Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a multifactorial, multisystem motor neuron disease for which currently there is no effective treatment. There is an urgent need to identify biomarkers to tackle the disease's complexity and help in early diagnosis, prognosis, and therapy. Extracellular vesicles (EVs) are nanostructures released by any cell type into body fluids.

The hypometabolic state: a good predictor of a better prognosis in amyotrophic lateral sclerosis.

Background: Malnutrition and weight loss are negative prognostic factors for survival in patients with amyotrophic lateral sclerosis (ALS). However, energy expenditure at rest (REE) is still not included in clinical practice, and no data are available concerning hypometabolic state in ALS.

Objective: To evaluate in a referral cohort of patients with ALS the prevalence of hypometabolic state as compared with normometabolic and hypermetabolic states, and to correlate it with clinical phenotype, rate of progression and survival.

Spinal muscular atrophy: state of the art and new therapeutic strategies.

Spinal muscular atrophy (SMA) is a severe disorder of motor neurons and the most frequent cause of genetic mortality, due to respiratory complications. We are facing an exciting era with three available therapeutic options in a disease considered incurable for more than a century. However, the availability of effective approaches has raised up ethical, medical, and financial issues that are routinely faced by the SMA community.

Management of respiratory complications and rehabilitation in individuals with muscular dystrophies: 1st Consensus Conference report from UILDM - Italian Muscular Dystrophy Association (Milan, January 25-26, 2019).

Respiratory complications are common in the patient with muscular dystrophy. The periodic clinical and instrumental respiratory evaluation is extremely important. Despite the presence in the literature of updated guidelines, patient associations often report lack of knowledge of these pathologies, particularly in peripheral hospitals.

Psychosocial burden and professional and social support in patients with hereditary transthyretin amyloidosis (ATTRv) and their relatives in Italy.

Background: Hereditary transthyretin amyloidosis (hATTR), alias ATTR variant (ATTRv) is a severe and disabling disease causing sensory and motor neuropathy, autonomic dysfunction, and cardiomyopathy. The progressive decline of patient's functional autonomy negatively affects the patient's quality of life and requires increasing involvement of relatives in the patient's daily life. Family caregiving may become particularly demanding when the patient is no longer able to move independently.

Mouthpiece ventilation in neuromuscular disorders: Narrative review of technical issues important for clinical success.

In neuromuscular disorders (NMDs), nocturnal non-invasive ventilation (NIV) via a nasal mask is offered when hypercapnic respiratory failure occurs. With disease progression, nocturnal NIV needs to be extended into the daytime. Mouthpiece ventilation (MPV) is an option for daytime NIV.

ALS Mimics due to Affection of the Cervical Spine: From Common Compressive Myelopathy to Rare CSF Epidural Collection.

Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disease, with chameleon presentations and several mimics. Considering the poor prognosis of ALS, their precise and timely identification is pivotal. Affection of the cervical spine represents one potential source of ALS mimics that should never be missed, since it is potentially treatable.

The Spinal Muscular Atrophy Health Index: A novel outcome for measuring how a patient feels and functions.

Introduction: The Spinal Muscular Atrophy Health Index (SMA-HI) is a multifaceted, disease-specific, patient-reported outcome to measure an SMA patient's perception of their disease burden. In preparation for upcoming therapeutic trials, we examine the validity, reliability, and usability of the SMA-HI in adults, teenagers, and children with SMA.

Methods: Using data from a cross-sectional study of 359 international adult patients with SMA, we identified the most relevant symptoms to include in the SMA-HI.

Ocular Involvement Occurs Frequently at All Stages of Amyotrophic Lateral Sclerosis: Preliminary Experience in a Large Italian Cohort.

Background And Purpose: The study aimed to obtain optometric findings of amyotrophic lateral sclerosis (ALS) patients in different stages of the disease, and to determine the relation between ocular data and ALS-related features; that is, functional and cognitive impairment and staging.

Methods: The optometric protocol included tests of the ocular motility [broad-H test and Northeastern State University College of Optometry (NSUCO) test], near point of convergence (NPC), error refraction, best-corrected visual acuity, and binocular visual alignment, and an ocular symptoms questionnaire. The functional measures included the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-r) and Milano-Torino staging (MiToS), and cognitive impairment was assessed using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).

Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) patients express significant clinical heterogeneity that often hinders a correct diagnostic definition. Intracellular deposition of TDP-43, a protein involved in RNA metabolism characterizes the pathology. Interestingly, this protein can be detected in serum, wherein cognate naturally-occurring auto-antibodies (anti-TDP-43 NAb) might be also present, albeit they have never been documented before.

12-Month progression of motor and functional outcomes in congenital myotonic dystrophy.

Background: We aim to describe 12-mo functional and motor outcome performance in a cohort of participants with congenital myotonic dystrophy (CDM).

Methods: CDM participants performed the 6 Minute Walk Test (6MWT), 10 Meter Run, 4 Stair Climb, Grip Strength, and Lip Force at baseline and 12-mo visits. Parents completed the Vineland Adaptive Behavior Scale.

Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus.

Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington's disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies.

Estimating the impact of COVID-19 pandemic on services provided by Italian Neuromuscular Centers: an Italian Association of Myology survey of the acute phase.

Introduction: Since February 2020, the outbreak of COVID-19 in Italy has forced the health care system to undergo profound rearrangements in its services and facilities, especially in the worst-hit areas in Northern Italy. In this setting, inpatient and outpatient services had to rethink and reorganize their activities to meet the needs of patients during the "lockdown". The Italian Association of Myology developed a survey to estimate the impact of these changes on patients affected by neuromuscular disorders and on specialized neuromuscular centers during the acute phase of COVID-19 pandemic.

Reliability of the Charcot-Marie-Tooth functional outcome measure.

The CMT-FOM is a 13-item clinical outcome assessment (COA) that measures physical ability in adults with Charcot-Marie-Tooth disease (CMT). Test-retest reliability, internal consistency and convergent validity have been established for the CMT-FOM. This current study sought to establish inter-rater reliability.

New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges.

Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases with progressive weakness of skeletal and respiratory muscles, leading to significant disability. The disorder is caused by mutations in the survival motor neuron 1 () gene and a consequent decrease in the protein leading to lower motor neuron degeneration. Recently, Food and Drug Administration (FDA) and European Medical Agency (EMA) approved the antisense oligonucleotide nusinersen, the first SMA disease-modifying treatment and gene replacement therapy by onasemnogene abeparvovec.

Focus on the heterogeneity of amyotrophic lateral sclerosis.

The clinical manifestations of amyotrophic lateral sclerosis (ALS) are variable in terms of age at disease onset, site of onset, progression of symptoms, motor neuron involvement, and the occurrence of cognitive and behavioral changes. Genetic background is a key determinant of the ALS phenotype. The mortality of the disease also varies with the ancestral origin of the affected population and environmental factors are likely to be associated with ALS at least within some cohorts.

RELEVANCE OF DIAGNOSTIC INVESTIGATIONS IN CHRONIC INFLAMMATORY DEMYELINATING POLIRADICULONEUROPATHY: DATA FROM THE ITALIAN CIDP DATABASE.

Background and aims to report the clinical features and the relevance of diagnostic investigations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We retrospectively reviewed data from patients with a clinical diagnosis of CIDP included in a national database. Among the 500 included patients with a clinical diagnosis of CIDP, 437 patients (87%) fulfilled the EFNS/PNS criteria for CIDP (definite in 407, probable in 26, possible in four).

miR-129-5p: A key factor and therapeutic target in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a relentless and fatal neurological disease characterized by the selective degeneration of motor neurons. No effective therapy is available for this disease. Several lines of evidence indicate that alteration of RNA metabolism, including microRNA (miRNA) processing, is a relevant pathogenetic factor and a possible therapeutic target for ALS.

Guidelines on clinical presentation and management of nondystrophic myotonias.

The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation.

G-CSF (filgrastim) treatment for amyotrophic lateral sclerosis: protocol for a phase II randomised, double-blind, placebo-controlled, parallel group, multicentre clinical study (STEMALS-II trial).

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurological disorder characterised by a selective degeneration of motor neurons (MNs). Stem cell transplantation is considered as a promising strategy in neurological disorders therapy and the possibility of inducing bone marrow cells (BMCs) to circulate in the peripheral blood is suggested to investigate stem cells migration in degenerated ALS nerve tissues where potentially repair MN damage. Granulocyte-colony stimulating factor (G-CSF) is a growth factor which stimulates haematopoietic progenitor cells, mobilises BMCs into injured brain and it is itself a neurotrophic factor for MN.

Diagnostic and prognostic values of PBMC proteins in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which there are no validated biomarkers. Previous exploratory studies have identified a panel of candidate protein biomarkers in peripheral blood mononuclear cells (PBMCs) that include peptidyl-prolyl cis-trans isomerase A (PPIA), heat shock cognate protein 71 kDa (HSC70), heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) and TDP-43. It has also been found that PPIA plays a key role in the assembly and dynamics of ribonucleoprotein (RNP) complexes and interacts with TDP-43.