Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS (PALS) who ask about them. Here, we review withania somnifera (WS) commonly known as ashwagandha or winter cherry. WS has plausible mechanisms for slowing ALS progression because of its effects on inflammation, oxidative stress, autophagy, mitochondrial function, and apoptosis. Preclinical trials demonstrate that WS slows disease progression in multiple different animal models of ALS. Of the five individuals we found who described using WS for their ALS, two individuals reported moderate benefit while none reported experiencing any significant side effects. There is currently one clinical trial using WS to treat PALS; the results are not yet published. There are no serious side effects associated with WS and the associated cost of this treatment is low. Based on the above information, WS appears to us to be a good candidate for future ALS trials.

Introduction: Serum heat shock protein (HSP) concentrations have been reported as potential biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigate the role of serum HSP70, HSP90, and DNAJC7 as biomarkers for ALS. Methods: Serum samples were collected from ALS patients and volunteer controls from three different clinical cohorts (in Germany, Ireland, and Italy). Serum HSP concentrations were determined using enzyme-linked immunosorbent assay. Descriptive statistics, generalized logistic regression, and Cox proportional hazards models were used to model associations between log serum HSP concentrations and ALS risk. Results: In total, 251 ALS patients and 184 healthy volunteers were included. Logistic regression models failed to find associations between ALS risk and log serum concentration of HSP70 (OR 0.43, 95% CI: 0.10-1.78, p = 0.242), HSP90 (OR 0.95, 95% CI: 0.39-2.37, p = 0.904), or DNAJC7 (OR 1.55, 95% CI: 0.90-2.68, p = 0.118). Survival of ALS patients was not associated with log serum concentration of HSP HSP70 (HR1.06, 95% CI: 0.36-3.14, p = 0.916), HSP90 (HR 1.17, 95% CI: 0.67-2.02, p = 0.584), or DNAJC7 (HR 0.83, 95% CI: 0.57-1.21, p = 0.337). Discussion: We did not replicate previous findings that serum HSP70 and HSP90 concentrations were associated with risk of ALS. DNAJC7 was not associated with ALS risk, and there were no obvious longitudinal patterns in log serum concentrations of HSP70, HSP90, or DNAJC7. In addition, serum HSP concentrations were not associated with ALS survival.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition with observable cognitive and behavioral impairment. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a tool developed specifically for people with ALS (pwALS) and previously translated into Russian, but the psychometric properties have not yet been explored. The aim was to explore and determine the psychometric properties of the Russian-version of ECAS (ECAS-R).

Methods: 56 Russian speaking pwALS, 32 of their caregivers and 26 healthy controls were recruited for the study. They completed the ECAS-R, Patient Health Questionnaire-9 (PHQ-9) and Montreal Cognitive Assessment (MoCA). King Staging System was also utilized. Internal consistency, divergent and convergent validity, as well as culturally-derived cutoff scores of ECAS-R were determined.

Results: The internal consistency of ECAS-R was good (Cronbach's alpha = 0.73). Convergent validity was observed though a strong correlation between the ECAS-R and MoCA scores. No correlation between ECAS-R and PHQ-9 were observed in terms of divergent validity. Based on culturally-derived cutoff scores, 64.2% (N = 36) of pwALS displayed cognitive impairment, with the most affected cognitive domains as executive function and language. Apathy was the most common behavioral impairment for pwALS followed by a loss of sympathy/empathy.

Conclusions: The ECAS-R is valid and reliable tool for the screening for the cognitive and behavioral impairment in Russian-speaking pwALS, with culturally-derived cutoffs presented.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease usually associated with severe weakness and death within 2-5 years. SOD1 mutations cause hereditary ALS in autosomal dominant and rarely in recessive pattern. We describe a new phenotype of slowly progressive fALS due to homozygous SOD1 mutations (c.358G > C, p.Val120Leu) in a Brazilian family. We reviewed the medical chart and interviewed the index patient and other relatives. A 41-year-old man developed weakness in his legs, leading to frequent falls, followed over the next few months with progressive arm fasciculations and muscle atrophy. The SOD1 enzymatic activity in erythrocytes was slightly decreased. A genetic test panel disclosed homozygous SOD1 mutations (c.358G > C, p.Val120Leu). His asymptomatic parents also carried one mutant allele and 2 brothers and a sister had died with ALS. We reported a new family with homozygous SOD1 mutation and slowly progressive ALS course. Further studies are necessary to confirm whether this mutation can also lead to disease in heterozygosis with incomplete penetrance.

Objective: To summarize the prevalence of ALS in all 50 states and Washington, DC in the United States from 2011 to 2018 using data collected and analyzed by the National ALS Registry. In October 2010, the federal Agency for Toxic Substances and Disease Registry (ATSDR) launched the congressionally mandated Registry to determine the incidence and prevalence of ALS within the USA, characterize the demographics of persons with ALS, and identify the potential risk factors for the disease. This is the first analysis of state-level ALS prevalence estimates. Methods: ALS is not a notifiable disease in the USA, so the Registry uses a two-pronged approach to identify cases. The first approach uses existing national administrative databases (Medicare, Veterans Health Administration, and Veterans Benefits Administration). The second method uses a secure web portal to gather voluntary participant data and identify cases not included in the national administrative databases. Results: State-level age-adjusted average prevalence from 2011-2018 ranged from 2.6 per 100,000 persons (Hawaii) to 7.8 per 100,000 persons (Vermont), with an average of 4.4 per 100,000 persons in the US. New England and Midwest regions had higher prevalence rates than the national average. Conclusions: These findings summarize the prevalence of ALS for all 50 states from 2011 to 2018. This is a continuing effort to identify ALS cases on a national population basis. The establishment of the National ALS Registry has allowed for epidemiological trends of this disease and the assessment of potential risk factors that could cause ALS.

Objective: Although studies have shown that digital measures of speech detected ALS speech impairment and correlated with the ALSFRS-R speech item, no study has yet compared their performance in detecting speech changes. In this study, we compared the performances of the ALSFRS-R speech item and an algorithmic speech measure in detecting clinically important changes in speech. Importantly, the study was part of a FDA submission which received the breakthrough device designation for monitoring ALS; we provide this paper as a roadmap for validating other speech measures for monitoring disease progression. Methods: We obtained ALSFRS-R speech subscores and speech samples from participants with ALS. We computed the minimum detectable change (MDC) of both measures; using clinician-reported listener effort and a perceptual ratings of severity, we calculated the minimal clinically important difference (MCID) of each measure with respect to both sets of clinical ratings. Results: For articulatory precision, the MDC (.85) was lower than both MCID measures (2.74 and 2.28), and for the ALSFRS-R speech item, MDC (.86) was greater than both MCID measures (.82 and .72), indicating that while the articulatory precision measure detected minimal clinically important differences in speech, the ALSFRS-R speech item did not. Conclusion: The results demonstrate that the digital measure of articulatory precision effectively detects clinically important differences in speech ratings, outperforming the ALSFRS-R speech item. Taken together, the results herein suggest that this speech outcome is a clinically meaningful measure of speech change.

Objective: To assess current practices of U.S. professionals providing outpatient ALS nutrition care.

Methods: A cross-sectional survey assessing nutrition care practices was distributed in February/March 2023 through electronic mailing lists of relevant professional organizations.

Results: Of the 87 professionals completing the survey, 85.1% were registered dietitians and 50.6% had five or fewer years of experience in ALS care. Many (44.2%) professionals reported receiving no training on the nutrition care of people with ALS (PALS), and 40.2% reported having no other ALS dietitians in their close network. Methods utilized to estimate calorie and protein requirements in PALS varied widely. Although 95.4% of respondents reported that their clinic's dietitian participates in feeding tube discussions, many practitioners may be waiting until ALS symptoms negatively impact PALS' breathing, eating, swallowing, or weight to begin discussing feeding tubes. Additionally, few professionals reported institutional practices conducive for refeeding syndrome prevention or monitoring.

Conclusions: Many professionals providing outpatient nutrition care to PALS possess limited experience, received insufficient training, and are not connected to other ALS dietitians. Specific nutrition care practices, including nutrient need estimation, vary widely among health professionals. Practices surrounding feeding tube discussions and refeeding syndrome may be suboptimal at many institutions. These findings highlight the need for initiatives that educate and connect practitioners providing nutrition care to PALS.