Predicting functional impairment trajectories in amyotrophic lateral sclerosis: a probabilistic, multifactorial model of disease progression.

Objective: To employ Artificial Intelligence to model, predict and simulate the amyotrophic lateral sclerosis (ALS) progression over time in terms of variable interactions, functional impairments, and survival.

Methods: We employed demographic and clinical variables, including functional scores and the utilisation of support interventions, of 3940 ALS patients from four Italian and two Israeli registers to develop a new approach based on Dynamic Bayesian Networks (DBNs) that models the ALS evolution over time, in two distinct scenarios of variable availability. The method allows to simulate patients' disease trajectories and predict the probability of functional impairment and survival at different time points.

Common genetic basis of ALS patients and soccer players may contribute to disease risk.

Objective: The aim of the present study was to determine the prevalence of the ACSL A/G single nucleotide polymorphism among athletes and patients with amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disorder of motor neurons that leads to paralysis and death usually within 3-5 years from onset. Previous epidemiological studies reported a higher risk of ALS among soccer players.

The NEALS primary lateral sclerosis registry.

Primary lateral sclerosis (PLS) is a neurodegenerative disease characterized by progressive upper motor neuron dysfunction. Because PLS patients represent only 1 to 4% of patients with adult motor neuron diseases, there is limited information about the disease's natural history. The objective of this study was to establish a large multicenter retrospective longitudinal registry of PLS patients seen at Northeast ALS Consortium (NEALS) sites to better characterize the natural progression of PLS.

A novel mutation in segregates with amyotrophic lateral sclerosis in a large family with early onset and fast progression.

To identify the genetic background of ALS segregating in a large Bedouin family in Israel. Exome sequencing was carried out on three siblings in a family segregating ALS, two affected and one without neurological symptoms. Filtering for causative variants and for modifiers was carried out.

Rare homozygosity in amyotrophic lateral sclerosis suggests the contribution of recessive variants to disease genetics.

Objective: to determine the occurrence of homozygous rare, in-silico damaging variants in a genetically relatively homogenous group of amyotrophic lateral sclerosis (ALS) patients.

Methods: Whole-exome-sequencing of 43 ALS patients of North-Africa Jewish origin was performed. Data were filtered to identify very rare homozygous recessive in-silico damaging variants, in genes annotated to ALS-associated cellular pathways.

Early post-marketing experience with edaravone in an unselected group of patients with ALS.

: Treatment with edaravone has shown efficacy in a subgroup of patients with amyotrophic lateral sclerosis (ALS). However, it has been estimated that <7% of ALS patients fulfill the stringent inclusion criteria of the trial. In the current study, we aimed to explore retrospectively the efficacy of edaravone in unselected ALS patients.

"ALS reversals": demographics, disease characteristics, treatments, and co-morbidities.

Objective: To identify differences in demographics, disease characteristics, treatments, and co-morbidities between patients with "amyotrophic lateral sclerosis (ALS) reversals" and those with typically progressive ALS.

Methods: Cases of possible ALS reversals were found in prior publications, in the Duke ALS clinic, through self-referral or referral from other Neurologists, and on the internet. Of 89 possible reversals identified, 36 cases were included because chart or literature review confirmed their diagnosis and a robust, sustained improvement in at least one objective measure.

High frequency of C9orf72 hexanucleotide repeat expansion in amyotrophic lateral sclerosis patients from two founder populations sharing the same risk haplotype.

We characterized the C9orf72 hexanucleotide repeat expansion (RE) mutation in amyotrophic lateral sclerosis (ALS) patients of 2 distinct origins, Ashkenazi and North Africa Jews (AJ, NAJ), its frequency, and genotype-phenotype correlations. In AJ, 80% of familial ALS (fALS) and 11% of sporadic ALS carried the RE, a total of 12.9% of all AJ-ALS compared to 0.

OPTN 691_692insAG is a founder mutation causing recessive ALS and increased risk in heterozygotes.

Objective: To detect genetic variants underlying familial and sporadic amyotrophic lateral sclerosis (ALS).

Methods: We analyzed 2 founder Jewish populations of Moroccan and Ashkenazi origins and ethnic matched controls. Exome sequencing of 2 sisters with ALS from Morocco was followed by genotyping the identified causative null mutation in 379 unrelated patients with ALS and 1,000 controls.

Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis.

Importance: Celiac disease is an autoimmune disorder triggered by gluten in genetically predisposed individuals. Gluten sensitivity can cause neurologic manifestations, such as ataxia or neuropathy, with or without gastrointestinal symptoms. Many patients with gluten ataxia produce antibodies toward the newly identified neuronal transglutaminase 6 (TG6).

Outcome of percutaneous endoscopic gastrostomy insertion in patients with amyotrophic lateral sclerosis in relation to respiratory dysfunction.

Our objective was to describe a group of ALS patients who underwent percutaneous endoscopic gastrostomy (PEG) insertion, with emphasis on the respiratory function, by comparing patients with forced vital capacity (FVC) > 30% versus FVC ≤ 30%, and the effect of respiratory dysfunction on the perioperative complication rate and survival. Thirty consecutive ALS patients in whom FVC status was known underwent PEG insertion at our centre. Twenty of them had FVC > 30% (50.

Glycans in sera of amyotrophic lateral sclerosis patients and their role in killing neuronal cells.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by degeneration of upper and lower motor neurons. To date, glycosylation patterns of glycoproteins in fluids of ALS patients have not been described. Moreover, the aberrant glycosylation related to the pathogenesis of other neurodegenerative diseases encouraged us to explore the glycome of ALS patient sera.

A potential tool for the diagnosis of ALS based on diffusion tensor imaging.

Our objective was to quantify and better understand white matter (WM) impairment in patients with amyotrophic lateral sclerosis (ALS) and to propose a model based on diffusion tensor imaging (DTI) for diagnosing patients with suspected ALS with upper motor neuron (UMN) signs. Twenty-six ALS patients (24 with prominent UMN signs and two with an isolated lower-motor neuron (LMN) syndrome) and 22 healthy volunteers were examined using DTI. Data analysis included voxel-based WM tract-based spatial statistics (TBSS), volume-of-interest analysis of the TBSS results and stream-line tractography analysis.

Gender-based effect of statins on functional decline in amyotrophic lateral sclerosis.

Recently an association between statins and the onset and more rapid disease course of amyotrophic lateral sclerosis (ALS) was reported, while other studies rejected such a link. The role of gender in that controversy is unclear. We evaluated the gender-specific effect of statins on the rate of functional decline in patients with ALS, based on data retrieved from the medical records of all ALS patients who participated in two previously reported clinical trials on the efficacy of topiramate and of celecoxib in ALS.

Autonomic impairment in a transgenic mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of motor neurons, however it is increasingly recognized that nonmotor manifestations may occur, including autonomic nervous system dysfunction. To better understand the autonomic involvement in ALS we measured autonomic functions in transgenic (TG) mice carrying an SOD1 (G93A) mutation and wild-type (WT) control mice. TG mice had a higher heart rate at rest and following stress than WT mice at all ages except for the advanced stages of the disease (19-20weeks of age).

Moving toward a predictive and personalized clinical approach in amyotrophic lateral sclerosis: novel developments and future directions in diagnosis, genetics, pathogenesis and therapies.

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that affects upper and lower motor neurons in the brain and spinal cord, with progressive weakness and atrophy of most muscles in the body and is almost always fatal within 3-5 years. A small proportion of cases are familial, and remarkable achievements have been made during the last years in understanding the genetics of the disease. In spite of this, the basic pathogenic mechanisms underlying the sporadic disease are still poorly understood.

Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress?

Background: The exact cause of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress is one of the factors implicated in the etiology of ALS as well as in that of other neurodegenerative diseases. Uric acid is an important natural antioxidant that may reduce oxidative stress.

Recombinant human granulocyte-colony stimulating factor administration for treating amyotrophic lateral sclerosis: A pilot study.

Granulocyte-colony stimulating factor (G-CSF) is used to mobilize CD34+ haematopoietic stem cells from the bone marrow to the peripheral blood. We proposed to use cell subsets induced by G-CSF to slow down disease progression in patients with amyotrophic lateral sclerosis (ALS). Patients with definite or probable ALS were assigned in a double-blind manner to receive G-CSF or placebo every three months for a year.

Do patients with amyotrophic lateral sclerosis (ALS) have increased energy needs?

Background And Aims: Nutritional status is a prognostic factor for survival in amyotrophic lateral sclerosis (ALS) patients. We investigated the contribution of some of the components contributing to resting energy expenditure (REE) in order to determine whether potentially higher energy needs should be considered for these patients.

Methods: Thirty three ALS patients and 33 age- and gender-matched healthy controls participated.

Low-grade systemic inflammation in patients with amyotrophic lateral sclerosis.

Objective: To prospectively determine the intensity of systemic low-grade inflammation in patients with amyotrophic lateral sclerosis (ALS).

Patients And Methods: Patients with ALS and matched healthy controls underwent blood tests for inflammation-sensitive biomarkers: erythrocyte sedimentation rate (ESR), quantitative fibrinogen, wide-range C-reactive protein (wrCRP) concentrations, leukocyte count and neutrophil-to-lymphocyte ratio (NLR). The correlation between these inflammatory biomarkers and disability status of the patients, expressed by the ALS Functional Rating Scale (ALSFRS-R), was evaluated.

Influence of statins treatment on survival in patients with amyotrophic lateral sclerosis.

Background: Statins are increasingly recognized as causing muscle damage and, more rarely, peripheral neuropathy. A preliminary report that there are more cases of amyotrophic lateral sclerosis (ALS) among people treated with statins caused considerable concern. We considered the possibility that statins could affect survival in patients already diagnosed as having amyotropic lateral sclerosis who were taking statins for dyslipidemia.