Rheumatic heart disease is the most common cause of acquired childhood cardiac disease globally and, in Australia, affects First Nations peoples at disproportionately high rates. Australian guidelines recommend that skin and throat infections, which can be due to Group A Streptococcus, should be managed with antibiotics in high-risk individuals to prevent rheumatic fever and rheumatic heart disease. Regular long-acting intramuscular penicillin is recommended for secondary prevention of rheumatic fever. Injections are painful and should be administered by competent clinicians using strategies and techniques for minimising pain and distress. The Australian Guideline for the Prevention, Diagnosis and Management of Acute Rheumatic Fever and Rheumatic Heart Disease (2025) includes recommendations for clinical care delivered within a cultural framework that puts the person and their family at the centre of care.

Neurodegenerative diseases are characterized by impairment of neuronal functions and neuronal loss. Huntington's disease is one of the neurodegenerative diseases caused by the formation of mutant Huntingtin protein aggregates in the brain. The other pathological reasons behind this disease are oxidative stress, mitochondrial dysfunction, and excitotoxicity, which lead to impairment of motor, cognitive, and psychiatric functions. The vitamins are considered an essential part of a healthy diet, as they tend to increase the nutritional value of the diet. Insufficient intake of macro- and micronutrients can deteriorate human health, which may lead to malnutrition. Nowadays, these vitamins are also considered molecules to manage neurodegenerative disease with the intention of a dual response, along with nourishment. In vivo research reflects the antioxidant potential of vitamins and also functions as an integral part of various metabolic processes of the body that play a vital role in the pathology of Huntington's disease. Despite several neuroprotective properties, current research on vitamins remains limited. The review focuses on evidences exploring the functional significance of vitamins in maintaining neuronal and brain health and their possible impact on the symptoms and pathogenesis of Huntington's disease. It also highlights how the vitamins' potential is at stake to reach the clinical perspective, along with different strategies to overcome their limitations using novel drug delivery and biomarker-based approaches.

Huntington's disease (HD) is known for its abnormal polyQ stretch in the first exon of the HTT gene. HD is listed among the fatal autosomal dominant neurodegenerative disorders targeting the central nervous system and interfering with motor, cognitive, and psychiatric functions. The HTT gene codes for Huntingtin (Htt), a large three-domain protein with a polyQ stretch present in the N-terminal domain. In diseased cells, inclusion bodies are enriched in Htt fragments containing an extended polyQ region. The expansion of the polyQ correlates with aggregate size and onset of HD. However, the exact role of the full-length Htt in aggregate formation has not been fully known. Using coarse-grained molecular dynamics simulations at the near-atom level, our study indicates that the conformational dynamics of Htt─twisting and open-close motions of the domains─are dependent on the length of polyQ. In the presence of HAP40, the global conformational landscape is restricted, and the degree of dependence on polyQ length is low. The intra- and intercontact analyses suggest that the polyQ region can loop like a hairpin with a higher probability for a larger polyQ length. However, the looping probability is reduced in the presence of HAP40 due to increased contacts between polyQ and other regions of Htt. Thus, our findings indicate that polyQ has a significant role in the disease's pathogenesis, which includes altered functional activity and structural modifications leading to inclusion body formation. These effects can be controlled with the help of HAP40.

Levels of gangliosides are reduced in several neurological conditions, and their restoration has shown therapeutic potential in animal models of Huntington's disease and Parkinson's disease. However, the full range of functions of gangliosides in the brain, along with their molecular targets and mechanisms of action following exogenous administration, remains ill-defined. Due to their poor blood-brain barrier (BBB) permeability, gangliosides face significant challenges when delivered through non-invasive routes. Direct intracerebroventricular (ICV) infusion circumvents this issue by bypassing the BBB, ensuring a more precise delivery to brain structures and eliminating uncertainties related to brain penetration. Here, we describe a protocol for ICV infusion of gangliosides in mice that enables in vivo pre-clinical studies of their effects, while eliminating uncertainties about the extent of drug delivery to the brain through the BBB.

Diabetic striatopathy is a reversible cause of acute chorea occurring in patients with poorly controlled diabetes mellitus, including those even with complex comorbidities like HIV. Timely neuroimaging and prompt metabolic correction are crucial, emphasizing the need for high clinical suspicion.

Polycythemia vera (PV) is a clonal myeloproliferative neoplasm primarily caused by the JAK2V617F mutation, present in 95% of patients. It results in erythropoietin-independent hematopoietic proliferation, erythrocytosis, increased hematocrit (Hct), leukocytosis, thrombocytosis, and hyperviscosity, predisposing patients to thrombotic events and neurologic deficits, including erythromelalgia and pruritus. Neurologic manifestations can occur, such as transient ischemic attack (TIA) and stroke. We report an 83-year-old woman, PV patient who presented with chorea and magnetic resonance imaging (MRI) of her brain showed pachymeningeal enhancement (dural-arachnoid enhancement); this radiological finding is most commonly described in intracranial hypotension, autoimmune conditions, infection, and neoplastic processes and has not been reported in PV. Laboratory findings included complete blood count (CBC) showed severe erythrocytosis, moderate leukocytosis with moderate, mild thrombocytosis; bone marrow (BM) aspiration and biopsy showed hypercellular BM and marked megakaryocytic hyperplasia; and positive JAK2V617F mutation with 80% JAK2 DNA, suggestive of PV as the underlying cause. The patient underwent phlebotomy and was started on Aspirin. Following treatment, she showed dramatic improvement in choreiform movements. Hydroxyurea 500 mg three times daily was subsequently added, leading to complete hematologic response and resolution of pachymeningeal thickening on follow up MRI. This case suggested association between polycythemia vera and choreiform movements and a possible mechanism is proposed.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a proposed postinfectious neuroimmune syndrome characterized by the abrupt onset of obsessive-compulsive disorder, tic disorders, and associated neuropsychiatric symptoms temporally associated with Group A beta-hemolytic Streptococcus infection. Since its initial description by Swedo and colleagues in 1998, PANDAS has generated notable scientific interest and controversy. Increasing evidence from immunology, neuroimaging, epidemiology, and translational neuroscience suggests that infection-triggered autoimmune processes may contribute to neuropsychiatric symptom development in a subset of pediatric patients. However, significant uncertainty remains regarding diagnostic validity, biomarker reproducibility, pathophysiologic mechanisms, and optimal treatment strategies. This review carefully evaluates current evidence regarding the epidemiology, immunopathogenesis, clinical manifestations, diagnosis, treatment, prognosis, and controversies surrounding PANDAS and related Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Relevant literature published from 1998 through May 2026 was critically reviewed. Recent publications from 2021-2026 were incorporated to update evidence on clinical guidance, neuroimaging, immune biomarkers, autoimmune comorbidity, and IVIG outcomes. Evidence supporting the PANDAS construct includes epidemiologic associations with streptococcal infection, parallels with Sydenham chorea, identification of antineuronal antibodies, neuroimaging abnormalities involving basal ganglia structures, translational animal models, and selective responsiveness to immunomodulatory therapies. Conversely, substantial concerns remain regarding inconsistent biomarker replication, methodological heterogeneity, diagnostic overlap with primary psychiatric disorders, and the absence of universally accepted diagnostic tests. Current evidence supports the biologic plausibility of infection-triggered neuroimmune neuropsychiatric syndromes in a subset of pediatric patients. However, the specificity of the PANDAS construct, the boundaries between PANDAS and Pediatric Acute-Onset Neuropsychiatric Syndrome, and the identification of immune-responsive subgroups remain incompletely defined. Future multicenter prospective studies incorporating standardized diagnostic criteria, advanced immunophenotyping, neuroimaging, genomics, and longitudinal outcome measures are required to clarify disease mechanisms and optimize patient management.

IntroductionReal-world evidence of deutetrabenazine (DTBZ) treatment for Huntington disease (HD)-associated chorea is limited.MethodsThis is a non-interventional, retrospective chart review study from a Huntington's Disease Society of America clinical practice at the University of Alabama at Birmingham (UAB). Patients had a diagnosis of HD-associated chorea, DTBZ initiation (4/2017-12/2021), ≥2 visits at UAB, and ≥3 months of chorea-related care records post DTBZ initiation. The last Unified HD Rating Scale-Total Maximal Chorea (TMC) score within 3 months prior to DTBZ initiation and first after reaching the last stable dose during follow-up were analyzed.ResultsAmong 80 eligible patient charts, mean (SD) age was 52.1 (12.6) years and 45 (56.3%) were female. Fifty patients had pre- and post-DTBZ TMC scores and reached a stable dose, including 30 with no prior tetrabenazine (TBZ) or DTBZ exposure, 8 with prior TBZ exposure with a switch to DTBZ after a gap, and 9 with prior TBZ exposure with a switch to DTBZ without a gap. Mean (SD) TMC score decreased (i.e., improved) by 3.7 (4.5), 7.8 (2.8), and 2.1 (4.2), respectively. Overall, 27 (33.8%) patients had ≥1 adverse event recorded between DTBZ initiation and the first visit with a TMC score after reaching their last stable DTBZ dose or DTBZ discontinuation for those without a stable dose.DiscussionThis real-world study describes improvements in TMC scores among patients with HD-associated chorea treated with DTBZ, regardless of prior treatment. The observed safety profile supports the known safety profile of DTBZ in this population.

Huntington's disease (HD) is a progressive neurodegenerative disorder with no approved therapies. Despite multiple clinical trials, huntingtin (HTT)-lowering strategies have yet to show meaningful clinical benefit. Both somatic expansion and toxic HTT species are key molecular drivers of HD, yet therapeutic strategies targeting these pathways have never been directly compared or evaluated in combination. Using therapeutic divalent siRNAs, we assessed the long-term impact of silencing MutS homolog 3 (MSH3), a critical regulator of somatic expansion, HTT, or both in Q111 HD mice (>110 CAGs), which develop robust expansion, mutant HTT inclusions, and transcriptional dysregulation by 12 months. Long-term MSH3 silencing blocked somatic expansion, reduced inclusions, and normalized gene expression. HTT silencing alone had a limited effect, whereas combined MSH3/HTT targeting synergistically eliminated inclusions and restored transcriptomic profiles. Parallel treatment in wild-type mice showed no toxicity, supporting the safety of long-term intervention. These findings position somatic expansion as a promising therapeutic target and demonstrate the potential of RNAi-based cosilencing of MSH3 and HTT as a disease-modifying strategy for HD.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by progressive cognitive and motor decline driven by basal ganglia (BG) atrophy. Clinical trials of novel disease-modifying therapies are ongoing, creating a need for sensitive non-invasive imaging biomarkers. Soma and Neurite Density Imaging (SANDI) is a multi-shell diffusion MRI model that estimates intracellular signal fractions from sphere-shaped soma and shows promise as a marker of neurodegeneration. The objectives of this study were to characterise HD-related microstructural abnormalities in the BG using SANDI and to examine relationships between SANDI and volumetric measurements and motor performance. T1- and diffusion-weighted images (b-values 200-6000 s/mm[2]) were acquired on a 3T Siemens Connectom scanner (300 mT/m) in 56 individuals with HD and 57 age- and sex-matched controls. HD participants completed Quantitative Motor (Q-Motor) tasks, summarised using principal component analysis. SANDI estimated apparent soma and neurite density, apparent soma size, and extracellular signal fraction. Microstructural and volumetric indices were extracted from bilateral caudate, putamen, pallidum and thalamus regions, compared between groups, and correlated with Q-Motor performance. HD was associated with reduced apparent soma density and increased apparent soma size and extracellular signal fraction in the BG but not the thalami. No group differences were present for apparent neurite density. SANDI metrics correlated with Q-Motor performance and explained up to 63% of striatal atrophy in HD. SANDI indices detected HD-related striatal neurodegeneration, explained atrophy, and correlated with motor impairments, demonstrating its potential as an in vivo biomarker and surrogate clinical outcome measure for HD and other neurodegenerative diseases.

We present a rare case of striatal encephalitis associated with small cell lung cancer (SCLC), manifesting as a choreiform movement disorder. A 57-year-old woman presented with a subacute onset of involuntary movements. Despite extensive investigations, the etiology of this choreiform movement disorder remained elusive until a detailed evaluation of clinical signs and radiological findings revealed SCLC. In addition, she had an asymptomatic metastatic brain parenchymal lesion. This case highlights the importance of considering paraneoplastic striatal encephalitis (PSE), a rare presenting neurological syndrome.

Diabetic striatopathy is a rare complication of uncontrolled diabetes, typically presenting with involuntary movements, striatal hyperdensity on computed tomography, and T1-weighted hyperintensity on magnetic resonance imaging. We describe a 52-year-old woman with hyperosmolar hyperglycemic state (glucose 34.0 mmol/L; osmolality 323 mOsm/kg) who developed left-sided weakness without chorea or ballism. Brain computed tomography showed subtle hypodensity of the right caudate nucleus and putamen, closely mimicking acute ischemic stroke; densitometry demonstrated a consistent side-to-side difference (5.89 Hounsfield units, P < .001). T1-weighted imaging showed concordant hyperintensity in the same region (mean per-pair signal-intensity ratio 1.117, P < .001). The weakness resolved within 1 week of glycemic optimization. Follow-up imaging at 12 months showed normalization of the signal abnormality (mean per-pair signal-intensity ratio 0.979, near unity). To our knowledge, the combination of movement-free, stroke-mimicking presentation with nonhemorrhagic striatal hypodensity showing no evidence of acute infarction has not been previously reported. Whether this reflects the timing of imaging relative to metabolic correction rather than a distinct radiologic entity remains to be established.