BackgroundIgG4-related disease (Immunoglobulin G4-related disease) is an immune-mediated condition characterized by elevated serum IgG4 levels, clinically presenting as multi-organ enlargement. However, only case reports exist of IgG4-related disease presenting initially with peripheral neuropathy. This study aims to elucidate the clinical features of IgG4-related disease with prominent peripheral neuropathy manifestations.MethodsWe reviewed 16 cases of IgG4-related disease with peripheral neuropathy as the initial presentation, including 15 cases from the literature and one case from our institution. Patient data were extracted and analyzed, encompassing clinical characteristics, pathological features, electrophysiological findings, and treatment information.ResultsThe median age of onset was 64.5 years, with 3 female and 13 male patients. Initially, 15 patients presented with limb numbness and weakness, while 1 exhibited hoarseness. All 16 patients demonstrated organ enlargement in addition to peripheral nerve damage. Peripheral nerve electrophysiology revealed demyelination and/or axonal lesions. All cases received oral corticosteroids, with immunosuppressants added in 3 cases. All patients responded well to corticosteroid therapy.ConclusionPeripheral neuropathy may present as the initial manifestation of IgG4-related disease. Such neuropathy demonstrates favorable response to corticosteroid therapy, and the indication for adding immunosuppressive agents should be evaluated based on individual circumstances.

Background:This study aimed to investigate the differences in neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) between patients with neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS), as well as their potential associations with disease onset and progression. Methods:Clinical, laboratory, and imaging data of NMOSD and MS patients admitted to Peking University Third Hospital were retrospectively analyzed. Blood test results within 1 week of new clinical symptoms or imaging abnormalities were used to calculate NLR and PLR. These ratios were compared with those of 100 healthy controls. Results:A total of 79 NMOSD patients, 75 MS patients, and 100 healthy controls were included. The mean age of NMOSD patients was significantly higher than that of MS patients (p = 0.012). The Expanded Disability Status Scale (EDSS) scores at onset and after 1 year were significantly higher in NMOSD patients compared to MS patients (both p = 0.002). NLR was significantly elevated in NMOSD patients compared to both MS patients and healthy controls (p = 0.002 and p = 0.001, respectively), while no significant difference was observed between MS patients and healthy controls (p = 0.407). No significant differences in PLR were found among the three groups. After adjusting for age and gender, significant differences in NLR but not PLR remained between NMOSD and MS patients (p = 0.010 and p = 0.364). Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.717 for NLR (p = 0.001, 95% CI: 0.636-0.798) and 0.567 for PLR (p = 0.152, 95% CI: 0.476-0.658) in distinguishing NMOSD from MS. In NMOSD patients, baseline and 12-month EDSS scores were significantly lower in the low NLR group (NLR < 2.44) compared to the high NLR group (NLR ≥ 2.44; both p = 0.008). Similarly, in MS patients, baseline and 12-month EDSS scores were significantly lower in the low NLR group (NLR < 1.68) compared to the high NLR group (NLR ≥ 1.68; both p = 0.003). Conclusion:NLR may serve as a useful auxiliary tool for differentiating acute attacks or relapses of NMOSD from MS and is associated with prognosis in both NMOSD and MS patients.

BackgroundThe island sign is a predictor of hematoma expansion and worse outcomes in patients of spontaneous primary intracerebral hemorrhage (ICH). The biological mechanism of the island sign remains unclear, but its presence might be influenced by the underlying vasculopathy related to Apolipoprotein E (APOE) genotypes. Therefore, we aimed to research the association between APOE genotypes and the island sign.MethodsWe enrolled patients with primary supratentorial ICH in a multicenter cohort in northern China with baseline noncontrast CT images performed within 14 days after symptoms onset and APOE genotype available. The island sign was rated on the CT images according to validated criteria. Univariable and multivariable analyses were used to identify the association between APOE genotypes and the island sign, stratified by the ICH location.ResultsAmong 460 patients enrolled, 122 were lobar ICH. In all patients, after adjusting for age, sex, hypertension, and time to CT, the presence of the APOE ε4 allele (OR 2.020, 95% CI 1.064–3.834, p = 0.032) was associated with the island sign, whereas the presence of the APOE ε2 allele (OR 0.734, 95% CI 0.339–1.593, p = 0.435) was not. After stratifying by ICH location, multivariable analysis revealed that APOE ε4 (OR 3.510, 95% CI 1.393–8.846, p = 0.008), rather than ε2 (OR 0.621, 95% CI 0.203–1.901, p = 0.404), was associated with the island sign in lobar ICH patients. Neither the ε2 nor the ε4 allele was associated with the island sign among nonlobar ICH patients.ConclusionThe APOE ε4 allele was associated with the island sign in lobar ICH patients. Our findings indicate that the presence of the island sign may be influenced by the underlying vasculopathy related to APOE ε4, which increases amyloid deposition in the cerebral vasculature.

Background Periaxins (encoded by PRX ) play an important role in the stabilization of peripheral nerve myelin. Mutations in PRX can lead to Charcot-Marie-Tooth disease type 4F (CMT4F). Methods In this study, we screened for PRX mutations using next-generation sequencing and whole-exome sequencing in a large Chinese CMT cohort consisting of 465 unrelated index patients and 650 healthy controls. Sanger sequencing was used for the validation of all identified variants. We also reviewed all previously reported PRX -related CMT cases and summarized the clinical manifestations and genetic features of PRX -related CMTs. Results The hit rate for biallelic PRX variants in our cohort of Chinese CMT patients was 0.43% (2/465). One patient carried a previously unreported splice-site mutation (c.25_27 + 9del) compound heterozygous with a known nonsense variant. Compiling data on CMT4F cases and PRX variants from the medical literature confirmed that early-onset (95.2%), distal amyotrophy or weakness (94.0%), feet deformity (75.0%), sensory impairment or sensory ataxia (65.5%), delayed motor milestones (60.7%), and spinal deformity (59.5%) are typical features for CMT4F. Less frequent features were auditory impairments, respiratory symptoms, late onset, dysarthria or hoarseness, ophthalmic problems, and central nervous system involvement. The two cases with biallelic missense mutations have later onset age than those with nonsense or frameshift mutations. We did not note clear correlations between the type and site of mutations and clinical severity or distinct constellations of symptoms. Conclusion Consistent with observations in other countries and ethnic groups, PRX -related CMT is rare in China. The clinical spectrum is wider than previously anticipated.

Background and Objective In amyotrophic lateral sclerosis (ALS), progressive weakness significantly limits the ability to exercise. However, measurements of the impaired exercise function and their practical value to assess disease progression in ALS are scarce. Cardiopulmonary exercise testing (CPET) is a non-invasive accurate method used to comprehensively quantify exercise physiology in a variety of diseases. This study aimed to evaluate the clinical value of CPET and to explore its association with disease severity and prognosis prediction in ALS. Methods A total of 319 participants were enrolled in this 3-year prospective study. After strict quality control, 109 patients with ALS and 150 age- and sex-matched healthy controls were included with comprehensive clinical assessment and follow-ups. The incremental ramp protocol for symptom-limited CPET was applied in both groups. The exercise physiology during peak effort exercise was systematically measured, including the overall aerobic capacity of exercise (VO2 peak) and the respective capacity of the exercise-involved organs [cardiac response (heart rate peak—HR peak), ventilatory efficiency (VE/VCO2 slope), breathing economy (VE/VO2 peak), and other relevant parameters]. Disease severity and progression were evaluated using recognized scales. Survival was monitored with regular follow-ups every 6 months. Results Decreased exercise capacity (VO2 peak < 16 ml/kg/min) occurred more frequently in patients with ALS than in controls (44.95% vs. 9.33%, p < 0.01). In patients with ALS, the average VO2 peak (16.16 ± 5.43 ml/kg/min) and HR peak [135 (112–153) bpm] were significantly lower (p < 0.01) than in controls [22.26 ± 7.09 ml/kg/min; 148 (135–164) bpm], but the VE/VCO2 slope was significantly higher [28.05 (25.03–32.16) vs. 26.72 (24.37–29.58); p = 0.03]. In patients with ALS, the VO2 peak and HR peak were significantly correlated with disease severity and progression scores (p < 0.05). Survival analyses revealed the VO2 peak and HR peak as protective indicators while the VE/VO2 peak as a detrimental indicator for the prognostic prediction in ALS (HR = 0.839, p = 0.001; HR = 0.967, p < 0.001; HR = 1.137, p = 0.028, respectively). Conclusion Our prospective study quantified the significantly decreased exercise capacity in ALS through non-invasive CPET. The impaired VO2 peak and HR peak closely correlated with disease severity and independently predicted a worse prognosis. Our findings identified the clinical value of CPET as an objective indicator of disease progression in ALS.

回望2021年，我国在卒中研究领域依旧百花齐放，百家争鸣。一项项重要的研究结果为我国以及世界的卒中研究作出了重要贡献，也向世界展示了中国力量。本文对2021年中国卒中临床转化研究领域的主要研究成果进行了回顾总结。一、卒中的流行病学及卒中防治质量改进（一）卒中的流行病学研究香港中文大学同牛津大学合作比较了高加索人和中国人颅内动脉狭窄（intracranial arterial stenosis,ICAS）的患病率、

DNAJC7 has recently been recognized as a novel amyotrophic lateral sclerosis (ALS) risk gene. To date, few studies have screened DNAJC7 mutations in Chinese population. Further studies are needed to clarify the clinical and genetic features of DNAJC7-related ALS. Sporadic ALS (sALS) patients and controls were enrolled in this study. Variants were detected by whole-exome sequencing and validated via Sanger sequencing. Gene-based burden analysis was conducted. Potentially damaging variants in DNAJC7 were identified in 3 sALS patients. The frequency of bulbar onset was significantly higher in DNAJC7-related ALS patients than in the whole group. However, burden analysis showed no enrichment of rare DNAJC7 variants in sALS patients. Reported variant N369T showed no significant difference in distribution among different groups. In conclusion, DNAJC7 variants may be associated with ALS but not play a main role in Chinese patients. DNAJC7-related ALS patients tended to have a bulbar onset. Our study supported the pathogenic role of DNAJC7 in ALS and expanded the phenotypic and genetic spectrum of DNAJC7-related ALS.

患者男,50岁,因“肌肉颤动3年半,双上肢无力2年,肌萎缩1年半”于2019年1月17日入院.3年半前家属偶然发现患者胸肌有肌肉颤动,无不适.2年前患者举重物后突发双上肢酸痛无力,并出现上肢肌肉和腹肌负重后痉挛.此后无力及负重后痉挛症状持续存在,均于活动后加重.1个月后患者发现双上肢及胸腹部出现持续性肌肉颤动,不受控制,紧张劳累后加重,睡眠后无缓解.当时外院上肢电生理检查示:右侧臂丛神经传导未见异常,右侧肱二头肌、三角肌、冈下肌神经源性损害.曾口服舒乐安定无效.1年半前患者发现双上肢肌萎缩,右侧为著,肌肉颤动程度逐渐减轻,但范围扩大至双下肢,小腿活动后易痉挛.伴有无力加重,逐渐出现右上肢不能上抬,半年前外院诊为右侧肩袖损伤并手术,术后右上肢痉挛好转,但双上肢无力仍逐渐加重.患者自发病以来,双下肢肌力正常,出汗明显增多.既往血脂异常5年,空腹血糖异常1年;右侧肩袖修补术后半年.吸烟20年,40支/d,已戒烟6年.无特殊接触史.无家族史.

肌萎缩侧索硬化 (amyotrophic lateral sclerosis, ALS)是以运动神经元退变为特征的疾病[1]. 其中约10％的患者可发现致病基因,其余90％为散发型[1].既往研究显示中国散发型 ALS 患者中位生存期约为 71 个月,10 年生存率约32％[2].ALS的预后受到许多因素影响.近期欧洲的一项大规模多中心研究发现,起病部位、发病年龄、诊断级别、诊断延迟时间、 用力肺活量、 进展率、 额颞叶痴呆(frontotemperal dementia,FTD)、C9orf72扩增情况这8个变量可用于构建模型,预测个体预后情况[3]. 除上述因素,许多其他环境及遗传因素也对ALS预后产生影响. 现将关于ALS预后的影响因素研究进展综述如下.

Background: REEP1 is a common cause of autosomal dominant hereditary spastic paraplegia (HSP) but is rare in China. The pathological mechanism of REEP1 is not fully understood. Methods: We screened for REEP1 mutations in 31 unrelated probands from Chinese HSP families using next-generation sequencing targeting pathogenic genes for HSP and other related diseases. All variants were validated by Sanger sequencing. The proband family members were also screened for variants for the segregation analysis. All previously reported REEP1 mutations and cases were reviewed to clarify the genetic and clinical features of REEP1-related HSP. Results: A pathogenic mutation, REEP1c. 125G>A (p.Trp42*), was detected in a pure HSP family from North China out of 31 HSP families (1/31). This locus, which is located in the second hydrophobic domain of REEP1, is detected in both Caucasian patients with complicated HSP phenotypes and Chinese pure HSP families. Conclusion: REEP1-related HSP can be found in the Chinese population. The 42nd residue is a novel transethnic mutation hotspot. Mutations in this spot can lead to both complicated and pure form of HSP. Identification of transethnic hotspot will contribute to clarify the underlying pathological mechanisms.

脑表达的X连锁基因1 (brain-expressed X-linked 1,BEX1)是一种在脑组织高表达的位于X染色体的基因.BEX1主要通过P75神经营养因子受体通路参与神经细胞的分化、凋亡的调控,也可通过其他通路发挥功能,在不同疾病中作用不同.目前在脑肿瘤、脑血管病、神经损伤以及肌萎缩侧索硬化等多种神经系统疾病中均发现BEX1有重要作用.但是由于人类、大鼠、小鼠的BEX1蛋白结构不完全相同,动物研究结果尚需验证.

脑小血管病是指脑的小血管包括小穿支动脉、小动脉、毛细血管和小静脉病变所导致的一组综合征,其诊断主要依靠影像学检查及临床表现.脑小血管病的临床表现多种多样,主要包括脑卒中、认知和情感障碍以及步态障碍等,其中步态障碍受到了越来越多关注.本研究报道以冻结步态为主要表现的脑小血管病1例,并对脑小血管病步态障碍的研究进展进行分析.

Objective To analyze related factors affecting the prognosis of patients with Acinetobacter baumannii (A.baumannii)bloodstream infection(BSI),guide clinical prevention and treatment.Methods A case-control study was conducted to retrospectively analyze patients with A.baumannii BSI in Peking University Third Hospital from January 2012 to December 2016.According to prognosis,patients were dividedinto poor prognosis group and good prognosis group. Univariate analysis and logistic regression analysis were used to analyze the risk factors of poor prognosis in patients with A.baumannii BSI.Results There were 58 confirmed cases of A.baumannii BSI,including 31 patients with poor prognosis and 27 with good prognosis. Univariate analysis revealed that risk factors for poor prognosis of A.baumannii BSI were antimicrobial use and at least two kinds of antimicrobial agent use three months before admission,at least two kinds of antimicrobial use,and carbapenems use before infection after admission,increase of white blood cell(WBC)count after infection(P<0.05). After 3-day anti-infective treat-ment,examination results of WBC count and X-ray chest film in good prognosis group were all better than poor prognosis group(P<0.05). Logistic multivariate regression analysis showed that independent risk factors for poor prognosis of A.bau m annii BSI were antimicrobial use three months before admission,at least three kinds of antimicrobial use and carbapenem use before infection after admission,increase of WBC count and WBC count>12×109/L after infec-tion,as well as increase of WBC count and WBC count>15×109/L after 3-day anti-infective treatment(P<0.05). Conclusion The probability of poor prognosis is high in patients with A.baumannii infection. For patients receiv-ing≥2 kinds of antimicrobial agents three months before admission,patients receiving≥3 kinds of antimicrobial agents as well as patients receiving carbapenems before infection after admission,the likelihood of A.baumannii BSI should be paid attention.For patients with WBC count>12×109/L after infection and WBC count>15×109/L after 3-day treatment,poor prognosis should be alerted,treatment plan needs to be adjusted in time to reduce the mortality.