Robert L Carruthers

• MD FRCPC
• Professor (Assistant) at University of British Columbia

Background An increasing number of women with multiple sclerosis (wMS) are considering pregnancy. Prior studies suggest increased rate of elective cesarian sections (C-sections) in wMS. Methods The Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS) is a prospective study on pregnant wMS. This report shows comparisons between (i) CANPREG-MS w...

Autoimmune encephalitis is increasingly recognized as a neurologic cause of acute mental status changes with similar prevalence to infectious encephalitis. Despite rising awareness, approaches to diagnosis remain inconsistent and evidence for optimal treatment is limited. The following Canadian guidelines represent a consensus and evidence (where a...

Background There is increasing need for evidence-based data on reproduction for women with multiple sclerosis (MS). First-trimester (first 13 weeks) miscarriages are relatively common in the general population. It is therefore important to have information on the frequency with which this occurs in women with MS. Methods The Canadian Multiple Scle...

Background and purpose: Conventional MRI measures of multiple sclerosis (MS) disease severity, such as lesion volume and brain atrophy, do not provide information about microstructural tissue changes, which may be driving physical and cognitive progression. Myelin damage in normal-appearing white matter (NAWM) is likely an important contributor to...

MRI-based myelin water fraction (MWF) and PET-based Pittsburgh compound B (PiB) imaging both have potential to measure myelin in multiple sclerosis (MS). We characterised the differences in MWF and PiB binding in MS lesions relative to normal-appearing white matter and assessed the correlation between MWF and PiB binding in 11 MS participants and 3...

Background Susac Syndrome (SuS) is an autoimmune endotheliopathy impacting the brain, retina and cochlea that can clinically mimic multiple sclerosis (MS). Objective To evaluate non-lesional white matter demyelination changes in SuS compared to MS and healthy controls (HC) using quantitative MRI. Methods 3T MRI including myelin water imaging and...

Background Spinal cord atrophy provides a clinically relevant metric for monitoring MS. However, the spinal cord is imaged far less frequently than brain due to artefacts and acquisition time, whereas MRI of the brain is routinely performed. Objective To validate spinal cord cross-sectional area measurements from routine 3DT1 whole-brain MRI versu...

MRI enables detailed in vivo depiction of multiple sclerosis (MS) pathology. Localized areas of MS damage, commonly referred to as lesions, or plaques, have been a focus of clinical and research MRI studies for over four decades. A nonplaque MRI abnormality which is present in at least 25% of MS patients but has received far less attention is diffu...

Background Neurofilaments are cytoskeletal proteins that are detectable in the blood after neuroaxonal injury. Multiple sclerosis (MS) disease progression, greater lesion volume, and brain atrophy are associated with higher levels of serum neurofilament light chain (NfL), but few studies have examined the relationship between NfL and advanced magne...

We characterized the frequency of diffusely abnormal white matter (DAWM) across a broad spectrum of multiple sclerosis (MS) participants. 35% of clinically isolated syndrome (CIS), 57% of relapsing remitting and 64% of secondary progressive MS participants demonstrated DAWM. CIS with DAWM had decreased cortical thickness, higher lesion load and a h...

Objective: The objective of this prospective "real world" study is to gain insight into the different "roads to conception" that women with MS take as part of the prospective Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS). Methods: Participants are women with MS who are planning a pregnancy. Data cut-off for analyses was April 30, 2020...

Background: Multiple first-line disease modifying therapies (DMTs) are available for relapsing-remitting multiple sclerosis (RRMS), each with different characteristics. We developed an interactive patient decision aid (PtDA) to promote informed shared decision-making (SDM). Objective: To test the preliminary effectiveness of the PtDA in particip...

Background Advanced magnetic resonance imaging (MRI) methods can provide more specific information about various microstructural tissue changes in multiple sclerosis (MS) brain. Quantitative measurement of T1 and T2 relaxation, and diffusion basis spectrum imaging (DBSI) yield metrics related to the pathology of neuroinflammation and neurodegenerat...

Background Myelin water imaging (MWI) was recently optimized to provide quantitative in vivo measurement of spinal cord myelin, which is critically involved in multiple sclerosis (MS) disability. Objective To assess cervical cord myelin measurements in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (ProgMS) partic...

Purpose: To determine whether optical coherence tomography angiography is of diagnostic utility for Susac syndrome (SuS) by quantifying microvascular retinal changes. Methods: We enrolled 18 eyes of 9 healthy controls and 18 eyes of 9 patients with chronic SuS (12 had previous branch retinal artery occlusions and 6 were clinically unaffected). I...

Objective To evaluate whether corpus callosum (CC) lesions are inextricably linked to CNS symptoms of Susac Syndrome (SuS) by reviewing published cases to find instances where: 1) CC lesions occur without CNS symptoms, and 2) whether patients with CNS symptoms lack CC lesions. Methods 100 reported cases of SuS were identified in PubMed. Clinical s...

Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease is a recently described central nervous system (CNS) inflammatory disorder with phenotypic overlap with Neuromyelitis Optica Spectrum Disorder (NMOSD). NMOSD seronegative patients, and those with limited forms of the disorder, become suspects for MOG antibody-associ...

Background Real-world safety data for the oral multiple sclerosis (MS) disease-modifying therapies (DMTs), dimethyl fumarate (DMF), fingolimod, and teriflunomide are important. We examined laboratory test abnormalities and adverse health conditions in new users. Methods Linked laboratory and administrative health data were accessed for all persons...

Objective We assessed the comorbidity burden associated with multiple sclerosis (MS) severity by performing a phenome-wide association study (PheWAS). Methods We conducted a PheWAS in 2 independent cohorts: a discovery (Boston, United States; 1993–2014) and extension cohort (British Columbia, Canada; 1991–2008). We included adults with MS, ≥1 Expa...

Objective To examine laboratory testing adherence by persons initiating an oral disease-modifying therapy (DMT) for multiple sclerosis (MS). Methods Population-based health administrative and laboratory data were accessed in British Columbia, Canada, to identify everyone filling their first prescription for dimethyl fumarate (DMF), fingolimod or t...

Background and purpose: Cognitive impairment is a core symptom in multiple sclerosis (MS). Damage to normal appearing white matter (NAWM) is likely involved. We sought to determine if greater myelin heterogeneity in NAWM is associated with decreased cognitive performance in MS. Methods: A total of 27 participants with MS and 13 controls matched...

Background Multiple sclerosis (MS) is the most common cause of neurological disability, other than trauma, among young adults of reproductive age. In contrast to the past, today there is very little lag time from clinical onset to diagnosis. Disease-modifying therapies are also now available outside of clinical trials. However, there is very little...

Background: Enhanced prediction of progression in secondary progressive multiple sclerosis (SPMS) could improve clinical trial design. Machine learning (ML) algorithms are methods for training predictive models with minimal human intervention. Objective: To evaluate individual and ensemble model performance built using decision tree (DT)-based a...

Objective To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods To illustrate its research enabling purpose, epidemiologic patterns and disease phenotypes were assessed a...

Background: Multiple sclerosis (MS) patients often struggle with treatment decisions, in part due to the increasing number of approved disease modifying therapies, each with different characteristics, and also since physicians can struggle to identify which of these characteristics matter most to each individual patient. Decision uncertainty can c...

Objective: The objective of this study was to characterize the use of cannabis-based products (CBPs) by multiple sclerosis (MS) patients who attend the University of British Columbia Hospital (UBCH) MS clinic. Methods: All patients attending the UBCH MS clinic from January to March 2018 were invited to participate in an anonymous survey that inc...

Background: Advances in multiple sclerosis (MS) disease modifying therapy (DMT) have increased laboratory monitoring requirements. Our goal was to survey existing practices and perceptions of risk in laboratory monitoring throughout Canada and assess whether opportunities to improve patient care and safety exist. Methods: A web-based survey asse...

Background: Patients with multiple sclerosis (MS) experience progressive thinning in optical coherence tomography (OCT) measures of neuroaxonal structure regardless of optic neuritis history. Few prospective studies have investigated the effects of disease-modifying therapies on neuroaxonal degeneration in the retina. Alemtuzumab is a monoclonal a...

Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly gre...

Objective: To examine the association between socioeconomic status (SES) and disability outcomes and progression in multiple sclerosis (MS). Methods: Health administrative and MS clinical data were linked for 2 cohorts of patients with MS in British Columbia (Canada) and South East Wales (UK). SES was measured at MS symptom onset (±3 years) base...

Objective The objective of this paper is to evaluate potential dose-dependent adverse effects of gadolinium-based contrast agents (GBCAs) on MS progression. Methods Outcomes from a cohort of 612 secondary progressive MS (SPMS) patients, enrolled in a two-year, placebo-controlled (negative) trial assessing the efficacy of MBP8298, were acquired. Pa...

Background Progressive solitary sclerosis is a unifocal demyelinating disease recently proposed as a possible multiple sclerosis variant. Objective To compare myelin content and brain metabolite ratio qualitatively in the normal-appearing white matter of progressive solitary sclerosis cases compared to multiple sclerosis and healthy control partic...

Supplemental material for Advanced imaging findings in progressive solitary sclerosis: a single lesion or a global disease?

Objective To examine persistence and adherence to the oral disease-modifying therapies (DMTs) for multiple sclerosis (MS). Methods Population-based health administrative databases in British Columbia, Canada were accessed to identify all individuals filling an oral DMT prescription for MS (fingolimod, dimethyl fumarate, teriflunomide) between Janu...

Background: Little is known about the use of the new oral disease-modifying therapies (DMTs: fingolimod, dimethyl fumarate, teriflunomide) for multiple sclerosis (MS) in clinical practice. We describe their rate of uptake, and their use as compared to the established first-generation (beta-interferon and glatiramer acetate) and second-generation (...

Objectives We aimed at designing a nomogram, a prediction tool, to predict the individual’s risk of conversion to secondary progressive multiple sclerosis (SPMS) at the time of multiple sclerosis (MS) onset. Methods One derivation and three validation cohorts were established. The derivation cohort included 8825 relapsing-onset MS patients in Swed...

Objective: To examine the association between physical comorbidities and disability progression in multiple sclerosis (MS). Methods: We conducted a retrospective cohort study using linked health administrative and clinical databases in 2 Canadian provinces. Participants included adults with incident MS between 1990 and 2010 who entered the cohor...

Background: Paraneoplastic syndromes are remote effects of cancer caused by an autoimmune response triggered by tumor cells. Paraneoplastic Neuromyelitis Optica Spectrum Disorders (NMOSD) has been previously described, but the underlying mechanism for these rare cases is not well characterized. This paper presents a newly described case series of...

Supplementary materials include: Table S1. Population characteristics and baseline MRI metrics for the longitudinal sample; Figure S1. Distribution of lesions by group.

Spinal cord pathology is a feature of both neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (MS). While subclinical disease activity has been described in MS using quantitative magnetic resonance imaging measures, current evidence suggests that neurodegeneration is absent between relapses in NMOSD, although...

Introduction Adverse drug reactions (ADRs) are a global public health issue. The potential for pharmacogenomic biomarkers has been demonstrated in several therapeutical areas, including HIV infection and oncology. Dimethyl fumarate (DMF) is a licensed disease-modifying therapy for the treatment of multiple sclerosis (MS). The use of DMF in MS has b...

Background The Multiple Sclerosis Severity Score (MSSS) is obtained by normalising the Expanded Disability Status Scale (EDSS) score for disease duration and has been a valuable tool in cross-sectional studies. Objective To assess whether use of age rather than the inherently ambiguous disease duration was a feasible approach. Method We pooled di...

\textbf{Background:}$ The Multiple Sclerosis Severity Score (MSSS) is obtained by normalising the Expanded Disability Status Scale (EDSS) score for disease duration and has been a valuable tool in cross-sectional studies. $\textbf{Objective:}$ To assess whether use of age rather than the inherently ambiguous disease duration was a feasible approach...

Background: The Multiple Sclerosis Severity Score (MSSS) is obtained by normalising the Expanded Disability Status Scale (EDSS) score for disease duration and has been a valuable tool in cross-sectional studies. Objective: To assess whether use of age rather than the inherently ambiguous disease duration was a feasible approach. Method: We pooled d...

Background: Benefits of selective serotonin reuptake inhibitors (SSRIs) in modifying the multiple sclerosis (MS) disease course have been suggested, but their ability to delay disability progression remains unknown. We examined the association between SSRI exposure and MS disability progression. Methods: A nested case-control study was conducted...

Background: The optic nerve is frequently injured in multiple sclerosis and neuromyelitis optica, resulting in visual dysfunction, which may be reflected by measures distant from the site of injury. Objective: To determine how retinal nerve fiber layer as a measure of axonal health, and macular volume as a measure of neuronal health are related to...

Co-author; AAN 2016 Poster Session

Background Interleukin-6 (IL6) blockage is a treatment strategy used in many inflammatory conditions. Trials in Neuromyelitis Optica Spectrum Disorder (NMOSD) are ongoing. Secondary auto-immunity affecting the central nervous system (CNS) is well described with some biologic agents, mainly tumor necrosis factor (TNF)-alpha inhibitors. These treatme...

Background: Neuromyelitis optica spectrum disorder (NMOSD) has emerged as a disorder distinct from multiple sclerosis, largely due to the discovery in 2004 of a novel disease marker, aquaporin-4 immunoglobulin or AQP4-IgG (also known as NMO-IgG). Differentiating NMOSD from multiple sclerosis has important prognostic and treatment implications. The...

Background Exposure to parental chronic illness is associated with adverse developmental outcomes. Objective We examined the association between parental multiple sclerosis (MS) and parental MS-related clinical factors on developmental health. Methods We conducted a population-based cohort study in British Columbia, Canada, using linked health da...

Objective: To determine whether vitamin D status predicts disease activity in patients with multiple sclerosis (MS) taking interferon-β (IFN), glatiramer acetate (GA), and fingolimod (FTY). Methods: Participants (n = 324) with relapsing-remitting MS on IFN (96), GA (151), or FTY (77) were identified from the Comprehensive Longitudinal Investigat...

Immunoglobulin-4 (IgG4-) related disease is a newly described treatable condition that has recently expanded the differential diagnosis of inflammatory meningeal disorders. This review will discuss the main clinical and pathophysiological features of IgG4-related meningeal disease in the context of meningeal inflammatory disorders in general. Parti...

Background The clinical trial design for primary progressive multiple sclerosis (PPMS) requires understanding of disability progression in modern patient cohorts. Objective The objective of this paper is to characterize demographic and clinical characteristics of PPMS and assess rate of disability progression. Methods We studied PPMS (n = 73) and...

The natural history and clinical import of Progressive Multifocal Leukoencephalopathy has changed enormously in the last thirty years. After a resurgence of PML during the HIV/AIDS epidemic, advances in the treatment of multiple sclerosis created another group of 'at risk' patients. With a focus on issues pertaining to the multiple sclerosis patien...

Background The lack of prospective trial data comparing certain multiple sclerosis (MS) therapies could be addressed with observational research. Objective The objective of this paper is to investigate outcomes of natalizumab versus fingolimod treatment in an MS cohort using a novel method of patient selection. Methods We reviewed entries from ou...

JCV serologic status is used to determine PML risk in natalizumab-treated patients. Given two cases of natalizumab-associated PML in JCV sero-negative patients and two publications that question the false negative rate of the JCV serologic test, clinicians may question whether our understanding of PML risk is adequate. Given that there is no gold s...

Hypertrophic pachymeningitis (HP) is an inflammatory condition in which the dura mater of the cranium or spine becomes thickened, leading to symptoms that result from mass effect, nerve compression, or vascular compromise. The differential diagnosis of HP includes immune-mediated conditions such as rheumatoid arthritis and vasculitis, malignancies,...

The mechanisms of dysautonomia from carotid artery dissection were discussed recently in Circulation . A case was presented of a 49-year-old woman with a history of hypertension and vasovagal syncope who developed abrupt slurred speech and left hemiplegia.1 She had a right internal carotid artery dissection and right cerebral hemispheric infarction...

The primary action of several antidepressant treatments used in the clinic raises extracellular concentrations of serotonin (5-HT), which subsequently act on multiple 5-HT receptors. The present study examined whether 5-HT6 receptors might be involved in the antidepressant-like effects mediated by enhanced neurotransmission at 5-HT synapses. A sele...

Three distinct classes of drugs: dopaminergic agonists (such as D-amphetamine), serotonergic agonists (such as LSD), and glutamatergic antagonists (such as PCP) all induce psychotomimetic states in experimental animals that closely resemble schizophrenia symptoms in humans. Here we implicate a common signaling pathway in mediating these effects. In...