Publications by authors named "Fraser Moore"

39 Publications

Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years.

Neurology 2021 02 28;96(5):e783-e797. Epub 2020 Dec 28.

From CORe (T.K., I.D., S.S., C.M.), Department of Medicine, University of Melbourne; MS Centre (T.K., I.D., S.S., C.M.), Department of Neurology, Royal Melbourne Hospital, Australia; Karolinska Institute (T.S.), Stockholm, Sweden; Department of Neuroscience (T.S., V.J., A.v.d.W., O.S., H.B.), Central Clinical School, Monash University, Melbourne; Burnet Institute (T.S.), Melbourne, Australia; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), General University Hospital and Charles University in Prague, Czech Republic; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; Hospital Universitario Virgen Macarena (G.I.), Sevilla, Spain; Department of Neuroscience, Imaging and Clinical Sciences (A.L.), University "G. d'Annunzio," Chieti; Department of Biomedical and Neuromotor Sciences (A.L.), University of Bologna, IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; Hopital Notre Dame (A.P., M.G., P.D.), Montreal; CHUM and Universite de Montreal (A.P., M.G., P.D.); CISSS Chaudière-Appalache (P.G.), Levis, Canada; Department of Neurology (V.J., A.v.d.W., O.S., H.B.), Alfred Hospital, Melbourne, Australia; Neuro Rive-Sud (F. Grand'Maison), Quebec, Canada; Department of Neuroscience (P.S., D.F.), Azienda Ospedaliera Universitaria, Modena, Italy; Isfahan University of Medical Sciences (V.S.), Isfahan, Iran; Amiri Hospital (R. Alroughani), Kuwait City, Kuwait; Zuyderland Ziekenhuis (R.H.), Sittard, the Netherlands; Medical Faculty (M. Terzi), 19 Mayis University, Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Karadeniz Technical University, Trabzon, Turkey; School of Medicine and Public Health (J.L.-S.), University Newcastle; Department of Neurology (J.L.-S.), John Hunter Hospital, Newcastle, Australia; UOC Neurologia (E.P.), Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy; Cliniques Universitaires Saint-Luc (V.V.P.), Brussels, Belgium; University of Parma (F. Granella); C. Mondino National Neurological Institute (R.B.), Pavia; Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino (D.S.), Italy; Flinders University (M. Slee), Adelaide; Westmead Hospital (S.V.), Sydney, Australia; Nemocnice Jihlava (R. Ampapa), Czech Republic; University of Queensland (P.M.), Brisbane; Royal Brisbane and Women's Hospital (P.M.), Brisbane, Australia; Hospital Germans Trias i Pujol (C.R.-T.), Badalona, Spain; CSSS Saint-Jérôme (J.P.), Canada; Hospital Universitario Donostia (J.O.), Paseo de Begiristain, San Sebastián, Spain; Hospital Italiano (E.C.), Buenos Aires, Argentina; Brain and Mind Centre (M.B.), University of Sydney, Australia; INEBA-Institute of Neuroscience Buenos Aires (M.L.S.), Argentina; Hospital de Galdakao-Usansolo (J.L.S.-M.), Galdakao, Spain; Liverpool Hospital (S. Hodgkinson), Sydney, Australia; Jahn Ferenc Teaching Hospital (C.R.), Budapest, Hungary; Craigavon Area Hospital (S. Hughes), UK; Jewish General Hospital (F.M.), Montreal, Canada; Deakin University (C.S.), Geelong; Monash Medical Centre (E.B.), Melbourne, Australia; South East Trust (O.G.), Belfast, UK; Perron Institute (A.K.), University of Western Australia, Nedlands; Institute of Immunology and Infectious Diseases (A.K.), Murdoch University; Sir Charles Gairdner Hospital (A.K.), Perth, Australia; Department of Neurology (T.C.), Faculty of Medicine, University of Debrecen, Hungary; Bombay Hospital Institute of Medical Sciences (B.S.), Mumbai, India; St Vincents Hospital (N.S.), Fitzroy, Melbourne, Australia; Veszprém Megyei Csolnoky Ferenc Kórház zrt (I.P.), Veszprem, Hungary; Royal Hobart Hospital (B.T.), Australia; Semmelweis University Budapest (M. Simo), Hungary; Central Military Emergency University Hospital (C.-A.S.), Bucharest; Titu Maiorescu University (C.-A.S.), Bucharest, Romania; BAZ County Hospital (A.S.), Miskolc, Hungary; and Box Hill Hospital (H.B.), Melbourne, Australia.

Objective: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.

Methods: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.

Results: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, = 0.0016), worsening of disability (0.56, 0.38-0.82, = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, = 10) and worsening of disability (0.81, 0.67-0.99, = 0.043).

Conclusion: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.

Classification Of Evidence: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
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http://dx.doi.org/10.1212/WNL.0000000000011242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884998PMC
February 2021

Don't Make the Best of It, Make It Better: Matching to Residency Programs During COVID-19.

Can J Neurol Sci 2021 01 20;48(1):3-4. Epub 2020 Oct 20.

Department of Neurology, Institute for Health Sciences Education, McGill University, Montréal, Canada.

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http://dx.doi.org/10.1017/cjn.2020.236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853738PMC
January 2021

Practice Guidelines for Canadian Neurophysiology Laboratories During the COVID-19 Pandemic.

Can J Neurol Sci 2021 01 19;48(1):25-30. Epub 2020 Aug 19.

Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.

The COVID-19 pandemic has had a major impact on clinical practice. Safe standards of practice are essential to protect health care workers while still allowing them to provide good care. The Canadian Society of Clinical Neurophysiologists, the Canadian Association of Electroneurophysiology Technologists, the Association of Electromyography Technologists of Canada, the Board of Registration of Electromyography Technologists of Canada, and the Canadian Board of Registration of Electroencephalograph Technologists have combined to review current published literature about safe practices for neurophysiology laboratories. Herein, we present the results of our review and provide our expert opinion regarding the safe practice of neurophysiology during the COVID-19 pandemic in Canada.
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http://dx.doi.org/10.1017/cjn.2020.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578631PMC
January 2021

A Diverse Specialty: What Students Teach Us About Neurology and "Neurophobia".

Authors:
Fraser G A Moore

Can J Neurol Sci 2020 09 26;47(5):675-680. Epub 2020 May 26.

Department of Neurology, McGill University, Montréal, Québec, Canada.

Objective: To explore what elective students learn about the specialty of Neurology.

Methods: A prospective qualitative study using pre- and post-elective written questionnaires.

Results: Analysis concentrated on three main themes: What did students learn about the specialty of Neurology? What would they change about their experience? Did their opinions change? Major findings were (i) pre- and post-elective the most frequent response for "what is the best thing about Neurology?" was the "process of localization" and (ii) post-elective students were less likely to cite the challenge or problem-solving aspect of Neurology as the best thing while more emphasized the importance of the physical exam and the variety of cases. (iii) Students were most surprised by the scope of neurological practice. (iv) They would diversify the setting of their elective to include less time spent in the emergency room and more time in clinic. (v) The perception of Neurology as a specialty in which patients have a poor prognosis was the opinion that changed the most.

Conclusions: Showcasing the diversity of cases and careers in Neurology may be a useful strategy to increase interest in the specialty and reduce neurophobia. Lectures or small groups early in medical school should concentrate on clear examples of common neurological conditions and emphasize the role of general neurologists and subspecialists involved in patient care. Whenever possible students should rotate through different clinics and not concentrate exclusively on emergency room and in-patient cases.
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http://dx.doi.org/10.1017/cjn.2020.102DOI Listing
September 2020

Risk of secondary progressive multiple sclerosis: A longitudinal study.

Mult Scler 2020 01 9;26(1):79-90. Epub 2019 Aug 9.

CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia/L4 Centre, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia.

Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested.

Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis.

Methods: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed.

Results: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02,  < 0.001), longer disease duration (HR = 1.01,  = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30,  < 0.001), more rapid disability trajectory (HR = 2.82,  < 0.001) and greater number of relapses in the previous year (HR = 1.07,  = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62,  = 0.039) and disease-modifying therapy exposure (HR = 0.71,  = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion.

Conclusion: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.
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http://dx.doi.org/10.1177/1352458519868990DOI Listing
January 2020

The neurologist's role in disabling multiple sclerosis: A qualitative study of patient and care provider perspectives.

Mult Scler 2020 06 10;26(7):837-842. Epub 2019 May 10.

Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

Background: Patients with advanced, disabling multiple sclerosis (MS) have few effective treatment options. Little is known about the role that patients and their care providers want their neurologist to fill in this situation.

Objective: To better understand the role that patients with disabling MS and their care providers want their neurologist to have in their care.

Methods: In this exploratory qualitative study, we conducted semi-structured interviews with 29 participants (19 patients with severe disability due to MS and 10 care providers). Interview transcripts were analyzed using inductive thematic analysis.

Results: Participants identified three main roles for their neurologist: a source of hope for therapeutic advances, an educator about the disease and its management, and a source of support.

Conclusion: Despite sustaining a level of disability that may be refractory to standard medical therapy, patients with disabling MS and care providers continue to value certain roles of their neurologist. The neurologist's role as a source of hope and support in particular has not received enough attention in the literature.
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http://dx.doi.org/10.1177/1352458519845107DOI Listing
June 2020

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

Brain 2017 Sep;140(9):2426-2443

Department of Neurology, Royal Melbourne Hospital, 300 Grattan St, Melbourne, 3050, Australia.

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (>80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement.
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http://dx.doi.org/10.1093/brain/awx185DOI Listing
September 2017

Peer-led small groups: Are we on the right track?

Authors:
Fraser Moore

Perspect Med Educ 2017 Oct;6(5):325-330

McGill University Centre for Medical Education, Montreal, Quebec, Canada.

Introduction: Peer tutor-led small group sessions are a valuable learning strategy but students may lack confidence in the absence of a content expert. This study examined whether faculty reinforcement of peer tutor-led small group content was beneficial.

Methods: Two peer tutor-led small group sessions were compared with one faculty-led small group session using questionnaires sent to student participants and interviews with the peer tutors. One peer tutor-led session was followed by a lecture with revision of the small group content; after the second, students submitted a group report which was corrected and returned to them with comments.

Results: Student participants and peer tutors identified increased discussion and opportunity for personal reflection as major benefits of the peer tutor-led small group sessions, but students did express uncertainty about gaps in their learning following these sessions. Both methods of subsequent faculty reinforcement were perceived as valuable by student participants and peer tutors. Knowing in advance that the group report would be corrected reduced discussion in some groups, potentially negating one of the major benefits of the peer tutor-led sessions.

Discussion: Faculty reinforcement of peer-tutor led small group content benefits students but close attention should be paid to the method of reinforcement.
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http://dx.doi.org/10.1007/s40037-017-0370-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630531PMC
October 2017

Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice.

Mult Scler 2017 Sep 25;23(10):1346-1357. Epub 2016 Nov 25.

Department of Neurology, Box Hill hospital, Monash University, Box Hill, VIC, Australia.

Background: Characteristics at clinically isolated syndrome (CIS) examination assist in identification of patient at highest risk of early second attack and could benefit the most from early disease-modifying drugs (DMDs).

Objective: To examine determinants of second attack and validate a prognostic nomogram for individualised risk assessment of clinical conversion.

Methods: Patients with CIS were prospectively followed up in the MSBase Incident Study. Predictors of clinical conversion were analysed using Cox proportional hazards regression. Prognostic nomograms were derived to calculate conversion probability and validated using concordance indices.

Results: A total of 3296 patients from 50 clinics in 22 countries were followed up for a median (inter-quartile range (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first symptom location, oligoclonal bands and various brain and spinal magnetic resonance imaging (MRI) metrics were all predictors of conversion. Conversely, older age and DMD exposure post-CIS were associated with reduced rates. Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities.

Conclusion: This multinational study shows that age at CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and oligoclonal bands are associated with shorter time to relapse. Nomogram assessment may be useful in clinical practice for estimating future clinical conversion.
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http://dx.doi.org/10.1177/1352458516679893DOI Listing
September 2017

Defining secondary progressive multiple sclerosis.

Brain 2016 09 7;139(Pt 9):2395-405. Epub 2016 Jul 7.

1 Department of Medicine, University of Melbourne, Melbourne, Australia 2 Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.

A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple sclerosis based on the Expanded Disability Status Scale and information about preceding relapses provides a tool for a reproducible, accurate and timely diagnosis that requires a very short confirmation period. If applied broadly, the definition has the potential to strengthen the design and improve comparability of clinical trials and observational studies in secondary progressive multiple sclerosis.
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http://dx.doi.org/10.1093/brain/aww173DOI Listing
September 2016

De novo FUS P525L mutation in Juvenile amyotrophic lateral sclerosis with dysphonia and diplopia.

Neurol Genet 2016 Apr 10;2(2):e63. Epub 2016 Mar 10.

Department of Human Genetics (C.S.L., Z.G.-O.), Montreal Neurological Institute and Hospital (C.S.L., A.W., Z.G.-O., F.M., A.D., P.A.D., G.A.R.), and Department of Neurology and Neurosurgery (A.W., F.M., A.D., P.A.D., G.A.R.), McGill University, Montreal, Quebec, Canada.

Juvenile amyotrophic lateral sclerosis (jALS) is characterized by progressive upper and lower motor neuron degeneration leading to facial muscle spasticity, spastic dysarthria, and spastic gait with an early onset (before 25 years old). Unlike adult-onset amyotrophic lateral sclerosis (ALS), patients with jALS tend to have slower progression of motor neuron disease and prolonged survival to a normal life expectancy. Mutations in FUS gene have been reported in jALS,(1) including p.P525L mutation that has been consistently associated with early onset and aggressive presentation.(2) Here, we report a patient carrying p.P525L FUS mutation and experiencing an aggressive course of ALS presenting with dysphonia and diplopia.
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http://dx.doi.org/10.1212/NXG.0000000000000063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830191PMC
April 2016

Contribution of different relapse phenotypes to disability in multiple sclerosis.

Mult Scler 2017 Feb 11;23(2):266-276. Epub 2016 Jul 11.

Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia.

Objective: This study evaluated the effect of relapse phenotype on disability accumulation in multiple sclerosis.

Methods: Analysis of prospectively collected data was conducted in 19,504 patients with relapse-onset multiple sclerosis and minimum 1-year prospective follow-up from the MSBase cohort study. Multivariable linear regression models assessed associations between relapse incidence, phenotype and changes in disability (quantified with Expanded Disability Status Scale and its Functional System scores). Sensitivity analyses were conducted.

Results: In 34,858 relapses recorded during 136,462 patient-years (median follow-up 5.9 years), higher relapse incidence was associated with greater disability accumulation (β = 0.16, p < 0.001). Relapses of all phenotypes promoted disability accumulation, with the most pronounced increase associated with pyramidal (β = 0.27 (0.25-0.29)), cerebellar (β = 0.35 (0.30-0.39)) and bowel/bladder (β = 0.42 (0.35-0.49)) phenotypes (mean (95% confidence interval)). Higher incidence of each relapse phenotype was associated with an increase in disability in the corresponding neurological domain, as well as anatomically related domains.

Conclusion: Relapses are associated with accumulation of neurological disability. Relapses in pyramidal, cerebellar and bowel/bladder systems have the greatest association with disability change. Therefore, prevention of these relapses is an important objective of disease-modifying therapy. The differential impact of relapse phenotypes on disability outcomes could influence management of treatment failure in multiple sclerosis.
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http://dx.doi.org/10.1177/1352458516643392DOI Listing
February 2017

The Under-Utilization of the Head Impulse Test in the Emergency Department.

Can J Neurol Sci 2016 May 20;43(3):398-401. Epub 2016 Jan 20.

McGill University,Department of Neurology,Montreal,Quebec,Canada.

Background: The head impulse test (HIT) is an evidenced based clinical tool to differentiate between peripheral and central causes of vertigo. Our objective was to determine the rate of utilization of the HIT in the emergency room (ER).

Methods: A retrospective chart review of patients presenting to the ER over one year who received a final diagnosis of dizziness or vertigo. Details of clinical examinations, investigations, and diagnosis were recorded. Patients were grouped into episodic, acute constant, and chronic vertigo groups.

Results: HIT was performed in only 31 of 642 (5%) patients with vertigo. In the acute constant group it was negative in 6 of 6 patients ultimately diagnosed with stroke and positive in 6 of 13 cases of peripheral vertigo.

Discussion: Despite good published evidence regarding its use the HIT is under-utilized in the ER. Physicians need to be aware of the HIT and newer video HITs and make use of them in practice.
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http://dx.doi.org/10.1017/cjn.2015.330DOI Listing
May 2016

Multiple sclerosis in Latin America: A different disease course severity? A collaborative study from the MSBase Registry.

Mult Scler J Exp Transl Clin 2015 Jan-Dec;1:2055217315600193. Epub 2015 Aug 17.

Multiple Sclerosis Center, Hospital Italiano, Argentina.

Limited data suggest that multiple sclerosis (MS) in Latin America (LA) could be less severe than in the rest of the world. The objective was to compare the course of MS between LA and other regions.

Methods: Centers from 18 countries with >20 cases enrolled in the MSBase Registry participated. Patients with MS with a disease duration of >1 year and <30 years at time of EDSS measurement were evaluated. The MS Severity Score (MSSS) was used as a measure of disease progression. Comparisons among regions (North America, Europe, Australia and LA), hemispheres and countries were performed.

Results: A total of 9610 patients were included. Patients were from: Europe, 6290 (65.6%); North America, 1609 (16.7%); Australia, 1119 (11.6%); and LA, 592 (6.1%). The mean MSSS in patients from LA was 4.47 ± 2.8, 4.53 ± 2.8 in North America, 4.51 ± 2.8 in Europe and 4.49 ± 2.7 in Australia. Mean MSSS in the northern hemisphere was 4.51 ± 1.6 compared to 4.48 ± 1.9 in the southern hemisphere. No differences were found for MSSS among hemispheres ( = 0.68), regions ( = 0.96) or countries ( = 0.50).

Conclusions: Our analyses did not discover any difference in mean MSSS among patients from different regions, hemispheres or countries.
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http://dx.doi.org/10.1177/2055217315600193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408755PMC
August 2015

EDSS Change Relates to Physical HRQoL While Relapse Occurrence Relates to Overall HRQoL in Patients with Multiple Sclerosis Receiving Subcutaneous Interferon β -1a.

Mult Scler Int 2015 5;2015:631989. Epub 2015 Jul 5.

Department of Medical Affairs, EMD Serono, 2695 North Sheridan Way, Suite 200, Mississauga, ON, Canada L5K 2N6.

Objective. To compare patterns of associations of changes in mental and physical health dimensions of health-related quality of life (HRQoL) over time with relapse occurrence and changes in Expanded Disability Status Scale (EDSS) scores in patients with relapsing multiple sclerosis (RMS). Methods. This 24-month, phase IV, observational study enrolled 334 patients with RMS who received interferon β-1a 44 μg or 22 μg subcutaneously three times weekly. At each 6-month visit, patients completed the Multiple Sclerosis Quality of Life-54 (MSQOL-54) and site investigators assessed EDSS and recorded relapse occurrence. A generalized linear model procedure was used for multivariable analyses (per protocol) that explored unique associations of EDSS score change and relapse occurrence with MSQOL-54 physical health composite score (PCS) and mental health composite score (MCS). Results. HRQoL improved over 2 years among those who completed the study. Occurrence of ≥1 relapse was significantly associated with lower MSQOL-54 PCS and MCS. Changes in EDSS score were significantly associated with MSQOL-54 PCS, but not MCS. Conclusions. HRQoL assessments, particularly those that examine mental health, may provide information on the general health status of patients with RMS that would not be recognized using traditional clinician-assessed measures of disease severity and activity. This trial is registered with ClinicalTrials.gov; identifier: NCT01141751.
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http://dx.doi.org/10.1155/2015/631989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506821PMC
August 2015

The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis.

Mult Scler 2016 Apr 21;22(4):520-32. Epub 2015 Jul 21.

Department of Medicine, University of Melbourne, Melbourne, Australia

Objective: We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS).

Methods: MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence.

Results: A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, p<0.001) while more patients switched to fingolimod than any other therapy (42.3% of switches). Patients switched to fingolimod due to convenience. Patients treated with fingolimod were less likely to discontinue treatment compared with other therapies (p<0.001). Female sex, country of residence, younger age, a high Expanded Disability Status Scale score and relapse activity were all independently associated with higher rates of treatment discontinuation.

Conclusion: Following the availability of fingolimod, patients were more likely to discontinue injectable treatments. Those who switched to fingolimod were more likely to do so for convenience. Persistence was improved on fingolimod compared to other medications.
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http://dx.doi.org/10.1177/1352458515594041DOI Listing
April 2016

Tolerability and Safety of Combined Glatiramer Acetate and N-Acetylcysteine in Relapsing-Remitting Multiple Sclerosis.

Clin Neuropharmacol 2015 Jul-Aug;38(4):127-31

Departments of *Neurology and Neurosurgery, and †Medicine (Geriatrics), McGill University; ‡Lady Davis Institute for Medical Research, Jewish GeneralHospital; §NeuroRx Research; ∥Hôpital Charles Lemoyne; ¶Department of Radiology, Jewish General Hospital; and #Teva Neuroscience Canada, Montreal,Quebec, Canada.

Introduction: Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system where inflammation and neurodegeneration play key roles. Mounting evidence implicates oxidative stress in the development of irreversible neuronal and glial injury in this condition. N-acetylcysteine (NAC) is a sulfhydryl amino acid derivative with antioxidant and antiapoptotic properties. Administration of NAC to mice attenuated the induction of or improved experimental autoimmune encephalomyelitis (an MS model).

Methods: We performed an open-label study to explore the tolerability and safety of the combination of glatiramer acetate (GA) and NAC in patients with relapsing-remitting multiple sclerosis at the outpatient MS clinics of the Jewish General Hospital and Hôpital Charles Lemoyne, Montreal, Canada. Seven patients with relapsing-remitting multiple sclerosis with at least one T1 gadolinium-enhancing lesion on screening magnetic resonance imaging were recruited. Treatment consisted of a 10-week run-in period followed by 36-week treatment with a combination of GA 20 mg subcutaneously once daily plus NAC 2.5 g orally twice daily. Outcome measures included safety and tolerability, redox biochemistry, and magnetic resonance imaging effect.

Results: Treatment with the combination of GA and NAC was safe and well tolerated.

Conclusions: In light of the favorable safety profile, an efficacy-demonstrating study may be considered.
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http://dx.doi.org/10.1097/WNF.0000000000000090DOI Listing
April 2016

General Practitioner Preferences in Managing Care of Multiple Sclerosis Patients.

Can J Neurol Sci 2016 Jan 1;43(1):142-8. Epub 2015 Jul 1.

5Neuroepidemiology Research Unit,McGill University Health Centre.

Background: Multiple sclerosis (MS) is a lifelong neurological disorder requiring care in a variety of settings. The purpose of this study is to describe preferences of general practitioners (GPs) with regards to providing care for MS patients.

Methods: A stratified sample of 900 GPs in the province of Quebec were sent a questionnaire, with 266 returning completed questionnaires. Respondents were surveyed about their preferences using four clinical scenarios describing hypothetical patients experiencing different stages of MS. Respondents were asked whether they would continue managing the patient themselves, formally refer the patient to a specialist, or seek specialist advice.

Results: In two scenarios representing stable courses, 40.9% and 61.6% of GPs, respectively, intended to manage the patient themselves. GPs who reported having experience with MS patients were more likely to report an intention to continue management. In one scenario, GPs operating in rural areas were less likely to consider management than those in the Montreal metropolitan area (odds ratio=0.422, 95% confidence interval 0.20-0.90).

Conclusions: For MS patients with a stable disease course, an important proportion of GPs appear to be willing to manage long-term care for MS patients.
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http://dx.doi.org/10.1017/cjn.2015.239DOI Listing
January 2016

Predictors of disability worsening in clinically isolated syndrome.

Ann Clin Transl Neurol 2015 May 27;2(5):479-91. Epub 2015 Mar 27.

Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Bari, Italy.

Objective: To assess demographic, clinical, magnetic resonance imaging, and treatment exposure predictors of time to 3 or 12-month confirmed disability worsening in clinically isolated syndrome (CIS) and early multiple sclerosis (MS).

Methods: We utilized the MSBase Incident Study (MSBasis), a prospective cohort study of outcome after CIS. Predictors of time to first 3 and 12-month confirmed expanded disability status scale worsening were analyzed using Cox proportional hazards regression.

Results: About 1989 patients were analyzed, the largest seen-from-onset cohort reported to-date. A total of 391 patients had a first 3-month confirmed disability worsening event, of which 307 were sustained for 12 months. Older age at CIS onset (adjusted hazard ratio: aHR 1.17, 95% 1.06, 1.30), pyramidal (aHR 1.45, 95% CI 1.13, 1.89) and ambulation (HR 1.60, 95% CI 1.09, 2.34) system dysfunction, annualized relapse rate (aHR 1.20, 95% CI 1.18, 1.22), and lower proportion of observation time on treatment were associated with 3-month confirmed worsening. Predictors of time to 12-month sustained worsening included pyramidal system dysfunction (Hazard ratio: aHR 1.38, 95% CI 1.05, 1.83), and older age at CIS onset (aHR 1.17, 95% CI 1.04, 1.31). Greater proportion of follow-up time exposed to treatment was associated with greater reductions in the rate of worsening.

Interpretation: This study provides class IV evidence for a strong protective effect of disease-modifying treatment to reduce disability worsening events in patients with CIS and early MS, and confirms age and pyramidal dysfunction at onset as risk factors.
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http://dx.doi.org/10.1002/acn3.187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435703PMC
May 2015

Two Multiple Sclerosis Quality-of-Life Measures: Comparison in a National Sample.

Can J Neurol Sci 2015 Jan 14;42(1):55-63. Epub 2015 Jan 14.

4Division of Neurology,Sunnybrook Health Science Center,Toronto,Ontario,Canada.

Background: Multiple sclerosis (MS) has a profound impact on patients' health-related quality of life (HRQoL). It is unclear how HRQoL can be best assessed for different purposes. This study aimed to compare two HRQoL questionnaires of differing lengths for feasibility of administration, patient perceptions and psychometric properties.

Methods: This was an open-label, 24-month study in 334 patients with relapsing MS treated with subcutaneous interferon β-1a. At baseline and months 6, 12, 18 and 24, patients completed the Multiple Sclerosis International Quality of Life (MusiQoL) and Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaires and compared them using an evaluation questionnaire. HRQoL scores over time and psychometric properties (correlations with clinical disease measures, relative validity and responsiveness to change) of the questionnaires were assessed.

Results: A minority of patients had missing items on either HRQoL measure. Completion time was significantly shorter for MusiQoL versus MSQOL-54 (p<0.0001). Patients felt that MusiQoL was easier to use than MSQOL-54 but preferred MSQOL-54 in terms of thoroughness. Mean HRQoL scores increased significantly from baseline to 24 months; correlations of both measures were stronger with an anxiety and depression measure than with disability or recent relapse occurrence. Relative validity and responsiveness to change were similar for both instruments.

Conclusion: The shorter MusiQoL is suitable for evaluating HRQoL in patients with MS and may be more practical to administer than the more thorough MSQOL-54.
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http://dx.doi.org/10.1017/cjn.2014.128DOI Listing
January 2015

Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing-remitting multiple sclerosis.

Mult Scler 2015 Aug 5;21(9):1159-71. Epub 2014 Dec 5.

Department of Medicine, University of Melbourne, Melbourne, Australia, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia, and Department of Neurology, Box Hill Hospital, Monash University, Box Hill, Australia.

Background: The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed.

Objective: We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators.

Methods: Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted.

Results: Of the 3326 included patients, 345-1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b (p≤0.001). No differences in 12-month confirmed progression of disability were observed.

Conclusion: Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely.
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http://dx.doi.org/10.1177/1352458514559865DOI Listing
August 2015

Seasonal variation of relapse rate in multiple sclerosis is latitude dependent.

Ann Neurol 2014 Dec 20;76(6):880-90. Epub 2014 Oct 20.

Department of Neurology, Royal Melbourne Hospital, Parkville, Australia.

Objective: Previous studies assessing seasonal variation of relapse onset in multiple sclerosis have had conflicting results. Small relapse numbers, differing diagnostic criteria, and single region studies limit the generalizability of prior results. The aim of this study was to determine whether there is a temporal variation in onset of relapses in both hemispheres and to determine whether seasonal peak relapse probability varies with latitude.

Methods: The international MSBase Registry was utilized to analyze seasonal relapse onset distribution by hemisphere and latitudinal location. All analyses were weighted for the patient number contributed by each center. A sine regression model was used to model relapse onset and ultraviolet radiation (UVR) seasonality. Linear regression was used to investigate associations of latitude and lag between UVR trough and subsequent relapse peak.

Results: A total of 32,762 relapses from 9,811 patients across 30 countries were analyzed. Relapse onset followed an annual cyclical sinusoidal pattern with peaks in early spring and troughs in autumn in both hemispheres. Every 10° of latitude away from the equator was associated with a mean decrease in UVR trough to subsequent relapse peak lag of 28.5 days (95% confidence interval = 3.29-53.71, p = 0.028).

Interpretation: We demonstrate for the first time that there is a latitude-dependent relationship between seasonal UVR trough and relapse onset probability peak independent of location-specific UVR levels, with more distal latitude associated with shorter gaps. We confirm prior meta-analyses showing a strong seasonal relapse onset probability variation in the northern hemisphere, and extend this observation to the southern hemisphere.
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http://dx.doi.org/10.1002/ana.24287DOI Listing
December 2014

Risk of relapse phenotype recurrence in multiple sclerosis.

Mult Scler 2014 Oct 28;20(11):1511-22. Epub 2014 Apr 28.

Royal Melbourne Hospital, AustraliaUniversity of Melbourne, Australia.

Objectives: The aim was to analyse risk of relapse phenotype recurrence in multiple sclerosis and to characterise the effect of demographic and clinical features on this phenotype.

Methods: Information about relapses was collected using MSBase, an international observational registry. Associations between relapse phenotypes and history of similar relapses or patient characteristics were tested with multivariable logistic regression models. Tendency of relapse phenotypes to recur sequentially was assessed with principal component analysis.

Results: Among 14,969 eligible patients (89,949 patient-years), 49,279 phenotypically characterised relapses were recorded. Visual and brainstem relapses occurred more frequently in early disease and in younger patients. Sensory relapses were more frequent in early or non-progressive disease. Pyramidal, sphincter and cerebellar relapses were more common in older patients and in progressive disease. Women presented more often with sensory or visual symptoms. Men were more prone to pyramidal, brainstem and cerebellar relapses. Importantly, relapse phenotype was predicted by the phenotypes of previous relapses. (OR = 1.8-5, p = 10(-14)). Sensory, visual and brainstem relapses showed better recovery than other relapse phenotypes. Relapse severity increased and the ability to recover decreased with age or more advanced disease.

Conclusion: Relapse phenotype was associated with demographic and clinical characteristics, with phenotypic recurrence significantly more common than expected by chance.
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http://dx.doi.org/10.1177/1352458514528762DOI Listing
October 2014

Sex as a determinant of relapse incidence and progressive course of multiple sclerosis.

Brain 2013 Dec 18;136(Pt 12):3609-17. Epub 2013 Oct 18.

1 Department of Medicine, University of Melbourne, Melbourne, Australia.

The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48,362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10(-12)). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10(-12)). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.
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http://dx.doi.org/10.1093/brain/awt281DOI Listing
December 2013

Predictors and dynamics of postpartum relapses in women with multiple sclerosis.

Mult Scler 2014 May 9;20(6):739-46. Epub 2013 Oct 9.

Department of Neurology, Royal Victoria Hospital, Belfast, UK.

Background: Several studies have shown that pregnancy reduces multiple sclerosis (MS) relapses, which increase in the early postpartum period. Postpartum relapse risk has been predicted by pre-pregnancy disease activity in some studies.

Objective: To re-examine effect of pregnancy on relapses using the large international MSBase Registry, examining predictors of early postpartum relapse.

Methods: An observational case-control study was performed including pregnancies post-MS onset. Annualised relapse rate (ARR) and median Expanded Disability Status Scale (EDSS) scores were compared for the 24 months pre-conception, pregnancy and 24 months postpartum periods. Clustered logistic regression was used to investigate predictors of early postpartum relapses.

Results: The study included 893 pregnancies in 674 females with MS. ARR (standard error) pre-pregnancy was 0.32 (0.02), which fell to 0.13 (0.03) in the third trimester and rose to 0.61 (0.06) in the first three months postpartum. Median EDSS remained unchanged. Pre-conception ARR and disease-modifying treatment (DMT) predicted early postpartum relapse in a multivariable model.

Conclusion: Results confirm a favourable effect on relapses as pregnancy proceeds, and an early postpartum peak. Pre-conception DMT exposure and low ARR were independently protective against postpartum relapse. This novel finding could provide clinicians with a strategy to minimise postpartum relapse risk in women with MS planning pregnancy.
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http://dx.doi.org/10.1177/1352458513507816DOI Listing
May 2014

Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis.

PLoS One 2013 21;8(5):e63480. Epub 2013 May 21.

Departments of Medicine and Neurology, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.

Objectives: To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics.

Methods: Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded.

Results: Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages.

Conclusions: Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063480PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660604PMC
December 2013

The usefulness of gadolinium-enhanced images on a follow-up magnetic resonance image in suspected multiple sclerosis.

Can Assoc Radiol J 2013 Nov 23;64(4):358-62. Epub 2012 Dec 23.

Department of Neurology, Jewish General Hospital, McGill University, Montréal, Canada. Electronic address:

Purpose: Multiple sclerosis diagnostic criteria include the presence of gadolinium-enhancing lesions when determining dissemination in space and time. Gadolinium is expensive, increases scan time and patient discomfort, and can, rarely, cause serious adverse effects. Our objective was to determine the usefulness of including gadolinium-enhanced images as part of a follow-up brain magnetic resonance imaging (MRI) in patients with a clinically isolated syndrome.

Methods: Consecutive patients seen between 2008 and 2010 with a clinically isolated syndrome suggestive of multiple sclerosis were prospectively enrolled, had a non-gadolinium-enhanced brain MRI, and consented to a follow-up gadolinium-enhanced brain MRI. The primary outcome was a comparison of the number of patients diagnosed with multiple sclerosis compared with the number who would have been diagnosed without the gadolinium-enhanced images.

Results: Twenty-one patients enrolled, and 2 withdrew. Follow-up MRIs were performed a median of 241 days after the initial MRI. Eleven patients met the primary outcome and were diagnosed with multiple sclerosis: 6 as a result of a second clinical attack and 5 by using imaging criteria for dissemination in space and time. If the gadolinium-enhanced images had not been obtained, then there would have been no change in the primary outcome.

Conclusions: In Canadian centers with similar MRI waiting times to those in our study, the routine use of gadolinium as part of a follow-up MRI in patients with suspected multiple sclerosis may not be clinically useful. Gadolinium-enhanced images could still be obtained on an as-needed basis for specific clinical indications.
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http://dx.doi.org/10.1016/j.carj.2012.07.003DOI Listing
November 2013

Country, sex, EDSS change and therapy choice independently predict treatment discontinuation in multiple sclerosis and clinically isolated syndrome.

PLoS One 2012 29;7(6):e38661. Epub 2012 Jun 29.

Department of Neurology, Royal Melbourne Hospital, Victoria, Australia.

Objectives: We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS).

Methods: The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation.

Results: A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation.

Conclusion: In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038661PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387159PMC
November 2012

Improving the neurological exam skills of medical students.

Can J Neurol Sci 2012 Jan;39(1):83-6

Department of Neurology and Neurosurgery, Department of Medicine, Centre for Medical Education, McGill University, Montréal, Quebec, Canada.

Objective: Determine if distributed practice of of neurological exam (NE) skills in first year medical school produces sustained improvements in the skills of second year students.

Methods: A prospective, controlled, non-blinded study conducted at McGill University (class size = 180 students). Expanded teaching of muscle stretch reflexes was provided to first year medical students. A structured examination of muscle stretch reflexes (max score = 100) was administered in second year medical school after a required two week rotation in Neurology. Results for class A (received the intervention in first year) were compared to the results for the preceding class B (had not received the intervention).

Results: 77 of 177 (44%) eligible in class A and 69 of 166 (42%) eligible students in class B participated. Results were analyzed separately for each of the two examiners. Mean (SD) scores were 95.2 (5.6) for class A (intervention) and 81.7 (11.1) for class B (control) for the first examiner and 90.4 (8.2) for class A and 83.8 (11.7) for class B for the second examiner. Results were statistically significant (Mann-Whitney test z = 5.27, p<0.0001 first examiner and z = 2.67, p<0.0038 second examiner).

Conclusions: Distributed practice of muscle stretch reflexes during first year medical school results in improved performance by second year medical students after their mandatory clinical rotation in neurology, even when examined up to 14 months after the intervention. This finding has implications for the teaching of the NE.
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http://dx.doi.org/10.1017/s0317167100012749DOI Listing
January 2012