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Background and purpose: The prognostic value of serum neurofilament light chain (sNfL), a biomarker of neurodegeneration, compared to other prognostic factors of amyotrophic lateral sclerosis (ALS) at the time of diagnosis, remains unclear. Methods: Sera from ALS patients were prospectively collected at the first diagnostic visit in our centre. sNfL levels were determined by single molecule array in 207 ALS patients and in 21 healthy controls. The prognostic value of sNfL was compared with that of other known clinical prognostic factors using a Cox regression model and multivariate analysis. Results: Serum neurofilament light chain levels were higher in ALS patients than in controls (P < 0.0001). Seven parameters were predictive of death in ALS: older age, bulbar onset, higher ALS Functional Rating Scale revised (ALSFRS‐R) score, greater weight loss, lower maximal inspiratory pressure, forced vital capacity and higher sNfL levels. A Cox regression model showed that sNfL (P < 0.0001), weight loss (P = 0.040) and site at onset (P = 0.048) were independent predictive factors of death. In a sub‐cohort restricted to 139 patients with complete spirometry data, sNfL level (P < 0.005) and forced vital capacity (P = 0.022) were independent factors predictive of death. In a subgroup of 142 patients in whom ALSFRS‐R score was available at several time points, sNfL levels positively correlated with ALSFRS‐R rate of decline (r = 0.571, P < 10−12). Conclusions: Higher sNfL concentration is a strong and independent prognostic factor of death in ALS as early as the time of diagnosis. [ABSTRACT FROM AUTHOR]

Background and purpose Vitamin D deficiency is a recognized risk factor for multiple sclerosis ( MS) and is associated with increased disease activity. It has also been proposed that the lower the vitamin D levels are, the higher is the handicap. Methods To refine the links between vitamin D insufficiency and disability in MS patients, a retrospective cohort analysis was performed including 181 patients prospectively followed without previous vitamin D supplementation, and age, gender, age at MS onset, MS type, MS activity, Expanded Disability Status Scale ( EDSS) were analysed in correlation with plasma vitamin D levels. Results Vitamin D levels were significantly higher in relapsing-remitting MS than in progressive forms of MS in multivariate analyses adjusted for age, ethnicity, gender, disease duration and season ( P = 0.0487). Overall, there was a negative correlation between vitamin D level and EDSS score ( P = 0.0001, r = -0.33). In relapsing-remitting MS, vitamin D levels were only correlated with disability scores for EDSS < 4 ( P = 0.0012). Patients with >20 ng/ml of vitamin D were 2.78 times more likely to have an EDSS < 4 ( P = 0.0011, 95% confidence interval 1.49-5.00). Conclusion Data support previous work suggesting that vitamin D deficiency is associated with higher risk of disability in MS. Vitamin D levels also correlated with the degree of disability in fully ambulatory patients with relapsing-remitting MS. These additional results support the pertinence of randomized controlled trials analysing the interest of an early vitamin D supplementation in MS patients to influence evolution of disability. [ABSTRACT FROM AUTHOR]

Background and purpose BIONAT is a French multicentric phase IV study of natalizumab ( NTZ)-treated relapsing−remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. Methods Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago ( n = 793; BIONAT2Y). Results NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti- NTZantibodies ( Abs) detected only two supplementary patients with anti- NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. Conclusions The efficacy of NTZ therapy on relapsing−remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events. [ABSTRACT FROM AUTHOR]

Objective: Several association studies have identified possible susceptibility factors for sporadic amyotrophic lateral sclerosis (SALS). Studies on the APOE gene provided conflicting results, especially about the effect on bulbar onset. We assessed the possible role of APOE gene in a large cohort of patients with ALS and matched controls. Methods: The APOE alleles were determined in 1482 patients with SALS and 955 controls and analysed by univariate and multivariate statistics, taking into account gender, site-of-onset and age-at-onset. Results: Patients with bulbar onset were more likely to be women [odds ratio (OR) = 2.17; 95% CI: 1.74-2.72] and to be older (OR = 3.47; 95% CI: 2.58-4.67). The ε4-carriers were more frequent in the bulbar-onset group than in the limb-onset group (OR = 1.39 bulbar onset versus limb onset; 95% CI: 1.08-1.80) but this association was observed amongst men (OR = 1.78; 95% CI: 1.25-2.53) and not women (OR = 1.09; 95% CI: 0.75-1.59). Conclusion: Our study provides evidence for a contribution of the ε4 allele in the occurrence of bulbar-onset ALS amongst men. We propose that men are normally protected by androgens against bulbar onset and that the ε4 allele inhibits this protection, perhaps by interfering with the androgen pathway. [ABSTRACT FROM AUTHOR]

Background and purpose: To prospectively investigate causes of death and the circumstances surrounding death in 302 patients with amyotrophic lateral sclerosis (ALS). The functional status of patients immediately before death was also determined. Methods: Information was obtained from neurologists at ALS centres, patients’ files, and, when deaths occurred outside a medical facility, attending physicians. Results: Most patients (63%) died in a medical facility. The most frequently reported cause of death was respiratory failure (77%), including terminal respiratory insufficiency (58%), pneumonia (14%), asphyxia due to a foreign body (3%) and pulmonary embolism (2%). Ten per cent of patients died from other causes: post-surgical or traumatic conditions (5%), cardiac causes (3.4%), suicide (1.3%) and sudden death of unknown origin (0.7%). The cause of death could not be determined in 13% of cases (6% inside a medical facility and 25% outside). At the time of death, only 55% of patients were receiving riluzole, 33% were undergoing non-invasive ventilation, 3% had a tracheotomy and 37% a gastrostomy. Conclusion: The information provided by this study helps to improve our understanding of the natural history of the disease and may help optimize the quality of care we can offer patients at the end of life. [ABSTRACT FROM AUTHOR]

The Cu,Zn superoxide dismutase (Cu,Zn SOD) mutations described in amyotrophic lateral sclerosis (ALS) have, for the most part, a dominant influence. However, while a few cases with a heterozygous D90A mutation have been described in different countries, D90A has been recently proven to be recessively inherited with a common founder effect in Scandinavia. We screened French ALS families for Cu,Zn SOD mutations. The presence of the D90A allele was found in two index-cases, and their families were subsequently studied. In the first family the ALS patients were homozygotes for D90A, while in the second, all ALS patients were heterozygotes. In both families the disease was found to initially involve the lower limbs with slower progression than in sporadic cases, and frequent atypical signs such as paresthesia and urgency of micturition. We determined the D90A allele frequency in controls (n = 200) and sporadic ALS patients (n = 408). No D90A allele was found. This is the first report of coexistence of dominant and recessive families with the D90A Cu,Zn SOD mutation within the same country. [ABSTRACT FROM AUTHOR]

The article focuses on a study about the potential toxic effect of N19S on the survival of motor neurons and the need for more evidence to support a pathogenic role for the mutation due to the absence of co-segregation in amyotrophic lateral sclerosis (AML). Topics discussed include the clinical data of the ALS cases with N19S mutation and the importance of the study result in daily medical practice and in the field of pre-symptomatic counselling.

The article discusses the occurrence of cutaneous complications related to the treatment of relapsing-remitting forms multiple sclerosis through glatiramer acetate (GA). Skin necrosis and lobular panniculitis are included in direct cutaneous GA. The T-cell response to myelin antigens is curbed by GA which binds to major histocompatibility complex molecules.

The article discusses the occurrence of cutaneous complications related to the treatment of relapsing-remitting forms multiple sclerosis through glatiramer acetate (GA). Skin necrosis and lobular panniculitis are included in direct cutaneous GA. The T-cell response to myelin antigens is curbed by GA which binds to major histocompatibility complex molecules.

Background: Little is known about the influence of Riluzole on serum neurofilament light chain (sNfL) levels, a biomarker of prognosis in amyotrophic lateral sclerosis (ALS), and variations with time of sNfL concentrations are controversial., Methods: Sera from ALS patients (n = 141) and controls (n = 33) were collected at inclusion (sNfL1) and second visit (sNfL2, mean delay 10.4 ± 8.7 months). sNfL levels, determined by single-molecule array, were compared between ALS and controls at both time points. sNfL concentration changes were compared between patients with Riluzole (w/Ril) at inclusion in the study and those who were treated by Riluzole following inclusion (w/o Ril). The factors influencing sNfL concentrations and changes were studied using linear regression and multivariate analysis., Results: sNfL levels were higher in ALS patients than in controls at the two time points (p < 0.00001). In ALS patients, sNfL concentrations were higher in females for both sNfL1 (p = 0.014) and sNfL2 (p < 0.001). In the whole ALS group, sNfL levels were higher at sNfL2 than at sNfL1 (p < 0.001). sNfL1 and sNfL2 concentrations were similar between the two ALS subgroups (w/ and w/o Ril). ALS functional rating scale-revised rate of decline and gender were the two main factors significantly influencing both sNfL1 and sNfL2 levels (p < 0.01). However, only gender was shown to significantly influence sNfL changes with time (p = 0.003)., Conclusions: In this study, sNfL levels increased with time in ALS patients and there was no difference between subjects already treated by Riluzole and those treated after sNfL1. Further studies with larger population samples and different sampling intervals are warranted to better determine the real potential of sNfL measurement as a tool to monitor treatment response in ALS., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Data from the literature about plasma and CSF amino acid (AA) levels in amyotrophic lateral sclerosis (ALS) remain controversial. To refine such analyses we used HPLC, and report a study of plasma and CSF AA concentrations in patients with ALS, the type of the disease (spinal and bulbar onset) being precisely determined. In ALS, there is a decrease in the plasma levels of the large neutral amino acids (LNAA) alanine, isoleucine, leucine, methionine and tyrosine which was particularly striking in the bulbar type (p < 0.05). Plasma glutamate levels do not differ between ALS and controls, but are significantly increased in ALS with spinal onset and decreased in the bulbar type (p < 0.05 vs controls, p < 0.001 bulbar vs spinal). In CSF, the analysis of the whole ALS group shows no difference from controls. However, there is an increase of CSF serine, glutamine and alanine in ALS with spinal onset (p < 0.05). Our results do not support an abnormal profile of excitatory AA concentrations in ALS. The heterogeneous changes we observed, mainly concerning LNAAs, may be explained by a blood-CSF barrier disturbance in the disease. As AA levels clearly differ between ALS types, with low concentrations in bulbar ALS, this dual profile probably explains some of the discrepancies between previous studies.