To identify potentially useful objective indicators for early assessment of respiratory dysfunction in amyotrophic lateral sclerosis (ALS). Forty ALS patients were enrolled and followed every 3 months for one year. Baseline assessments included dyspnea complaints, ALSFRS-R, the ALS Respiratory Symptom Score (ARES), physical examination (including lower lung mobility), phrenic nerve conduction studies, diaphragm ultrasound, and multi-region ultrasound fasciculation detection. Forced vital capacity (FVC

To evaluate the early diagnostic value of muscle ultrasound (US)-detected fasciculations in motor neuron disease (MND) patients presenting with single‑region, pure lower motor neuron (LMN) involvement. Prospective cohort study enrolling 60 patients with clinical LMN signs confined to one body region. All underwent standardized needle EMG and muscle US at baseline. Final diagnosis determined by follow-up. Agreement between EMG and US, and net diagnostic gain of US were analyzed. 54 MND patients (median disease duration 9 months) were analyzed. US detection rates: bulbar 38.9

Objective To explore the prognostic values of muscle enzymes in amyotrophic lateral sclerosis (ALS) and provide evidence for clinical applications of these blood parameters in evidence-based medicine (EBM). Methods ALS patients were consecutively recruited and blood tests of muscle enzymes were recommended. Correlation analyses between muscle enzymes and clinical variables including progression rate were conducted. Multivariate survival analyses were conducted to explore impacts of parameters on ALS survival. PubMed, EMBASE, OVID, Web of Science, and Medline were searched to identify relevant studies, and meta-analyses were conducted to explore the relationships between muscle enzymes and ALS progression rate and survival time. Results A total of 454 ALS patients in our cohort were included in analysis, around half of which reported abnormal creatine kinase (CK) levels. There were negative correlations between progression rate of ALS and levels of CK-MB, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) (p < 0.05). Pooled analysis of two longitudinal studies indicated a weak correlation between serum levels of alanine aminotransferase (ALT) and survival time of ALS (HR 1.02, 95% CI 1.01, 1.02). Combined analysis indicated a significant relationship between serum levels of creatinine and ALS survival time (HR 0.93, 95% CI 0.92-0.95). Conclusions Abnormal CK levels were common in the ALS population, which were not significantly related to ALS progression rate or survival time. CK-MB, AST, and LDH were potential indicators for ALS progression. ALT was weakly correlated to ALS survival time. Serum level of creatinine significantly declined in ALS patients, which was related to the longer survival time of ALS.

Objective: Young-onset amyotrophic lateral sclerosis (ALS), defined as symptom onset at or before 45 years, remains poorly characterized in Chinese patients. We aimed to describe its clinical and genetic features and compare them with adult-onset ALS. Methods: We retrospectively analyzed 536 young-onset ALS patients registered at Peking Union Medical College Hospital (2014-2022) alongside 1136 adult-onset patients (onset >45 years). Whole exome sequencing targeting 41 established ALS-related genes was performed in all young-onset patients. Results: Young-onset ALS accounted for 32.0% of the cohort, with a median onset age of 39.5 years (IQR 34.25-44.0). Compared with adult-onset patients, young-onset cases had less bulbar onset (14.2% vs. 19.5%, p = 0.008), more frequent predominant upper motor neuron phenotype (25.9% vs. 15.4%, p < 0.001), higher baseline ALSFRS-R scores (p < 0.001), slower progression (p = 0.001), and longer median survival (36 vs. 30 months, p = 0.009). Familial ALS was more common in the young-onset group (8.4% vs. 3.8%, p < 0.001). Rare variants were identified in 20.0% of young-onset patients across 32 genes; pathogenic or likely pathogenic variants were predominantly in SOD1 and FUS. Compared with adult-onset patients, SOD1 was proportionally more common in adult-onset disease, whereas FUS variants were markedly enriched among young-onset cases, suggesting age-dependent differences in genetic architecture. Conclusion: Young-onset ALS in China is characterized by a slower clinical course and a distinct genetic profile dominated by SOD1 and FUS, with near-absent C9orf72 expansions. Routine genetic testing and age-stratified trial design are warranted in this population.

To explore the predictive effects of fasciculation by ultrasound in amyotrophic lateral sclerosis (ALS) progression. Sporadic ALS patients were consecutively recruited and followed up 3 to 6 months after the initial visit. Muscle ultrasound examination was conducted at the baseline to detect the severity score of fasciculations on bilateral elbow flexor and extensor, ankle dorsiflexor and plantar flexor of each patient, the sum of which was defined as the total fasciculation score. Baseline and follow-up ALS functional research scale-revised (ALSFRS-R) score and muscle strength were collected. The progression of ALS was reflected by the decline rate of ALSFRS-R score and proportion of muscles with decreased strength. Among 33 ALS patients who completed the follow-up, the total fasciculation score was positively correlated with the ALSFRS-R progression rate (rho = 0.029, p < 0.001). Patients with low levels of the total fasciculation score had a significantly lower risk of rapid ALSFRS-R progression during follow-up compared to those with high levels of the total fasciculation score (HR 0.132, 95

Objective: To investigate the prevalence and influential factors of depression, anxiety, suicidal tendency and sleep disorders in caregivers of Chinese amyotrophic lateral sclerosis (ALS) patients. Methods: A total of 153 ALS caregivers were investigated using the Patient Health Questionnaire-9 (PHQ-9), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), the Nurses’ Global Assessment of Suicide Risk scale (NGASR) and Pittsburgh sleep quality index (PSQI). The risk factors related to psychological disorders in Chinese ALS caregivers were analyzed. Results: The medians (range) of PHQ-9, SAS, SDS, PSQI were 12 (0-27), 43 (25-80). 55.20% (25.10%-82.11%), 9 (1-21), respectively. A total of 40 (26.14%), 37 (24.18%) and 22 (14.38%) showed moderate, high and extremely high risk of suicide evaluated by NGASR. There was a negative correlation between disease duration of ALS patients and PHQ-9, SAS, SDS, NGASR, PSQI of their caregivers (p<0.05). Onset age of ALS was negatively related to PHQ-9 (p<0.001) and SDS (p=0.003) in ALS caregivers. Bulbar involvement was significantly related to high level of SDS in caregivers (p=0.028). Pet raising and regular reading was significantly associated with low PHQ-9, SDS, NGASR and PSQI (p<0.05). Participation in ALS- related social activities was negatively related to NGASR of ALS caregivers (p<0.001). Conclusion: Depression, anxiety, poor sleep quality and risk of suicide were commonly reported by ALS caregivers. Early onset, bulbar involvement and rapid progression might exacerbate the psychological distress of ALS caregivers. Regular reading, pet raising and participation in social activities could decrease risk of suicide and improve sleep quality of ALS caregivers.

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of both lower and upper motor neurons (UMN). Clinical heterogeneity manifests in subtypes such as bulbar-onset ALS (bALS) and spinal-onset ALS (sALS), with emerging evidence suggesting that oculomotor dysfunction may reflect broader multisystem involvement. This study aims to investigate oculomotor parameters across different ALS phenotypes and their associations with neuropsychological domains. METHODS:A total of 46 patients meeting the Gold Coast Criteria for ALS were enrolled, alongside 23 age- and education-matched healthy controls (HCs). Participants were assessed for demographic variables and clinical features, and underwent cognitive and oculomotor testing using the EyeKnow system. Eye movement performance was compared between groups, and correlations between oculomotor metrics and cognitive and clinical data were examined. RESULTS:ALS patients displayed longer reaction times in anti-saccade tasks (357.48 ± 61.28 ms vs. 316.10 ± 52.70 ms, p = 0.005) and significantly lower predictive saccade accuracy (86.77 ± 19.17% vs. 99.36 ± 2.22%, p < 0.001) compared to HCs. There is no significant difference in the eye movement parameters between sALS and bALS. Patients with bulbar involvement exhibited poorer performance in predictive saccade accuracy (77.53 ± 26.66% vs. 96.01 ± 4.92%, p < 0.001) and longer initial time in the smooth pursuit task (647.43 [402.14, 760.64] ms vs. 452.43 [131.62, 598.20] ms, U = 161.00, p = 0.037) compared to those without bulbar involvement. UMN involvement was associated with poorer performance across prosaccade, anti-saccade, and predictive saccade tasks. No significant correlation between oculomotor metrics and cognitive tests or clinical data was detected. CONCLUSIONS:The findings highlight the impact of bulbar and UMN involvement on oculomotor dysfunction in ALS, demonstrating distinct patterns across various phenotypes. Although oculomotor metrics show sensitivity to the pathophysiology of ALS, their effectiveness as independent biomarkers needs further validation through longitudinal studies that include larger cohorts, advanced neuroimaging techniques, and multimodal assessments to capture the complex interplay between motor, cognitive, and anatomical changes in this varied disease.

This cross-sectional study aimed to investigate the disease status, motor function, and medication treatment choices of genetically confirmed SMA patients. A single-center, cross-sectional survey was conducted using web-based questionnaires and telephone interviews. Data were collected from genetically diagnosed SMA patients, including general information, SMA complications, motor function and medication treatment regimens. Among the 106 patients finally included in analysis, the median age was 18.5 years (IQR, 14.00-25.75), with SMA types distributed as 10.4

Objective: To investigate the prevalence and influential factors of depression, anxiety, suicidal tendency and sleep disorders in a group of Chinese amyotrophic lateral sclerosis (ALS) patients. Methods: A total of 103 ALS patients were investigated using the Patient Health Questionnaire-9 (PHQ-9), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), the Nurses' Global Assessment of Suicide Risk scale (NGASR) and Pittsburgh sleep quality index (PSQI). The risk factors related to psychological disorders in the patients were analyzed. Results: The medians (range) of PHQ-9, SDS, SAS, PSQI of patients were 8 (1-27), 45 (24-95), 51.30% (25.43%-83.41%), 7 (1-27), respectively. There were 17 (16.50%), 27 (26.21%) and 12 (11.65%) of ALS patients were classified as moderate, high and extremely high suicide risk as showed by NGASR, respectively. Financial supports were negatively associated with PHQ-9 (p<0.001), SAS (p<0.001), SDS (p<0.001) and NGASR (p<0.001) of ALS patients. Less food intake was strongly associated to high levels of PHQ-9 (p=0.009), SAS (p=0.012), SDS (p<0.001) and NGASR (p=0.028) in ALS patients. Regular reading was significantly related to higher QOL (p=0.019) and lower NGASR (p=0.007) in ALS population. Conclusion: Depression, anxiety and poor sleep quality were commonly reported by ALS patients, which may result in high risk of suicide. Decrease in food intake, low financial support, poor functional status and rapid progression were risk factors of psychological distress in ALS population. Psychological treatments were crucial for ALS population, which deserved more attention of clinicians.

Background:Rare ERBB4 variants have been implicated in amyotrophic lateral sclerosis (ALS), but their prevalence and clinical significance remain poorly understood, particularly across different ethnic populations. Methods:We performed genetic screening of ERBB4 in 1627 Chinese ALS patients using whole-exome sequencing. A systematic review and meta-analysis of the published literature were conducted to evaluate the global frequency of ERBB4 variants and their clinical correlations. Results:We identified 14 missense variants and 6 splice region variants in 23 unrelated patients, with four variants classified as damaging (p.R782P, p.M799T, p.R847C, and p.S997R). The splice variant c.1490-3C > T, associated with a 50% reduction in ERBB4 mRNA expression, was maternally inherited by a male ALS patient, while its presence in his asymptomatic mother suggests the involvement of potential genetic modifiers. ERBB4 variant carriers demonstrated earlier disease onset compared to non-carriers (46.9 ± 10.3 vs. 52.6 ± 11.2 years; p = 0.015), though survival duration remained comparable. Meta-analysis revealed a pooled ERBB4 variant frequency of 0.83% (95% CI, 0.56-1.10%) in ALS patients globally, with notable ethnic differences (1.36% in Chinese, 0.66% in European, and 1.44% in American populations). Conclusion:Our findings establish the prevalence of ERBB4 variants in ALS across different populations and suggest their potential role as disease modifiers, particularly affecting the age of onset. The ethnic variation in mutation frequency highlights the importance of population-specific genetic screening strategies in ALS.

Objective: To establish a quantitative method for strength evaluation targeting cranial muscle groups and applied it in amyotrophic lateral sclerosis (ALS) patients. Methods: Detailed physical examination were conducted on patients with neuromuscular disorders or healthy population for the selection of the actions innervated by cranial nerves. The six-level strength by manual assessment was designed according to the Medical Research Council (MRC) score. ALS patients were consecutively recruited to explore the clinical significance of the quantitative method. Results: A total of fourteen actions regarding cranial muscle groups were finally involved in our quantitative evaluation method which was named the MRC cranial score, all of which showed satisfied inter-observer and intra-observer consistency. Among 58 ALS patients, 40 (68.97%) showed decrease in the MRC cranial score at baseline, mainly presenting dysfunction in cheek bulging, swallowing, speech and tongue extension. During the 3-month follow up, there was a significantly negative correlation between the baseline MRC cranial score and ALS progression rate (p<0.001). Low MRC cranial score was significantly related to the need of invasive respiratory support (p=0.005) and gastric catheterization (p=0.003). Conclusion: In the study, we designed the MRC cranial score, which was a easily operating evaluation method of the strength involving 14 actions innervated by cranial nerves. The MRC cranial score could quantify the involvement of cranial nerves in neuromuscular diseases comprehensively, which was negatively related to the progression rate and might be a predictor of the need of gastric tube or respiratory support in ALS patients.

Objective: To investigate the impacts of environmental and lifestyle factors on progression and survival in a large Chinese amyotrophic lateral sclerosis (ALS) cohort. Methods: We investigated a cohort of 1,312 sALS patients prospectively. A questionnaire was designed to collect information on environmental exposure and lifestyle at baseline. Uni-and multivariate analysis were performed to analyze the influence of environmental and lifestyle factors on the onset age, bulbar onset, progression rate and survival time of ALS. Results: A total of 1,050 questionnaires were finally received from the patients, among which 407 questionnaires were fully filled out. Low educational level and ever smoked were significantly related to late onset in both univariate and multivariate analysis with backward section (p<0.05). Exposure to organophosphorus pesticide was significantly related to bulbar onset (p=0.027) and rapid progression (p=0.007). Ever drinking alcohol was related to longer survival time in Cox regression model (p=0.040) and the mean survival time of non-drinkers was significantly higher than patients with history of drinking alcohol (p=0.023). Conclusion: In Chinese ALS population, low educational level was an independent indicator of late onset. Exposure to organophosphorus pesticide was the risk factor for bulbar onset and rapid progression. Smoking and drinking alcohol were less common among ALS patients with late onset and long survival time.

Traditionally understood as a motor neuron disease, amyotrophic lateral sclerosis (ALS) is now recognized to involve broader neurodegenerative processes, including the oculomotor system. This narrative review summarizes current evidence on oculomotor dysfunction in ALS, with a focus on its relationship to disease-related motor and cognitive impairments. Specifically, the review examines key eye-tracking (ET) metrics, including saccades, smooth pursuit, and fixation, highlighting their potential to reflect both motor and extramotor degeneration. Notably, patients with bulbar-onset ALS exhibit more pronounced oculomotor impairments. By synthesizing findings on the connection between oculomotor dysfunction and cognitive decline, this review underscores the potential of ET as a noninvasive tool for assessing ALS progression. Oculomotor metrics, as part of a broader understanding of ALS's impact on multiple neural networks, may offer valuable insights to refine patient assessment and care strategies, particularly in advanced disease stages.

OBJECTIVE:We investigate the impact of plasma levels of folate, vitamin B12 (VB12), homocysteine (HCY) and oral supplementation of folate and VB12 on amyotrophic lateral sclerosis (ALS) progression and survival. METHODS:Patients with sporadic ALS were consecutively enrolled and regularly followed up. Oral supplementation of folate and VB12 was recommended to all involved patients. Tests of plasma levels of folate, VB12 and HCY were conducted before or after medication. RESULTS:A total of 120 sporadic ALS patients with results of plasma folate, VB12 or HCY were finally included. Oral supplementation of VB12 significantly increased the plasma levels of folate (p < 0.01) and VB12 (p < 0.01), and lower HCY (p < 0.001). The progression rate of ALS patients in the first 3-6 months was negatively related to the plasma level of VB12 (p = 0.008). After taking VB supplements, the progression rate in the first 3-6 months was comparable to previous progression rate (p = 0.102) and significantly lower than that in the 9-12 month follow-up (p < 0.01). There was no significant difference in survival time between the two groups that took VB12 and those who did not take it neither between patients with high and low serum levels of folate, VB12 or HCY. CONCLUSION:Oral intake of VB12 supplements may significantly increase plasma levels of folate and VB12 and decrease plasma levels of HCY in ALS patients. Oral supplementation of folate and VB12, and subsequent high levels of VB12 in serum, may lower the ALS progression at the early stages but show no significant impact on ALS survival time.

BackgroundIntranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson’s disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial.MethodsThis was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy.Results7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels.ConclusionsTreatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. In recent years, continuous discoveries of new ALS-causing genes have enhanced the understanding of the genotype–phenotype relationship in ALS, aiding in disease progression prediction and providing a more comprehensive basis for genetic diagnosis. A total of 1672 ALS patients who visited the Neurology Department of Peking Union Medical College Hospital between January 2014 and December 2022 and met the revised El Escorial diagnostic criteria were included. Clinical data were collected, whole exome sequencing and dynamic mutation screening of the C9ORF72 gene were performed, and the clinical phenotypes and genotypes of the patients were analyzed. The average age of onset for the 1672 ALS patients was 52.6 ± 11.2 years (range 17–85 years), with a median disease duration of 14 months at the time of visit (interquartile range 9–24 months, range 2–204 months). The male to female ratio was 833:839. The patients included 297 (17.8

Objective: To clarify the impact of specific risk/protective factors on the disease progression and survival in a large population of Chinese sporadic ALS (sALS) patients. Methods: We investigated a cohort of 937 sALS patients prospectively. Uni- and multivariate regression analysis were performed to analyze the influence of demographic factors, comorbidities and medication on the progression and survival of ALS. Results: Our results showed younger age of onset (p < 0.05), long diagnostic delay (p < 0.001) and intake of riluzole (p < 0.001) were significantly related to low progression rate and long survival time. History of smoking (p < 0.05) and bulbar onset (p < 0.001) were risk factors for rapid progression and poor prognosis. Baseline ALSFRS-R score (p < 0.001) and total MRC score (p < 0.05) were positively related to mean survival time of included patients. Neither comorbidities nor intake of antihypertensive drugs, antidiabetics, and statins as dependent variables showed considerable influence on ALS progression or survival. Conclusion: Our study revealed early onset and long diagnostic delay were indicators of slow progression and long survival. Smoking and bulbar onset were risk factors for shorter survival times and abstaining from smoking was beneficial to patients with ALS in improving median survival time. Long-term intake of riluzole should be recommended for affordable patients.

Amyotrophic lateral sclerosis(ALS)is a neurodegenerative disorder characterized by progressive muscle weakness and atrophy.1 The widespread implementation of next-genera-tion sequencing in clinical practice has facilitated the iden-tification of over 40 ALS-associated genes,among which copper/zinc-superoxide dismutase 1(SOD1)assumes a pivotal role in East Asian populations.1

Amyotrophic lateral sclerosis (ALS) is a progressive neurogenerative disorder with uncertain origins. Emerging evidence implicates N6-methyladenosine (m6A) modification in ALS pathogenesis. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and liquid chromatography-mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis, respectively, in patients with ALS (n = 16) and controls (n = 6). The single-cell transcriptomic dataset (GSE174332) of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes. Analysis of peripheral immune cells revealed extensive RNA hypermethylation, highlighting candidate genes with differential m6A modification and expression, including C-X3-C motif chemokine receptor 1 (CX3CR1). In RAW264.7 macrophages, disrupted CX3CR1 signaling affected chemotaxis, potentially influencing immune cell migration in ALS. Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS. Cell type-specific expression variations of these genes in the central nervous system (CNS), particularly microglia, were observed. Intercellular communication between neurons and glial cells was selectively altered in ALS CNS. This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.