Search

Background: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS)., Methods: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available., Results: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management., Conclusions: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Fitness in micro-organisms can be proxied by growth parameters on different media and/or temperatures. This is achieved by measuring optical density at 600 nm using a spectrophotometer, which measures the effect of absorbance and side scattering due to turbidity of cells suspensions. However, when growth kinetics must be monitored in many 96-well plates at the same time, buying several 96-channel spectrophotometers is often beyond budgets. The MiniRead device presented here is a simple and inexpensive do-it-yourself 96-well temperature-controlled turbidimeter designed to measure the interception of white light via absorption or side scattering through liquid culture medium. Turbidity is automatically recorded in each well at regular time intervals for up to several days or weeks. Output tabulated text files are recorded into a micro-SD memory card to be easily transferred to a computer. We propose also an R package which allows (1) to compute the nonlinear calibration curves required to convert raw readings into cell concentration values, and (2) to analyze growth kinetics output files to automatically estimate proxies of growth parameters such as lag time, maximum growth rate, or cell concentration at the plateau., (© 2024 The Authors. Yeast published by John Wiley & Sons Ltd.)

Background and Purpose: Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). The impact of diabetes mellitus (DM) on respiratory function of ALS patients is uncertain., Methods: A retrospective cohort study was carried out. From the 1710 patients with motor neuron disease followed in our unit, ALS and progressive muscular atrophy patients were included. We recorded demographic characteristics, functional ALS rating scale (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R]) and its subscores at first visit, respiratory function tests, arterial blood gases, phrenic nerve amplitude (PhrenAmpl), and mean nocturnal oxygen saturation (SpO 2 mean). We excluded patients with other relevant diseases. Two subgroups were analysed: DIAB (patients with DM) and noDIAB (patients without DM). Independent t-test, χ 2 , or Fisher exact test was applied. Binomial logistic regression analyses assessed DM effects. Kaplan-Meier analysis assessed survival. p < 0.05 was considered significant., Results: We included 1639 patients (922 men, mean onset age = 62.5 ± 12.6 years, mean disease duration = 18.1 ± 22.0 months). Mean survival was 43.3 ± 40.7 months. More men had DM (p = 0.021). Disease duration was similar between groups (p = 0.063). Time to noninvasive ventilation (NIV) was shorter in DIAB (p = 0.004); total survival was similar. No differences were seen for ALSFRS-R or its decay rate. At entry, DIAB patients were older (p < 0.001), with lower forced vital capacity (p = 0.001), arterial oxygen pressure (p = 0.01), PhrenAmpl (p < 0.001), and SpO 2 mean (p = 0.014)., Conclusions: ALS patients with DM had increased risk of respiratory impairment and should be closely monitored. Early NIV allowed for similar survival rate between groups., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Many secondary metabolites isolated from plants have been described in the literature owing to their important biological properties and possible pharmacological applications. However, the identification of compounds present in complex plant extracts has remained a great scientific challenge, is often laborious, and requires a long research time with high financial cost., Objectives: The aim of this study was to develop a method that allows the identification of secondary metabolites in plant extracts with a high degree of confidence in a short period of time., Material and Methods: In this study, an ethanolic extract of Coffea arabica leaves was used to validate the proposed method. Countercurrent chromatography was chosen as the initial step for extraction fractionation using gradient elution. Resulting fractions presented a variation of compounds concentrations, allowing for statistical total correlation spectroscopy (STOCSY) calculations between liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS/MS) and NMR across fractions., Results: The proposed method allowed the identification of 57 compounds. Of the annotated compounds, 20 were previously described in the literature for the species and 37 were reported for the first time. Among the inedited compounds, we identified flavonoids, alkaloids, phenolic acids, coumarins, and terpenes., Conclusion: The proposed method presents itself as a valid alternative for the study of complex extracts in an effective, fast, and reliable way that can be reproduced in the study of other extracts., (© 2023 John Wiley & Sons Ltd.)

Background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease, and the time from symptom onset to diagnosis remains long. With the advent of disease-modifying treatments, the need to identify and diagnose ALS in a timely fashion has never been greater., Methods: We reviewed the literature to define the severity of ALS diagnostic delay, the various factors that contribute to this delay (including patient and physician factors), and the role that site of symptom onset plays in a patient's diagnostic journey., Results: Diagnostic delay is influenced by general practitioners' lack of recognition of ALS due to disease rarity and heterogenous presentations. As a result, patients are referred to non-neurologists, have unnecessary diagnostic testing, and may ultimately be misdiagnosed. Patient factors include their illness behavior-which impacts diagnostic delay-and their site of symptom onset. Limb-onset patients have the greatest diagnostic delay because they are frequently misdiagnosed with degenerative spine disease or peripheral neuropathy., Conclusion: Prompt ALS diagnosis results in more effective clinical management, with earlier access to disease-modifying therapies, multidisciplinary care, and, if desired, clinical trial involvement. Due to lack of commercially available ALS biomarkers, alternative strategies to identify and triage patients who likely have ALS must be employed. Several diagnostic tools have been developed to encourage general practitioners to consider ALS and make an urgent referral to ALS specialists, bypassing unnecessary referrals to non-neurologists and unnecessary diagnostic workup., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear., Methods: Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO 2 mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors., Results: We included 276 patients (153 men, onset age = 62.6 ± 11.0 years, disease duration = 13.0 ± 9.6 months, spinal onset in 182) with mean survival of 40.1 ± 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1 > G2 > G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO 2 mean. Independent predictors for G2 were MIP and SpO 2 mean; for G3, the only independent predictor was PhrenAmpl., Conclusions: These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Progression rate is quite variable in amyotrophic lateral sclerosis (ALS); thus, tools for profiling disease progression are essential for timely interventions. The objective was to apply dynamic Bayesian networks (DBNs) to establish the influence of clinical and demographic variables on disease progression rate., Methods: In all, 664 ALS patients from our database were included stratified into slow (SP), average (AP) and fast (FP) progressors, according to the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) rate of decay. The sdtDBN framework was used, a machine learning model which learnt optimal DBNs with both static (gender, age at onset, onset region, body mass index, disease duration at entry, familial history, revised El Escorial criteria and C9orf72) and dynamic (ALSFRS-R scores and sub-scores, forced vital capacity, maximum inspiratory pressure, maximum expiratory pressure and phrenic amplitude) variables., Results: Disease duration and body mass index at diagnosis are the foremost influences amongst static variables. Disease duration is the variable that better discriminates the three groups. Maximum expiratory pressure is the respiratory test with prevalent influence on all groups. ALSFRS score has a higher influence on FP, but lower on AP and SP. The bulbar sub-score has considerable influence on FP but limited on SP. Limb function has a more decisive influence on AP and SP. The respiratory sub-score has little influence in all groups. ALSFRS-R questions 1 (speech) and 9 (climbing stairs) are the most influential in FP and SP, respectively., Conclusions: The sdtDBN analysis identified five variables, easily obtained during clinical evaluation, which are the most influential for each progression group. This insightful information may help to improve prognosis and care., (© 2022 European Academy of Neurology.)

Diagnostic tests are of critical importance in health care and medical research. Motivated by the impact that atypical and outlying test outcomes might have on the assessment of the discriminatory ability of a diagnostic test, we develop a robust and flexible model for conducting inference about the covariate-specific receiver operating characteristic (ROC) curve that safeguards against outlying test results while also accommodating for possible nonlinear effects of the covariates. Specifically, we postulate a location-scale regression model for the test outcomes in both the diseased and nondiseased populations, combining additive regression B-splines and M-estimation for the regression function, while the distribution of the error term is estimated via a weighted empirical distribution function of the standardized residuals. The results of the simulation study show that our approach successfully recovers the true covariate-specific area under the ROC curve on a variety of conceivable test outcomes contamination scenarios. Our method is applied to a dataset derived from a prostate cancer study where we seek to assess the ability of the Prostate Health Index to discriminate between men with and without Gleason 7 or above prostate cancer, and if and how such discriminatory capacity changes with age., (© 2021 John Wiley & Sons Ltd.)

Background and Purpose: Short-interval intracortical inhibition by threshold tracking (T-SICI) has been proposed as a diagnostic tool for amyotrophic lateral sclerosis (ALS) but has not been compared directly with conventional amplitude measurements (A-SICI). This study compared A-SICI and T-SICI for sensitivity and clinical usefulness as biomarkers for ALS., Methods: In all, 104 consecutive patients referred with suspicion of ALS were prospectively included and were subsequently divided into 62 patients with motor neuron disease (MND) and 42 patient controls (ALS mimics) by clinical follow-up. T-SICI and A-SICI recorded in the first dorsal interosseus muscle (index test) were compared with recordings from 53 age-matched healthy controls. The reference standard was the Awaji criteria. Clinical scorings, conventional nerve conduction studies and electromyography were also performed on the patients., Results: Motor neuron disease patients had significantly reduced T-SICI and A-SICI compared with the healthy and patient control groups, which were similar. Sensitivity and specificity for discriminating MND patients from patient controls were high (areas under the receiver operating characteristic curves 0.762 and 0.810 for T-SICI and A-SICI respectively at 1-3.5 ms). Paradoxically, T-SICI was most reduced in MND patients with the fewest upper motor neuron (UMN) signs (Spearman ρ = 0.565, p = 4.3 × 10 -6 )., Conclusions: Amplitude-based measure of cortical inhibition and T-SICI are both sensitive measures for the detection of cortical involvement in MND patients and may help early diagnosis of ALS, with T-SICI most abnormal before UMN signs have developed. The gradation in T-SICI from pathological facilitation in patients with minimal UMN signs to inhibition in those with the most UMN signs may be due to progressive degeneration of the subset of UMNs experiencing facilitation., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Primary lateral sclerosis (PLS) is a motor neuron disorder characterized by a pure upper motor neuron degeneration in the bulbar and spinal regions. The key difference with amyotrophic lateral sclerosis (ALS) is the lower motor neuron system integrity. Despite important literature on this disease, the pathophysiology of PLS remains unknown, and the link with ALS still balances between a continuum and a separate entity from ALS., Methods: We report nine families in which both PLS and ALS cases occurred, in general among first-degree relatives., Results: The patients with PLS and ALS had a typical disease presentation. Genetic studies revealed mutations in SQSMT1, TBK1, and TREM2 genes in two PLS patients and one ALS patient., Conclusions: These results strongly support a phenotypic continuum between PLS and ALS., (© 2021 European Academy of Neurology.)

Muscular cramp is a common symptom in healthy people, especially among the elderly and in young people after vigorous or peak exercise. It is prominent in a number of benign neurological syndromes. It is a particular feature of chronic neurogenic disorders, especially amyotrophic lateral sclerosis. A literature review was undertaken to understand the diverse clinical associations of cramp and its neurophysiological basis, taking into account recent developments in membrane physiology and modulation of motor neuronal excitability. Many aspects of cramping remain incompletely understood and require further study. Current treatment options are correspondingly limited., (© 2018 EAN.)

Discrimination surfaces are here introduced as a diagnostic tool for localizing brain regions where discrimination between diseased and nondiseased participants is higher. To estimate discrimination surfaces, we introduce a Mann-Whitney type of statistic for random fields and present large-sample results characterizing its asymptotic behavior. Simulation results demonstrate that our estimator accurately recovers the true surface and corresponding interval of maximal discrimination. The empirical analysis suggests that in the anterior region of the brain, schizophrenic patients tend to present lower local asymmetry scores in comparison with participants in the control group., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak., Objectives: To provide evidence-based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel., Methods: All available medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus., Recommendations: Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non-invasive positive-pressure ventilation also improves survival and quality of life. Maintaining the patient's ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end-of-life care should be discussed early with the patient and carers, respecting the patient's social and cultural background., (© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.)

Neuromuscular diseases are a known risk factor for immobilization-induced osteoporosis. The aim of the study was to analyse bone mineral density (BMD) in patients with familial amyloid polyneuropathy (FAP) type I (Val30 Met) and to compare them with a population of patients with other neuromuscular disorders. We studied 24, ambulatory, neuromuscular patients, all men and premenopausal women. We included 12 FAP patients (GI) and 12 patients with other disorders (GII). Clinical data included age, sex, height, weight, alcohol intake, smoking, calcium intake, physical activity and history of fractures. Serum and urinary calcium, osteocalcin, bone alkaline phosphatase, parathyroid hormone, thyroid stimulating hormone and urinary N-telopeptide cross-linked type 1 collagen were determined in all patients. Bone mineral density of lumbar spine, hip and wrist were determined by dual energy X-ray absorptiometry scan. No statistical differences were found in clinical or analytic data between the two groups, except for body mass index and calciuria, which were lower in GI. In GI, 54.5% were osteoporotic, against 23.1% in GII (P = 0.04). Bone mineral density was lower in GI when compared with GII, and tended to decrease with disease duration. Decreased BMI and the early autonomic involvement in GI probably explain the results. The prevention and early treatment of osteoporosis, in FAP patients should be considered a priority.