Author
Luanne M. Metz
Other affiliations: Foothills Medical Centre
Bio: Luanne M. Metz is an academic researcher from University of Calgary. The author has contributed to research in topics: Multiple sclerosis & Depression (differential diagnoses). The author has an hindex of 49, co-authored 159 publications receiving 13386 citations. Previous affiliations of Luanne M. Metz include Foothills Medical Centre.
Papers published on a yearly basis
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VU University Amsterdam1, University of Rennes2, Vita-Salute San Raffaele University3, University of Düsseldorf4, University of Basel5, Icahn School of Medicine at Mount Sinai6, Foothills Medical Centre7, National Institutes of Health8, University of Toronto9, Lund University10, Mayo Clinic11, University of Texas Health Science Center at Houston12
TL;DR: New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease.
Abstract: New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.
4,862 citations
University of Western Ontario1, University of Saskatchewan2, University of Alberta3, University of Toronto4, University of Manitoba5, University of Calgary6, McGill University7, McMaster University8, Dalhousie University9, Memorial University of Newfoundland10, University of Ottawa11, Queen's University12, Stanford University13
TL;DR: The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility in multiple sclerosis.
Abstract: The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.
688 citations
TL;DR: The evidence for the efficacy of minocyCline in several animal models of neurological disease is described, the mechanisms by which minocycline affects a range of neurological diseases with diverse causes are discussed, and the emerging investigation of minocrycline in clinical neurology is introduced.
Abstract: Summary The capacity of minocycline to alleviate disease for several neurological disorders in animals is increasingly being recognised. Indeed, that one drug alone can attenuate the severity of disease in stroke, multiple sclerosis, spinal-cord injury, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is astounding. In this review, we describe the evidence for the efficacy of minocycline in several animal models of neurological disease, discuss the mechanisms by which minocycline affects a range of neurological diseases with diverse causes, and introduce the emerging investigation of minocycline in clinical neurology. The encouraging results of minocycline in experimental neurology bode well for its therapeutic use in human neurological diseases.
481 citations
TL;DR: The prevalence of major depression in the population with MS is elevated and exceeds that associated with having one or more other long-term conditions.
Abstract: Objective: To determine the prevalence of major depression in multiple sclerosis (MS) in a population-based sample controlling for nonspecific illness effects. Methods: This study used data from a large-scale national survey conducted in Canada: the Canadian Community Health Survey (CCHS). The analysis included 115,071 CCHS subjects who were 18 years or older at the time of data collection. The CCHS interview obtained self-reported diagnoses of MS and employed a brief predictive interview for major depression: the Composite International Diagnostic Interview Short Form for Major Depression. The 12-month period prevalence of major depression was estimated in subjects with and without MS and with and without other long-term medical conditions. Results: The prevalence of major depression was elevated in persons with MS relative to those without MS and those reporting other conditions. The association persisted after adjustment for age and sex (adjusted odds ratio = 2.3, 95% CI 1.6 to 3.3). Major depression prevalence in MS for those in the 18- to 45-year age range was high at 25.7% (95% CI 15.6 to 35.7). Conclusions: The prevalence of major depression in the population with MS is elevated. This elevation is not an artifact of selection bias and exceeds that associated with having one or more other long-term conditions.
481 citations
TL;DR: Results indicate that minocycline may constitute a safe and inexpensive therapy for multiple sclerosis and inhibit MMP activity, reduced production of MMP-9 and decreased the transmigration of T lymphocytes across a fibronectin matrix barrier.
Abstract: Multiple sclerosis is characterized by the infiltration of leukocytes into the CNS. As matrix metalloproteinases (MMPs) facilitate the passage of leukocytes across matrix barriers, we tested the hypothesis that targeting MMPs could attenuate neuro-inflammation. We report that minocycline, a widely used generic drug with a good safety record, inhibited MMP activity, reduced production of MMP-9 and decreased the transmigration of T lymphocytes across a fibronectin matrix barrier. In addition, minocycline was efficacious against both mild and severe experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis. When severe EAE was produced, minocycline pre-treatment delayed the course of the disease: when maximal disease activity occurred in vehicle-treated EAE mice, minocycline animals were relatively normal and had minimal signs of inflammation and demyelination in the CNS. When tested in mice afflicted with mild EAE, minocycline attenuated the clinical severity of disease throughout the course of treatment. These results indicate that minocycline may constitute a safe and inexpensive therapy for multiple sclerosis.
418 citations
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University of Amsterdam1, University of Toronto2, Centre Hospitalier Universitaire de Toulouse3, Cleveland Clinic4, Tohoku University5, Charles University in Prague6, University College Dublin7, University of Basel8, Icahn School of Medicine at Mount Sinai9, Lund University10, University College London11, University of California, San Francisco12, Mayo Clinic13, University of Texas Health Science Center at Houston14
TL;DR: These revisions simplify the McDonald Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
Abstract: New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
8,883 citations
TL;DR: This paper reviews the major deep learning concepts pertinent to medical image analysis and summarizes over 300 contributions to the field, most of which appeared in the last year, to survey the use of deep learning for image classification, object detection, segmentation, registration, and other tasks.
8,730 citations
University College London1, Children's Hospital of Philadelphia2, VU University Medical Center3, Sir Charles Gairdner Hospital4, National Multiple Sclerosis Society5, Vita-Salute San Raffaele University6, Medical University of Graz7, Ottawa Hospital Research Institute8, Fukushima Medical University9, New York University10, University of Düsseldorf11, University of Basel12, Corinne Goldsmith Dickinson Center for Multiple Sclerosis13, University of Manitoba14, St. Michael's Hospital15, Hebron University16, Johns Hopkins University17, University of Copenhagen18, University of British Columbia19, University of Bari20, French Institute of Health and Medical Research21, Claude Bernard University Lyon 122, University of California, San Francisco23, Mayo Clinic24, Salisbury University25, Cleveland Clinic26
TL;DR: The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation.
Abstract: The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
3,945 citations
TL;DR: Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.
Abstract: Background Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults. Despite antiinflammatory or immunosuppressive therapy, most patients have progressive neurologic deterioration that may reflect axonal loss. We conducted pathological studies of brain tissues to define the changes in axons in patients with multiple sclerosis. Methods Brain tissue was obtained at autopsy from 11 patients with multiple sclerosis and 4 subjects without brain disease. Fourteen active multiple-sclerosis lesions, 33 chronic active lesions, and samples of normal-appearing white matter were examined for demyelination, inflammation, and axonal pathologic changes by immunohistochemistry and confocal microscopy. Axonal transection, identified by the presence of terminal axonal ovoids, was detected in all 47 lesions and quantified in 18 lesions. Results Transected axons were a consistent feature of the lesions of multiple sclerosis...
3,903 citations