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Objective: To examine the relationship between body mass index (BMI) and genotype among pre-symptomatic carriers of different pathogenic variants associated with amyotrophic lateral sclerosis. Methods: C9orf72+ carriers, SOD1+ carriers, and pathogenic variant negative controls (Gene-Negatives) were included from 3 largely independent cohorts: ALS Families Project (ALS-Families); Dominantly inherited ALS (DIALS); and Pre-symptomatic Familial ALS (Pre-fALS). First reported (ALS-Families) or measured (DIALS and Pre-fALS) weight and height were used to calculate BMI. Age at weight measurement, self-reported sex (male vs. female), and highest education (high school or below vs. college education vs. graduate school or above) were extracted. The associations between BMI and genotype in each cohort were examined with multivariable linear regression models, adjusted for age, sex, and education. Results: A total of 223 C9orf72+ carriers, 135 SOD1+ carriers, and 191 Gene-Negatives were included, deriving from ALS-Families (n = 114, median age 46, 37% male), DIALS (n = 221, median age 46, 30% male), and Pre-fALS (n = 214, median age 44, 39% male). Adjusting for age, sex, and education, the mean BMI of C9orf72+ carriers was lower than Gene-Negatives by 2.4 units (95% confidence interval [CI] = 0.3–4.6, p = 0.02) in ALS-Families; 2.7 units (95% CI = 0.9–4.4, p = 0.003) in DIALS; and 1.9 units (95% CI = 0.5–4.2, p = 0.12) in Pre-fALS. There were no significant differences in BMI between SOD1+ carriers and Gene-Negatives in any of the 3 cohorts. Conclusions: Compared to Gene-Negatives, average BMI is lower in asymptomatic C9orf72+ carriers across 3 cohorts while no significant difference was found between Gene-Negatives and SOD1+ carriers. [ABSTRACT FROM AUTHOR]

AbstractObjective: A high glycemic index and high glycemic load diet has been associated with slower progression of amyotrophic lateral sclerosis (ALS), suggesting a benefit from high blood glucose levels. We examined the association between average blood glucose level and ALS progression in two independent cohorts. Methods: Sporadic ALS patients enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS) who completed a 3-month follow-up visit and had available blood samples were included. Hemoglobin A1c (HbA1c) was measured from whole blood collected at the 3-month follow-up. From the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, we included ALS patients with one or more HbA1c measurements at enrollment and available death information. Associations between HbA1c with revised ALS functional rating scale (ALSFRS-R)/ALSFRS total score change, and tracheostomy-free survival/survival were examined in these cohorts using linear regression, linear mixed-effects models, and Cox proportional hazard models, adjusted for covariates. Results: In the ALS COSMOS cohort (n = 193), HbA1c level was not significantly associated with the change in the ALSFRS-R total score from baseline to the 3-month follow-up (p = 0.8) nor baseline to the 6-month follow-up (p = 0.4). No significant association was found between HbA1c level and tracheostomy-free survival (p = 0.8). In the PRO-ACT cohort (n = 928), no significant association was found between HbA1c level and the rate of ALSFRS decline in the first 200 days (p = 0.81 for interaction) nor between HbA1c level and survival (p = 0.45). Interpretation: We did not find convincing evidence that mean blood glucose level is associated with disease progression among ALS patients. [ABSTRACT FROM AUTHOR]

Hydrophilic endogenous bile acids ursodeoxycholic acid (UDCA), tauroursodeoxycholic acid (TUDCA), and glucourosodeoxycholic acid (GUDCA) have suggested neuroprotective effects. We performed a case–control study to examine the association between ALS diagnosis and serum levels of bile acids. Sporadic and familial ALS patients, age‐ and sex‐matched healthy controls, and presymptomatic gene carriers who donated blood samples were included. Non‐fasted serum samples stored at −80°C were used for the analysis. Serum bile acid levels were measured by liquid chromatography‐mass spectrometry (LC–MS). Concentrations of 15 bile acids were obtained, 5 non‐conjugated and 10 conjugated, and compared between ALS versus control groups (presymptomatic gene carriers + healthy controls) using the Wilcoxon‐Rank‐Sum test. In total, 80 participants were included: 31 ALS (17 sporadic and 14 familial ALS); 49 controls (22 gene carriers, 27 healthy controls). The mean age was 50 years old and 50% were male. In the ALS group, 45% had familial disease with a pathogenic variant in C9orf72 (29%), TARDBP (10%), FUS (3%), and CHCHD10 (3%) genes. In the control group, 43% carried pathogenic variants: C9orf72 (27%), SOD1 (10%), and FUS (6%). The serum levels of UDCA, TUDCA, and GUDCA trended higher in the ALS group compared to controls (median 27 vs. 7 nM, 4 vs. 3 nM, 110 vs. 47 nM, p‐values 0.04, 0.06, 0.04, respectively). No significant group differences were found in other bile acids serum levels. In conclusion, the serum level of UDCA, TUDCA, GUDCA trended higher in ALS patients compared to controls, and no evidence of deficiencies was found. [ABSTRACT FROM AUTHOR]

Objective: High‐caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the rate of progression and length of survival among the prospective cohort study participants. Methods: Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304). We evaluated baseline macronutrient intake assessed by food frequency questionnaire in relation to change in revised amyotrophic lateral sclerosis functional rating scale total‐score, and tracheostomy‐free survival using linear regression and Cox proportional hazard models. Baseline age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised amyotrophic lateral sclerosis functional rating scale total‐score, and forced vital capacity were included as covariates. Results: Baseline higher glycemic index and load were associated with less decline of revised amyotrophic lateral sclerosis functional rating scale total score at 3‐month follow‐up (β = −0.13, 95% CI −0.2, −0.01, p = 0.03) and (β = −0.01, 95% CI −0.03, −0.0007, p = 0.04), respectively. Glycemic index second‐quartile, third‐quartile, and fourth‐quartile groups were associated with less decline at 3 months by 1.9 (95% CI −3.3, −0.5, p = 0.008), 2.0 (95% CI −3.3, −0.6, p = 0.006), and 1.6 (95% CI −3.0, −0.2, p = 0.03) points compared with the first‐quartile group; the glycemic load fourth‐quartile group had 1.4 points less decline compared with the first‐quartile group (95% CI −2.8, 0.1, p = 0.07). Higher glycemic index was associated with a trend toward longer tracheostomy‐free survival (HR 0.97, 95% CI 0.93, 1.00, p = 0.07). Interpretation: Higher dietary glycemic index and load are associated with slower disease progression in amyotrophic lateral sclerosis. ANN NEUROL 2024;95:217–229 [ABSTRACT FROM AUTHOR]

A recently published article titled "Higher Glycemic Index and Glycemic Load Diet Is Associated with Slower Disease Progression in Amyotrophic Lateral Sclerosis" found a significant association between dietary glycemic index (GI) and glycemic load (GL) with functional decline and survival in patients with amyotrophic lateral sclerosis (ALS). However, questions have been raised about the potential interaction between riluzole intake, the most commonly used medication for ALS patients, and the association between GI/GL and disease progression. The authors plan to analyze the dataset further to examine whether dietary GI or GL have different associations with functional decline and survival among those with or without riluzole intake. The authors have no conflicts of interest related to the product discussed in the study. [Extracted from the article]

Background and Objectives: Epidemiologic studies suggest increasing incidence and prevalence of myasthenia gravis (MG) among the elderly population outside the United States. We aimed to provide an estimation of MG incidence and prevalence and their trend among the Medicare Fee-For-Service (FFS)-covered elderly US population., Methods: We performed a retrospective longitudinal study using Medicare claims data (2006-2019). Study-eligible beneficiaries were aged 65 years and older, had at least 1 month of FFS Part A/B coverage, and were without any health maintenance organization insurance coverage. Study-eligible beneficiaries were aggregated into 2-year periods from 2006-2007 through 2018-2019. MG cases were ascertained using a validated algorithm of 2 MG claims within each 2-year period, from 2 outpatient office visits or a combination of 1 inpatient admission and 1 outpatient office visit, separated by ≥ 28 days. Period prevalence was calculated from MG-ascertained cases divided by FFS Part A/B beneficiaries and reported as cases per 100,000 population. Incident cases were determined among MG prevalent cases if the initial MG claim occurred in that period after a full calendar year since coverage initiation. Incidence was calculated as case counts per 100,000 at-risk beneficiary person-years (PYs) in each period excluding 2006-2007. Trends of prevalence and incidence over time were examined with Poisson regression. All-cause mortality of each 2-year period was calculated., Results: The period prevalence of MG increased from 81 to 119 per 100,000 FFS A/B population from 2006-2007 to 2018-2019 ( p < 0.001). Increasing trends of prevalence were observed in all sex (male/female), age (65-69/70-74/75-79/80+), race/ethnic (African American/Asian/Hispanics of any race/non-Hispanic White/other), and census region (Northeast/Midwest/South/West) subgroups. MG incidence increased from 12.2 to 13.3 per 100,000 PYs from 2008-2009 to 2018-2019 ( p < 0.05). Increasing incidence trends were significant in the following subgroups: men and women; all age groups except 75-79 years; White non-Hispanic race; Northeast, Midwest, and South census regions. All-cause mortality among MG beneficiaries was stable from 6.26 deaths per 100 PYs in 2006-2007 to 5.67 in 2018-2019 ( p = 0.18)., Discussion: Increasing trends in MG prevalence and incidence in the elderly US population, with variation in rates of certain subgroups, are confirmed in this 14-year period.

Study Objectives: Inflammatory and immune mechanisms are considered in restless legs syndrome (RLS) pathophysiology with several autoimmune diseases associated with RLS. There is a paucity of studies examining RLS prevalence in myasthenia gravis (MG), an autoimmune neuromuscular disease. This study investigated RLS prevalence and association with patient-reported measures in a large registry of participants with MG using a validated RLS diagnostic questionnaire., Methods: The Myasthenia Gravis Foundation of America MG Patient Registry is used on a semi-annual basis to survey participants with MG. Patients aged ≥18 years, living in the United States, and answering "Yes" to physician diagnosed MG were invited by email to enroll in an RLS-customized web-based survey. Collection of data included demographics, disease variables, patient-reported measures with a simple depression scale, MG 15-item Quality of Life (MG-QOL15r), MG-Activities of Daily Living (MG-ADL) instruments, and 13-item short-form Cambridge-Hopkins diagnostic questionnaire for RLS (CH-RLSq13). Multivariable logistic regression models explored the association between RLS and MG variables of interest., Results: 630 eligible participants with MG (age: 62.8±13.2; 54.9% female; 91.6% White) completed the survey. The overall prevalence of RLS was 14.8%. The prevalence of clinically significant RLS was 8.4%. The odds of having RLS were increased with higher (worse) MG-ADL, MG-QOL15r, and depression scores. History of "Thymic tumor with thymectomy" and "CPAP therapy" were also independent predictors of RLS., Conclusions: RLS is common in patients with MG and is associated with worse functional status, quality of life, and depression. The thymus could play a key role in an autoimmune process associating MG with RLS., (© 2024 American Academy of Sleep Medicine.)