Publications by authors named "James Overell"

Background: Cognitive impairment is a well-recognized symptom of multiple sclerosis (MS) that can manifest early in the disease course. Deficits in cognitive function can have a major impact on daily life. However, cognitive decline is often under-examined in clinical trials and clinical practice due to lack of adequate data.

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Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by central nervous system demyelination and axonal degeneration. Fatigue affects a major portion of MS patients, significantly impairing their daily activities and quality of life. Despite its prevalence, the mechanisms underlying fatigue in MS are poorly understood, and measuring fatigue remains a challenging task.

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Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS.

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Article Synopsis
  • - Autoimmune encephalitis (AIE) is a rare neurological disorder characterized by brain inflammation, often linked to specific autoantibodies; currently, there are no approved treatments for AIE despite the involvement of interleukin-6 (IL-6) signaling in its pathology.
  • - The CIELO study aims to test the efficacy and safety of satralizumab, an IL-6 receptor-targeting monoclonal antibody, in patients with specific types of AIE, using a randomized, double-blind design with 152 participants.
  • - The study will follow a 52-week treatment period with possible extensions, enabling participants to receive either the study drug, placebo, or additional treatment options depending on the
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Objectives: Detection and prediction of disability progression is a significant unmet need in people with progressive multiple sclerosis (PwPMS). Government and health agencies have deemed the use of patient-reported outcomes measurements (PROMs) in clinical practice and clinical trials a major strategic priority. Nevertheless, data documenting the clinical utility of PROMs in neurological diseases is scarce.

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Background: Global increases in opioid prescribing and misuse have prompted calls for closer regulation. Opioid prescription following surgery may lead to long term opioid use. A study was conducted evaluating opioid prescriptions on hospital discharge following common general surgery operations in the Bay of Plenty.

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Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis by combining non-invasive neuroimaging and blood biomarkers.

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Background: Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis.

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Background And Purpose: Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.

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Background And Purpose: Requiring a walking aid is a fundamental milestone in multiple sclerosis (MS), represented by an Expanded Disability Status Scale (EDSS) score ≥6.0. In the present study, we assess the effect of ocrelizumab (OCR) on time to EDSS score ≥6.

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Background: The safety and efficacy of ocrelizumab in primary progressive multiple sclerosis were shown in the phase 3 ORATORIO trial. In this study, we assessed the effects of maintaining or switching to ocrelizumab therapy on measures of disease progression and safety in the open-label extension phase of ORATORIO.

Methods: ORATORIO was an international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done at 182 study locations including academic centres, hospitals, and community speciality centres within 29 countries across the Americas, Australia, Europe, Israel, New Zealand, and Russia.

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Background: Recent changes in the understanding and management of multiple sclerosis (MS) have increased the role of MRI in supporting diagnosis and disease monitoring. However, published guidelines on the use of MRI in MS do not translate easily into different clinical settings and considerable variation in practice remains. Here, informed by published guidelines for the use of MRI in MS, we identified a clinically informative MRI protocol applicable in a variety of clinical settings, from district general hospitals to tertiary centres.

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Objective: Neurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case-control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.

Methods: Guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed.

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Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system which leads to demyelination and neurodegeneration. The T and B cells, the body's immune cells, start attacking the brain and spinal cord, leading to a variety of symptoms. Alemtuzumab is a recently approved disease-modifying therapy that has been shown to have a very high impact on MS.

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Background: The proportion of people with relapsing-remitting multiple sclerosis prescribed disease modifying treatments (DMTs) in the United Kingdom (UK) is considered low compared with other countries. There are differences in DMT prescription rates between UK nations (England, Wales, Scotland, Northern Ireland). Despite this, there has been little research into decision-making processes and prescribing practices.

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Background: Time matters in multiple sclerosis (MS). Irreversible neural damage and cell loss occur from disease onset. The MS community has endorsed a management strategy of prompt diagnosis, timely intervention and regular proactive monitoring of treatment effectiveness and disease activity to improve outcomes in people with MS.

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The outcome of Guillain-Barré syndrome (GBS) remains unchanged since plasma exchange and intravenous immunoglobulin (IVIg) were introduced over 20 years ago. Pathogenesis studies on GBS have identified the terminal component of complement cascade as a key disease mediator and therapeutic target. We report the first use of terminal complement pathway inhibition with eculizumab in humans with GBS.

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Many drugs have been reported to cause thrombotic microangiopathy (TMA), yet evidence supporting a direct association is often weak. In particular, TMA has been reported in association with recombinant type I interferon (IFN) therapies, with recent concern regarding the use of IFN in multiple sclerosis patients. However, a causal association has yet to be demonstrated.

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Long lists of causes of peripheral neuropathy make peripheral nerve disease a dry and uninspiring subject. A simple scheme based on the answers to just six questions should enable the clinician to recognise characteristic patterns, investigate relevant subgroups appropriately, and identify treatable disorders quickly: which systems are involved? What is the distribution of weakness? What is the nature of the sensory involvement? Is there any evidence of upper motor neuron involvement? What is the temporal evolution? Is there any evidence for a hereditary neuropathy? Standard screening investigations suffice for the common length dependent axonal neuropathies while complex presentations need more detailed investigations targeted to their clinical phenotype.

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Human and animal studies on antibody-mediated neuropathy implicate complement in pathogenesis. In animal models complement inhibition is therapeutically beneficial. The monoclonal antibody, eculizumab (Soliris™, Alexion Pharmaceuticals, Cheshire, CT), prevents cleavage of C5 and thus inhibits terminal complement activation.

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Long lists of causes of peripheral neuropathy make peripheral nerve disease a dry and uninspiring subject. A simple scheme based on the answers to just six questions should enable the clinician to recognise characteristic patterns, investigate relevant subgroups appropriately, and identify treatable disorders quickly: which systems are involved? What is the distribution of weakness? What is the nature of the sensory involvement? Is there any evidence of upper motor neuron involvement? What is the temporal evolution? Is there any evidence for a hereditary neuropathy? Standard screening investigations suffice for the common length dependent axonal neuropathies while complex presentations need more detailed investigations targeted to their clinical phenotype.

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