Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

Objective: The Return of Answer ALS Results (RoAR) Study was designed to provide a mechanism for participants in Answer ALS, a large, prospectively designed natural history and biorepository study to receive select clinical genetic testing results and study participants' experience with the results disclosure. Methods: Participants consented to receive results of five ALS genes (C9orf72, SOD1, FUS, TARDP, TBK1) and/or 59 medically actionable genes as designated by the American College of Medical Genetics. Patient-reported genetic testing outcomes were measured via a post-disclosure survey. Results: Of 645 eligible Answer ALS enrollees, 143 (22%) enrolled and completed participation in RoAR. Pathogenic variants were identified in 22/143 (15.4%) participants, including 13/143 (9.0%) in ALS genes and 9/143 (6.3%) in ACMG genes. Participant-reported measures of result utility indicated the research result disclosure was as or more successful than published patient-reported outcomes of result disclosure the clinical setting. Conclusions: This study serves as a model of a "disclosure study" to share results from genomic research with participants who were not initially offered the option to receive results, and our findings can inform the design of future, large scale genomic projects to empower research participants to access their genetic information.

Objectives: Recent studies suggest that psychological resilience (PR) is associated with more well-preserved cognition in healthy subjects (HS), but an investigation of such phenomenon in patients with motor neuron diseases (MNDs) is still lacking. The aim of our study was therefore to evaluate PR and its relationship with baseline cognitive/behavioral and mood symptoms, as well as longitudinal cognitive functioning, in MNDs.

Methods: 94 MND patients and 87 demographically matched HS were enrolled. PR was assessed using the Connor-Davidson Resilience Scale (CD-RISC). Patients were further evaluated both at baseline and every 6 months for cognitive/behavioral disturbances using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), and for mood symptoms using the Hospital Anxiety and Depression Scale (HADS). CD-RISC scores were compared between patients and HS using the Mann-Whitney U test, and regression models were applied to evaluate the role of CD-RISC scores in predicting baseline cognitive/behavioral and mood measures, as well as longitudinal cognitive performances, in MND patients.

Results: MND cases showed significantly greater PR compared to HS (p from <0.001 to 0.02). In MNDs, higher PR levels were significant predictors of both greater cognitive performance (p from 0.01 to 0.05) and milder mood symptoms (p from <0.001 to 0.04) at baseline, as well as less severe memory decline (p from 0.001 to 0.04) longitudinally.

Conclusions: PR is an important protective factor against the onset and evolution of cognitive/mood disturbances in MNDs, suggesting the usefulness of resilience enhancement psychological interventions to prevent or delay cognitive and mood disorders in these neurodegenerative conditions.

Introduction: Amyotrophic lateral sclerosis (ALS) has heterogeneous manifestations ranging from motor neuron degeneration to cognitive and behavioral impairment. This study aims to clarify the interactions between cognition and behavioral symptoms with relevant disease predictors and with cognitive reserve (CR), quantified through education, physical activity, and occupation proxies. Methods: A prospective sample of 162 ALS patients and 61 controls were evaluated with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) (dependent variable), a Cognitive Reserve Index questionnaire (CRIq) and demographic data (age and sex), and, for patients, clinical variables: disease duration, site of onset, the ALS Functional Rating Scale (ALSFRS), forced vital capacity (FVC), and gene mutation chromosome 9 open reading frame 72 (C9orf72) (independent variables). Multiple regression and mediation analyses were performed to predict cognitive and behavioral symptoms. Results: For the ALS group, the statistical model explained 38.8% of variance in ECAS total (p < 0.001), 59.4% of executive functions (p < 0.001), and 55% of behavioral symptoms (p < 0.001). For controls, it accounted for 52.8% of variance in ECAS total (p < 0.001). Interaction effects and mediation analysis showed CR is an ECAS total modulator, with a differential effect within groups (p < 0.001). Verbal fluency was the single best cognitive score to differentiate patients from controls (p = 0.004), and the gene mutation C9orf72 was found to be a behavioral symptom' predictor in patients (p = 0.009). Conclusion: This study supports the proposed concept that CR acts as a cognitive modulator in ALS patients and healthy individuals. Moreover, CR also modulates behavioral manifestations in ALS.

Objective: To systematically assess decline in respiratory measures in amyotrophic lateral sclerosis (ALS) and to examine the impact of sex, disease onset type and baseline morbidity on progression.

Methods: The REVEALS study (Registry of Endpoints and Validated Experiences in ALS) was conducted between April 2018 and February 2021 in six European ALS centers. Slow and forced vital capacity (S/FVC), sniff nasal inspiratory pressure (SNIP), peak cough flow, amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R), and respiratory morbidity were collected. Data were analyzed using a Bayesian multiple outcomes random effects model.

Results: Two hundred and eighty participants had a median of three assessments (IQR 2.0, 5.0) over a median of 8 months (IQR 2.3, 14.1). There were 974 data collection timepoints. Differences in respiratory measures and rates of decline between disease-onset and sex subgroups were identified. Females had lower scores in all respiratory measures and females with bulbar onset ALS had faster decline compared with other sub-groups. These differences were not detected by the ALSFRS-r respiratory subscale. Dyspnea, orthopnea, and a higher King's stage at baseline were associated with lower respiratory scores throughout follow-up, while having a regular productive cough at baseline was associated with lower peak cough flow scores.

Conclusion: Respiratory function declines more quickly in females with ALS compared with males when measured by FVC, SVC, SNIP, or PCF, but not the ALSFRS-R respiratory sub-score. Higher baseline King's staging and the presence of clinical respiratory symptoms at baseline were associated with worse respiratory function. The ALSFRS-R respiratory sub-score is poorly correlated with objective respiratory measurements.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the gradual death of motor neurons in the brain and spinal cord, leading to fatal paralysis. Socioeconomic status (SES) is a measure of an individual's shared economic and social status, which has been shown to have an association with health outcomes. Understanding the impact of SES on health conditions is crucial, as it can influence and be influenced by health-related variables. The role of socioeconomic status in influencing the risk and progression of ALS has not been established, and understanding the various factors that impact ALS is important in developing strategies for treatment and prevention. To investigate this relationship, we recruited 413 participants with definite, probable, or possible ALS according to the El Escorial criteria, from three tertiary centers in London, Sheffield, and Birmingham. Logistic regression was used to examine the association between case-control status, socioeconomic criteria, and ALS risk. Linear regression was used to examine the association between age of onset and socioeconomic variables. Two sensitivity analyses were performed, one using an alternative occupational classifier, and the other using Mendelian Randomization analysis to examine association. There was no significant relationship between any variables and ALS risk. We found an inverse relationship between mean lifetime salary and age of ALS onset (Beta = -0.157, p = 0.011), but no effect of education or occupation on the age of onset. The finding was confirmed in both sensitivity analyses and in Mendelian Randomization. We find that a higher salary is associated with a younger age of ALS onset taking into account sex, occupation, years of education, and clinical presentation.

Objective: Radiologically inserted gastrostomy placement may be performed in patients with dysphagia secondary to amyotrophic lateral sclerosis (ALS). This study assessed technical outcomes and complications related to gastrostomy placement in patients with ALS.

Methods: A retrospective review of patients with ALS who underwent gastrostomy placement between 2021 and 2023 was performed. Patient demographics, medical history, ALS disease manifestations, survival, and post-procedural complications were obtained from the electronic medical record. Technical outcomes related to gastrostomy placement were obtained from operative notes and review of procedural imaging.

Results: A total of 100 patients were included in the study. The mean duration of ALS diagnosis at time of gastrostomy placement was 1.3 +/-1.2 years. The mean slow vital capacity at time of gastrostomy placement was 54.0 +/-20.2% (range 10-155%). Technical success was 100%, with 91 placed using fluoroscopic guidance and 9 placed with computed tomography guidance. Eighty-three percent of gastrostomies were performed as outpatient procedures, while 17/100 patients were admitted following the procedure for monitoring. Post-procedural adverse events were noted in 21/100 patients (15 mild and 6 moderate or greater). Three patients developed respiratory failure after gastrostomy tube placement and died within 1-week post-procedure. Lower pre-procedural slow vital capacity was associated with higher risk of post-procedural respiratory failure (p = 0.0003*).

Conclusions: Gastrostomy placement in patients with ALS has a high technical success rate and may be performed safely in the outpatient setting in appropriate patients. Patients with low slow vital capacity related to ALS should be admitted post-procedurally for airway monitoring and support.