Segmental brainstem myoclonus in ADCK3-Related ataxia: A novel phenomenon?

Segmental Brainstem Myoclonus (SBM) is a rare movement disorder characterized by rhythmic contractions of muscles innervated by brainstem segments. We report a 20-year-old patient with ADCK3-related spinocerebellar ataxia type 9 (SCAR9) presenting with sudden-onset myoclonic movements of the throat, tongue, and soft palate. Brain MRI showed stable findings, including dentate nucleus hyperintensities.

De Novo GRID2 Variant as a Cause of Ataxia with Oculomotor Apraxia and Alpha-Fetoprotein Elevation.

Bi-allelic pathogenic variants in GRID2 have been initially associated to an autosomal recessive form of spinocerebellar ataxia, namely SCAR18. Subsequently, few monoallelic cases have been described. Here we present a new subject harboring a novel de novo heterozygous GRID2 missense variant presenting with progressive ataxia together with cerebellar atrophy and, for the first time, alpha-fetoprotein (AFP) elevation.

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals.

Improving paediatric movement disorders care: Insights on rating scales utilization and clinical practice.

Aim: This exploratory study evaluates rating scale usage by experts from the European Reference Network for Rare Neurological Diseases (ERN-RND) for paediatric MD, considering factors like diagnosis, intellectual disability, age, and transition to adult care. The aim is to propose a preliminary framework for consistent application.

Methods: A multicentre survey among 25 ERN-RND experts from 10 European countries examined rating scale usage in paediatric MD, categorizing MD into acute, non-progressive, and neurodegenerative types.

Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy.

The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8.

Endogenous origin of infecting hospitalized patients in Ecuador.

Recent evidence suggests that , a bacterium that has the ability to cause deadly infections in hospitalized patients, could originate in the patient's own flora. We employed the Oxford Nanopore platform to obtain whole genome sequences (WGS) from clinical and rectal screen strains belonging to 15 patients from two hospitals. Our study found evidence that clinical and rectal isolates were clonal, with some evidence suggesting that the infecting strain was present in the patient's intestine at the time of admission, ruling out hospital acquisition.

Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers.

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.

Quantitative Speech Assessment in Ataxia-Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Markers.

Dysarthria is a common and debilitating symptom of many neurodegenerative diseases, including those resulting in ataxia. Changes to speech lead to significant reductions in quality of life, impacting the speaker in most daily activities. Recognition of its importance as an objective outcome measure in clinical trials for ataxia is growing.

Child-to-adult transition: a survey of current practices within the European Reference Network for Rare Neurological Diseases (ERN-RND).

Background: Transition from child-centered to adult-centered healthcare is a gradual process that addresses the medical, psychological, and educational needs of young people in the management of their autonomy in making decisions about their health and their future clinical assistance. This transfer is challenging across all chronic diseases but can be particularly arduous in rare neurological conditions.

Aim: To describe the current practice on the transition process for young patients in centers participating in the European Reference Network for Rare Neurological Diseases (ERN-RND).

White matter abnormalities in 15 subjects with SPG76.

Background And Objectives: Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders characterized by progressive pyramidal tract involvement. SPG76 is a recently identified form of HSP, caused by biallelic calpain-1 (CAPN1) variants. The most frequently described MRI abnormality in SPG76 is mild cerebellar atrophy and non-specific white matter abnormalities were reported in only one case.

Antioxidant Response in Human X-Linked Adrenoleukodystrophy Fibroblasts.

Redox imbalance, mitochondrial dysfunction, and inflammation play a major role in the pathophysiology of X-linked adrenoleukodystrophy (X-ALD), an inherited neurodegenerative disease caused by mutations in the ABCD1 gene, encoding the protein responsible for peroxisomal import and degradation of very long chain fatty acids (VLCFAs). Therefore, VLCFAs accumulate in tissues and plasma, constituting a pathognomonic biomarker for diagnosis. However, the precise role of VLCFA accumulation on the diverse clinical phenotypes of X-ALD and the pathogenic link between VLCFAs and oxidative stress remain currently unclear.

Influence of sagittal pelvic attitude on gait pattern in normally developed people and interactions with neurological pathologies: A pilot study.

Background: Gait Analysis of healthy people, imitating pathological conditions while walking, has increased our understanding of biomechanical factors. The influence of the pelvis as a biomechanical constraint during gait is not specifically studied. How could mimicking a pelvic attitude influence the dynamic mechanical interaction of the body segments? We proposed an investigation of the pelvic attitude role on the gait pattern of typically developed people when they mimicked pelvic anteversion and posteroversion.

A Clinical and Epidemiological Prevalence Study on Friedreich's Ataxia in Latium, Italy.

Objective: The aim of this study was to estimate the Friedreich's ataxia (FRDA) prevalence in a highly populated region of Italy (previous studies in small geographic areas gave a largely variable prevalence) and to define the patients' molecular and clinical characteristics.

Methods: For the point-prevalence study, we considered patients belonging to families with a molecular diagnosis of FRDA and resident in Latium on 1 January 2019. The crude prevalence of FRDA, specific for age and sex, was calculated and standardized for age using the Italian population.

Comparison of the Gait Biomechanical Constraints in Three Different Type of Neuromotor Damages.

Background And Objective: Absolute angle represents the inclination of a body segment relative to a fixed reference in space. This work compares the absolute and relative angles for exploring biomechanical gait constraints.

Methods: Gait patterns of different neuromotor conditions were analyzed using 3D gait analysis: normal gait (healthy, H), Cerebral Palsy (CP), Charcot Marie Tooth (CMT) and Duchenne Muscular Dystrophy (DMD), representing central and peripheral nervous system and muscular disorders, respectively.

Upper Body Physical Rehabilitation for Children with Ataxia through IMU-Based Exergame.

Background: Children with ataxia experience balance and movement coordination difficulties and needs intensive physical intervention to maintain functional abilities and counteract the disorder. Exergaming represents a valuable strategy to provide engaging physical intervention to children with ataxia, sustaining their motivation to perform the intervention. This paper aims to describe the effect of a home-conducted exergame-based exercise training for upper body movements control of children with ataxia on their ataxic symptoms, walking ability, and hand dexterity.

Clinical variability at the mild end of BRAT1-related spectrum: Evidence from two families with genotype-phenotype discordance.

Biallelic mutations in the BRAT1 gene, encoding BRCA1-associated ATM activator 1, result in variable phenotypes, from rigidity and multifocal seizure syndrome, lethal neonatal to neurodevelopmental disorder, and cerebellar atrophy with or without seizures, without obvious genotype-phenotype associations. We describe two families at the mildest end of the spectrum, differing in clinical presentation despite a common genotype at the BRAT1 locus. Two siblings displayed nonprogressive congenital ataxia and shrunken cerebellum on magnetic resonance imaging.

Gut microbiome, enteric infections and child growth across a rural-urban gradient: protocol for the ECoMiD prospective cohort study.

Introduction: The functional consequences of the bacterial gut microbiome for child health are not well understood. Characteristics of the early child gut microbiome may influence the course of enteric infections, and enteric infections may change the composition of the gut microbiome, all of which may have long-term implications for child growth and development.

Methods And Analysis: We are conducting a community-based birth cohort study to examine interactions between gut microbiome conditions and enteric infections, and how environmental conditions affect the development of the gut microbiome.

haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum.

Background: Joubert syndrome (JS) is a recessively inherited ciliopathy characterised by congenital ocular motor apraxia (COMA), developmental delay (DD), intellectual disability, ataxia, multiorgan involvement, and a unique cerebellar and brainstem malformation. Over 40 JS-associated genes are known with a diagnostic yield of 60%-75%.In 2018, we reported homozygous hypomorphic missense variants of the gene in two families with mild JS.

PIGQ-Related Glycophosphatidylinositol Deficiency Associated with Nonprogressive Congenital Ataxia.

The glycophosphatidylinositol (GPI) anchor pathway plays an essential role in posttranslational modification of proteins to facilitate proper membrane anchoring and trafficking to lipid rafts, which is critical for many cell functions, including embryogenesis and neurogenesis. GPI biosynthesis is a multi-step process requiring the activity of over 25 distinct genes, most of them belonging to the phosphatidylinositol glycan (PIG) family and associated with rare neurodevelopmental disorders. PIGQ encodes the phosphatidylinositol glycan class Q protein and is part of the GPI-N-acetylglucosaminyltransferase complex that initiates GPI biosynthesis from phosphatidylinositol (PI) and N-acetylglucosamine (GlcNAc) on the cytoplasmic side of the endoplasmic reticulum (ER).

LBSL: Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations.

Objective: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in , encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described.

Remember Friedreich ataxia even in a toddler with apparently isolated dilated (not hypertrophic!) cardiomyopathy. Revisited.

Friedreich ataxia (FRDA) is the most common form of ataxia in late childhood. Neurological manifestations often precede cardiac involvement, presenting mainly as hypertrophic cardiomyopathy. We describe a toddler with apparently isolated severe heart failure, successfully managed with heart transplant (HT).

Expanding the Clinical and Mutational Spectrum of the -Related Hypomyelination of Early Myelinated Structures (HEMS).

The gene, located on chromosome Xq22, encodes the proteolipid protein 1 and its isoform DM20. Mutations in cause a spectrum of white matter disorders of variable severity. Here we report on four additional HEMS patients from three families harboring three novel mutations in exon 3B detected by targeted next-generation sequencing.

Friedreich ataxia in COVID-19 time: current impact and future possibilities.

COVID-19 outbreak profoundly impacted on daily-life of patients with neurodegenerative diseases, including those with ataxia. Effects on interventional trials have been recently described. Conversely, changes in physical activity programs, which are crucial in care of ataxic patients, have not been assessed yet.