GDF15-GFRAL signaling drives weight loss and lipid metabolism in mouse model of amyotrophic lateral sclerosis.

Weight loss is a common early sign in amyotrophic lateral sclerosis (ALS) patients and negatively correlates with survival. In different cancers and metabolic disorders, high levels of serum growth differentiation factor 15 (GDF15) contribute to a decrease of food intake and body weight, acting through GDNF family receptor alpha-like (GFRAL). Here we report that GDF15 is highly expressed in the peripheral blood of ALS patients and in the hSOD1 mouse model and that GFRAL is upregulated in the brainstem of hSOD1 mice.

Comparison of the diagnostic accuracy of the 2010 European Federation of Neurological Societies/Peripheral Nerve Society and American Association of Electrodiagnostic Medicine diagnostic criteria for multifocal motor neuropathy.

Background And Purpose: This study was undertaken to compare the sensitivity and specificity of the 2010 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria for multifocal motor neuropathy (MMN) with those of the American Association of Electrodiagnostic Medicine (AAEM).

Methods: Sensitivity and specificity of the two sets of criteria were retrospectively evaluated in 53 patients with MMN and 280 controls with axonal peripheral neuropathy, inflammatory demyelinating polyneuropathy, or amyotrophic lateral sclerosis. Comparison of the utility of nerve conduction studies with different numbers of nerves examined was also assessed.

Oxidative Stress in Transthyretin-Mediated Amyloidosis: An Exploratory Study.

Transthyretin-mediated amyloidosis (ATTR) is a systemic disease with protein precipitation in many tissues, mainly the peripheral nerve and heart. Both genetic (ATTRv, "v" for variant) and wild-type (ATTRwt) forms are known. Beyond the steric encumbrance, precipitated transthyretin seems to have a toxic effect.

Prediction of cough effectiveness in amyotrophic lateral sclerosis patients assessed by ultrasuond of the diaphragm during the cough expiration phase.

Assessing cough effectiveness, using Cough Peak Flow, is crucial for patients with Neuromuscular Diseases, such as Amyotrophic Lateral Sclerosis. Impaired cough function can contribute to respiratory decline and failure. The goal of the study is to determine the correlation between diaphragmatic excursion and cough expiratory phase, potentially utilizing ultrasonographic indices to estimate Cough Peak Flow in these patients.

Emotion recognition in amyotrophic lateral sclerosis in a dynamic environment.

Objective: The aim of our study was to measure the ability of ALS patients to process dynamic facial expressions as compared to a control group of healthy subjects and to correlate this ability in ALS patients with neuropsychological, clinical and neurological measures of the disease.

Methods: Sixty-three ALS patients and 47 healthy controls were recruited. All the ALS patients also underwent i) the Geneva Emotion Recognition Test (GERT) in which ten actors express 14 types of dynamic emotions in brief video clips with audio, ii) the Edimburgh Cognitive and Behavioral ALS Screen (ECAS) test; iii) the ALS Functional Rating Scale Revised (ALSFRS-R) and iv) the Medical Research Council (MRC) for the evaluation of muscle strength.

Chronic inflammatory demyelinating polyneuropathy and HEV antibody status: A case-control study from Lazio, Italy.

Introduction: Few studies have pointed to the possible role of infectious diseases in triggering Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). Given the association of Hepatitis E Virus (HEV) with Guillain Barrè syndrome, we conducted a case-control study to determine the possible association of HEV infection with CIDP, analyzing possible risk factors for acquiring HEV infection in both CIDP patients and controls.

Materials And Methods: 82 CIDP and 260 from the general population have provided some personal information (demographics, anamnestic data and recognized risk factors for HEV infection) and underwent venipuncture blood sampling for virological assays testing for anti-HEV IgG and IgM with ELISA and RNA-HEV performing RT-PCR.

Assessment of diagnostic criteria for multifocal motor neuropathy in patients included in the Italian database.

Background And Purpose: This study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real-life data in multifocal motor neuropathy (MMN) patients.

Methods: Clinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty-six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis.

Genetics screening in an Italian cohort of patients with Amyotrophic Lateral Sclerosis: the importance of early testing and its implication.

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with an elusive etiology. While environmental factors have been considered, familial ALS cases have raised the possibility of genetic involvement. This genetic connection is increasingly evident, even in patients with sporadic ALS.

Serum neurofilament light chain: a promising early diagnostic biomarker for hereditary transthyretin amyloidosis?

Background And Purpose: Hereditary transthyretin amyloidosis (ATTRv) is a life-threatening disease caused by mutations in the gene encoding transthyretin (TTR). The recent therapeutic advances have underlined the importance of easily accessible, objective biomarkers of both disease onset and progression. Preliminary evidence suggests a potential role in this respect for neurofilament light chain (NfL).

RNA Interference and Neuromuscular Diseases: A Focus on Hereditary Transthyretin Amyloidosis.

Neuromuscular diseases are severe disorders affecting the peripheral nervous system, usually driving to death in a limited time. Many new drugs, through RNA-interference technology, are revolutionizing the prognosis and quality of life for these patients. Nevertheless, given the increased life expectancy, some new issues and phenotypes are expected to be revealed.

Retrospective observational study on the use of acetyl-L-carnitine in ALS.

ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC.

Does Patisiran Reduce Ocular Transthyretin Synthesis? A Pilot Study of Two Cases.

Background: Variant transthyretin-mediated amyloidosis (ATTR-v) is a well-characterized disease affecting the neurologic and cardiovascular systems. Patisiran has been approved for neurologic involvement as it reduces hepatic synthesis of transthyretin (TTR). Eye involvement is a lateonset feature increasing the risk of glaucoma and cataracts in patients.

Unclassified clinical presentations of chronic inflammatory demyelinating polyradiculoneuropathy.

Background: To assess the ability of the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) clinical criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) to include within their classification the whole spectrum of clinical heterogeneity of the disease and to define the clinical characteristics of the unclassifiable clinical forms.

Methods: The 2021 EAN/PNS clinical criteria for CIDP were applied to 329 patients fulfilling the electrodiagnostic (and in some cases also the supportive) criteria for the diagnosis of CIDP. Clinical characteristics were reviewed for each patient not strictly fulfilling the clinical criteria ('unclassifiable').

Immune-mediated myogenesis and acetylcholine receptor clustering promote a slow disease progression in ALS mouse models.

Background: Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease in terms of onset and progression rate. This may account for therapeutic clinical trial failure. Transgenic SOD1G93A mice on C57 or 129Sv background have a slow and fast disease progression rate, mimicking the variability observed in patients.

SMN Deficiency Destabilizes ABCA1 Expression in Human Fibroblasts: Novel Insights in Pathophysiology of Spinal Muscular Atrophy.

The deficiency of survival motor neuron protein (SMN) causes spinal muscular atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins.

Effect of RNS60 in amyotrophic lateral sclerosis: a phase II multicentre, randomized, double-blind, placebo-controlled trial.

Background And Purpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials.

The Silent Period for Small Fiber Sensory Neuropathy Assessment in a Mixed Cohort of Transthyretin-Mediated Amyloidosis.

Background: Transthyretin-mediated amyloidosis (ATTR) is a rare multisystemic disease involving the peripheral nervous system and heart. Autonomic and small fiber involvement is one of the hallmarks of ATTR, and many tools have been proposed to assess this aspect.

Aim: The aim of this study was to investigate cutaneous and mixed nerve silent periods (CSP and MnSP) as instruments for small fiber assessment.

Functional and morphometric assessment of small-fibre damage in late-onset hereditary transthyretin amyloidosis with polyneuropathy: the controversial relation between small-fibre-related symptoms and diagnostic test findings.

Introduction: We aimed at investigating whether functional and morphometric tests assessing small-fibre damage, ie quantitative sensory testing, Sudoscan and skin biopsy, reliably reflect neuropathic pain and autonomic symptoms in patients with late-onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).

Methods: In 30 patients with late-onset ATTRv-PN, we collected quantitative sensory testing, Sudoscan and skin biopsy with assessment of intraepidermal, piloerector muscle and sweat gland nerve fibre density. We then correlated these functional and morphometric parameters with neuropathic pain and autonomic symptoms as assessed with the Neuropathic Pain Symptom Inventory (NPSI) and Composite Autonomic Symptom Score-31 (COMPASS-31).