Publications by authors named "Alice Schabas"

12 Publications

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Elevated levels of serum CD5 antigen-like protein distinguish secondary progressive multiple sclerosis from other disease subtypes.

Mult Scler Relat Disord 2021 Sep 20;56:103269. Epub 2021 Sep 20.

Department of Pathology & Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada; International Collaboration on Repair Discoveries (ICORD), Faculty of Medicine, University of British Columbia, Vancouver, Canada. Electronic address:

CD5 antigen-like (CD5L) protein is a macrophage-secreted protein with roles in immunomodulation and lipid homeostasis. We compared serum CD5L levels in healthy controls to individuals diagnosed with clinically isolated syndrome, relapsing remitting (RR), secondary progressive (SP), and primary progressive (PP) multiple sclerosis (MS). CD5L was increased in SPMS relative to controls, RRMS, and PPMS. SPMS CD5L was associated with longer disease duration independent of age, sex, or disease severity. The positive relationship between CD5L and disease duration in SPMS suggests a chronic peripheral inflammatory profile compared to other subtypes, particularly PPMS, warranting investigation of functional roles for CD5L in MS.
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http://dx.doi.org/10.1016/j.msard.2021.103269DOI Listing
September 2021

The road to conception for women with multiple sclerosis.

Mult Scler J Exp Transl Clin 2021 Jul-Sep;7(3):20552173211032313. Epub 2021 Jul 15.

Department of Medicine (Neurology), University of Alberta, Edmonton, Alberta, Canada.

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.

Results: We believe this is the first prospective National study of women with MS planning pregnancies.The data are for the first 44 women enrolled of whom 26 achieved pregnancy by cut-off date. Seven women used assisted reproductive technologies (ARTs); 6 stopped disease modifying therapy (DMT) against their neurologists' recommendations; 6 had an interruption(s) in trying to conceive due to MS relapses, MRI-detected inflammation, or limited "windows of opportunity" between DMT courses.

Conclusion: The study illustrates the roads that women take to conception, even if they are on the same therapy and have similar clinical expression of MS. Advice given by treating neurologists on washout periods show discrepancies. This paper highlights the real problem that there is no definitive, international consensus on managing these women due to the lack of "real world" data and thus the goal of CANPREG-MS is to provide such real world data.
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http://dx.doi.org/10.1177/20552173211032313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287372PMC
July 2021

Preliminary testing of a patient decision aid for patients with relapsing-remitting multiple sclerosis.

Mult Scler J Exp Transl Clin 2021 Jul-Sep;7(3):20552173211029966. Epub 2021 Jul 15.

Division of Neurology, University of British Columbia, Vancouver, Canada.

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 participants with RRMS.

Methods: Knowledge, and decisional conflict were measured pre- and post- implementation of the PtDA, SDM after the consultation, and 6-month treatment patterns were observed. Differences in scores were analyzed using descriptive statistics and paired t-tests. Qualitative interviews with patients and neurologists were analyzed using thematic analysis.

Results: 52 participants were recruited: most were female (81%), 40 years of age or younger (62%), and had experienced MS for less than 5 years (56%). After participants used the PtDA, there was a significant improvement in decisional conflict (change = 1.00;  < 0.001) and knowledge (change = 2.15, p < 0.001). Nearly all patients wanted SDM, and 25 (56%) reported this occurred in their consult. Qualitative results suggested the PtDA supported both patients and neurologists in making decisions.

Conclusion: This pilot study suggests that PtDA use helps RRMS patients and their clinician select a DMT. Future studies will assess the feasibility of implementation and the impact of the PtDA on timely DMT initiation and longer-term adherence.
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http://dx.doi.org/10.1177/20552173211029966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287362PMC
July 2021

Characterization of multiple sclerosis neuroinflammation and neurodegeneration with relaxation and diffusion basis spectrum imaging.

Mult Scler 2021 Jun 16:13524585211023345. Epub 2021 Jun 16.

Department of Radiology, The University of British Columbia, Vancouver, BC, Canada/International Collaboration on Repair Discoveries (ICORD), The University of British Columbia, Vancouver, BC, Canada/Department of Physics & Astronomy, The University of British Columbia, Vancouver, BC, Canada/Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada.

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 T and T relaxation, and diffusion basis spectrum imaging (DBSI) yield metrics related to the pathology of neuroinflammation and neurodegeneration that occurs across the spectrum of MS.

Objective: To use relaxation and DBSI MRI metrics to describe measures of neuroinflammation, myelin and axons in different MS subtypes.

Methods: 103 participants (20 clinically isolated syndrome (CIS), 33 relapsing-remitting MS (RRMS), 30 secondary progressive MS and 20 primary progressive MS) underwent quantitative T, T, DBSI and conventional 3T MRI. Whole brain, normal-appearing white matter, lesion and corpus callosum MRI metrics were compared across MS subtypes.

Results: A gradation of MRI metric values was seen from CIS to RRMS to progressive MS. RRMS demonstrated large oedema-related differences, while progressive MS had the most extensive abnormalities in myelin and axonal measures.

Conclusion: Relaxation and DBSI-derived MRI measures show differences between MS subtypes related to the severity and composition of underlying tissue damage. RRMS showed oedema, demyelination and axonal loss compared with CIS. Progressive MS had even more evidence of increased oedema, demyelination and axonal loss compared with CIS and RRMS.
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http://dx.doi.org/10.1177/13524585211023345DOI Listing
June 2021

Cervical cord myelin abnormality is associated with clinical disability in multiple sclerosis.

Mult Scler 2021 Mar 22:13524585211001780. Epub 2021 Mar 22.

Division of Neurology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada; Department of Radiology, The University of British Columbia, Vancouver, BC, Canada/Department of Physics and Astronomy, The University of British Columbia, Vancouver, BC, Canada; International Collaboration on Repair and Discoveries, Vancouver, BC, Canada.

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) participants and evaluate the correlation between myelin measures and clinical disability.

Methods: We used MWI data from 35 RRMS, 30 ProgMS, and 28 healthy control (HC) participants collected at cord level C2/C3 on a 3 T magnetic resonance imaging (MRI) scanner. Myelin heterogeneity index (MHI), a measurement of myelin variability, was calculated for whole cervical cord, global white matter, dorsal column, lateral and ventral funiculi. Correlations were assessed between MHI and Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9HPT), timed 25-foot walk, and disease duration.

Results: In various regions of the cervical cord, ProgMS MHI was higher compared to HC (between 9.5% and 31%,  ⩽ 0.04) and RRMS (between 13% and 26%,  ⩽ 0.02), and ProgMS MHI was associated with EDSS ( = 0.42-0.52) and 9HPT ( = 0.45-0.52).

Conclusion: Myelin abnormalities within clinically eloquent areas are related to clinical disability. MWI metrics have a potential role for monitoring subclinical disease progression and adjudicating treatment efficacy for new therapies targeting ProgMS.
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http://dx.doi.org/10.1177/13524585211001780DOI Listing
March 2021

Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Positive Patients in a Multi-Ethnic Canadian Cohort.

Front Neurol 2020 12;11:525933. Epub 2021 Jan 12.

UBC MS/NMO Clinic, University of British Columbia, Vancouver, BC, Canada.

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-associated disease. We describe a multi-ethnic population with MOG antibody seropositivity from the University of British Columbia MS/NMO clinic. AQP4-antibody seronegative patients presenting 2005-2016 with CNS inflammatory disease suspicious for NMOSD, as well as 20 MS controls, were retrospectively tested for MOG-IgG1 antibodies by live cell-based assay at Oxford Autoimmune Neurology Diagnostic Laboratory (UK) and by a commercial fixed cell-based assay at MitogenDx (Calgary, Canada). Additional MOG seropositive cases were identified through routine clinical interaction (2016-2018) using one of these laboratories. Clinical data was reviewed retrospectively. Retrospective testing identified 21 MOG seropositives (14 by live assay only, 3 by fixed assay only and 4 by both) representing 14% of the "NMOSD suspects" cohort. One multiple sclerosis (MS) control serum was MOG seropositive. Twenty additional MOG positive cases were identified prospectively. Of 42 patients (27 female), median disease onset age was 29 years (range 3-62; 9 pediatric cases), 20 (47%) were non-Caucasian, and 3 (7%) had comorbid autoimmune disease. Most common onset phenotypes were optic neuritis (23, 55%; 8 bilateral) and myelitis (9, 21%; 6 longitudinally extensive) Three of the patients in our cohort experienced cortical encephalitis; two presented with seizures. Onset was moderate-severe in 64%, but 74% had good response to initial steroid therapy. Cumulative relapse probability for the MOG positive group at 1 year was 0.428 and at 4 years was 0.628. Most had abnormal brain imaging, including cortical encephalitis and poorly demarcated subcortical and infratentorial lesions. Few "classic MS" lesions were seen. Optic nerve lesions (frequently bilateral) were long and predominantly anterior, but 5 extended to the chiasm. Spinal cord lesions were long and short, with involvement of multiple spinal regions simultaneously, including the conus medullaris. Our MOG seropositive patients display phenotypes similar to previous descriptions, including cortical lesions with seizures and conus medullaris involvement. Many patients relapsed, predominantly in a different CNS location from onset. Serologic data from two different cell-based antibody assays highlight the discrepancies between live and fixed testing for MOG antibodies.
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http://dx.doi.org/10.3389/fneur.2020.525933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835710PMC
January 2021

Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis.

JAMA Netw Open 2020 09 1;3(9):e2014220. Epub 2020 Sep 1.

Department of Medicine (Neurology), The University of British Columbia, Vancouver, British Columbia, Canada.

Importance: Cognitive impairment is a debilitating symptom of multiple sclerosis (MS) that affects up to 70% of patients. An improved understanding of the underlying pathology of MS-related cognitive impairment would provide considerable benefit to patients and clinicians.

Objective: To determine whether there is an association between myelin damage in tissue that appears completely normal on standard clinical imaging, but can be detected by myelin water imaging (MWI), with cognitive performance in MS.

Design, Setting, And Participants: In this cross-sectional study, participants with MS and controls underwent cognitive testing and magnetic resonance imaging (MRI) from August 23, 2017, to February 20, 2019. Participants were recruited through the University of British Columbia Hospital MS clinic and via online recruitment advertisements on local health authority websites. Cognitive testing was performed in the MS clinic, and MRI was performed at the adjacent academic research neuroimaging center. Seventy-three participants with clinically definite MS fulfilling the 2017 revised McDonald criteria for diagnosis and 22 age-, sex-, and education-matched healthy volunteers without neurological disease were included in the study. Data analysis was performed from March to November 2019.

Exposures: MWI was performed at 3 T with a 48-echo, 3-dimensional, gradient and spin-echo (GRASE) sequence. Cognitive testing was performed with assessments drawn from cognitive batteries validated for use in MS.

Main Outcomes And Measures: The association between myelin water measures, a measurement of the T2 relaxation signal from water in the myelin bilayers providing a specific marker for myelin, and cognitive test scores was assessed using Pearson correlation. Three white matter regions of interest-the cingulum, superior longitudinal fasciculus (SLF), and corpus callosum-were selected a priori according to their known involvement in MS-related cognitive impairment.

Results: For the 95 total participants, the mean (SD) age was 49.33 (11.44) years. The mean (SD) age was 50.2 (10.7) years for the 73 participants with MS and 46.4 (13.5) for the 22 controls. Forty-eight participants with MS (66%) and 14 controls (64%) were women. The mean (SD) years of education were 14.7 (2.2) for patients and 15.8 (2.5) years for controls. In MS, significant associations were observed between myelin water measures and scores on the Symbol Digit Modalities Test (SLF, r = -0.490; 95% CI, -0.697 to -0.284; P < .001; corpus callosum, r = -0.471; 95% CI, -0.680 to -0.262; P < .001; and cingulum, r = -0.419; 95% CI, -0.634 to -0.205; P < .001), Selective Reminding Test (SLF, r = -0.444; 95% CI, -0.660 to -0.217; P < .001; corpus callosum, r = -0.411; 95% CI, -0.630 to -0.181; P = .001; and cingulum, r = -0.361; 95% CI, -0.602 to -0.130; P = .003), and Controlled Oral Word Association Test (SLF, r = -0.317; 95% CI, -0.549 to -0.078; P = .01; and cingulum, r = -0.335; 95% CI, -0.658 to -0.113; P = .006). No significant associations were found in controls.

Conclusions And Relevance: This study used MWI to demonstrate that otherwise normal-appearing brain tissue is diffusely damaged in MS, and the findings suggest that myelin water measures are associated with cognitive performance. MWI offers an in vivo biomarker feasible for use in clinical trials investigating cognition, providing a means for monitoring changes in myelination and its association with symptom worsening or improvement.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.14220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525360PMC
September 2020

Myelin Damage in Normal Appearing White Matter Contributes to Impaired Cognitive Processing Speed in Multiple Sclerosis.

J Neuroimaging 2020 03 24;30(2):205-211. Epub 2019 Nov 24.

Department of Medicine (Neurology), Radiology, Physics & Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.

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 for age, sex, and education underwent myelin water imaging (MWI) from which the myelin water fraction (MWF) was calculated. Corpus callosum, superior longitudinal fasciculus, and cingulum were chosen as regions of interest (ROIs) a priori based on their involvement in MS-related cognitive impairment. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT). Pearson ́s product moment correlations were performed to assess relationships between cognitive performance and myelin heterogeneity (variance of MWF within an ROI).

Results: In MS, myelin heterogeneity in all three ROIs was significantly associated with performance on the SDMT. These correlations ranged from moderate (r = -.561) to moderately strong (r = -.654) and were highly significant (P values ranged from .001 to .0002). Conversely, myelin heterogeneity was not associated with SDMT performance in controls in any ROI (P > .108).

Conclusion: Increased myelin heterogeneity in NAWM is associated with decreased cognitive processing speed performance in MS.
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http://dx.doi.org/10.1111/jon.12679DOI Listing
March 2020

Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS): Rationale and Methodology.

Can J Neurol Sci 2020 Jan 29;47(1):109-114. Epub 2019 Oct 29.

Department of Medicine (Neurology), University of Alberta, Edmonton, Alberta, Canada.

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 evidence-based population data to help an individual with MS make informed decisions with respect to reproductive options.

Objective: The objective of this study is to develop a Canada-wide, prospective population-based registry of women with MS who are either trying to become pregnant and/or have become pregnant.

Methods: The study represents a "real-world" scenario. Women with MS are invited to participate, regardless of clinical course, therapy, disease duration, and/or disability. The methodology to develop such a registry is very complex making it imperative to understand the design and rationale when interpreting results for clinical purposes.

Results: This paper is a comprehensive discussion of the study rationale and methodology.

Conclusions: The study is ongoing, with over 100 potential participants. Numerous future publications are envisioned as the study progresses. The present paper is thus designed to be the key referral paper for subsequent publications in which it will not be possible to provide the necessary detailed information on rationale and methodology.
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http://dx.doi.org/10.1017/cjn.2019.296DOI Listing
January 2020

Development and usability testing of a patient decision aid for newly diagnosed relapsing multiple sclerosis patients.

BMC Neurol 2019 Jul 20;19(1):173. Epub 2019 Jul 20.

Division of Neurology, University of British Columbia, Djavad Mowafaghian Center for Brain Health, 2215 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.

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 contribute to late treatment initiation and treatment non-adherence-causes of 'undertreatment' in MS. An interactive online patient decision aid that informs patients of their options, considers their individual preferences and goals, and facilitates conversations with their physicians, could improve how patients with relapsing forms of MS make evidence-based treatment decisions.

Objective: To develop and evaluate a prototype patient decision aid (PtDA) for first-line disease modifying therapies for relapsing-remitting multiple sclerosis.

Methods: Informed by previous studies and International Patient Decision Aid Standards guidelines, a prototype PtDA was developed for patients with relapsing multiple sclerosis considering first line treatment. Patients with relapsing multiple sclerosis were recruited from the University of British Columbia's Multiple Sclerosis Clinic to participate in either an online survey or a focus group. Online survey participants completed the PtDA, followed by measures of acceptability, usability, and preparedness for decision-making, and provided general feedback. Focus group participants assessed usability of the revised PtDA. The analysis of qualitative and quantitative data led to improvements of the PtDA prototype.

Results: The prototype PtDA received high ratings for acceptability and usability, and after its use, participants reported high-levels of preparedness for decision-making. Analysis of all qualitative data identified three key themes: the need for credible information; the usefulness of the PtDA; and the importance of normalizing and sharing experiences. Nine content areas were identified for revision. Overall, participants found the PtDA to be a valuable tool for facilitating treatment decisions.

Conclusions: This mixed methods study has led to the development of a PtDA that can support patients with RRMS as they make treatment decisions. Future studies will assess the feasibility of implementation and the impact of the PtDA on both the timely treatment initiation and longer-term adherence.
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http://dx.doi.org/10.1186/s12883-019-1382-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642472PMC
July 2019

Laboratory Monitoring Practices Among Canadian Multiple Sclerosis Clinicians.

Can J Neurol Sci 2019 07 21;46(4):389-393. Epub 2019 May 21.

Undergraduate Medicine,University of British Columbia,Vancouver, British Columbia,Canada.

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 assessing prescriber demographics, current infrastructure, and concerns for lab monitoring was sent to the Canadian Network of MS Clinics (CNMSC) listserv, inviting MS clinicians across the country to participate.

Results: Respondents included 32/65 CNMSC-affiliated neurologists (49%), 6 registered nurses (RN), 2 nurse practitioners (NP), and 2 non-neurologist physicians from 8/10 provinces. For some questions, analysis was limited to 34 DMT-prescribing clinicians only. Despite broad implementation of electronic medical records (25/34, 74%), many prescribers (15/34, 44%) still receive laboratory results in paper form. In terms of lab monitoring infrastructure, we noted regional variability in the employment of nursing to monitor patient compliance with required laboratory monitoring. There is also a gap in laboratory surveillance, as less than 5% of respondents reported regularly reviewing results on weekends. Providers' length of practice and volume of MS patients were not associated with different perception of DMT laboratory monitoring risk.

Conclusions: This nation-wide survey showed variability in infrastructure used in laboratory monitoring and regional variation in nursing involvement. Providers' level of concern for laboratory monitoring for DMTs did not vary by years of experience or volume of MS patients followed, suggesting that improved systems, rather than education, could ameliorate perceptions of risk.
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http://dx.doi.org/10.1017/cjn.2019.19DOI Listing
July 2019

Control of Clostridium difficile-associated diarrhea by antibiotic stewardship in a small community hospital.

Can J Infect Dis Med Microbiol 2012 ;23(2):82-3

Alice Schabas is a fourth year medical student at Queen's University, Kingston, Ontario.

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http://dx.doi.org/10.1155/2012/358059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403666PMC
June 2013
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