Clinical Characterization of a Multicenter International Cohort of Patients With Aicardi-Goutières Syndrome Homozygous for the RNASEH2B:p.Ala177Thr Variant: Early Clinical Markers of Disease Severity.

Background: Aicardi-Goutières syndrome (AGS) is a rare monogenic leukodystrophy belonging to type I interferonopathies caused by alterations in one of nine genes. Among them, homozygous RNASEH2B:c.529G>A(p.

A Tool for the Assessment of Electromagnetic Compatibility in Active Implantable Devices: The Pacemaker Physical Twin.

Background: The increasing use of technologies operating between 10 and 200 kHz, such as RFID, wireless power transfer systems, and induction cooktops, raises concerns about electromagnetic interference (EMI) with cardiac implantable electronic devices (CIEDs). The mechanisms of interaction within this frequency range have been only partially addressed by both the scientific and regulatory communities.

Methods: A physical twin of a pacemaker/implantable defibrillator (PM/ICD) was developed to experimentally assess voltages induced at the input stage by low-to-mid-frequency magnetic fields.

Longitudinal Assessment of 4-Year HFMSE Changes in SMA II and III Patients Treated With Nusinersen.

Background: The aim of this international retrospective study was to assess 4-year change using the Hammersmith Functional Motor Scale Expanded (HFMSE) in individuals with type II and III spinal muscular atrophy (SMA) treated with nusinersen and to establish predictors of HFMSE changes.

Methods: Individuals with type II or III SMA, and at least 4 years of nusinersen-only treatment were included. All were assessed using the HFMSE.

Opinion of the Italian Association of Myology on Ataluren for the Treatment of Nonsense Mutation Duchenne Muscular Dystrophy.

The Italian Duchenne muscular dystrophy expert clinicians, gathered in the Italian Association of Myology (AIM), intend to express a position against the suspension of the Marketing Authorization of ataluren (Translarna) for the treatment of nonsense mutation Duchenne muscular dystrophy. The marketing authorization has been recently withdrawn by the European Commission following a recommendation from the Committee for Medicinal Products for Human Use of the European Medicines Agency. This negative recommendation was based on the fact that three randomized controlled trials of ataluren in nonsense mutation Duchenne muscular dystrophy (007, 020, and 041) have failed to show statistically significant differencs in favor of the treatment in the selected primary outcomes for each individual study, i.

Home detection of atrial fibrillation using cardiac activity analysis: technologies available to the patient.

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia, whose incidence and prevalence have increased over the last 20 years and will continue to increase over the next 30 years. It is characterized by irregular atrial activation, leading to complications as stroke and heart failure. Due to its intermittent and asymptomatic nature, diagnosing and monitoring AF is challenging but crucial for effective treatment and prevention of serious complications.

Patients on treatment with risdiplam in Italy: challenges in the interpretation of the real-world data.

Aims: (i) provide a snapshot from a large cohort of Italian patients with SMA on risdiplam in the real-world setting; (ii) identify any differences in the cohorts before and after commercial drug approval considering the different eligibility access criteria (iii) describe preliminary data on adherence to treatment and reasons for shifting from nusinersen to risdiplam.

Methods: Charts from patients on risdiplam were retrospectively reviewed. Results were then compared between patients accessing the drug during an initial restricted compassionate use program (cohort 1) and those after commercial approval, with no restrictions (cohort 2).

Type I spinal muscular atrophy and disease modifying treatments: a nationwide study in children born since 2016.

Background: The advent of disease-modifying treatments (DMT) has changed natural history in 5q Spinal muscular atrophy (SMA). The aim of this study was to report survival and functional aspects in all the Italian type I children born since 2016.

Methods: The study included all symptomatic children with type I SMA born since January 1st, 2016, when DMTs became available in Italy.

Association between Reported Sleep Disorders and Behavioral Issues in Children with Myotonic Dystrophy Type 1-Results from a Retrospective Analysis in Italy.

Sleep disorders have been poorly described in congenital (CDM) and childhood (ChDM) myotonic dystrophy despite being highly burdensome. The aims of this study were to explore sleep disorders in a cohort of Italian CDM and ChDM and to assess their association with motor and respiratory function and disease-specific cognitive and behavioral assessments. This was an observational multicenter study.

Internal Consistency and Floor/Ceiling Effects of the Gross Motor Function Measure for Use with Children Affected by Cancer: A Cross-Sectional Study.

Children/adolescents with cancer can develop adverse effects impacting gross motor function. There is a lack of gross motor function assessment tools that have been validated for this population. The aim of this multicenter cross-sectional study was to preliminary validate the 88-item Gross Motor Function Measure (GMFM-88) for use in children/adolescents with cancer, exploring internal consistency and floor/ceiling effect.

Parental diagnostic delay and developmental outcomes in congenital and childhood-onset myotonic dystrophy type 1.

Aim: To investigate the timing of type 1 myotonic dystrophy (DM1) diagnosis in parents of affected children and describe children's perinatal characteristics and developmental outcomes.

Method: This was a descriptive case series of children with congenital myotonic dystrophy (CDM) and childhood-onset myotonic dystrophy (ChDM). Parental timing of DM1 diagnosis and the perinatal, motor, and cognitive outcomes of paediatric patients were recorded.

Tumor-derived GLI1 promotes remodeling of the immune tumor microenvironment in melanoma.

Background: Melanoma progression is based on a close interaction between cancer cells and immune cells in the tumor microenvironment (TME). Thus, a better understanding of the mechanisms controlling TME dynamics and composition will help improve the management of this dismal disease. Work from our and other groups has reported the requirement of an active Hedgehog-GLI (HH-GLI) signaling for melanoma growth and stemness.

The Italian Consensus Conference on the role of rehabilitation for children and adolescents with leukemia, central nervous system tumors, and bone cancer, part 2: general principles for the rehabilitation treatment of motor function impairments.

In Italy, 1400 children and 800 adolescents are diagnosed with cancer every year. About 80% of them can be cured but are at high risk of experiencing severe side effects, many of which respond to rehabilitation treatment. Due to the paucity of literature on this topic, the Italian Association of Pediatric Hematology and Oncology organized a Consensus Conference on the role of rehabilitation of motor impairments in children/adolescents affected by leukemia, central nervous system tumors, and bone cancer to state recommendations to improve clinical practice.

Biochemical characterization on muscle tissue of a novel biallelic mutation in an infant with progressive encephalopathy.

The gene encodes the mitochondrial protein aconitate hydratase, which is responsible for catalyzing the interconversion of citrate into isocitrate in the tricarboxylic acid (TCA) cycle. Mitochondrial aconitase is expressed ubiquitously, and deficiencies in TCA-cycle enzymes have been reported to cause various neurodegenerative diseases due to disruption of cellular energy metabolism and development of oxidative stress. We investigated a severe early infantile-onset neurometabolic syndrome due to a homozygous novel variant in exon 13 of the gene.

Gain and loss of upper limb abilities in Duchenne muscular dystrophy patients: A 24-month study.

Duchenne muscular dystrophy (DMD) is a neuromuscular condition characterized by muscle weakness. The Performance of upper limb (PUL) test is designed to evaluate upper limb function in DMD patients across three domains. The aim of this study is to identify frequently lost or gained PUL 2.

Titin copy number variations associated with dominant inherited phenotypes.

Background: Titinopathies are caused by mutations in the titin gene (). Titin is the largest known human protein; its gene has the longest coding phase with 364 exons. Titinopathies are very complex neuromuscular pathologies due to the variable age of onset of symptoms, the great diversity of pathological and muscular impairment patterns (cardiac, skeletal muscle or mixed) and both autosomal dominant and recessive modes of transmission.

Adults living with Duchenne muscular dystrophy: old and new challenges in a cohort of 19 patients in their third to fifth decade.

Background And Purpose: Advances in multidisciplinary care are extending overall survival in Duchenne muscular dystrophy (DMD) patients. Our research objective was to delineate the clinical characteristics of this particular cohort and identify novel challenges associated with the disease.

Methods: Nineteen individuals aged 25-48 years (median 34 years) with a confirmed diagnosis of out-of-frame DMD gene mutation were selected.

Clinical Phenotype of Pediatric and Adult Patients With Spinal Muscular Atrophy With Four SMN2 Copies: Are They Really All Stable?

Objective: The aim of this study was to provide an overview of the clinical phenotypes associated with 4 SMN2 copies.

Methods: Clinical phenotypes were analyzed in all the patients with 4 SMN2 copies as part of a nationwide effort including all the Italian pediatric and adult reference centers for spinal muscular atrophy (SMA).

Results: The cohort includes 169 patients (102 men and 67 women) with confirmed 4 SMN2 copies (mean age at last follow-up = 36.

Neurocognitive and Psychological Outcomes among Children and Adolescents with Brain Tumors: Development of an Observational and Longitudinal Prospective Study Protocol.

Children and adolescents affected by brain tumors are at risk for neuropsychological sequelae that need to be evaluated in order to plan adequate rehabilitation programs, and to support their development and recovery. This work aims to describe an innovative prospective observational study protocol for the early evaluation and monitoring over time of neuropsychological outcomes in this pediatric population. Pediatric patients aged 3-17 with a brain tumor diagnosis will be assessed through the use of a battery of Italian standardized neuropsychological tests, with good psychometric properties and age-appropiate, at three different time points of their clinical course: at diagnosis and before surgery (T0), after surgical removal and before the start of potential adjuvant therapies (T1), and at the one-year follow-up after potential adjuvant therapies (T2).