Summary Background The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. Aim To investigate the association between specific environmental factors and the generalization of OMG. Design The cohort study was conducted in China based on a nationwide multicenter database. Methods Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. Results A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37–9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10–15.66) years. Latitude of 20–50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28–2.11 times higher risk of generalization. No significant association was observed with education or smoking. Conclusions Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.

Background: The role of glaucoma in predicting Alzheimer’s disease (AD) factors is unknown. This current meta-analysis was aimed at evaluating the risk of AD events in individuals suffering from glaucoma based on a meta-analysis. Materials and methods: Databases which included Cochrane Library, PubMed, and EMBASE were searched to detect the relevant articles, with language being restricted to English. The risk of AD events in patients with glaucoma was analyzed using the combined hazard ratios. Results: This study included 8 articles with 131,987 subjects published after 2012. We identified glaucoma as the risk factor for disease-free survival (hazard ratio = 1.29; 95% confidence interval = 1.05–1.59; P = .000; I2 = 95.1%) in AD patients. According to subgroup analyses, normal tension glaucoma group was the major risk factor for disease-free survival of AD patients. Conclusions: Although diverse approaches have been used for AD cases of various events, the current meta-analysis indicates that that glaucoma patients have a higher AD risk.

Background:The role of glaucoma in predicting Alzheimer's disease (AD) factors is unknown. This current meta-analysis was aimed at evaluating the risk of AD events in individuals suffering from glaucoma based on a meta-analysis.Materials and methods:Databases which included Cochrane Library, PubMed, and EMBASE were searched to detect the relevant articles, with language being restricted to English. The risk of AD events in patients with glaucoma was analyzed using the combined hazard ratios.Results:This study included 8 articles with 131,987 subjects published after 2012. We identified glaucoma as the risk factor for disease-free survival (hazard ratio = 1.29; 95% confidence interval = 1.05-1.59; P = .000; I2 = 95.1%) in AD patients. According to subgroup analyses, normal tension glaucoma group was the major risk factor for disease-free survival of AD patients.Conclusions:Although diverse approaches have been used for AD cases of various events, the current meta-analysis indicates that that glaucoma patients have a higher AD risk.

BACKGROUND:Ischemic stroke events impose a substantial burden on both families and society, underscoring the critical importance of early intervention and prevention strategies. The dearth of familial and societal support significantly impacts coping styles and family resilience, with negative coping styles potentially linked to diminished levels of family resilience. However, empirical evidence supporting these associations remains lacking. OBJECTIVE:The aim of this study was to examine the association between simplified coping style, perceived social support and family resilience in patients with ischemic stroke, while also investigating the potential mediating role of simplified coping style in the relationship between perceived social support and family resilience. METHODS:Convenience sampling was employed to select patients with ischemic stroke from three tertiary hospitals in Hunan Province between May and November 2021. A comprehensive investigation was conducted using a General data questionnaire, Simplified Coping Style Questionnaire, Perceived Social Support Scale and Family Resilience Rating Scale. The mediating effect was analyzed using PROCESS macros in SPSS, while the significance was tested through the Bootstrap method. RESULTS:A total of 310 questionnaires were distributed, with 7 identified as containing errors, omissions, or losses. Of these, 303 valid questionnaires were collected, yielding an effective response rate of 97.74 %. The scores for family resilience among ischemic stroke patients showed significant positive correlations with simple coping style (r = 0.59, P < 0.01) and perceived social support (r = 0.69, P < 0.01). Additionally, there was a positive correlation between perceived social support and simple coping style (r = 0.56, P < 0.01). Furthermore, the simple coping style played a crucial mediating role in the relationship between perceived social support and family resilience by accounting for approximately 20.70 % of the effect size. CONCLUSION:The findings suggest that enhancing positive coping styles and effective social support can enhance the level of family resilience in patients with ischemic stroke. Therefore, medical professionals should focus on improving social support while targeting coping styles as an intervention strategy to actively adjust the coping modes, ultimately elevating the level of family resilience in patients with ischemic stroke.

Twenty-seven glaucoma patients (54 eyes in total) with well-controlled intraocular pressure were trained with binocular virtual reality visual software for 3 months to investigate whether virtual reality visual perceptual plastic training promotes macular retinal structure and macular function recovery in glaucoma patients. The thickness of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer-inner plexiform layer (mGCIPL), and mean macular sensitivity (mMS) were evaluated 3 months after training. The mean value of pRNFL thickness in glaucoma patients did not change significantly (Z = 0.642, p = 0.521), nor did the mean value (t = 1.916, p = 0.061) and minimum value (Z = 1.428, p = 0.153) of mGCIPL after 3 months. However, the significant increases were found in superior temporal mGCIPL thickness (t = 2.430, p = 0.019) as well as superior mGCIPL thickness (t = 2.262, p = 0.028). Additionally, the mMS was increased (Z = 2.259, p < 0.05), with the inferior square to be a more pronounced mMS increase (Z = 2.070, p = 0.038). In conclusion, virtual reality visual perceptual plastic training can increase the thickness of retinal ganglion cells complexes in the macular area of glaucoma patients and improve the macular function of the corresponding area.Clinical Trial registration number: ChiCTR1900027909.

BackgroundGut-brain axis might play an important role in cognitive impairments by various diseases including Alzheimer’s disease (AD).ObjectiveTo investigate the differences in gut microbial composition, intestinal barrier function, and systemic inflammation in patients with AD or mild cognitive impairment (MCI), and normal control (NC) cases.MethodsA total of 118 subjects (45 AD, 38 MCI, and 35 NC) were recruited. Cognitive function was assessed using Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment Scale (MoCA). Functional ability was assessed using Activity of Daily Living Scale (ADL). The composition of gut microbiome was examined by 16S rRNA high-throughput sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict functional transfer of gut microbiota. Gut barrier dysfunction was evaluated by measuring the levels of diamine oxidase (DAO), D-lactic acid (DA), and endotoxin (ET). The serum high-sensitivity C-reactive protein (hs-CRP) level was used to indicate systemic inflammation.ResultsCompared with normal controls, patients with cognitive impairments (AD and MCI) had lower abundance of Dorea and higher levels of DAO, DA, and ET. Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the pathways related to glycan biosynthesis and metabolism increased in MCI patients, while the ones related to membrane transport decreased. The abundance of Bacteroides and Faecalibacterium was negatively correlated with the content of ET, and positively correlated with the scores of MMSE and MoCA. The hs-CRP levels were similar among the three groups. A significant negative correlation was observed between the severity of gut barrier dysfunction and cognitive function.ConclusionCognitive impairments might be associated with gut microbial dysbiosis and intestinal barrier dysfunction.

目的 比较双眼视觉训练前后青光眼患者包括精细立体视、粗糙立体视和动态立体视在内的视感知觉变化,探究双眼视觉训练效果.方法 青光眼患者35例,接受双眼视觉训练3个月.比较训练前、训练后1个月及3个月患者的静态0阶随机点立体视、动态0阶条栅整合立体视、动态1阶随机点立体视以及静态2阶大范围立体视功能.结果 训练1个月后,静态0阶立体视开始出现明显改善(P=0.009).训练3个月后,动态0阶条栅整合立体视(P=0.007)以及动态1阶随机点立体视(P=0.034)出现改善.结论 双眼视觉训练后青光眼患者的视感知觉有明显提高,其中精细立体视恢复先于动态立体视.

Visual field defect caused by glaucoma seriously affects the quality of life of patients, and clinically, this type of visual field defect has been considered to be irreversible. The aim of this study is to use binocular virtual reality training (VR training) to repair visual field defect in glaucoma patients, improve the quality of life of patients, and provide a new therapeutic strategy for the rehabilitation of glaucoma. Seventy glaucoma patients (median 56, range 15-84 years) were recruited and divided into control and training groups. Fifty-four patients' data were analyzed. The training group (n = 30) received binocular VR training for 3 months. The control group (n = 24) maintained the conventional treatment without any other intervention. Their visual field index (VFI) and mean defect (MD), and retinal nerve fiber layer average thickness (RNFL) and ganglion cell layer average thickness (GCL) average thickness before training and during followup were analyzed. In the training group, the VFI value (Z = 3.277; p = 0.001) and MD value (Z = 3.913; p < 0.0001) were significantly improved after 1 month of training. After 3 months of training, the VFI value (Z = 3.761; p < 0.0001) and MD value (Z = 3.133; p = 0.002) were significantly improved. There was no significant difference with the changes of average thickness of RNFL (p = 0.350) and GCL average (p = 0.383) after 3 months of training; whereas in the control group, except for a further reduction in GCL average thickness (Z = 3.158; p = 0.002) compared with the baseline data, the other followup data were not statistically significant compared with the baseline data. Our data suggested that binocular VR training can significantly improve the visual field defect of glaucoma patients but warrants further study with large sample size. Clinical Trail registration number: ChiCTR1900027909.

Background: Selenoprotein N-related myopathies (SEPN1-RMs) are a subset of congenital myopathies caused by mutations of Selenoprotein N gene ( SELENON or SEPN1 ). Clinical phenotype is considered as highly consistent and little attention has been given to the extramuscular abnormalities. Methods: We reported clinical, histopathological, and genetic features of four Chinese patients with SEPN1-RM and performed literature review on delayed respiratory insufficiency and extramuscular involvement. Results: A total of four patients exhibited both the typical and atypical clinical features of SEPN1-RM. The classical manifestations included axial and limb girdle weakness, spinal rigidity, scoliosis, respiratory insufficiency, and multiminicore morphological lesions. However, high interindividual variability was noticed on disease severity, especially the onset of respiratory involvement. Two adult patients postponed respiratory insufficiency to the third decade of life, while two juvenile patients manifested early hypoventilation with puberty exacerbation. As atypical features, extramuscular involvement of weight gain, subcutaneous adipose tissue accumulation, intellectual disability, and mild cardiac changes were observed. Molecular findings revealed three novel mutations of SELENON such as c.1286_1288 del CCT, c.1078_1086dupGGCTACATA, and c.785 G>C. Ten cases with delayed respiratory insufficiency were identified from previous publications. A total of 18 studies described extramuscular abnormalities including joint contractures, alterations of body mass index (BMI), mild cardiac changes, and insulin resistance. Intellectual impairment was extremely rare. Conclusion: SEPN1-RM should be considered as a differential diagnosis in adult patients with delayed respiratory involvement. Extramuscular involvement such as body composition alterations deserves more clinical attention. The novel mutations of SELENON widened the genetic spectrum of patients with SEPN1-RM.

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease, characterized by a great variety of both clinical presentations and genetic causes. Previous studies had identified two different missense mutations in SOD1 (p.R116C and p.R116G) causing familial ALS. In this study, we report a novel heterozygous missense mutation in the SOD1 gene (p.R116S) in a family with inherited ALS manifested as fast-deteriorating pure lower motor neuron symptoms. The patient displayed similar clinical picture and prognostic value to previous reported cases with different R116 substitution mutations. Modeling of all R116 substitutions in the resolved SOD1 protein structure revealed a shared mechanism with destroyed hydrogen bonds between R116 and other two residues, which might lead to protein unfolding and oligomer formation, ultimately conferring neurotoxicity.

目的 观察半量睫状体光凝术治疗难治性青光眼中的疗效,并评估前房注射曲安奈德对抑制睫状体光凝术后炎症反应的作用.方法 收集2019年2～12月在首都医科大学附属北京世纪坛医院眼科接受半量睫状体光凝治疗的难治性青光眼患者(术中前房注射曲安奈德1.0 mg).记录并分析患者的一般资料、术前和术后不同随访时间点的视力、眼压、炎症反应及并发症等.结果 本研究共纳入患者17例(20只眼),平均随访时间为(22.36±19.72)周.术后第1天大多数患者为轻度前房反应,无严重角膜水肿.末次随访时术后视力改善者5只眼(25.0％),视力保持不变者11只眼(55.0％),视力下降者4只眼(20.0％),无视力严重下降.眼压由术前平均眼压(33.47±6.04)mmHg降至末次随访时(17.34±9.86)mmHg(P<0.05).20只眼均未出现严重并发症.结论 半量睫状体光凝能够安全有效地降低难治性青光眼患者眼压,曲安奈德对抑制睫状体光凝术后炎症反应有较好效果.

Amyotrophic lateral sclerosis type 4 (ALS4) is a familial form of ALS caused by mutations in the SETX gene. To date, there are seven unrelated ALS4 families with four missense mutations (L389S, T31I, R2136H, and M386T) in SETX. ALS4 is characterized by early onset, distal muscle weakness and atrophy, pyramidal signs, and the absence of sensory deficits. Motor conduction studies often present normality or reduced amplitudes of compound muscle action potential (CMAP). The conduction blocks (CBs) are rare and only observed in one male of an Italian ALS4 family. Our study showed that seven symptomatic patients presented the classical ALS4 phenotype with two asymptomatic females in a Chinese family spanning three generations. Sequencing analysis revealed a heterozygous c.1166T > C/p.L389S mutation in SETX that co-segregated with disease phenotype in the family. The same mutation has been identified previously in three ALS4 families from the United States and Italy, respectively. Specifically, three young males presented multiple CBs and abnormal temporal dispersions (TD) in the median, ulnar and tibial nerves over the three-year follow-up period. Moreover, for the first time, we found that senataxin was also expressed in the myelin sheath of peripheral nerves besides axons. The study indicates that CBs and abnormal TD are the characteristics in the ALS4 family, providing pivotal familial evidence of CBs and TD of motor nerves in ALS4. The unusual electrophysiological features may be associated with the expression of senataxin in peripheral nerves.

Background To evaluate the efficacy of transient vision restoration training (tVRT) with an augmented virtual reality platform in glaucoma patients. Design: A self-control, prospective study. Methods This study recruited subjects with glaucoma. All participants were treated with tVRT which based on an augmented virtual reality platform for 20 minutes. The intraocular pressure (IOP), the best-corrected visual acuity (BCVA), global mean defect (MD) values, global indices mean sensitivity (MS) were evaluated and compared before and after treatment. Results While the IOP and BCVA after tVRT did not change obviously compared to baseline. However, the global MD significantly reduced, consistently the global MS changed better in the treated patients. Conclusions The glaucomatous optic neuropathy remains potentially neuroplasticity. And the training based on an augmented virtual reality platform may have a positive impact on vision restoration.

目的 评价青光眼患者视觉训练前后立体视功能的变化,对其立体视功能损伤进行描述,初步探讨视觉训练对改善青光眼患者立体视功能的作用.方法 收集2018年10月至2019年10月确诊的原发性青光眼患者54例.使用视感知觉检查系统进行双眼立体视功能检查.采用基于虚拟现实的双眼视功能推拉模型训练方法进行视觉训练.入组患者每天进行2次视觉训练,每次20min.在训练后1周及1个月进行随访,评估患者训练前后立体视功能的变化.结果 视觉训练1周后青光眼患者立体视功能有所改善(P=0.051),训练1月后立体视功能明显改善,差异具有统计学意义(P<0.05).结论 青光眼可能导致立体视功能受损.通过视觉训练,部分青光眼患者的立体视功能可以改善.

Objective To find determinants of the occurrence of repetitive compound muscle action potential (R-CMAP) and to assess the efficacy of channel blocker therapy in slow-channel congenital myasthenic syndrome (SCCMS). Methods Neurologic examination, EMG study, laboratory test, muscle biopsy, and next-generation and Sanger sequencing; literature review of reported patients with SCCMS, including EMG, kinetics of mutant acetylcholine receptors (AChRs), and response to therapy; and simulation of the decay phase of endplate potential (EPP) were performed. Results Three newly characterized and 57 reported patients with SCCMS with mutations of AChR subunits were included. In patients with R-CMAP, the length of channel opening bursts of mutant AChR was increased 8.68 ± 2.82 (mean ± SD)-fold compared to wild-type; in patients without R-CMAP, the length was increased 3.84 ± 0.65-fold (95% confidence interval 3.18–6.50, p = 0.000014). The EPP amplitude after refractory period of action potential in muscle fiber is above the threshold in patients with R-CMAP but below the threshold in patients without R-CMAP. In patients with good results from channel blocker therapy, treatment was initiated 11.60 ± 5.17 years after onset of symptoms; in patients with no to moderate benefit from channel blocker therapy, treatment was initiated 30.70 ± 12.72 years after onset (95% confidence interval −28.57 to −9.63, p = 0.00089). Conclusions In SCCMS, the R-CMAP occurrence is related to the extent of prolongation of the opening episodes of mutant AChR channel. Channel blocker treatment is more effective the sooner it is started after the onset of symptoms. Classification of evidence This study provides Class IV evidence that channel blocker therapy in patients with SCCMS improves symptoms.

To explore whether individualized visual training improves the visual acuity and visual field defects of patients with glaucoma. Patients with established primary glaucoma who visited the glaucoma clinic of Beijing Shijitan Hospital, Capital Medical University from January 2018 to April 2018 were recruited. The binocular visual perception examination was performed by using the visual perception examination system, and a personalized training program was developed according to the relevant threshold conditions between the eyes of the patients. The binocular visual perception training session for 20 minutes for two sessions was completed at home by using a virtual reality helmet. The visual function, intraocular pressure, and Octopus visual field were examined, before and at the first month and the third month after training. Seven patients completed the study. None of the seven patients has fine stereopsis, four of them have large stereopsis, and two patients are without large stereopsis. The visual acuity at 3 months after training was significantly improved compared with that before training. The mean defect value after 1 month of training was significantly lower than that before training, and it was further decreased after 3 months. Similarly, the mean sensitivity value was significantly increased in both follow-ups after training. There was no significant difference in loss variance after 1 and 3 months of training when compared with that before training (p > 0.05). Our small prospective observational study indicated that individualized visual perception training can improve the visual function and improve the visual field in patients with glaucoma, and a large sample size study is warranted to further assess the value of this novel treatment.

Alzheimer’s disease (AD) is a regular, age-related dementia and is also the most common type of senile dementia. Its pathological features include (1) Aβ plaques, (2) neurofibrillary tangles, (3) hyperphosphorylated tau, (4) neuronal degeneration, and (5) amyloid angiopathy. Retina is the extension of central nervous system (CNS), which makes it as the similar source of tissue and anatomical characteristics with CNS; hence, retina can be an indicator of CNS diseases at various circumstances. Several researches testified that the incidence of glaucoma in Alzheimer patients is higher than normal people, the mechanism of which remains unclear.

Background. To investigate the similarities and differences in the structure and function of the central nerve system (CNS) among normal tension glaucoma (NTG), primary open-angle glaucoma with high intraocular pressure (HTG) and primary angle-closure glaucoma (PACG) patients. Methods. Ophthalmic examinations and multimodal magnetic resonance imaging (MRI) were performed. The results of brain functional connectivity (FC) were obtained based on the resting state MRI (rs-fMRI). Voxel-based morphometry (VBM) was applied to analyze structural images to obtain the volume change in the gray matter on 3D T1-weighted imaging (T1WI). Results. We found that frontal lobe FC increased in all three groups. Temporal lobe FC increased in the NTG group, while the FC of the cingulate gyrus and postcentral gyrus increased in the HTG and PACG groups by rs-fMRI. There were no gray matter volume changes in the NTG, while the gray matter of the frontal gyrus changed in the HTG and PACG. Moreover, the gray matter of the precentral gyrus changed in PACG, and the parietal lobe and supra marginal lobe changed in the HTG. The white matter of the inferior parietal lobe and postcentral gyrus increased, while that in the inferior temporal lobe decreased in the NTG group. The white matter in the HTG and PACG groups showed significant alterations in the medial occipital gyrus. Conclusions. The NTG group had different manifestations compared with the HTG and PACG groups regarding changes in brain structure and function, suggesting that pathogenic processes might differ between patients with normal-tension and high-tension POAG.

To the Editor: Amyotrophic lateral sclerosis (ALS) is a heterogeneous disorder characterized by a loss of upper and lower motor neurons with neither clear pathogenesis nor effective treatment. Thus, potential biomarkers are needed to classify the disease and find new drug targets. Previous studies have shown that auto-antibodies against the low-density lipoprotein receptor-related protein 4 (LRP4), called the anti-LRP4 antibodies, are found in ∼23% patients of Greek and Italian ALS cohorts,[1] and in 10% of the American ALS population.[2] Anti-LRP4 antibodies were previously identified in myasthenia gravis (MG), the most common neuromuscular junction (NMJ) disorder, and were shown to cause NMJ abnormality in animal studies.[3] Here, we studied anti-LRP4 antibodies in Chinese patients and investigated the correlation between anti-LRP4 antibodies and abnormal neuromuscular transmission in ALS. This study was approved by the institutional review board of Xuanwu Hospital, Capital Medical University, Beijing, China. All study participants gave written informed consent and were enrolled from May 2015 to December 2016. Fifty-six patients with ALS met the El-Escorial criteria for possible, probable, or definite ALS, and were evaluated by the revised ALS functional rating scale score (ALSFRS-r) and rate of disease progression (disease progression rate = (48 − ALSFRS-r)/duration (months)). Anti-LRP4 antibodies were detected with a cell-based assay in blood samples. The results were compared to a control group, which consisted of 65 patients with MG, 60 patients with other neuroimmune diseases, and 63 healthy volunteers. Repetitive nerve stimulation (RNS) study, a widely-used technique for evaluating NMJ defects, was used to quantify the results of NMJ transmission at a frequency of 3 or 5 Hz. Compound muscle action potentials (CMAPs) were recorded in the abductor digiti minimi, trapezius, and orbicularis oculi muscles with stimulation of the ulnar, accessory, and facial nerves at frequencies of 3 or 5 Hz. A definite decremental response of CMAP was defined as a reduction of the amplitude by 10% or more. All patients with ALS were examined by the same technician, who was blinded to the patients' antibody status. Briefly, HEK-293T cells were transfected with human CMV6-LRP4-tGFP (OriGene, Rockville, MD, USA) or with pEGFP (a gift from the Cell Therapy Center, Beijing, China) as a control, with Lipofectamine 2000 (Invitrogen, Waltham, Massachusetts, USA), and cultured for 48 h at 37°C in 5% CO2. They were fixed with ice-cold methanol and blocked with 5% goat serum for 2 h at room temperature. After incubating overnight at 4°C with patients' sera at dilutions of 1:100 or 1:200, they were incubated with Alexa Fluor 568-conjugated anti-human immunoglobulin G (IgG) antibody (Life Technologies, Invitrogen) for 1.5 h at room temperature. The nuclei were counterstained with 4,6-diamidino-2-phenyiindole (DAPI) (1:1000) for 10 min. After mounting the cells onto slides, digital images were acquired with a confocal laser scanning microscope (TCS SP5 II; Leica, Wetzlar, Germany). The confocal settings, such as gain and offset, were kept constant to ensure that all images were collected with the same parameters. Based on the signal intensity and co-localization, the samples were classified as positive or negative by two independent observers, who were blinded to the patients' RNS results [Figure 1]. The positive samples were then retested at various dilutions (1/100–1/3200) with the rabbit anti-LRP4 antibody (Santa Cruz Biotechnology, Dallas, Texas, USA). Alexa Fluor 568-conjugated anti-rabbit IgG antibody (Invitrogen) was used as a positive control. All samples were tested at least twice.Figure 1: Detection of anti-LRP4 antibodies in patients with ALS by CBA. The immunofluorescence study of the binding of antibodies to HEK-293T cells transfected with pCMV6-LRP4-tGFP or pEGFP. Positive and negative control: Commercial rabbit LRP4 antibody (1:200 dilution) was incubated with pCMV6-LRP4-tGFP-transfected cells (Row 1; A, B, C) or pEGFP-transfected cells (Row 2; D, E, F). Patient 1 and 2: LRP4-GFP-transfected cells were incubated with a 1:100 dilution of serum from two patients with ALS (Row 3; G, H, I; Row 4; J, K, L). Only the commercial antibody and patients' sera bound on expressed LRP4 as visualized with red staining (B, H) and the merged images (C, I). ALS: Amyotrophic lateral sclerosis; Anti-LRP4 antibodies: Antibodies against LRP4; CBA: Cell-based assay; LRP4: Low-density lipoprotein receptor-related protein 4.Three of the 56 (5.4%) patients with ALS had anti-LRP4 antibodies, with titers of 1:800, 1:800, and 1:1600, respectively. In the one patient who was available for retesting 6 months later, anti-LRP4 antibodies had increased by 25% as her condition worsened. Among the controls, only one patient with MG was positive (titer of 1:800). No anti-LRP4 antibodies were found in patients with other neuroimmune diseases or in healthy subjects. While thirty patients with ALS had a decreased RNS response, all three seropositive patients showed a positive RNS response [Supplementary Table 1, https://links.lww.com/CM9/A44]. Among the seronegative group, 27 patients presented with a definite decrement, some with even as much as 35%, a decrement higher than in the seropositive subjects. We report anti-LRP4 antibodies in 5.4% of the Chinese patients with ALS in our study. However, this rate was much lower than that reported in previous studies.[1,2] Given that the number of anti-LRP4 antibodies in patients with MG is lower in China than in other countries,[4] we speculated that anti-LRP4 antibodies in ALS might also occur in an ethnicity-specific manner. However, we could not exclude the effect of clinical data differences. A major parameter, the mean disease course, was only 16 months in our populations, whereas it was 36 months in the Greek and Italian cohorts.[1] LRP4, a transmembrane protein of the low-density lipoprotein receptor family, is mostly concentrated at the post-synaptic membrane of NMJs. It is involved in the clustering of acetylcholine receptors and the formation of NMJs.[5] Anti-LRP4 antibodies can lead to abnormal structures and dysfunction of the NMJ.[3] Our results revealed that all three anti-LRP4-positive patients had impaired neuromuscular transmission as measured electrophysiologically, while nearly half of the seronegative patients also had neuromuscular dysfunction. This indicates that anti-LRP4 antibodies may be one of the factors resulting in NMJ dysfunction. Acknowledgements The authors thank Zhong-Feng Liu and Jing An for experimental assistance. Conflicts of interest None.