Publications by authors named "Marc Girard"
Background: Effectiveness of disease-modifying treatment (DMT) in people affected by primary progressive multiple sclerosis (PPMS) is limited. Whether specific subgroups may benefit more from DMT in a real-world setting remains unclear. Our aim was to investigate the potential effect of DMT on disability worsening among patients with PPMS stratified by different disability trajectories.
View Article and Find Full Text PDFBackground 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.
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- * Machine learning models were applied to predict confirmed disability progression after two years, achieving a ROC-AUC score of 0.71, indicating moderate accuracy, while historical disability was found to be a stronger predictor than treatment or relapse history.
- * The research followed strict guidelines and made its coding accessible for others to facilitate future benchmarking in predicting disability progression in MS patients.
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.
Background: Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance.
Objectives: Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate).
Design: This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD.
Article Synopsis
- Dimensionality reduction methods like PHATE, t-SNE, and UMAP help visualize complex biological data, but they often do so without the guidance of expert labels.
- The new method RF-PHATE combines expert knowledge with unsupervised techniques by using random forests to create low-dimensional visualizations that emphasize important data relationships while filtering out irrelevant features.
- RF-PHATE is effective for large datasets and has been successfully applied in multiple case studies, showing its ability to handle time-series data in multiple sclerosis research, analyze noisy Raman spectral data, and connect geometric structures with COVID-19 outcomes.
Article Synopsis
- The study aims to identify predictors of treatment switching in patients with relapsing-remitting MS using data from multiple national registries.
- A total of 269,822 treatment episodes from 110,326 patients were analyzed, focusing on those who started disease-modifying treatments during their RRMS phase.
- Key findings indicate that higher disability scores (EDSS), being female, and older age increase the likelihood of treatment switching, with certain DMTs initiated between 2007 and 2012 showing even higher rates of switching.
Article Synopsis
- This study investigates the relationship between environmental factors and progressive-onset multiple sclerosis (POMS) compared to relapse-onset multiple sclerosis (ROMS), aiming to better understand the causes of POMS.
- Data is drawn from two major studies, including a sample of 155 POMS, 204 ROMS, and 558 controls, ensuring that the POMS sample is representative of the broader Australian POMS population.
- The research addresses various methodological challenges, such as biases and differences between POMS and controls, and will present findings on the associations in future publications.
Risk of secondary progressive multiple sclerosis after early worsening of disability.
J Neurol Neurosurg Psychiatry
December 2023
Background: Whether progression independent of relapse activity (PIRA) heralds earlier onset of secondary progressive multiple sclerosis (SPMS) and more rapid accumulation of disability during SPMS remains to be determined. We investigated the association between early PIRA, relapse-associated worsening (RAW) of disability and time to SPMS, subsequent disability progression and their response to therapy.
Methods: This observational cohort study included patients with relapsing-remitting multiple sclerosis (RRMS) from the MSBase international registry across 146 centres and 39 countries.
Article Synopsis
- The study investigates geographical differences in the risk of secondary progressive multiple sclerosis (SPMS) and how these may be influenced by factors like latitude and treatment types.
- It utilizes data from a global patient registry, focusing on relapsing-remitting multiple sclerosis patients and factors such as age, sex, and treatment efficacy.
- The research analyzes data from over 51,000 patients across 27 countries to establish patterns in the progression from relapsing-remitting to secondary progressive phases of the disease.
Article Synopsis
- MOGAD is a newly identified neuroinflammatory disease characterized by the presence of anti-MOG antibodies, with symptoms varying widely among patients.
- A study conducted in Quebec found a prevalence of 0.52 cases per 100,000 people, with optic neuritis and acute disseminated encephalomyelitis being the most common initial symptoms.
- Only 38% of patients fully recovered within 4 weeks, and a significant number of patients experienced relapses and residual deficits, indicating a serious disease course for many.*
Article Synopsis
- The study highlights the risk of increased disease activity after stopping natalizumab, emphasizing the need for effective alternative therapies to manage relapsing-remitting multiple sclerosis (RRMS).
- It compares the effectiveness of switching to three disease-modifying therapies—dimethyl fumarate, fingolimod, and ocrelizumab—following natalizumab discontinuation among RRMS patients.
- The analysis included data from 1386 patients and focused on outcomes like annualized relapse rate and time to first relapse, revealing important insights into treatment persistence and effectiveness for managing disease after discontinuing natalizumab.
Disability accrual in primary and secondary progressive multiple sclerosis.
J Neurol Neurosurg Psychiatry
September 2023
Article Synopsis
- The study compares disability progression in primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS), revealing that SPMS has a later onset and slower disability accrual compared to PPMS.* -
- Analysis utilized data from the MSBase cohort, adjusting for factors like age, sex, and drug therapies, and included 1,872 PPMS patients and 2,575 SPMS patients.* -
- Findings suggest that although SPMS patients start with greater baseline disability, their slower progression may lead to similar disability levels over time, indicating the need for careful consideration when combining these groups in clinical trials.*
Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.
Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS.
Methods: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'.
Background: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models.
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- - The study investigates changes in T lymphocytes related to multiple sclerosis (MS) and focuses on the NKG2D pathway, which is crucial for CD4 and CD8 T cell activation, revealing that its activity varies across different forms of MS (RRMS, SPMS, and PPMS).
- - Using flow cytometry and microscopy, researchers found that NKG2D T lymphocytes are less abundant in RRMS patients compared to healthy controls, and their proportion decreases with age in PPMS patients due to reduced γδ and αβ CD4CD8 populations.
- - Blocking NKG2D in co-cultured CD8 T lymphocytes and astrocytes resulted in increased mobility and a shift from long-lasting
Background And Purpose: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS).
Methods: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year.
CLMP Promotes Leukocyte Migration Across Brain Barriers in Multiple Sclerosis.
Neurol Neuroimmunol Neuroinflamm
November 2022
Article Synopsis
- - The study investigates the role of coxsackie and adenovirus receptor-like membrane protein (CLMP) in the migration of immune cells into the central nervous system (CNS) of patients with multiple sclerosis (MS), focusing on how it contributes to CNS damage.
- - Researchers found that CLMP expression was significantly heightened in both the endothelial cells and immune cells of MS patients, particularly in active brain lesions, indicating its involvement in the inflammatory response associated with MS.
- - Blocking CLMP with specific antibodies reduced immune cell migration across brain endothelial cells in laboratory tests, suggesting that targeting CLMP may offer a potential therapeutic approach for managing MS-related inflammation.
Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national registry.
J Neurol Neurosurg Psychiatry
September 2022
Background: Early recognition of markers of faster disability worsening in paediatric-onset multiple sclerosis (MS) is a key requisite of personalised therapy for children with MS at the earliest possible time.
Objective: To identify early predictors of rapid disability accrual in patients with paediatric-onset MS.
Methods: Using the global MSBase registry, we identified patients who were <18 years old at the onset of MS symptoms.
Background: Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time.
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- Interleukin-27 (IL-27) can cause both pro-inflammatory and anti-inflammatory effects and is found at higher levels in the central nervous system of multiple sclerosis (MS) patients, but its specific role in neuroinflammation is not fully understood.
- * The study investigates how astrocytes respond to IL-27 and how this affects their interaction with activated T lymphocytes under both inflamed and non-inflamed conditions.
- * Results show that IL-27 exposure leads to increased immune-related gene expression in astrocytes, enhances the secretion of certain chemokines, and alters the activation status and motility of CD8 T lymphocytes, suggesting more dynamic interactions between these cells in the context of inflammation.
Article Synopsis
- This study evaluates the rate of disease activity return in multiple sclerosis (MS) patients after they stop using disease-modifying therapy, focusing on relapse rates and factors influencing relapse.
- A large sample of 14,213 patients showed that relapse rates typically increased within 2 months after stopping treatment, with earlier commencement of new therapy reducing these rates significantly.
- Factors predicting relapse included having a higher relapse rate prior to stopping therapy, being younger, being female, and having a higher Expanded Disability Status Scale (EDSS) score, with subsequent therapy reducing both relapse risk and disability progression.
Background: Patients with relapsing-remitting multiple sclerosis commonly switch between disease-modifying therapies (DMTs). Identifying predictors of relapse when switching could improve outcomes.
Objective: To determine predictors of relapse hazard when switching to cladribine.
Article Synopsis
- This study looks at how to predict long-term disability in people with multiple sclerosis (MS) after they show signs of worsening over six months.
- Researchers checked data from thousands of patients to figure out who is more likely to have lasting problems.
- They found that things like age, sex, and how MS affects the person can help tell if someone will continue to get worse, which can help doctors in future treatments.
Article Synopsis
- The study aimed to explore how the latitude of residence and UVB radiation exposure affects the severity of multiple sclerosis (MS) among patients, using data from the MSBase registry.
- Results indicated that patients living at higher latitudes (above 40°) experienced more severe MS symptoms, while this trend was not observed in those living below this latitude.
- Additionally, lower UVB exposure during childhood (ages 6 and 18) was linked to faster progression of disability in MS, suggesting the importance of environmental factors in disease severity.