Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

Objective: To adapt successive versions B and C of the Edinburgh Cognitive and Behavioral Screen (ECAS) into Persian and evaluate cognitive and behavioral changes over time in Iranian ALS patients.

Methods: This study included 38 ALS patients in the ECAS-B group and 29 in the ECAS-C group, diagnosed between May 2021 and February 2023 at the Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran, Iran. Additionally, 59 age- and education-matched healthy controls were enrolled (30 for ECAS-B and 29 for ECAS-C). The Montreal Cognitive Assessment (MoCA) was used to validate the ECAS versions.

Results: The Persian versions of ECAS-B and ECAS-C demonstrated strong internal consistency (Cronbach's alpha: 0.88 for ECAS-B and 0.89 for ECAS-C) and a positive correlation with MoCA and ALS-FRS-r scores. The area under the ROC curve was 0.851 for ECAS-B and 0.861 for ECAS-C. ECAS-C scores were significantly lower than ECAS-B scores, suggesting a faster cognitive decline over time. Optimal cutoff values of 72 for ECAS-B and 78 for ECAS-C were identified for detecting cognitive impairment. Cognitive impairment was observed in 10 patients (26.31%) in the ECAS-B group and 15 patients (51.72%) in the ECAS-C group.

Conclusions: The Persian versions of ECAS-B and ECAS-C demonstrate good validity and reliability for detecting cognitive impairment and tracking cognitive decline in ALS patients.

Objective: To describe the development of a methodology to characterize hospitalizations and their relationship to amyotrophic lateral sclerosis (ALS) and provide results using this process in a phase 3 trial of reldesemtiv in ALS. Methods: ALS clinical trialists assisted in developing a classification system to determine if a hospitalization was related to ALS (HR-ALS), unrelated (HU-ALS), or if the relationship was indeterminate (HI-ALS) and this was applied by the investigators to hospitalizations in COURAGE-ALS. Time to first hospitalization and number of hospitalizations were compared between those assigned reldesemtiv or placebo for up to 48 weeks. Demographic and clinical features were evaluated for prediction of hospitalization risk; this analysis was limited to those participants who completed the first 24-week double-blind placebo-controlled portion of the trial. Results: COURAGE-ALS terminated early due to futility. Time to first hospitalization was similar in the reldesemtiv compared to placebo arms as was the incidence, with 86 of the participants (17.6% of those originally assigned placebo and 18.0% originally on reldesemtiv) experiencing an event. The largest percentage of events was classified as HR-ALS for both placebo (64%, 18/28) and reldesemtiv (76%, 44/58). In a multivariate model, only bulbar or respiratory onset disease was a significant risk factor for hospitalization. Conclusion: While most hospitalizations in COURAGE-ALS were HR-ALS, HU-ALS and HI-ALS also occurred. When using hospitalization as an endpoint in an ALS clinical trial, recording its relationship to ALS provides additional details to characterize disease burden and clinical meaningfulness of the endpoint.

Background: The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a cognitive screening tool designed for patients with amyotrophic lateral sclerosis (ALS). It has been translated into various languages and used globally. This study aimed to establish normative data for the Chinese version of the ECAS to better serve the Mandarin population.

Methods: We enrolled 358 healthy individuals from different regions of China, all of whom completed the ECAS, and 340 also completed the Mini-Mental State Examination (MMSE). The participants were categorized into six age groups and five education groups.

Results: ECAS scores were found to be related to education level (p < 0.001). After Bonferroni correction for multiple comparisons, we determined that there were no significant differences in total ECAS scores between the junior middle school and senior middle school groups, leading to their combination into a single middle school group. We established cutoff values for the ECAS on the basis of education group. After adjusting for age, sex, and education level, a significant correlation was found between MMSE scores and total ECAS scores (p < 0.001), indicating a high level of consistency in the cognitive assessment.

Conclusion: We have established norms for the ECAS on the basis of education level, and the ECAS is highly consistent with the MMSE in the assessment of cognition. These norms will be instrumental in future clinical and follow-up work for Mandarin ALS patients.

Background: Amyotrophic lateral sclerosis (ALS) symptom onset is gradual and may include muscle weakness, dysarthria, dysphagia, and respiratory difficulties among others. The objective of this study is to describe sex and racial/ethnic variation in limb and bulbar symptom diagnoses before ALS diagnosis in the USA.

Methods: This retrospective cohort study was conducted using Optum's de-identified Market Clarity Data with a patient identification period between January 2015 and December 2019. Cases were identified using ICD-9/10 codes and were required to have ≥3 years of continuous enrollment or EHR activity prior to diagnosis. Descriptive statistics of symptom frequency and onset were stratified by sex and race.

Results: This study identified 7121 individuals with ALS, 3303 female (46%) and 3818 male (54%). Most identified as Non-Hispanic White (67.5%), followed by African American (6.6%), Hispanic (3.6%), and Asian (0.9%), with 21.4% missing race/ethnicity. In the 3 years before ALS diagnosis, 42.9% of subjects were diagnosed with ≥1 bulbar symptom, 74.5% with ≥1 limb symptom, and 34.6% with both. Females more likely to be diagnosed than males: any bulbar 47.1% versus 39.3%, (p < 0.0001), any limb 76.0% versus 73.2%, (p = 0.007), both 38.1% versus 31.6%, (p < 0.0001). Variation by race/ethnicity was observed for limb symptoms (p < 0.0001) and both bulbar and limb symptoms (p = 0.008), but not bulbar symptoms alone (p = 0.07). Symptom onset to ALS was longer for females and varied by race/ethnicity.

Conclusion: Females were more likely to present with bulbar and limb symptoms prior to ALS diagnosis and African American patients were more likely to present with limb symptoms than other race/ethnicities.

Amyotrophic lateral sclerosis (ALS) develops in a multistep process combining environmental variables and genes. Among the identified risk factors, the role of regular vigorous physical activity is still debatable. Objective: This case-control study investigated the relationship between ALS and different degrees of sports engagement, with federated status as a proxy for strenuous activity. Methods: 586 ALS patients and 558 controls were consecutively assessed by using a standard questionnaire. Due to low female participation in regular or intensive sports activity, the study focused on men (327 with ALS and 314 controls). Results: Overall, football (soccer) had the most practitioners (n = 137, 35.8%), accounting for 62.1% of ALS and 32.3% of control federated athletes. Male football players have a 3.07-fold increased ALS risk (95% CI: 1.82-5.19) compared to other men (p < 0.0001) and 3.43-fold increase (95% CI: 1.77-6.68) compared to those federated in other sports (p = 0.0003). After controlling for age and trauma, football players still had 2.91-fold (95% CI: 1.70-5.01) increased risk compared to non-federated and non-participants in contact sports intensively. No significant ALS risk difference existed for other sports practiced with identical intensity and contact levels. Clinical characteristics of ALS federated football players were similar to other ALS patients. Conclusion: Our results suggest ALS susceptibility is not linked to general physical activity, but specifically to competitive football, regardless of a history of head and neck trauma. Given football's popularity, even a small risk increase could impact many. Further research is required to understand the mechanisms linking football to ALS, and why this association is not observed in other sports.

Objective: Motor neuron diseases (MNDs) result in a spectrum of motor impairments, including considerable effects on speech function, which manifest as dysarthria-a motor speech disorder. Speech metrics are increasingly recognized as critical biomarkers with potential utility in disease diagnosis and phenotyping. This study aimed to (1) characterize acoustics of upper motor neuron (UMN) and lower motor neuron (LMN) dysarthria presentations in MNDs, and (2) identify relationships between bulbar disease severity scores and acoustic features, as these could collectively enable personalized approaches to management of these diseases.

Methods: Data from 16 individuals with primary lateral sclerosis (PLS) representing UMN disease, 14 individuals with spinal and bulbar muscular atrophy (SBMA) representing LMN disease, and 25 neurologically healthy individuals were analyzed. Clinical measures were also collected from PLS and SBMA groups. All participants were remotely recorded performing passage reading, rapid syllable repetition, and vowel phonation. Fifty-two acoustic features were extracted representing articulation, phonation, prosody, resonance, and overall speech timing. Features were compared using Kruskal-Wallis tests for between-group comparisons and Spearman correlations between acoustic features and clinical scores.

Results: Articulatory and prosodic features best differentiated PLS, SBMA and controls. Correlations were observed in the PLS group between the clinical score and various articulatory features, most notably those indexing tongue and jaw movements.

Conclusions: Our study demonstrated that acoustic assessment could capture fingerprints of dysarthrias associated with PLS and SBMA. These findings also demonstrate the potential for remote speech assessment to characterize diverse dysarthria profiles and pave the way for creating ways for personalized disease management approaches in clinical care and trials.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease predominantly affecting motor neurons resulting in substantial, progressive disability. The amyotrophic lateral sclerosis functional rating scale - revised (ALSFRS-R) is commonly used to assess and monitor functional status in patients with ALS. Additionally, it is the current regulatory accepted primary outcome measure documenting functional status in ALS clinical trials. The ALSFRS-R was originally designed to be administered to a patient by a trained professional. But over time it has been adapted to be performed independently by patients or their caregivers without assistance. Several different versions of the self-administered ALSFRS-R have been created over the past two decades, each with subtle but important differences. Some of these differences are related to language used in item wording or the platform for which the scale was intended to be administered (e.g. digitally). These differences across versions of the self-administered scale may be problematic as they could increase the heterogeneity of data collected across clinical trials or complicate interpretation of results across trials. Therefore, we highlight the need for a harmonized version of the self-administered ALSFRS-R to be used across all clinics and clinical trial sites internationally.

Objective: To understand the practices of healthcare professionals supporting people with Amyotrophic Lateral Sclerosis (ALS) to manage cough and secretion issues. This includes utilization of and confidence in assessment and treatment techniques and barriers and enablers of care.

Methods: An online cross-sectional survey was distributed to UK healthcare professionals involved in cough and/or secretion management care in people with ALS.

Results: A total of 113 responses were analyzed, over half were from physiotherapists (52%). The majority (71%) of respondents reported a role managing saliva and secretions. Just under two thirds (60%) routinely assessed cough and almost all (89%) routinely assessed secretions. Healthcare professionals reported reduced confidence assessing secretions compared with cough and very few (5%) used validated secretion outcome measures. Participants reported lower confidence implementing all treatment strategies than recommending them. Multiple barriers to care were identified, including access to specialist care and equipment, education and skills training and a lack of evidence-based care guidelines.

Conclusion: Cough and secretion management is complex and involves numerous professional groups. There is a need for clinical and educational interventions that address knowledge and skill gaps in managing cough and secretion issues, which will help increase healthcare professionals' confidence in assessing and treating these complex problems.

Objective: Mobile technology can significantly enhance self-care for individuals with amyotrophic lateral sclerosis (ALS). This study aims to develop and evaluate the usability of a mobile application that provides relevant information and manages disease-related data for ALS patients and their families.

Methods: A mobile application compatible with Android and iOS platforms was developed following the four phases of the System Development Life Cycle. The content was derived from a literature review, stakeholder focus group interviews, and in-depth interviews with ALS patients, family members, and healthcare professionals. The final application was validated by experts (n = 7), tested for usability by ALS patients and caregivers (n = 18), and evaluated using the System Usability Scale (SUS) to assess effectiveness and user satisfaction.

Results: The application includes features such as tailored health data visualization, symptom tracking, text-to-speech functionality, and access to information customized based on the overall the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, thereby supporting patient-centered care and daily disease management. The mean SUS score was 75.00 ± 9.57 for expert panel members and 63.75 ± 10.26 for the target users, indicating an acceptable level of usability.

Conclusions: The mobile application was evaluated as practical, acceptable, and feasible for ALS patients and their caregivers, with positive feedback on its usability and potential to improve self-care management.