Overcoming therapeutic challenges: Successful management of a supposedly triple seronegative, refractory generalized myasthenia gravis patient with efgartigimod.

Background And Purpose: This study was undertaken to highlight neonatal Fc receptor inhibition (efgartigimod) as a valuable therapeutic option for patients with refractory seronegative myasthenia gravis (MG) and to emphasize the concept that seronegative MG is greatly constrained by the limitations of currently available diagnostic methods and therapeutic measures.

Methods: We describe the first refractory, generalized MG (gMG) patient successfully treated with efgartigimod after testing negative on standard autoantibody detection tests.

Results: Our patient presented with severe fluctuating bulbar and generalized weakness, resulting in multiple myasthenic crises requiring intubation.

Physical activity practiced at a young age is associated with a less severe subsequent clinical presentation in facioscapulohumeral muscular dystrophy.

Background: In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA).

Methods: People aged between 18 and 60 were recruited as being DRA carriers.

Daytime sleepiness and sleep quality in Charcot-Marie-Tooth disease.

Background: Sleep abnormalities have been reported in Charcot-Marie-Tooth disease (CMT), but data are scanty. We investigated their presence and correlation in a large CMT patients' series.

Methods: Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were administered to CMT patients of the Italian registry and controls.

Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias.

Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34).

A smart tablet application to quantitatively assess the dominant hand dexterity.

Background And Objective: The Nine-Hole Peg Test (NHPT) is the most used test to assess hand dexterity in clinical practice and is considered the gold standard but only evaluates the time needed to complete the task. The aim of this work is to describe a graphic test on a smart tablet to assess in a quantitative as well qualitative way the dominant hand dexterity and to validate it in a cohort of neurological subjects and healthy controls.

Methods: The task consists in asking the subject to connect with a graphic line the start and the end point of a pre-defined path, with two different widths, in the most precise and fastest way possible.

Validation of a graphic test to quantitatively assess the dominant hand dexterity.

Dexterity dysfunction is a key feature of disability in many neurological and non-neurological diseases. The Nine-Hole Peg Test (NHPT) is the most used test to assess hand dexterity in clinical practice but presents limitations. A new graphic test to enhance objective evaluation of the of the dominant hand dexterity is proposed.

Clinical-Genetic Features Influencing Disability in Spastic Paraplegia Type 4: A Cross-sectional Study by the Italian DAISY Network.

Background And Objectives: Hereditary spastic paraplegias (HSPs) are a group of inherited rare neurologic disorders characterized by length-dependent degeneration of the corticospinal tracts and dorsal columns, whose prominent clinical feature is represented by spastic gait. Spastic paraplegia type 4 (SPG4, SPAST-HSP) is the most common form. We present both clinical and molecular findings of a large cohort of patients, with the aim of (1) defining the clinical spectrum of SPAST-HSP in Italy; (2) describing their molecular features; and (3) assessing genotype-phenotype correlations to identify features associated with worse disability.

Ample room for reducing agrochemical inputs without productivity loss: The case of vegetable production in Uruguay.

Vegetables are commonly produced with high inputs of pesticides and fertilisers to boost production and meet cosmetic market standards. Yet, reports on the relationships between agrochemical inputs and crop productivity are scattered and an overview is missing. We assessed the relationship between pesticide and nutrient inputs and crop productivity for five vegetable crops in the south of Uruguay at field and farm level and explored the relation with farm resource endowment.

Assessment of Sacsin Turnover in Patients With ARSACS: Implications for Molecular Diagnosis and Pathogenesis.

Background And Objectives: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by variations in gene encoding sacsin, a huge multimodular protein of unknown function. More than 200 variations have been described worldwide to date. Because ARSACS presents phenotypic variability, previous empirical studies attempted to correlate the nature and position of variations with the age at onset or with disease severity, although not considering the effect of the various variations on protein stability.

Out-of-Frame Mutations in Last Exon Cause a Dominant Distal Myopathy With Facial Weakness.

Background And Objectives: To clinically, genetically, and histopathologically characterize patients presenting with an unusual combination of distal myopathy and facial weakness, without involvement of upper limb or shoulder girdle muscles.

Methods: Two families with a novel form of actininopathy were identified. Patients had been followed up over 10 years.

Loss of function MPZ mutation causes milder CMT1B neuropathy.

Mutations in Myelin Protein Zero (MPZ) cause CMT1B, the second leading cause of CMT1. Many of the >200 mutations cause neuropathy through a toxic gain of function by the mutant protein such as ER retention, activation of the Unfolded Protein Response (UPR) or disruption of myelin compaction. While there is extensive literature on the loss of function consequences of MPZ in heterozygous Mpz +/- null mice, there is little known of the consequences of MPZ haploinsufficiency in humans.

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.

A 5-year clinical follow-up study from the Italian National Registry for FSHD.

Background: The natural history of facioscapulohumeral muscular dystrophy (FSHD) is undefined.

Methods: An observational cohort study was conducted in 246 FSHD1 patients. We split the analysis between index cases and carrier relatives and we classified all patients using the Comprehensive Clinical Evaluation Form (CCEF).

Sodium Channel Myotonia Due to Novel Mutations in Domain I of Na1.4.

Sodium channel myotonia is a form of muscle channelopathy due to mutations that affect the Na1.4 channel. We describe seven families with a series of symptoms ranging from asymptomatic to clearly myotonic signs that have in common two novel mutations, p.

Phenotypic Variability Among Patients With D4Z4 Reduced Allele Facioscapulohumeral Muscular Dystrophy.

Importance: Facioscapulohumeral muscular dystrophy (FSHD) is considered an autosomal dominant disorder, associated with the deletion of tandemly arrayed D4Z4 repetitive elements. The extensive use of molecular analysis of the D4Z4 locus for FSHD diagnosis has revealed wide clinical variability, suggesting that subgroups of patients exist among carriers of the D4Z4 reduced allele (DRA).

Objective: To investigate the clinical expression of FSHD in the genetic subgroup of carriers of a DRA with 7 to 8 repeat units (RUs).

Expanding the spectrum of genes responsible for hereditary motor neuropathies.

Background: Inherited peripheral neuropathies (IPNs) represent a broad group of genetically and clinically heterogeneous disorders, including axonal Charcot-Marie-Tooth type 2 (CMT2) and hereditary motor neuropathy (HMN). Approximately 60%-70% of cases with HMN/CMT2 still remain without a genetic diagnosis. Interestingly, mutations in HMN/CMT2 genes may also be responsible for motor neuron disorders or other neuromuscular diseases, suggesting a broad phenotypic spectrum of clinically and genetically related conditions.

ZFYVE26/SPASTIZIN and SPG11/SPATACSIN mutations in hereditary spastic paraplegia types AR-SPG15 and AR-SPG11 have different effects on autophagy and endocytosis.

ZFYVE26/Spastizin and SPG11/Spatacsin encode 2 large proteins that are mutated in hereditary autosomal-recessive spastic paraplegia/paraparesis (HSP) type 15 (AR-SPG15) and type 11 (AR-SPG11), respectively. We previously have reported that AR-SPG15-related ZFYVE26 mutations lead to autophagy defects with accumulation of immature autophagosomes. ZFYVE26 and SPG11 were found to be part of a complex including the AP5 (adaptor related protein complex 5) and to have a critical role in autophagic lysosomal reformation with identification of autophagic and lysosomal defects in cells with both AR-SPG15- and AR-SPG11-related mutations.

Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial.

Spastic paraplegia type 5 (SPG5) is a rare subtype of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative disorders defined by progressive neurodegeneration of the corticospinal tract motor neurons. SPG5 is caused by recessive mutations in the gene CYP7B1 encoding oxysterol-7α-hydroxylase. This enzyme is involved in the degradation of cholesterol into primary bile acids.

Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy.

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Longitudinal MRI quantification of muscle degeneration in Duchenne muscular dystrophy.

Objective: The aim of this study was to evaluate the usefulness of magnetic resonance imaging (MRI) in detecting the progression of Duchenne muscular dystrophy (DMD) by quantification of fat infiltration (FI) and muscle volume index (MVI, a residual-to-total muscle volume ratio).

Methods: Twenty-six patients (baseline age: 5-12 years) with genetically proven DMD were longitudinally analyzed with lower limb 3T MRI, force measurements, and functional tests (Gowers, 10-m time, North Star Ambulatory Assessment, 6-min walking test). Five age-matched controls were also examined, with a total of 85 MRI studies.