Semantic behavioral variant frontotemporal dementia and semantic dementia associated with mutations.

Frontotemporal dementia (FTD) is a highly heritable group of neurodegenerative disorders, characterized by varying clinical and pathological features. gene has been described worldwide within the FTD/ALS spectrum but its association with right and left temporal variant of FTD (tvFTD) is still unclear. This study aimed to reclassify a Sardinian FTD cohort according to proposed criteria for the semantic behavioral variant FTD (sbvFTD), explore mutations' association with tvFTD, and review related literature.

Takotsubo syndrome in a Sardinian amyotrophic lateral sclerosis cohort.

Introduction: Amyotrophic lateral sclerosis (ALS) is known to be associated with varying degrees of autonomic and cardiovascular dysfunction. Recent case reports showed that ALS may be linked to Takotsubo syndrome (TTS). We assessed the frequency of TTS in an incident ALS cohort from Sardinia, Italy, and investigated the relationship of TTS with ALS course.

Percutaneous gastrostomy, mechanical ventilation and survival in amyotrophic lateral sclerosis: an observational study in an incident cohort.

Objective: To analyze disease-modifying effects of percutaneous endoscopic gastrostomy (PEG) insertion for supporting nutrition, noninvasive ventilation (NIV), and tracheostomy-assisted ('invasive') ventilation (TIV) in amyotrophic lateral sclerosis (ALS).

Methods: We retrospectively analyzed survival in a large population-based incident cohort that was prospectively followed up in our center. Analysis considered several known ALS-related prognostic variables.

Point prevalence of epilepsy in dementia: A "real-world" estimate.

Objective: Several studies have demonstrated a higher frequency of seizures and epilepsy in Alzheimer's disease and other forms of dementia as compared with healthy elderly individuals. However, incidence and prevalence of epilepsy in the general population of dementia are unknown since most previous studies were performed in secondary-tertiary referral centres. In addition, all prior studies but one provided "period" rather than "point" prevalence estimates.

Disease survival and progression in TARDBP ALS patients from Sardinia, Italy.

Background: Common genes implicated in amyotrophic lateral sclerosis (ALS) development may also influence its progression rate. The C9orf72 mutations featured a faster progression rate while the European SOD1 mutations were associated with a slower progression. In this study, we assessed the relationship between TARDBP and ALS progression/survival.

Spatial clustering of amyotrophic lateral sclerosis in Sardinia, Italy: The contribution of age, sex, and genetic factors.

Introduction/aims: Several microgeographic clusters of higher/lower incidence of amyotrophic lateral sclerosis (ALS) have been identified worldwide. Differences in the distribution of local factors were proposed to explain the excess ALS risk, whereas the contribution of known genetic/epigenetic factors remains unclear. The aim is to identify restricted areas of higher risk in Sardinia and to assess whether age, sex, and the most common causative genetic mutations in Sardinia (C9orf72 and TARDBP mutations) contributed to the variation in the ALS risk.

Increasing prevalence 2015-2019 of amyotrophic lateral sclerosis in Sardinia, Italy.

Background: While amyotrophic lateral sclerosis (ALS) incidence has increased during the last decades, structured evidence on increased prevalence is lacking. After reporting a significant yearly increase of ALS incidence over a 10-year period, we checked for increased prevalence in Southern Sardinia over a quinquennium.

Methods: ALS patients (El Escorial Criteria) recruited from the study area and followed at ALS Centre, University of Cagliari, were included.

Incidence of amyotrophic lateral sclerosis in Sardinia, Italy: age-sex interaction and spatial-temporal variability.

This study assessed amyotrophic lateral sclerosis (ALS) incidence in Sardinia, Italy, and the combined contribution of age and gender to disease risk. We also checked disease incidence for spatial-temporal variability. : ALS patients from all neurological centers of the study area who had onset during 2010-2019 and fulfilled El Escorial revised diagnostic criteria were included.

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.

Objective: To identify the genetic variants associated with juvenile ALS.

Design, Setting, And Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation.

The unfolded protein response in amyotrophic later sclerosis: results of a phase 2 trial.

Strong evidence suggests that endoplasmic reticulum stress plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through altered regulation of proteostasis. Robust preclinical findings demonstrated that guanabenz selectively inhibits endoplasmic reticulum stress-induced eIF2α-phosphatase, allowing misfolded protein clearance, reduces neuronal death and prolongs survival in in vitro and in vivo models. However, its safety and efficacy in patients with ALS are unknown.

Sleep cardiac dysautonomia and EEG oscillations in amyotrophic lateral sclerosis.

Study Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease due to loss of motor neurons. However, the autonomic nervous system (ANS) can also be involved. The aim of this research was to assess the sleep macro- and microstructure, the cardiac ANS during sleep, and the relationships between sleep, autonomic features, and clinical parameters in a cohort of ALS patients.

Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials.

Objective: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders.

Methods: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the and genotype.

Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial).

Introduction: Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug.

Differential effects of phytotherapic preparations in the hSOD1 Drosophila melanogaster model of ALS.

The present study was aimed at characterizing the effects of Withania somnifera (Wse) and Mucuna pruriens (Mpe) on a Drosophila melanogaster model for Amyotrophic Lateral Sclerosis (ALS). In particular, the effects of Wse and Mpe were assessed following feeding the flies selectively overexpressing the wild human copper, zinc-superoxide dismutase (hSOD1-gain-of-function) in Drosophila motoneurons. Although ALS-hSOD1 mutants showed no impairment in life span, with respect to GAL4 controls, the results revealed impairment of climbing behaviour, muscle electrophysiological parameters (latency and amplitude of ePSPs) as well as thoracic ganglia mitochondrial functions.

Isolated rapid eye movement sleep without atonia in amyotrophic lateral sclerosis.

Objective: The aim of this study was to quantitatively analyze, with the most recent and advanced tools, the presence of periodic leg movements during sleep (PLMS) and/or rapid eye movement (REM) sleep without atonia (RSWA), in a group of patients with amyotrophic lateral sclerosis (ALS), and to assess their eventual correlation with the clinical severity of the disease.

Methods: Twenty-nine ALS patients were enrolled (mean age 63.6 years) along with 28 age-matched "normal" controls (mean age 63.

EEG functional network topology is associated with disability in patients with amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is one of the most severe neurodegenerative diseases, which is known to affect upper and lower motor neurons. In contrast to the classical tenet that ALS represents the outcome of extensive and progressive impairment of a fixed set of motor connections, recent neuroimaging findings suggest that the disease spreads along vast non-motor connections. Here, we hypothesised that functional network topology is perturbed in ALS, and that this reorganization is associated with disability.

VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies.

VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patients. We addressed VGF peptide changes in fibroblast cell cultures and in plasma obtained from ALS patients, in parallel with spinal cord and plasma samples from the G93A-SOD1 mouse model.

Monocytes of patients with amyotrophic lateral sclerosis linked to gene mutations display altered TDP-43 subcellular distribution.

Aims: Cytoplasmic accumulation of the nuclear protein transactive response DNA-binding protein 43 (TDP-43) is an early determinant of motor neuron degeneration in most amyotrophic lateral sclerosis (ALS) cases. We previously disclosed this accumulation in circulating lymphomonocytes (CLM) of ALS patients with mutant TARDBP, the TDP-43-coding gene, as well as of a healthy individual carrying the parental TARDBP mutation. Here, we investigate TDP-43 subcellular localization in CLM and in the constituent cells, lymphocytes and monocytes, of patients with various ALS-linked mutant genes.

TBK1 is associated with ALS and ALS-FTD in Sardinian patients.

Recently, mutations in the TANK-binding kinase 1 (TBK1) gene were identified as a cause for amyotrophic lateral sclerosis (ALS) with or without comorbid frontotemporal dementia. We have assessed the frequency and clinical characteristics of TBK1 mutations in a cohort of ALS patients of Sardinian ancestry. Whole-exome sequencing was performed on Hiseq2000 platform (Illumina).

REM sleep behavior disorder and periodic leg movements during sleep in ALS.

Objective: To assess sleep characteristics and the occurrence of abnormal muscle activity during sleep, such as REM sleep without atonia (RSWA), REM sleep behavior disorder (RBD), and periodic leg movements during sleep (PLMS), in patients with amyotrophic lateral sclerosis (ALS).

Methods: A total of 41 patients with ALS and 26 healthy subjects were submitted to clinical interview and overnight video-polysomnography.

Results: A total of 22 patients with ALS (53.