Publications by authors named "Mark Slee"

The diagnostic potential of paramagnetic rim lesions (PRLs) has been previously established; however, the prognostic significance of these lesions has not previously been consistently described. This study aimed to establish the prognostic role of PRLs in MS with respect to the Expanded Disability Status Scale (EDSS) and rates of disability progression. Databases of PubMed, EMBASE, Scopus and reference lists of selected articles were searched up to 29/04/2023.

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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.

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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.

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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.

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Introduction: Optic neuritis may occur in a variety of conditions, including as a manifestation of multiple sclerosis. Despite significant research into the efficacy of corticosteroids as a first-line treatment, the optimal route of administration has not been well defined. This review aims to explore the efficacy, adverse effects and economic implications of using oral versus intravenous methylprednisolone to treat acute optic neuritis.

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Article Synopsis
  • Epigenetic mechanisms, like DNA methylation (DNAm), affect how DNA is expressed without altering the sequence and are linked to diseases, including multiple sclerosis (MS).
  • This study analyzed DNA methylation profiles in a large group of people with MS and found significant differences compared to healthy controls that are independent of known genetic risk factors.
  • The findings highlight that these methylation differences mainly occur in immune cells such as B cells and monocytes, shedding light on specific biological pathways involved in the disease.
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Introduction: Lhermitte's phenomenon (LP) is a transient shock-like sensation that radiates down the spine into the extremities, usually with neck flexion. The potential efficacy and tolerability of various symptomatic therapies in the management of LP have not been systematically reviewed previously.

Method: A systematic review was conducted using PubMed, EMBASE, and the Cochrane Library from inception to August 2022 for peer-reviewed articles describing the treatment of patients with Lhermitte's phenomenon.

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Background And Objectives: In multiple sclerosis (MS), accelerated aging of the immune system (immunosenescence) may be associated with disease onset or drive progression. DNA methylation (DNAm) is an epigenetic factor that varies among lymphocyte subtypes, and cell-specific DNAm is associated with MS. DNAm varies across the life span and can be used to accurately estimate biological age acceleration, which has been linked to a range of morbidities.

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Background: Progression Independent of Relapse Activity (PIRA) is heterogeneously described in patients with multiple sclerosis (MS) regarding the frequency and nature of PIRA. This systematic review was conducted to characterise and define the elements of PIRA.

Method: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

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Article Synopsis
  • AHSCT is evaluated as a treatment for relapsing-remitting MS, comparing its effectiveness with medications like fingolimod, natalizumab, and ocrelizumab.
  • The study utilized data from 6 MS centers and tracked 4915 patients over time, ensuring they were matched on similar characteristics for a fair comparison.
  • Results showed that AHSCT had a lower annual relapse rate than fingolimod, with similar risks for disability worsening, suggesting it may be a more effective option for managing MS.
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  • This study examines the effectiveness of six different therapies for treating relapsing-remitting multiple sclerosis (RRMS) over 5 years, using a large dataset from 74 centers across 35 countries.
  • Researchers found that natalizumab and fingolimod were more effective in reducing relapses and worsening disability compared to other therapies like dimethyl fumarate, teriflunomide, glatiramer acetate, and interferon beta.
  • The findings highlight the potential of marginal structural models (MSMs) to simulate clinical trials and compare various treatment outcomes in real-world patient populations.
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  • 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.
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  • 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.
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Trinucleotide repeat disorders comprise ~20 severe, inherited, human neuromuscular and neurodegenerative disorders, which result from an abnormal expansion of repetitive sequences in the DNA. The most common of these, Huntington's disease (HD), results from expansion of the CAG repeat region in exon 1 of the gene via an unknown mechanism. Since non-coding RNAs have been implicated in the initiation and progression of many diseases, herein we focused on a circular RNA (circRNA) molecule arising from non-canonical splicing (backsplicing) of pre-mRNA.

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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.*
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Background: The diagnosis of myasthenia gravis (MG) may be challenging and require multiple specialised testing modalities. Accessing these investigations can involve significant waiting time and costs. The bedside icepack test (IPT) has been proposed to assist with the diagnosis of MG with ocular features, and may prove an economically viable; however, there have been there is heterogeneity in the literature evaluating the IPT.

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Background: Strategies to improve the selection of appropriate target journals may reduce delays in disseminating research results. Machine learning is increasingly used in content-based recommender algorithms to guide journal submissions for academic articles.

Objective: We sought to evaluate the performance of open-source artificial intelligence to predict the impact factor or Eigenfactor score tertile using academic article abstracts.

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Background: Pregnancy in women with multiple sclerosis (wwMS) is associated with a reduction of long-term disability progression. The mechanism that drives this effect is unknown, but converging evidence suggests a role for epigenetic mechanisms altering immune and/or central nervous system function. In this study, we aimed to identify whole blood and immune cell-specific DNA methylation patterns associated with parity in relapse-onset MS.

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Functional unresponsiveness can present a diagnostic challenge, but there are many positive physical examination findings that may help to confirm this diagnosis. Some of these are associated with pain or potential tissue damage for the patient, and potentially ethical and legal risk for the practitioner, but several lesser-known physical examination techniques do not carry these risks. Such examination techniques include non-damaging irritative stimuli, a modification to the conventional hand drop test and evaluation of eyelid opening.

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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.

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Multiple sclerosis is a leading cause of neurological disability in adults. Heterogeneity in multiple sclerosis clinical presentation has posed a major challenge for identifying genetic variants associated with disease outcomes. To overcome this challenge, we used prospectively ascertained clinical outcomes data from the largest international multiple sclerosis registry, MSBase.

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