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.

Codesign and evaluation of advanced therapeutic information resources for and with families of children with neurological conditions: a mixed methods cross-sectional study.

Objective: Parents and caregivers of children with neurological conditions express interest in new and developing treatments and trials; however, they have limited knowledge of, and access to, reliable information. This study aims to empower and equip decision-making and support communication in the application of advanced neurotherapeutics and personalised medicine, covering gene therapy, stem cell therapy, neurostimulation and neuroimmunotherapies.

Design: A suite of online psychoeducational resources has been created and evaluated to establish implementation success.

Clinician Understanding, Acceptance and utilization of Ketogenic diet therapy for epilepsy in Australia and New Zealand: An online survey.

Ketogenic diet therapy (KDT) is an established treatment for people with epilepsy. As increasing evidence demonstrates effectiveness and safety of KDT on seizure reduction, cognition and behaviour, it is essential to evaluate factors hindering and supporting neurologists in prescribing KDT to strengthen quality, evidence-based, appropriate and equitable care. A study of Australian and New Zealand (ANZ) neurologists was undertaken via an online survey.

Clinician Perceptions of Family-Centered Care in Pediatric and Congenital Heart Settings.

Importance: Family-centered care recognizes families as central to child health and well-being and prioritizes clinician collaboration with families to ensure optimal pediatric care and outcomes. Clinician interpersonal sensitivity and communication skills are key to this approach.

Objective: To examine perceptions of and factors associated with family-centered care among clinicians working in pediatric and congenital heart care.

'High hopes for treatment': Australian stakeholder perspectives of the clinical translation of advanced neurotherapeutics for rare neurological diseases.

Introduction: Advanced therapies offer unprecedented opportunities for treating rare neurological disorders (RNDs) in children. However, health literacy, perceptions and understanding of novel therapies need elucidation across the RND community. This study explored healthcare professionals' and carers' perspectives of advanced therapies in childhood-onset RNDs.

Newborn screening for Duchenne muscular dystrophy: the perspectives of stakeholders.

Background: The rapidly evolving clinical landscape of Duchenne muscular dystrophy (DMD) is driving innovative approaches for early diagnosis through genomic newborn bloodspot screening (NBS). However, the potential impact of these programs on families and healthcare systems remains unexplored. This study assessed the perceived benefits, harms, barriers, and enablers for DMD NBS amongst primary caregivers of children with DMD and healthcare professionals (HCPs).

'Integrating Ethics and Equity with Economics and Effectiveness for newborn screening in the genomic age: A qualitative study protocol of stakeholder perspectives.

Background: Newborn bloodspot screening is a well-established population health initiative that detects serious, childhood-onset, treatable conditions to improve health outcomes. With genomic technologies advancing rapidly, many countries are actively discussing the introduction of genomic assays into newborn screening programs. While adding genomic testing to Australia's newborn screening program could improve outcomes for infants and families, it must be considered against potential harms, ethical, legal, equity and social implications, and economic and health system impacts.

Gene therapy-based strategies for spinal muscular atrophy-an Asia-Pacific perspective.

Onasemnogene abeparvovec has been life-changing for children with spinal muscular atrophy (SMA), signifying the potential and progress occurring in gene- and cell-based therapies for rare genetic diseases. Hence, it is important that clinicians gain knowledge and understanding in gene therapy-based treatment strategies for SMA. In this review, we describe the development and translation of onasemnogene abeparvovec from clinical trials to healthcare practice and share knowledge on the facilitators and barriers to implementation.

Characterizing Common Phenotypes Across the Childhood Dementia Disorders: A Cross-sectional Study From Two Australian Centers.

Background: Childhood dementias are a group of rare pediatric conditions characterized by progressive neurocognitive decline. Quantifying and characterising phenotypes to identify similarities between specific conditions is critical to inform opportunities to optimize care and advance research.

Methods: This cross-sectional study recruited primary caregivers of children (<18 years) living with a dementia syndrome from neurology and metabolic clinics in Sydney and Adelaide, Australia.

Diagnosis and management of children with McArdle Syndrome (GSD V) in New South Wales.

Glycogen storage type V (GSD V-McArdle Syndrome) is a rare neuromuscular disorder characterised by severe pain early after the onset of physical activity. A recent series indicated a diagnostic delay of 29 years; hence reports of children affected by the disorder are uncommon (Lucia et al., 2021, , 31, 1296-1310).

The psychosocial impact of childhood dementia on children and their parents: a systematic review.

Background: Childhood dementias are a group of rare and ultra-rare paediatric conditions clinically characterised by enduring global decline in central nervous system function, associated with a progressive loss of developmentally acquired skills, quality of life and shortened life expectancy. Traditional research, service development and advocacy efforts have been fragmented due to a focus on individual disorders, or groups classified by specific mechanisms or molecular pathogenesis. There are significant knowledge and clinician skill gaps regarding the shared psychosocial impacts of childhood dementia conditions.

Prospective assessment of vincristine-induced peripheral neuropathy in paediatric acute lymphoblastic leukemia.

Objective: Vincristine is a mainstay treatment for paediatric cancers, particularly acute lymphoblastic leukemia (ALL), with common toxicity including vincristine-induced peripheral neuropathy (VIPN). The present study comprehensively assessed VIPN outcomes in patients receiving vincristine treatment for ALL.

Methods: Children diagnosed with ALL commencing vincristine treatment were prospectively evaluated (baseline, post-induction, pre-reinduction, post-reinduction, follow-up).

The Carrier Frequency of Two Genes in Parents of Symptomatic Children with SMA and the Significance of Exon 8 in Carriers.

Background: Current carrier screening methods do not identify a proportion of carriers that may have children affected by spinal muscular atrophy (SMA). Additional genetic data is essential to inform accurate risk assessment and genetic counselling of SMA carriers. This study aims to quantify the various genotypes among parents of children with SMA.

The collective burden of childhood dementia: a scoping review.

Childhood dementia is a devastating and under-recognized group of disorders with a high level of unmet need. Typically monogenic in origin, this collective of individual neurodegenerative conditions are defined by a progressive impairment of neurocognitive function, presenting in childhood and adolescence. This scoping review aims to clarify definitions and conceptual boundaries of childhood dementia and quantify the collective disease burden.

Decision-making and challenges within the evolving treatment algorithm in spinal muscular atrophy: a clinical perspective.

Introduction: The clinical application of disease modifying therapies has dramatically changed the paradigm of the management of people with spinal muscular atrophy (SMA), from sole reliance on symptomatic care directed toward the downstream consequences of muscle weakness, to proactive intervention and even preventative care.

Areas Covered: In this perspective, the authors evaluate the contemporary therapeutic landscape of SMA and discuss the evolution of novel phenotypes and the treatment algorithm, including the key factors that define individual treatment choice and treatment response. The benefits achieved by early diagnosis and treatment through newborn screening are highlighted, alongside an appraisal of emerging prognostic methods and classification frameworks to inform clinicians, patients, and families about disease course, manage expectations, and improve care planning.

CSF neopterin, quinolinic acid and kynurenine/tryptophan ratio are biomarkers of active neuroinflammation.

Background: Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy.

Structural and functional characterization of capsid binding by anti-AAV9 monoclonal antibodies from infants after SMA gene therapy.

Success in the treatment of infants with spinal muscular atrophy (SMA) underscores the potential of vectors based on adeno-associated virus (AAV). However, a major obstacle to the full realization of this potential is pre-existing natural and therapy-induced anti-capsid humoral immunity. Structure-guided capsid engineering is one possible approach to surmounting this challenge but necessitates an understanding of capsid-antibody interactions at high molecular resolution.