IQR: 37.0-127.0). RESULTS The main clinical manifestations included epilepsy (100%), faciobrachial dystonic seizures (FBDS; 44.2%), cognitive dysfunction (95.3%), neuropsychiatric disturbances (76.7%), sleep disorders (58.1%), and disturbance of consciousness (48.8%). Twenty-two patients (51.2%) had hyponatremia, 31 (72.1%) had abnormal EEG results, and 30 (69.8%) had abnormal brain MRI scans, mainly involving the hippocampus (76.7%) or temporal lobe (40%). Twenty of 34 patients (58.8%) in a follow-up MRI examination exhibited hippocampal atrophy. Twenty-five patients (58.2%) were administered corticosteroids and intravenous immunoglobulin, whereas 17 patients were treated only with corticosteroids. Forty-one patients (95.3%) had favorable outcomes after a median of 21.5 months (IQR: 7-43) of follow-up. Serum sodium level was a factor associated with a disabled status (odds ratio=0.81, 95% CI=0.66, 0.98, p=0.03). Anti-LGI1 encephalitis patients were characterized by seizures, FBDS, cognitive deficits, neuropsychiatric disturbances, and hyponatremia. CONCLUSIONS Most patients with anti-LGI1 encephalitis are nonparaneoplastic, have low recurrence rates, and have favorable prognostic outcomes. Rapid evaluation, prompt immunotherapy, and long-term follow-up are essential in the care of anti-LGI1 encephalitis patients.

目的 通过分析门诊就诊成年癫痫患者的发作诱因,总结针对性的管理策略,以减少患者发作频率.方法 选取2019年1-12月首都医科大学宣武医院就诊的成年癫痫患者518例,收集癫痫诱发因素资料,分析癫痫发作的常见诱因,以及诱因与人口学特征和癫痫临床特点之间的关系.结果 518例患者中,64.7％的患者在发作前至少存在一种诱发因素,其中疲劳(45.7％)是最常见的诱因,其余依次为睡眠紊乱(43.0％)、情绪因素(42.4％)和饮食相关(18.2％)等.同一患者可有多种诱因,在有诱因的患者中,62.4％认为同时存在≥2种诱因.常见诱因中疲劳与性别、病程和居住地有关,差异有统计学意义(P＜0.05),发作频率与情绪因素有关,差异有统计学意义(P＜0.05);518例患者的发病总诱因在性别、年龄、起病年龄、起病年龄分段、病程、民族、居住地、发作频率和发作类型方面,差异均无统计学意义(P＞0.05).结论 疲劳、睡眠紊乱和情绪因素是常见的癫痫诱因,总诱因与患者人口学和临床特征无关,但各种诱因在不同人口学和临床特征的患者之间的分布存在显著差异.明确癫痫发作的诱发因素,加强门诊癫痫患者的综合管理,有助于减少癫痫发作.

The Chinese guidelines for the management of women with epilepsy during periconceptional period are formulated to provide effective management and scientific guidance for female epilepsy patients during the periconceptional period by systematically reviewing the existing domestic and foreign evidences of evidence-based medicine and combining with the actual situation of Chinese female epilepsy patients. Through elaborating on the problems troubling women with epilepsy in childbearing age, such as the timing of pregnancy for women with epilepsy, the teratogenic risk of anti-seizure medications, medication adjustment during pregnancy and breastfeeding, a very systematic and comprehensive guidance is given. This paper reviews the contents of the Chinese guidelines for the management of women with epilepsy during periconceptional period.

ObjectivesTwo configurations of TTTTA/TTTCA expansion in SAMD12 have been identified in familial cortical myoclonic tremor with epilepsy type 1 (FCMTE1). This study investigated the clinical and neurophysiological features of FCMTE1 and their association with TTTTA/TTTCA expansion patterns.MethodsIn total, 76 patients from 20 Chinese pedigrees were enrolled. Genetic (TTTTA/TTTCA configuration), clinical (e.g., onset, medication, prognosis, and anticipation) and neurophysiological examination (e.g., electroencephalogram and magnetoencephalography) data were evaluated, and associations between these parameters were analyzed.ResultsAll patients carried the TTTTA/TTTCA expansion mutation, 19 displayed the (TTTTA)exp(TTTCA)exp (type I) configuration and 1 displayed the (TTTTA)exp (TTTCA)exp(TTTTA)exp (type II) configuration. All patients manifested as progressive tremor, but symptoms of patients carrying type II expansion were more severe. The onset of tremor but not generalized tonic and clonic seizures displayed clinical anticipation between generations of 7 pedigrees, but the pedigree carrying the type II mutation did not show anticipation. Nanopore sequencing showed that the repeats expanded during maternal/offspring transmission (pedigree #7) but shrank during paternal/offspring transmission (pedigree #9). Magnetoencephalographic dipoles were localized in the right frontal lobe near the central sulcus in 4 patients carrying the type I mutation and on the left side in one patient carrying the type II mutation.SignificanceWe confirmed the causative roles played by TTTTA/TTTCA repeat expansion in the SAMD12 gene in FCTME1. Both the length and the configuration of the repeats contribute to the clinical and neurophysiological characteristics of the disease.

目的 探讨抗Ro52抗体阳性的自身免疫性脑炎的临床特点.方法 回顾性分析8例抗Ro52抗体阳性的自身免疫性脑炎患者和32例抗Ro52抗体阴性的自身免疫性脑炎患者的临床资料.结果 8例伴Ro52抗体阳性的自身免疫性脑炎患者中4例为抗富含亮氨酸胶质瘤失活蛋白1(LGI1)抗体脑炎,2例为抗γ-氨基丁酸(GABA)受体脑炎,1例抗N-甲基-D-天冬氨酸(NMDA)受体脑炎,1例抗谷氨酸脱羧酶65(GAD65)脑炎.7例发生癫痫,5例为50岁以上女性,6例合并其他自身免疫性抗体增高,5例合并甲状腺抗体(TG-Ab)增高.经糖皮质激素冲击、免疫球蛋白免疫治疗后,随访1个月～3 a,预后均良好,仅1例复发且症状轻微.结论 伴Ro52抗体阳性的自身免疫性脑炎中LGI1脑炎最常见,癫痫发病率更高,老年女性多发,常合并其他自身免疫性抗体及甲状腺抗体增高,一线免疫治疗效果较好.

BACKGROUND:The co-existence of anti-N-methyl-D-aspartate receptor encephalitis (NMDARe) and anti-myelin oligodendrocyte glycoprotein (MOG) antibody disease has sparsely been reported, which needs to be investigated.METHOD:Among the patients with NMDARe in Xuanwu Hospital, MOG antibody disease and NMDARe overlapping syndrome (MNOS) were retrospectively identified. We combined our data with those from previously reported cases to characterize this new entity.RESULT:There were 45 patients with MNOS with a median onset age of 20. A total of 97.8% of the patients had symptoms of encephalitis; 68.9% of the patients had symptoms of demyelination, including optic neuritis (ON) (37.9%), longitudinally extensive transverse myelitis (LETM) (31.0%) and acute disseminated encephalomyelitis (ADEM) (27.6%). Abnormal signals on magnetic resonance imaging (MRI) usually involved cortical (46.7%), subcortical (31.1%) and basal ganglia (26.7%) lesions, as well as infratentorial (48.9%) and spinal cord (28.9%) lesions. No tumours were found. A total of 62.2% of the patients relapsed, with recurrence rates of 66.7% and 50.0% for those treated with first-line therapy alone and in combination with second-line immunotherapy, respectively. The pathological changes from the biopsy indicated immune-mediated inflammatory demyelination. Although some patients may have residual deficits, 93.3% of the patients became functionally independent.CONCLUSION:The possibility of MNOS should be considered when patients diagnosed with anti-NMDARe simultaneously or sequentially develop ON, LETM or ADEM. MNOS occurred without tumour association, and inflammatory demyelination may be the pathological change. Steroids combined with second-line immunotherapy can help to reduce high recurrence rates, and most patients will have substantial recovery.