A state-of-the-art review of registries in spinal muscular atrophy: A valuable resource for clinical research.

Since 2016/17, three disease modifying therapies for spinal muscular atrophy (SMA) have been translated into clinical practice. This has driven the implementation of newborn screening to transform health outcomes and clinical practice. SMA registries have provided important sources of data on the evolution of novel phenotypes within the therapeutic era, treatment patterns, epidemiology, genotype-phenotype correlations, care and lived experiences of people living with SMA, to enrich knowledge and learnings of the condition in this changed landscape.

International collaboration to improve knowledge on myotonic dystrophy type 2.

Background: The TREAT-NMD Global Registry Network is a global collaboration of neuromuscular disease registries, including myotonic dystrophy type 2 (DM2), which aims to facilitate collaborative research and clinical trials.

Objectives: This study aimed to assess DM2 patients included in the network, and to analyse their socio-demographic and clinical features.

Methods: Data were collected through email surveys sent to 16 TREAT-NMD myotonic dystrophy core member registries.

Generation of an iPSC line (with isogenic control) from the PBMCs of a COL6A1 (c.1056 + 2T > A) Bethlem myopathy patient.

To produce an in vitro model of Bethlem myopathy, we reprogrammed the peripheral blood mononuclear cells (PBMCs) of a patient with a heterozygous COL6A1 c.1056 + 2T > A mutation at the exon/intron 14 boundary of the COL6A1 gene to induced pluripotent stem cells (iPSCs). Using CRISPR/Cas9 gene editing, we corrected the mutation to generate an isogenic control line.

Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia.

Background: Dexamethasone sodium phosphate (DSP) encapsulated in autologous erythrocytes (EryDex) was developed as an alternative to standard glucocorticoids in an effort to eliminate chronic steroid toxicity while preserving efficacy. The primary objective of this report is to describe the safety of long-term use of EryDex in treatment of pediatric patients with ataxia telangiectasia.

Methods: This is a post-hoc analysis of patients treated with EryDex for a minimum of 24 months in two prospective clinical trials.

Hip Dysplasia in Charcot-Marie-Tooth Disease: Insights From a Large Cohort of Children and Adolescents.

Background And Aims: Despite the known association of hip dysplasia and Charcot Marie Tooth disease (CMT), evidence is limited regarding its exact prevalence. Available studies pre-date genetic confirmation of CMT subtypes and current hip reconstruction surgical options. This study examined the prevalence of hip dysplasia in CMT in a tertiary neuromuscular center.

A contemporary analysis of the Australian clinical and genetic landscape of spinal muscular atrophy: a registry based study.

Background: New paradigms of diagnosis and treatment have changed the neurodegenerative trajectory for individuals with spinal muscular atrophy (SMA). Registries are a critical tool to provide real-world data on treatment patterns, their effects and health care provision within this evolving paradigm of care. This study aimed to evaluate the phenotypic and genotypic landscape, treatment patterns and health impact of SMA in Australia through the national registry.

Intra-operative neuromonitoring in paediatric spinal deformity surgery: a retrospective single-centre experience.

Introduction: Intra-operative neuromonitoring including somatosensory evoked potentials, motor evoked potentials, and electromyography, have replaced the Stagnara wake-up test to allow early detection of neurological change during paediatric spinal deformity surgery. It is important for surgeons to recognize alerts triggered by loss of these potentials and act accordingly to prevent iatrogenic neurological damage intra-operatively. This study was conducted to determine the sensitivity and specificity of neuromonitoring alerts in paediatric spinal deformity correction surgery.

Nutrition outcomes of disease modifying therapies in spinal muscular atrophy: A systematic review.

The nutritional implications of spinal muscular atrophy (SMA) are profound. Disease modifying therapies (DMT) have improved clinical outcomes. This review describes the impact of DMT on nutrition outcomes.

Remediation of Perceptual Deficits in Progressive Auditory Neuropathy: A Case Study.

Background: Auditory neuropathy (AN) is a hearing disorder that affects neural activity in the VIIIth cranial nerve and central auditory pathways. Progressive forms have been reported in a number of neurodegenerative diseases and may occur as a result of both the deafferentiation and desynchronisation of neuronal processes. The purpose of this study was to describe changes in auditory function over time in a patient with axonal neuropathy and to explore the effect of auditory intervention.

Practical approach to the child presenting with acute generalised weakness.

Acute generalised muscle weakness in children is a paediatric emergency with a broad differential diagnosis. A careful history and neurologic examination guides timely investigation and management. We review some of the more common causes of acute generalised muscle weakness in children, highlighting key history and examination findings, along with an approach to lesion localisation to guide differential diagnosis and further investigation.

Rare homozygous disease-associated sequence variants in children with spinal muscular atrophy: a phenotypic description and review of the literature.

5q-associated spinal muscular atrophy (SMA) is the most common autosomal recessive neurological disease. Depletion in functional SMN protein leads to dysfunction and irreversible degeneration of the motor neurons. Over 95 % of individuals with SMA have homozygous exon 7 deletions in the SMN1 gene.

A phase 2 open-label study of the safety and efficacy of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne muscular dystrophy and pharmacology in mdx mice.

Background: ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment.

Geographic Expansion of Japanese Encephalitis Virus to Australia: Neuroinflammatory Sequelae and Consideration of Immunomodulation.

We report a child from Southern Australia (New South Wales) who presented during a La Niña event with encephalopathy and acute flaccid paralysis. Magnetic resonance imaging suggested Japanese encephalitis (JE). Steroids and intravenous immunoglobulin did not improve symptoms.

Fracture risk and impact in boys with Duchenne muscular dystrophy: A retrospective cohort study.

Introduction/aims: Boys with Duchenne muscular dystrophy (DMD) are at increased risk of fracture. This study investigated the incidence of fractures, factors contributing to risk of first fracture with emphasis on body mass index (BMI), and the impact of fractures on functional capacity in an Australian cohort of boys with DMD.

Methods: A retrospective cohort study included boys with DMD who attended a pediatric neuromuscular clinic from 2011 to 2018.

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy.

Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA).

Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations.

The Responsiveness of Gait and Balance Outcomes to Disease Progression in Friedreich Ataxia.

To identify gait and balance measures that are responsive to change during the timeline of a clinical trial in Friedreich ataxia (FRDA), we administered a battery of potential measures three times over a 12-month period. Sixty-one ambulant individuals with FRDA underwent assessment of gait and balance at baseline, 6 months and 12 months. Outcomes included GAITRite® spatiotemporal gait parameters; Biodex Balance System Postural Stability Test (PST) and Limits of Stability; Berg Balance Scale (BBS); Timed 25-Foot Walk Test; Dynamic Gait Index (DGI); SenseWear MF Armband step and energy activity; and the Friedreich Ataxia Rating Scale Upright Stability Subscale (FARS USS).

[Evidence based guidelines. Diagnosis and management of Guillain-Barré syndrome in ten steps].

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and in 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available.

MRI Patterns Distinguish AQP4 Antibody Positive Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis.

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a cross-sectional analysis of imaging data and developed predictive models to distinguish the two conditions.

Determining the Validity of Conducting Rating Scales in Friedreich Ataxia through Video.

Background: The Friedreich Ataxia Rating Scale (FARS) and the Scale for the Assessment and Rating of Ataxia (SARA) are commonly used neurological rating scales in Friedreich ataxia (FRDA). The modified Friedreich Ataxia Rating Scale (mFARS) has been accepted as an appropriate outcome measure for clinical trials in FRDA.

Objectives: The COVID-19 pandemic has resulted in limited face-to-face interactions with individuals involved in natural history studies and clinical trials.

The severe epilepsy syndromes of infancy: A population-based study.

Objective: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes.

Methods: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes.