Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target.

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes a comprehensive multiomic approach to investigate the early and sex-specific molecular mechanisms underlying ALS. By analyzing the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS), we have uncovered significant molecular alterations associated with the disease.

European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD).

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.

Attitudes of caregivers towards prolonging and shortening life in advanced stages of amyotrophic lateral sclerosis.

Introduction: Inevitable disease progression in amyotrophic lateral sclerosis (ALS) forces patients and their caregivers (CGs) to reflect on end-of-life treatment. The CGs are often heavily burdened with their role of surrogate decision-makers. The aim of the study was to analyze attitudes of CGs and presumable attitudes of ALS patients from the CGs' perspective towards palliative care in advanced disease stages.

Quality of life and depression in patients with amyotrophic lateral sclerosis - does the country of origin matter?

Background: Given the inevitable relentless progressing nature of amyotrophic lateral sclerosis (ALS), it is essential to identify factors influencing patients' wellbeing. The study aimed to prospectively assess factors influencing the quality of life (QoL) and depression in ALS patients compared to healthy controls (HCs) from Poland, Germany and Sweden and their relationship to socio-demographic and clinical factors.

Methods: 314 ALS patients (120 from Poland, 140 from Germany, 54 from Sweden) and 311 age-, sex- and education-level-matched HCs underwent standardized interviews for quality of life, depression, functional status and pain.

Association of the practice of contact sports with the development of amyotrophic lateral sclerosis.

: High-intensity physical activity and sports prone to repetitive injuries of the cervical spine and head (when associated with vigorous practice) have been suggested as possible risk factors for amyotrophic lateral sclerosis (ALS). Our objective was to evaluate the relationship between the practice of contact sports (boxing, hockey, football, rugby) and ALS. : The study included 2247 individuals, 1326 patients and 921 controls from several European countries.

Low intensity exercise training in patients with amyotrophic lateral sclerosis - factors influencing eligibility and compliance to the clinical trial.

Background: To date, there are no evidence-based recommendations for physical therapy in amyotrophic lateral sclerosis (ALS). The reason is a low number of related clinical trials (CTs), restricted sample sizes and a high dropout rate. It may influence the profile of the participants, while the final results might not translate to the general ALS population.

Religiosity in patients with amyotrophic lateral sclerosis, a cross-country comparison.

Purpose: Amyotrophic lateral sclerosis (ALS) is a progressive motor impairment leading to early death. Religiousness is one of the factors potentially alleviating the psychological burden of patients. However, its role might vary according to cultural context.

Trends in the diagnostic delay and pathway for amyotrophic lateral sclerosis patients across different countries.

Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with a median survival of 2-5 years. An early diagnosis is essential for providing ALS patients the finest management possible. Studies from different countries report a similar median diagnostic delay of around 12 months, which is still far from desirable.

The quality of life and depression in primary caregivers of patients with amyotrophic lateral sclerosis is affected by patient-related and culture-specific conditions.

: To analyze the quality of life (QoL) and frequency of depression in primary caregivers of patients with amyotrophic lateral sclerosis (ALS) in two neighboring European countries. : a cross-sectional study performed in 164 dyads of ALS patients and caregivers followed at clinical ALS centers in Poland and Germany between 2015 and 2018. The quality of life (Anamnestic Comparative Self-Assessment - ACSA, Quality of Life in Life-Threatening Illness - Family Carer Version - QOLLTI-F) and depression (ALS-Depression-Inventory 12-Items - ADI-12) of the caregivers was assessed and correlated with caregivers- and patient-related factors.

Well-being on supportive techniques in amyotrophic lateral sclerosis: from neurologists' perspective.

Objective: To investigate intercultural neurologists' perception of well-being in patients with amyotrophic lateral sclerosis (ALS) using gastrostomy (PEG), non-invasive, and/or invasive ventilation (NIV/IV) and to analyse the determinants and impact on the management of the above medical interventions (MIs).

Methods: The study was based on anonymous questionnaires addressing the clinical approach and personal attitude towards the use of PEG, NIV and IV in ALS patients completed by 465 neurologists: 228 from Germany and 237 from Poland.

Results: The German and Polish neurologists estimated the quality of life in ALS patients using PEG and NIV as neutral, whilst low in individuals using IV.

Role of DTI-MRI parameters in diagnosis of ALS: useful biomarkers for daily practice? Tertiary centre experience and literature review.

Introduction: Despite the rapid development of neuroimaging techniques, the diagnosis of amyotrophic lateral sclerosis (ALS) remains a significant challenge. Magnetic resonance imaging (MRI) is important for ruling out ALS mimickers, while Diffusion Tensor Imaging (DTI) is a useful tool for the identification of cortical tract damage. The aim of this study was to identify the optimal set of DTI parameters to support the diagnosis of ALS that could be applied to everyday MRI and be used as a disease biomarker in daily practice.

TREM2 Gene Compound Heterozygosity in Neurodegenerative Disorders.

Background: Homozygous variants of the TREM2 and TYROBP genes have been shown to be causative for multiple bone cysts and neurodegeneration leading to progressive dementia (NHD, Nasu-Hakola disease).

Objective: To determine if biallelic variants of these genes and/or oligogenic inheritance could be responsible for a wider spectrum of neurodegenerative conditions.

Methods: We analyzed 52 genes associated with neurodegenerative disorders using targeted next generation sequencing in a selected group of 29 patients (n = 14 Alzheimer's disease, n = 8 frontotemporal dementia, n = 7 amyotrophic lateral sclerosis) carrying diverse already determined rare variants in exon 2 of TREM2.

Analysis of routine blood parameters in patients with amyotrophic lateral sclerosis and evaluation of a possible correlation with disease progression-a multicenter study.

Objective: Amyotrophic lateral sclerosis (ALS) pathogenesis is still unclear, its course is considerably variable, and prognosis is hard to determine. Despite much research, there is still a lack of easily accessible markers predicting prognosis. We investigated routine blood parameters in ALS patients regarding correlations with disease severity, progression rate, and survival.

Physical activity in patients with amyotrophic lateral sclerosis: Prevalence, patients' perspectives and relation to the motor performance.

Background: There are no recommendations for physical activity in amyotrophic lateral sclerosis (ALS) patients.

Objective: (i) To describe the prevalence and pattern of physical activity (PA) in ALS patients; (ii) to explore patients' attitude towards PA; and (iii) to investigate the relationship between PA at home environment and the rate of functional decline.

Methods: 96 ALS patients were followed for 6 months at 3-month intervals and assessed by site of disease onset, disease duration, diagnosis delay, functional status, muscle strength, fatigue and prevalence of PA.

Clinical trials in pediatric ALS: a TRICALS feasibility study.

Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA). To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.

SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity.

Mutations in superoxide dismutase 1 gene (SOD1) are linked to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder predominantly affecting upper and lower motor neurons. The clinical phenotype of ALS shows inter- and intrafamilial heterogeneity. The aim of the study was to analyze the relations between individual SOD1 mutations and the clinical presentation using in silico methods to assess the SOD1 mutations severity.

Delayed Diagnosis and Diagnostic Pathway of ALS Patients in Portugal: Where Can We Improve?

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unsatisfactory treatment options. Best management and recruitment into clinical trials requires early diagnosis. However, diagnosis is often delayed.

Motor neuron disease beginning with frontotemporal dementia: clinical features and progression.

: To study disease characteristics, progression and outcome in a group of motor neuron disease (MND) patients beginning with frontotemporal dementia (FTD) by comparing them with patients with the typical motor-onset. 849 patients recruited from tertiary centers were studied according to FTD-onset and motor-onset. We studied clinical data, functional decline and survival.

Caregivers' divergent perspectives on patients' well-being and attitudes towards hastened death in Germany, Poland and Sweden.

During the course of amyotrophic lateral sclerosis (ALS), patients and their families are faced with existential decisions concerning life-prolonging and -shortening measures. Correct anticipation of patient's well-being and preferences is a prerequisite for patient-centered surrogate decision making. : In Germany ( = 84), Poland ( = 77) and Sweden ( = 73) patient-caregiver dyads were interviewed.

Cardiovascular comorbidities in amyotrophic lateral sclerosis.

Background: The role of cardiovascular risk factors in amyotrophic lateral sclerosis (ALS) is controversial. A favourable profile has been found in ALS patients, but previous studies have not specifically considered the profile in different disease phenotypes.

Methods: Demographic data, smoking habits, lifetime exercise, and medical history including diabetes mellitus, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, stroke, and cardiac events, were analysed in ALS patients and in controls with other neurological disorders, utilising a standardized questionnaire applied by the same neurologist.

Dyslipidemia in patients with amyotrophic lateral sclerosis - a case control retrospective study.

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder leading to quadriplegia and aphagia. While swallowing difficulties and increased energy demand lead to malnutrition, increased lipid concentration may correlate with survival and respiratory functions. : To analyze the frequency and type of dyslipidemias in a large population of clinically characterized ALS patients (PALS).