Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

Objective: Apathy is the most prevalent behavioral impairment or difficulty for people with ALS (pwALS), with Initiation apathy (a lack of motivation for self-generation of thoughts and/or actions) the most common subtype. Self-rated or self-perceived quality of life (sQoL) is impacted for pwALS, but the relationship to apathy subtypes is unknown. The aim was to explore the relationship between sQoL domains and apathy in pwALS. Methods: 32 pwALS were recruited and completed self-rated measures of apathy (Dimensional Apathy Scale), depression, anxiety, and emotional lability. The ALS-specific QoL short-form instrument was used to measure QoL. Cognitive functioning and functional disability were measured. Exploratory, comparative, and predictive multiple hierarchical regression analyses were performed. Results: Initiation apathy was the most common apathy subtype at 37.5% (N = 12). PwALS with Initiation apathy had higher depressive symptoms (p <.05, d = 1.11 large effect) and lower cognitive functioning (p <.05, d = 0.76 medium effect) than those without apathy. PwALS with Initiation apathy had significantly worse sQoL in domains of interaction with people and the environment (p <.05, d = 0.92, large effect) and negative emotions (p <.05, d = 0.80, large effect) than those without apathy. Regression analysis showed Initiation apathy was a significant negative predictor of the sQoL domain of interaction with people and the environment (beta =-.20, p <.01), controlling for confounders (functional disability, depression, cognitive functioning). Conclusions: Initiation apathy was associated with QoL domains of interaction with people and the environment, from the perspective of the pwALS. This emphasizes the importance of self-rating or self-perception for clinical and researcher assessment of apathy and QoL for pwALS.

Survival outcomes are commonly analyzed in studies with data from patients with progressive, neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Given the fast progression of ALS, survival analyses are, however, often difficult to perform and interpret. In this methodological article we demonstrate on real-world data how the choices we make in the study design, data collection, and analysis could influence the results. The factors we consider in this study are length of follow-up, sample size, timing of sample collection, and choice of covariables adjusted for in the models. We further discuss the importance of each of these contributing factors and about how to avoid mistakes in interpreting and reporting survival data in ALS and other rare, progressive diseases.

Objective: We aimed to determine diagnostic prevalence and symptom burden of pseudobulbar affect (PBA) in patients with Amyotrophic Lateral Sclerosis (ALS) in Denmark and differences in ongoing symptomatic treatment.

Methods: In this national cross-sectional survey study, participants with ALS completed an online survey regarding PBA and PBA symptoms, which were quantified through the Center for Neurologic Study Lability Scale (CNS-LS). A CNS-LS score ≥ 13 served as a threshold indicative of PBA.

Results: 157 participants with ALS were recruited. 12.1% were diagnosed with PBA and were more likely to receive antidepressant medication compared to those not diagnosed with PBA (47.4% compared to 15.2%, p = 0.002). 30.6% scored ≥13 in the CNS-LS; however, the proportion of participants treated with antidepressants was similar compared to those scoring below the ≥13 threshold (25% compared to 16.5%, p = 0.27). Of those not diagnosed with PBA, 23.2% scored ≥13 in the CNS-LS. This PBA symptomatic, but undiagnosed group was less likely to receive symptomatic treatment compared to patients with diagnosed PBA (12.5% compared to 47.4%, p = 0.009). No differences were seen in CNS-LS score between these groups.

Conclusions: The proportion of diagnosed PBA among the study population was low compared to previous studies; however, the proportion of patients with symptoms of possible PBA was markedly higher. Patients with known PBA were more likely to receive recommended symptomatic treatment compared to patients not diagnosed with PBA, despite symptoms indicative of PBA. These findings highlight the potential underrecognition of PBA in ALS and concurrent absence of symptomatic treatment.

Objective: Basic science research in spinal and bulbar muscular atrophy (SBMA) has facilitated the development of disease modifying therapeutics. However, there remains a need for disease-specific patient-reported outcome (PROs) measures to monitor changes in disease status. The spinal and bulbar muscular atrophy-health index (SBMA-HI) was designed to address this gap. Methods: Initial interviews with 21 individuals with SBMA and a subsequent international cross-sectional study with 232 participants were conducted to identify the most prevalent and impactful symptoms in SBMA. The most relevant symptoms were included in the SBMA-HI. We subsequently used patient interviews, test-retest reliability evaluation, known groups validity testing, and factor analysis to evaluate and optimize the SBMA-HI. Results: The SBMA-HI tool includes fourteen subscales and one supplemental subscale (for those who are able to ambulate independently) to measure SBMA disease burden from the patients' perspectives. Fifteen adults with SBMA participated in semi-structured beta interviews and found the SBMA-HI to be clear and relevant to them. Twenty-nine adults with SBMA participated in test-retest reliability assessments, which demonstrated high reliability of the SBMA-HI. The final SBMA-HI and its subscales demonstrated a high internal consistency. Conclusion: The SBMA-HI is a reliable disease-specific patient-reported outcome measure capable of quantifying disease burden in SBMA.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of upper and lower motor neurons. Most forms of ALS associated with a suspected causal variant are inherited in an autosomal dominant manner. However, there is an important subset of autosomal recessive (AR) variants, often associated with early-onset or atypical clinical features. Advances in genetic sequencing have led to increased recognition of AR ALS. In this review, we focus on four key confirmed AR ALS-associated genes, which appear to be most common-ALS2, SPG11, OPTN, and the D90A variant of SOD1-reviewing their pathophysiology and unique clinical manifestations. We also highlight very rare AR mutations implicated in ALS, including SYNE1, ATP13A2, and FUS, and some associated with overlap syndromes or debated pathogenicity including SIGMAR1, ERLIN1, and ERLIN2. These genes are involved in an array of processes including axonal transport, endosomal trafficking, oxidative stress response, and autophagy, suggesting distinct mechanisms of motor neuron degeneration. Some forms of AR ALS more frequently present with juvenile onset and slower progression, but other genes are associated with broader phenotypic spectra. This includes overlap with hereditary spastic paraplegia (HSP) and hereditary ataxias. Understanding these AR forms of ALS may enhance diagnostic precision, improve prognostication, and may pave the way for targeted gene therapies. This review underscores the emerging significance of AR inheritance in ALS and calls for deeper investigation into its molecular and clinical dimensions.

Objective: To define the minimum important slowing (MIS) of ALS progression that patients would expect from disease-modifying drug treatment in ALS. Methods: In a survey of ALS patients, the MIS in ALS progression (change in the ALS Functional Rating Scale-Revised, ALSFRS-R) was assessed by asking: "At what point of slowing of ALS, as determined by the ALSFRS-R, do you consider a drug to be important?" Data were collected during clinic visits or remotely via the ALS App. Participants were differentiated in the prognostic groups of slower (<0.5), intermediate (≥0.5 and ≤1.0), or faster (>1.0) ALS progression (ALSPR; ALSFRS-R/month). Results: Of 522 participants (ALS App, n = 397; clinic, n = 125), 395 (75.7%) completed the survey, while 127 (24.3%) selected the option "cannot estimate". The distribution of MIS was as follows: modest slowing of ALS progression (5% and 10% slowing, n = 146 patients, 36.9%), moderate slowing (20%, 30%, and 40% slowing, n = 135, 34.2%), and major slowing (≥50% slowing, n = 114, 28.9%). Median MIS was 20% (IQR 10-50%). Patients with faster ALSPR more frequently assessed a major slowing as the MIS (n = 18, 36.0%) compared to those with slower ALSPR (n = 54, 25.2%). Conclusion: A considerable number of participants viewed a modest slowing in ALS progression as the MIS, followed closely by preferences for moderate and major slowing. Expectations varied according to patients' individual ALS progression. These insights may inform the design of future clinical trials in ALS. Study limitations include potential selection and response biases, as well as the predominantly remote digital assessment.

Objective: Language and executive functioning are two domains commonly impacted in ALS and should be assessed sensitively and briefly. This paper investigates the utility of the Brief Executive Language Screen (BELS) in ALS. Methods: ALS patients (N = 27) were compared to age, education, and pre-morbid intelligence-matched healthy controls (N = 91) at the group level using ANCOVA and t-tests. A case series was also conducted to explore individual and subgroup performance on the BELS and Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Results: Groups were largely matched on neuropsychology baseline measures. The ALS group performed significantly worse on BELS Propositional Language and Executive Function subtests, and on overall BELS scores. Group results suggest setting a goal can increase phonemic fluency and spontaneous speech output, after controlling for motor speed. The case series revealed almost half of patients (across all subgroups) were impaired on the BELS, compared to 15% impaired on the ECAS (patients on the more severe end of the ALS-FTD spectrum). Conclusions: The BELS rapidly assesses language and executive functions, and provides valuable information for management of cognitive difficulties (i.e., goal setting), which can help improve or maintain conversational speech. The BELS may help to identify subtle impairments that may otherwise go undetected.

Objective: To identify current evidence on oral health-related quality of life in people with Motor Neurone Disease (MND), as well as identify barriers to oral health and care, and establish priorities for future research.

Methods: A scoping review was conducted. Electronic databases and grey literature sources were searched from 2000 to 2024. Articles discussing oral health in adults with MND were included. Findings were supplemented by stakeholder consultation with people with MND, caregivers, clinicians, and researchers.

Results: Fourteen articles met inclusion criteria, comprising eight cross-sectional studies, one prospective quality improvement project, one single center observational and four review articles. Five key themes emerged: dental status and oral hygiene activities, orofacial function, secretion management, service delivery and Oral health-related quality of life (OHRQoL). Studies indicated that MND negatively impacts oral health through impaired ability to perform oral hygiene and altered orofacial functioning. Only one study examined oral health-related quality of life. Stakeholder consultation highlighted additional concerns including challenges with service access, the impact of MND on oral health, and difficulties maintaining oral hygiene due to physical limitations.

Conclusions: Oral health remains an under-researched area in MND care despite its potential impact on quality of life and overall wellbeing. Future research priorities should include investigating relationships between oral health and MND outcomes, improving service delivery models, and increasing dental professional awareness. Active involvement of people with MND in research design and implementation is essential for developing effective interventions.

The common single nucleotide polymorphism (SNP) rs12608932 located at a cryptic splice in the UNC13A gene has been reported to modify the clinical phenotype of ALS, but it is unclear whether homozygosity for the C-allele at UNC13A rs12608932 modifies specific domains of cognition in ALS. We analyzed retrospective data from a German cohort and found that the proportion of cognitively or behaviorally impaired patients was higher in the high-risk group of homozygous C-allele carriers. Patients with C/C alleles had lower scores than controls on verbal fluency, executive functioning, and delayed memory recall, but did not differ significantly from other ALS genotypes. Furthermore, informant ratings suggested higher disinhibition in the C/C carriers. These findings indicate that the C/C risk variant of UNC13A rs12608932 may contribute to general cognitive vulnerability rather than domain-specific deficit.