Juvenile amyotrophic lateral sclerosis (JALS) is a rare and severe form of ALS. The development of sequencing methods has resulted in increased reports of JALS cases in recent years, this study, we identified a novel heterozygous mutation in exon 14, c.1509dupA:p.R503fs, of the RNA-binding protein fused in sarcoma (FUS) in a 17-year-old female patient with sporadic JALS who experienced rapid progression

Objective: Deficits in social cognition are part of the cognitive phenotype of amyotrophic lateral sclerosis (ALS). This study investigated the psychometric properties and test-retest reliability of two short-form versions of the Reading the Mind in the Eyes Test. Method: Patients with ALS (n = 50), alongside age and IQ matched controls (n = 50) were recruited. The Reading the Mind in the Eyes Test

Background: A cognitive impairment, ranging from frontotemporal dementia (FTD) to milder forms of dysexecutive or behavioral dysfunction, is detected in 30–50% of patients affected by amyotrophic lateral sclerosis (ALS) at diagnosis. Such condition considerably influences the prognosis, and possibly impacts on the decision-making process with regards to end-of-life choices. The aim of our study is

Neuroinflammation, meaning the establishment of a diffuse inflammatory condition in the CNS, is one of the main hallmarks of amyotrophic lateral sclerosis (ALS). Recently, a crucial role of regulatory T cells (Tregs) in this disease has been outlined. Tregs are a T cell subpopulation with immunomodulatory properties. In this review, we discuss the physiology of Tregs and their role in ALS disease onset

Objectives: To estimate the incidence of amyotrophic lateral sclerosis (ALS) in Moscow by investigating multiple sources of cases. Incidence rates from previous Russian studies ranged from 0.3 to 0.7 per 100,000/year. Methods: A retrospective study of the incidence of ALS was performed in the South district of Moscow (population, 1,760,000, 2015). Several data sources were investigated. The medical

(2020). ALSUntangled 56: “ten red flags”-things to be wary of in alternative or off-label products. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Ahead of Print.

Introduction: In the current study, we are going to look at different factors responsible for the diagnostic delay of ALS patients among the sample of Egyptian patients. Method/patients: This is a cohort study. ALS patients were recruited from December 2018 to January 2020 from the ALS clinic at the international medical center (IMC) (Cairo, Egypt). We analyzed the site of onset, the time from symptom

Objective: Amyotrophic lateral sclerosis (ALS) has profound effects on people with ALS (PALS) and caregivers. There is a paucity of research detailing and comparing PALS and caregiver day-to-day perspectives of ALS. Methods: A survey developed collaboratively by The ALS Association and a panel of experts in ALS care was designed to broadly sample the experience of PALS and caregivers with respect to

Abstract Objective: To evaluate whether a blended (face-to-face and online) psychosocial support program for caregivers of patients with Amyotrophic Lateral Sclerosis (ALS) and Progressive Muscular Atrophy (PMA), aimed at enhancing feeling of control over caregiving, reduces psychological distress. Methods: A randomized controlled trial using a wait-list control design was conducted. Caregiver-patient

(2020). ALSUntangled 55: vitamin E (α-tocopherol). Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Ahead of Print.

A total of 178 consecutive patients with definite sALS without frontotemporal dementia (FTD) were enrolled in this study, after complete clinical evaluation. A Repeat-Primed Polymerase Chain Reaction (RP-PCR) protocol was applied to detect the G4C2 repeats expansions. In the studied sALS patients, 5.06% (n = 9) carried the C9orf72 mutation. Among carriers, 2/3 of them were females and spinal onset

Abstract Objective: The majority of cases of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are of unknown etiology. A proportion of these cases are likely to be attributable to contaminant exposures, although the specific environmental etiology of ALS remains largely a mystery. Certain forms of the neurotoxic metal mercury readily cross into the central nervous system. Fish

Objective: Since the observation of several deaths from amyotrophic lateral sclerosis (ALS) among Italian professional soccer players, an association between ALS and soccer has been postulated. The objective of the study is to investigate the association between professional soccer and the risk of ALS in a large cohort of former professional soccer players with prolonged follow-up. Methods: All professional

Objectives: (a) to estimate the accuracy of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code for amyotrophic lateral sclerosis (ALS) in the Hospital Discharge Database (HDD) of the Italian region Friuli-Venezia Giulia; (b) to identify the predictors of a true positive ALS code; (c) to compare incident and prevalent cases obtained from HDD with those identified

Objective: Electrical Impedance Myography (EIM) was used to evaluate disease progression in subjects with C9ORF72 expansion mutations and to assess correlations with Medical Research Council (MRC) Scale and revised ALS Functional Rating Scale (ALSFRS-R) measurements. Four types of clinical presentations were assessed; Amyotrophic Lateral Sclerosis (ALS), Frontotemporal dementia (FTD) or other dementia

(2020). ALSUntangled No. 52: Glutathione. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration: Vol. 21, No. 1-2, pp. 154-157.

(2020). ALSUntangled 51: RCH4. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration: Vol. 21, No. 1-2, pp. 150-153.

We describe a patient with sporadic amyotrophic lateral sclerosis (ALS) who showed progressive deterioration of sensory cortex excitability at the advanced stage, while using invasive ventilation. At the time of diagnosis, the patient showed enlarged N20 of the median nerve somatosensory evoked potential (SEP). Following ventilator use through tracheostomy, the patient gradually fell into a totally

Sandhoff disease is an under-recognized disease that may present as a lower motor neuron disorder in adulthood. We report the case of siblings presenting in their late 40s with a motor neuron disease phenotype and were misdiagnosed as amyotrophic lateral sclerosis and later found to have Sandhoff disease. Sandhoff disease should be considered in patients presenting with a slowly progressive predominately

Objectives: To estimate the effect of riluzole on the stage-specific risk of progression of ALS. Methods: Patients from the PRO-ACT dataset were staged employing two methods (King's and FT9). Hazard ratios associated with riluzole treatment were estimated for forward transition between stages, using unadjusted and adjusted Markov multistate models. Results: Of 1903 patients, 1587 had received riluzole

Objective: To describe the phenotypic heterogeneity of amyotrophic lateral sclerosis (ALS) in Tunisian patients, and to define the sociodemographic features, treatments, and survival rate with ALS. Methodology: The study included 210 patients with ALS diagnosed between 2003 and 2019 in The Neurology department, Razi Hospital Tunisia. ALS patients were phenotyped and followed until their death. Results:

Amyotrophic lateral sclerosis (ALS) is a fatal, rare, and hard to diagnose neurological disease with unknown etiology. Objective: To understand the incidence, prevalence, and survival characteristics of ALS cases in the Atlanta metropolitan area. Methods: Neurologists in Clayton, Cobb, DeKalb, Fulton, and Gwinnett counties provided case reports for ALS patients under their care from 1 January 2009

Objectives: People with motor neurone disease (pwMND) experience communication impairments due to speech and motor dysfunction. Communication support in the form of Augmentative and Alternative Communication (AAC) in conjunction with Assistive Technology (AT) access methods are available, however, variation in provision care pathways exists across Scotland. We conducted a baseline study of communication

Objective: Previous studies, mostly from the United States, showed an increased risk of motor neuron disease (MND) in military personnel. We compared MND incidence rates in French military personnel to that in the general population. Methods: Among persons covered between 2010 and 2016 by the Caisse Nationale Militaire de Sécurité Sociale (CNMSS, military personnel) and the Caisse Nationale d'Assurance

Cognitive decline and behavioral changes are common features in amyotrophic lateral sclerosis (ALS) and imply worse prognosis as well as increased disease burden for patients and caregivers. Currently, there is a lack of studies regarding behavioral profile in Brazilian ALS cohorts. We assessed the prevalence and profile of behavioral impairment (ALSbi) in a Brazilian non-demented C9orf72-negative

Objectives. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a brief multi-domain assessment designed for people with Amyotrophic Lateral Sclerosis (ALS). This study evaluated the clinical impact of using the ECAS on ALS patients, carers and healthcare professionals. A secondary aim was to evaluate the clinical impact of neuropsychological intervention. Methods. A survey of current screening

To examine the equivalency of ECAS versions A, B, and C in an Irish cohort, and to examine potential practice effects, 236 healthy controls were recruited through the Irish ALS control database. One hundred and seventy-six (176) controls completed ECAS version A, B, or C. Separately, 60 controls completed all three versions (A-B-C), consecutively, four months apart. TOST analysis found that ECAS A

Objectives: (1) Adapt the ECAS into Greek, validate it in ALS patients and compare with the ALS-CBS. (2) Determine the sensitivity and specificity of ECAS in the differentiation between AD and non-demented ALS patients as compared with the ACE-III and mini-ACE. Methods: ALS patients (n = 28) were recruited and AD patients (n = 26) were matched in age, sex, and education with ALS patients (n = 24).

Objective: The rates of decline in respiratory measurements, including Peak Cough Flow (PCF) have not been established in Amyotrophic Lateral Sclerosis (ALS). Additionally, optimal prescription of cough adjuncts which aim to increase cough strength are unknown. The primary aim of this study was to quantify declines in respiratory function in ALS using PCF, Sniff Nasal Inspiratory Pressure (SNIP) and

Objective: Angiogenin (ANG) is a pro-angiogenic and neurotrophic factor with an important role in stress-induced injury, by promoting neovascularization and neuronal survival. Identification of loss-of-function mutations and evidence of beneficial effect of ANG administration in transgenic SOD1G93A mice have linked ANG to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), stimulating interest

Aim: The demonstration that chaperone-mediated autophagy (CMA) contributes to the degradation of TDP-43, the main constituent of cytoplasmic inclusions typically found in motor neurons of patients with sporadic amyotrophic lateral sclerosis (sALS), has pointed out a possible involvement of CMA in aggregate formation. To explore this possibility, in this study, we verified the presence of a possible

Objective: The use of speech measures is becoming a common practice in the assessment of bulbar disease progression in amyotrophic lateral sclerosis (ALS). This study aimed to establish psychometric properties (e.g. reliability, validity, sensitivity, specificity) of speech and pause timing measures during a standardized passage. Methods: A large number of passage recordings (ALS N = 775; Neurotypical

Objective: To assess the utility of novel measures derived from a rapid syllable repetition task (i.e. oral dysdiadochokinesis [DDK]) in early stratification of fast and slow progressive bulbar amyotrophic lateral sclerosis (ALS) and prediction of bulbar disease progression rate. Methods: Fifty-four individuals with ALS were tracked longitudinally on their oral DDK and global bulbar/speech performance

Objectives: To analyze the clinical features of flail arm syndrome (FAS) in a large Chinese clinic-based cohort, and to discuss whether it is proper to use a course of 12 months from symptoms onset as the criterion for FAS. Methods: This cohort study included patients with FAS or upper-limb-onset amyotrophic lateral sclerosis (UL-ALS) who visited Peking University Third Hospital between 2003 and 2013

Over the past two decades, the El Escorial criteria (EEC) have been used as eligibility criteria in major randomized controlled trials. One of the goals of the revised EEC was to allow earlier diagnosis and, thus earlier trial inclusion by introducing a new category, namely "clinically probable laboratory supported" ALS. This category allowed EMG findings to be taken into account assuming that EMG

Objective: To conduct a phase-II trial using a ranking and selection paradigm where multiple treatments are compared with limited sample size and the best is chosen for a subsequent efficacy trial versus placebo. This strategy can find an effective treatment faster than traditional strategy of conducting larger trials against placebo. Methods: Sixty amyotrophic lateral sclerosis (ALS) participants

Objective: To assess masitinib in the treatment of ALS. Methods: Double-blind study, randomly assigning 394 patients (1:1:1) to receive riluzole (100 mg/d) plus placebo or masitinib at 4.5 or 3.0 mg/kg/d. Following a blinded transition from phase 2 to phase 2/3, a prospectively defined two-tiered design was implemented based on ALSFRS-R progression rate from disease-onset to baseline (ΔFS). This approach

(2020). The rise of innovative clinical trial designs: what’s in it for amyotrophic lateral sclerosis? Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration: Vol. 21, No. 1-2, pp. 3-4.

(2020). In pursuit of the normal progressor: the holy grail for ALS clinical trial design? Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration: Vol. 21, No. 1-2, pp. 1-2.

Abstract Cognitive and behavioral abnormalities are recognized as an integral part of Motor Neurone Disease (MND) and occur at all stages of the disease. The early detection of cognitive and behavioral symptoms in MND is critical. Such symptoms are only reported when we explicitly ask, evaluate, document, and assess. In the National Institute for Health and Care Excellence (NICE) MND guideline (2016)

Cytoplasmic aggregation of TAR-DNA binding protein (TDP-43) in Amyotrophic Lateral Sclerosis (ALS) and fronto-temporal lobar dementia (FTLD) is associated with post-translational modifications (PTM) and delocalization. Studies on postmortem brains of ALS and FTLD patients showed the existence of TDP-43 fragments that end at position N291. We report a new heterozygous mutation p.N291H in a familial

Abstract Introduction: Susceptibility to amyotrophic lateral sclerosis (ALS) is associated with smoking in some studies, but it is not clear which aspect of smoking behavior is related. Using detailed records of lifetime smoking we investigated the relationship between smoking and ALS in a UK population. Methods: In this retrospective case-control study, smoking status was collected using environmental

(2020). Commissural fiber degeneration in motor neuron diseases. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Ahead of Print.

Recently, mutations in genes related to frontotemporal dementia and/or amyotrophic lateral sclerosis have been described as the cause of late onset psychosis. Here, we report a 68-year-old patient, carrier of a mutation in the gene encoding ubiquilin-2 (UBQLN2), who presented adult onset psychotic manifestations followed by a dysexecutive syndrome compatible with the diagnosis of behavioral variant

There are a number of physical restrictions that develop in the course of amyotrophic lateral sclerosis (ALS). While loss of speech and motor control may be partially compensated by the support of assistive devices, swallowing difficulty and respiratory insufficiency require medical interventions (percutaneous endoscopic gastrostomy, noninvasive, and invasive ventilation). Based on the data collected

Objectives: Mortality data have been used as a proxy for amyotrophic lateral sclerosis (ALS) incidence. However, the accuracy of death certificates (DCs) needs to be validated. This study aims to assess the accuracy of DCs in the identification of ALS cases. Methods: This is a retrospective population-based validation study. DC information, provided by the “Centre d’épidémiologie sur les causes médicales

Objective: To determine the associations between plasma creatinine (PCr), plasma uric acid (PUA), and urinary oxidative stress (OS) biomarkers with the ALSFRS-R at baseline and survival in a large epidemiological cohort study (ALS COSMOS) with a well-phenotyped patient population (N = 355). Methods: Fasting plasma and first void urine samples were obtained. PCr, PUA, urinary 8-oxo-deoxy guanosine (8-oxodG)

Objective: To identify the genetic background of ALS segregating in a large Bedouin family in Israel. Methods: 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. Eight variants were confirmed by Sanger sequencing and genotyped on nine available members

Objective: The Ljubljana ALS Centre, established in 2002, is the only tertiary center for amyotrophic lateral sclerosis (ALS) in Slovenia. The aim of our study was to evaluate the impact of therapeutic interventions and improvements in the multidisciplinary care on the survival of our patients. Methods: All patients diagnosed with ALS at our center during years 2003–2005 (early group) and 2011–2012

Introduction: To date more than 180 different mutations in the SOD1 gene have been described in ALS; some of these mutations are associated to peculiar clinical features and have contributed to the understanding of disease heterogeneity. Only 5% of SOD1 mutations involve exon 3. Here we report a novel mutation c.197A > C in the exon 3 of the SOD1 gene in two apparently unrelated ALS families with early

VRK1 encodes a serine/protein kinase possibly involved in pathways related to amyotrophic lateral sclerosis (ALS) pathogenesis. Pathogenic variants in VRK1 have been related to different phenotypes. We describe the clinical phenotype of two unrelated Portuguese patients with different VRK1 variants. Both patients presented a bilateral distal weakness in lower limbs beginning in childhood slowly progressing

(2020). ALSUntangled No. 54: “LEAP2BFIT”. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration: Vol. 21, No. 3-4, pp. 314-319.

(2020). Rare phenotype of ALS4 associated with heterozygous missense mutation c.5842A > G/p.M1948V in helicase domain of SETX gene. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration: Vol. 21, No. 3-4, pp. 312-313.

(2020). An exon 5 mutation (c.425G>C, p.Gly141Ala) in the SOD1 gene in a Chinese family associated with incomplete penetrance. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Ahead of Print.

Objective: Amyotrophic lateral sclerosis (ALS) is a rare worldwide heterogeneous neurodegenerative disease with sporadic and familial (FALS) forms. A rare autosomal dominant subtype of FALS was identified in a Brazilian family, classified as ALS type 8 (ALS8) linked to the VAPB gene. The aim of our study was to analyze a series of ALS8 patients from unrelated families in order to further characterize

Objective: Patients with amyotrophic lateral sclerosis (ALS) not only show motor deficits, but may also have cognitive and/or behavioral impairments. Recognizing these impairments is crucial as they are associated with lower quality of life, shorter survival, and increased caregiver burden. Therefore, ALS-specific neuropsychological screening instruments have been developed that can account for motor

Around 10% of all amyotrophic lateral sclerosis (ALS) cases are familial and around 3-5% are fused-in-sarcoma (FUS)-related in Europe. We report a 43-year-old patient with a pathogenic FUS mutation (c.1561C>G p.(Arg521Gly) who presented at our clinic with chorea and subsequently with progressive symptoms of classical ALS. As a result of progressive upper and lower motor neurone deterioration, chorea

Aim: Frontotemporal lobar degeneration (FTLD) is a significant cause of dementia in mid-life and older adults. The extent of interactions between FTLD and other neurodegenerative pathologies is unclear. We reviewed the occurrences of mixed pathology in cases of neuropathologically diagnosed FTLD from the UK Brain Bank Network. Materials and methods: Clinicopathological details of cases of FTLD were

Background and Objectives: The corpus callosum is a site of pathological involvement in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). The corpus callosum shows widespread cortical connectivity topographically distributed along its length. Initial limb weakness in ALS is typically unilateral, becoming bilateral with disease progression. The precise anatomical substrate for this

Objective: To perform a comprehensive lipid profiling to evaluate potential lipid metabolic differences between patients with amyotrophic lateral sclerosis (ALS) and controls, and to provide a more profound understanding of the metabolic abnormalities in ALS. Methods: Twenty patients with ALS and 20 healthy controls were enrolled in a cross-sectional study. Untargeted lipidomics profiling in fasting