Investigating the frequency of neural autoantibodies in refractory focal epilepsy.

Objectives: There have been conflicting reports about the frequency of neural autoantibodies in epilepsy cohorts, which is confounded by the lack of clear distinction of epilepsy from acute symptomatic seizures due to encephalitis. The aim of this study was to determine the frequency of neural autoantibodies in a well characterised population of refractory focal epilepsy of known and unknown cause.

Methods: Cases were recruited from epilepsy outpatient clinics at the Princess Alexandra, Mater, Royal Brisbane and Women's and Cairns Base Hospitals from 2021 - 2023.

Diagnosing Late-Onset Tay-Sachs Through Next Generation Sequencing and Functional Enzyme Testing: From Genes to Enzymes.

Tay-Sachs disease is a neurodegenerative disorder characterized by progressive neurologic impairment due to pathogenic variants in the gene that codes for the alpha subunit of β-hexosaminidase. We report 2 cases of adult-onset progressive weakness, ataxia, and neuropsychiatric symptoms in a 30-year-old man and 37-year-old woman. Both patients had compound heterozygosity in the gene with 4 distinct variants.

HLA typing in anti-GAD antibody associated epilepsy.

Objective: Anti-GAD65 antibodies have been identified in people with epilepsy for many years, but their pathophysiological relevance is still debated. Susceptibility to autoimmune disease has been associated with Human Leukocyte Antigen (HLA) subtypes. Therefore, this study aimed to determine if there are common HLA types in anti-GAD65 antibody associated epilepsy cases compared to epilepsy controls.

Routine blood biochemical biomarkers in amyotrophic lateral sclerosis: Systematic review and cohort analysis.

: Blood biochemical biomarkers, including urate, creatinine, albumin, and creatine kinase, have been shown to be useful in ALS. To provide further information about the roles of these four biomarkers roles we performed a systematic review. In addition, we also performed a new study of the role of these biomarkers in predicting survival, using data from our local ALS cohort.

Assessing the Effect of Riluzole on Motor Unit Discharge Properties.

This study aims to determine if Riluzole usage can change the function and excitability of motor neurons. The clinical data and indices of motor neuron excitability were assessed using high-density surface EMG parameters from 80 ALS participants. The persistent inward current was assessed using the discharge rate from paired motor units obtained from the tibialis anterior muscle.

Amyotrophic lateral sclerosis established as a multistep process across phenotypes.

Background And Purpose: Given the accepted multistep process of disease causation in amyotrophic lateral sclerosis (ALS), the present study was undertaken to determine the number of steps required for disease onset across each of the ALS phenotypes.

Methods: Clinical and demographic data were prospectively accumulated using the Australian Motor Neurone Disease Registry (2005-2016), and age-specific incidence rates were calculated. Poisson regression was utilized to assess the relationship between log age-specific incidence and log age of onset, with McFadden's R used to assess the goodness of fit of the model.

Disease Activity in Pregnant and Postpartum Women With Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies.

Background And Objectives: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods.

Predictors of relapse risk and treatment response in AQP4-IgG positive and seronegative NMOSD: A multicentre study.

Background: Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD.

Effectiveness of cladribine compared to fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting multiple sclerosis.

Background: Comparisons between cladribine and other potent immunotherapies for multiple sclerosis (MS) are lacking.

Objectives: To compare the effectiveness of cladribine against fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting MS.

Methods: Patients with relapsing-remitting MS treated with cladribine, fingolimod, natalizumab, ocrelizumab or alemtuzumab were identified in the global MSBase cohort and two additional UK centres.

A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the COVID-19 pandemic.

Background: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset.

Methods: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted.

Long-term efficacy and safety of rituximab in the treatment of neuromyelitis Optica Spectrum disorder.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory astrocytopathy. Rituximab for B-cell suppression is a common treatment for NMOSD; however, large-scale randomised controlled trials are lacking.

Objective: Evaluate long-term efficacy and safety of rituximab for NMOSD.

Neutrophil-to-lymphocyte ratio at diagnosis as a biomarker for survival of amyotrophic lateral sclerosis.

Introduction: The neutrophil-to-lymphocyte ratio (NLR) has previously been reported to be associated with survival in ALS. To provide further information about the role of NLR as a biomarker in ALS, we performed a systematic review, analyzed data from our local cohort of ALS subjects and performed a meta-analysis.

Methods: (1) The systematic review used established methods.

Tissue informative cell-free DNA methylation sites in amyotrophic lateral sclerosis.

Cell-free DNA (cfDNA) is increasingly recognized as a promising biomarker candidate for disease monitoring. However, its utility in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), remains underexplored. Existing biomarker discovery approaches are tailored to a specific disease context or are too expensive to be clinically practical.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study.

Background: It remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course.

Methods: This large-scale cohort study included persons with MS with CSF data documented in the MSBase registry. CSF parameters to predict time to reach confirmed Expanded Disability Status Scale (EDSS) scores 4, 6 and 7 and annualised relapse rate in the first 2 years after diagnosis (ARR2) were assessed using (cox) regression analysis.

Comparative efficacy of ofatumumab oral therapies for relapsing multiple sclerosis patients using propensity score analyses and simulated treatment comparisons.

Background: Evidence from network meta-analyses (NMAs) and real-world propensity score (PS) analyses suggest monoclonal antibodies (mAbs) offer a therapeutic advantage over currently available oral therapies and, therefore, warrant consideration as a distinct group of high-efficacy disease-modifying therapies (DMTs) for patients with relapsing multiple sclerosis (RMS). This is counter to the current perception of these therapies by some stakeholders, including payers.

Objectives: A multifaceted indirect treatment comparison (ITC) approach was undertaken to clarify the relative efficacy of mAbs and oral therapies.

Transient binocular vision loss and pain insensitivity in Klippel-Feil syndrome: a case report.

Background: Klippel-Feil syndrome is a rare congenital bone disorder characterized by an abnormal fusion of two or more cervical spine vertebrae. Individuals with Klippel-Feil syndrome exhibit diverse clinical manifestations, including skeletal irregularities, visual and hearing impairments, orofacial anomalies, and anomalies in various internal organs, such as the heart, kidneys, genitourinary system, and nervous system.

Case Presentation: This case report describes a 12-year-old Pashtun female patient who presented with acute bilateral visual loss.

Variation in Resting Metabolic Rate Affects Identification of Metabolic Change in Geographically Distinct Cohorts of Patients With ALS.

Background And Objectives: Altered metabolism is observed in amyotrophic lateral sclerosis (ALS). However, without a standardized methodology to define metabolic changes, our understanding of factors contributing to and the clinical significance of altered metabolism in ALS is limited.

Methods: We aimed to determine how geographic variation in metabolic rates influences estimates and accuracy of predicted resting energy expenditure (REE) in patients with ALS and controls, while validating the effectiveness of cohort-specific approaches in predicting altered metabolic rate in ALS.

Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS.

Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have a range of functions and could influence ALS by several mechanisms.

Onboarding of siponimod in secondary progressive multiple sclerosis patients in Australia: Novel, real-world evidence from the MSGo digital support programme.

Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up.

Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia.

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

Aim: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS).

Methods: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups.

Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.

Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown.