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Mirmosayyeb O, Yazdan Panah M, Mokary Y, Mohammadi M, Moases Ghaffary E, Shaygannejad V, Weinstock-Guttman B, Zivadinov R, Jakimovski D. Neuroimaging markers and disability scales in multiple sclerosis: A systematic review and meta-analysis. PLoS One 2024; 19:e0312421. [PMID: 39637162 PMCID: PMC11620670 DOI: 10.1371/journal.pone.0312421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 10/06/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND Multiple sclerosis (MS) is a central nervous system disorder marked by progressive neurological impairments. Magnetic resonance imaging (MRI) parameters are key paraclinical measures that play a crucial role in the diagnosis, prognosis, and monitoring of MS-related disability. This study aims to analyze and summarize the existing literature on the correlation between MRI parameters and disability in people with MS (pwMS). METHODS The PubMed/MEDLINE, Embase, Scopus, and Web of Science databases were searched from inception to July 19, 2024, and a meta-analysis was carried out using R software version 4.4.0 and the random effects model used to determine the pooled correlation coefficient, with its 95% confidence interval (CI), between MRI measurements and disability scales. RESULTS Among 5741 studies, 383 studies with 39707 pwMS were included. The meta-analysis demonstrated that Expanded Disability Status Scale (EDSS) had significant correlations with cervical cord volume (r = -0.51, 95% CI: -0.62 to -0.38, I2 = 0%, p-heterogeneity = 0.86, p-value<0.01), cortical lesion volume (r = 0.45, 95% CI: 0.36 to 0.53, I2 = 68%, p-heterogeneity<0.01, p-value<0.01), brain volume (r = -0.40, 95% CI: -0.47 to -0.33, I2 = 41%, p-heterogeneity = 0.05, p-value<0.05), and grey matter volume (GMV) (r = -0.36, 95% CI: -0.49 to -0.21, I2 = 0%, p-heterogeneity = 0.53, p-value<0.01), respectively. CONCLUSION This study offers evidence suggesting that cortical lesion volume, brain volume, GMV, and MRI measurements of the spinal cord may constitute reliable indicators for assessing disability in pwMS.
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Affiliation(s)
- Omid Mirmosayyeb
- Department of Neurology, Jacobs Comprehensive MS Treatment and Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States of America
| | - Mohammad Yazdan Panah
- Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Yousef Mokary
- Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Mohammadi
- Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Elham Moases Ghaffary
- Pharmacy School, University of Missouri-Kansas City, Kansas City, MO, United States of America
| | - Vahid Shaygannejad
- Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Bianca Weinstock-Guttman
- Department of Neurology, Jacobs Comprehensive MS Treatment and Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States of America
| | - Robert Zivadinov
- Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States of America
- Center for Biomedical Imaging at the Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, United States of America
| | - Dejan Jakimovski
- Department of Neurology, Jacobs Comprehensive MS Treatment and Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States of America
- Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States of America
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Nabizadeh F, Zafari R, Mohamadi M, Maleki T, Fallahi MS, Rafiei N. MRI features and disability in multiple sclerosis: A systematic review and meta-analysis. J Neuroradiol 2024; 51:24-37. [PMID: 38172026 DOI: 10.1016/j.neurad.2023.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 11/28/2023] [Accepted: 11/28/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND In this systematic review and meta-analysis, we aimed to investigate the correlation between disability in patients with Multiple sclerosis (MS) measured by the Expanded Disability Status Scale (EDSS) and brain Magnetic Resonance Imaging (MRI) features to provide reliable results on which characteristics in the MRI can predict disability and prognosis of the disease. METHODS A systematic literature search was performed using three databases including PubMed, Scopus, and Web of Science. The selected peer-reviewed studies must report a correlation between EDSS scores and MRI features. The correlation coefficients of included studies were converted to the Fisher's z scale, and the results were pooled. RESULTS Overall, 105 studies A total of 16,613 patients with MS entered our study. We found no significant correlation between total brain volume and EDSS assessment (95 % CI: -0.37 to 0.08; z-score: -0.15). We examined the potential correlation between the volume of T1 and T2 lesions and the level of disability. A positive significant correlation was found (95 % CI: 0.19 to 0.43; z-score: 0.31), (95 % CI: 0.17 to 0.33; z-score: 0.25). We observed a significant correlation between white matter volume and EDSS score in patients with MS (95 % CI: -0.37 to -0.03; z-score: -0.21). Moreover, there was a significant negative correlation between gray matter volume and disability (95 % CI: -0.025 to -0.07; z-score: -0.16). CONCLUSION In conclusion, this systematic review and meta-analysis revealed that disability in patients with MS is linked to extensive changes in different brain regions, encompassing gray and white matter, as well as T1 and T2 weighted MRI lesions.
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Affiliation(s)
- Fardin Nabizadeh
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Rasa Zafari
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mobin Mohamadi
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Tahereh Maleki
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Nazanin Rafiei
- School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Predictive MRI Biomarkers in MS—A Critical Review. Medicina (B Aires) 2022; 58:medicina58030377. [PMID: 35334554 PMCID: PMC8949449 DOI: 10.3390/medicina58030377] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 02/12/2022] [Accepted: 02/21/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Objectives: In this critical review, we explore the potential use of MRI measurements as prognostic biomarkers in multiple sclerosis (MS) patients, for both conventional measurements and more novel techniques such as magnetization transfer, diffusion tensor, and proton spectroscopy MRI. Materials and Methods: All authors individually and comprehensively reviewed each of the aspects listed below in PubMed, Medline, and Google Scholar. Results: There are numerous MRI metrics that have been proven by clinical studies to hold important prognostic value for MS patients, most of which can be readily obtained from standard 1.5T MRI scans. Conclusions: While some of these parameters have passed the test of time and seem to be associated with a reliable predictive power, some are still better interpreted with caution. We hope this will serve as a reminder of how vast a resource we have on our hands in this versatile tool—it is up to us to make use of it.
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Dahan A, Pereira R, Malpas CB, Kalincik T, Gaillard F. PACS Integration of Semiautomated Imaging Software Improves Day-to-Day MS Disease Activity Detection. AJNR Am J Neuroradiol 2019; 40:1624-1629. [PMID: 31515214 DOI: 10.3174/ajnr.a6195] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 07/19/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND PURPOSE The standard for evaluating interval radiologic activity in MS, side-by-side MR imaging comparison, is restricted by its time-consuming nature and limited sensitivity. VisTarsier, a semiautomated software for comparing volumetric FLAIR sequences, has shown better disease-activity detection than conventional comparison in retrospective studies. Our objective was to determine whether implementing this software in day-to-day practice would show similar efficacy. MATERIALS AND METHODS VisTarsier created an additional coregistered image series for reporting a color-coded disease-activity change map for every new MS MR imaging brain study that contained volumetric FLAIR sequences. All other MS studies, including those generated during software-maintenance periods, were interpreted with side-by-side comparison only. The number of new lesions reported with software assistance was compared with those observed with traditional assessment in a generalized linear mixed model. Questionnaires were sent to participating radiologists to evaluate the perceived day-to-day impact of the software. RESULTS Nine hundred six study pairs from 538 patients during 2 years were included. The semiautomated software was used in 841 study pairs, while the remaining 65 used conventional comparison only. Twenty percent of software-aided studies reported having new lesions versus 9% with standard comparison only. The use of this software was associated with an odds ratio of 4.15 for detection of new or enlarging lesions (P = .040), and 86.9% of respondents from the survey found that the software saved at least 2-5 minutes per scan report. CONCLUSIONS VisTarsier can be implemented in real-world clinical settings with good acceptance and preservation of accuracy demonstrated in a retrospective environment.
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Affiliation(s)
- A Dahan
- From the Department of Radiology (A.D.), Austin Hospital, Heidelberg, Australia
| | - R Pereira
- Departments of Radiology (R.P., F.G.)
- Department of Radiology (R.P.), University of Queensland, Brisbane, Queensland, Australia
| | - C B Malpas
- Neurology (T.K., C.M.), Royal Melbourne Hospital, Parkville, Victoria, Australia
- Clinical Outcomes Research Unit (CORe) (C.M., T.K.)
| | - T Kalincik
- Neurology (T.K., C.M.), Royal Melbourne Hospital, Parkville, Victoria, Australia
- Clinical Outcomes Research Unit (CORe) (C.M., T.K.)
| | - F Gaillard
- Departments of Radiology (R.P., F.G.)
- Departments of Medicine and Radiology (F.G.), University of Melbourne, Melbourne, Australia
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Pravatà E, Valsasina P, Gobbi C, Zecca C, Riccitelli GC, Filippi M, Rocca MA. Influence of CNS T2-focal lesions on cervical cord atrophy and disability in multiple sclerosis. Mult Scler 2019; 26:1402-1409. [DOI: 10.1177/1352458519865989] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background: Mechanisms associated with cervical spinal cord (CSC) and upper thoracic spinal cord (TSC) atrophy in multiple sclerosis (MS) are poorly understood. Objective: To assess the influence of brain, CSC and TSC T2-hyperintense lesions on cord atrophy and disability in MS. Methods: Thirty-four MS patients underwent 3T brain, cervical and thoracic cord magnetic resonance imaging (MRI) and Expanded Disability Status Scale (EDSS) score assessment. CSC/TSC lesion number and volume (LV), whole-brain and cortico-spinal tract (CST) LVs were obtained. Normalized whole CSC and upper TSC cross-sectional areas (CSAn) were also derived. Age- and sex-adjusted regression models assessed associations of brain/cord lesions with CSAn and EDSS and identified variables independently associated with CSAn and EDSS with a stepwise variable selection. Results: CSC CSAn (β = −0.36, p = 0.03) and TSC CSAn (β = −0.60, p < 0.001) were associated with CSC T2 LV. EDSS (median = 3.0) was correlated with CSC T2 LV (β = 0.42, p = 0.01), brain (β = 0.34, p = 0.04) and CST LV (β = 0.35, p = 0.03). The multivariate analysis retained CSC LV as significant predictor of CSC CSAn ( R2 = 0.20, p = 0.023) and TSC CSAn ( R2 = 0.51, p < 0.001) and retained CSC and CST LVs as significant predictors of EDSS ( R2 = 0.55, p = 0.001). Conclusions: CSC LV is an independent predictor of cord atrophy. When neurological impairment is relatively mild, central nervous system (CNS) lesion burden is a better correlate of disability than atrophy.
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Affiliation(s)
- Emanuele Pravatà
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy/Department of Neuroradiology, Neurocenter of Southern Switzerland, Civic Hospital, Lugano, Switzerland
| | - Paola Valsasina
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Claudio Gobbi
- Department of Neurology, Neurocenter of Southern Switzerland, Civic Hospital, Lugano, Switzerland
| | - Chiara Zecca
- Department of Neurology, Neurocenter of Southern Switzerland, Civic Hospital, Lugano, Switzerland
| | - Gianna C Riccitelli
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy/Department of Neurology, Neurocenter of Southern Switzerland, Civic Hospital, Lugano, Switzerland
| | - Massimo Filippi
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy/Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy/Vita-Salute San Raffaele University, Milan, Italy
| | - Maria A Rocca
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy/Department of Neurology, IRCCS San Raffaele Scientific Institute, Milan, Italy
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Abstract
Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. This disorder is a heterogeneous, multifactorial, immune-mediated disease that is influenced by both genetic and environmental factors. In most patients, reversible episodes of neurological dysfunction lasting several days or weeks characterize the initial stages of the disease (that is, clinically isolated syndrome and relapsing-remitting MS). Over time, irreversible clinical and cognitive deficits develop. A minority of patients have a progressive disease course from the onset. The pathological hallmark of MS is the formation of demyelinating lesions in the brain and spinal cord, which can be associated with neuro-axonal damage. Focal lesions are thought to be caused by the infiltration of immune cells, including T cells, B cells and myeloid cells, into the central nervous system parenchyma, with associated injury. MS is associated with a substantial burden on society owing to the high cost of the available treatments and poorer employment prospects and job retention for patients and their caregivers.
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Affiliation(s)
- Massimo Filippi
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. .,Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
| | - Amit Bar-Or
- Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Fredrik Piehl
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.,Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.,Neuroimmunology Unit, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
| | - Paolo Preziosa
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.,Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Alessandra Solari
- Unit of Neuroepidemiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Sandra Vukusic
- Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Fondation Eugène Devic EDMUS Contre la Sclérose en Plaques, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France
| | - Maria A Rocca
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.,Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
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Vermersch P, Berger T, Gold R, Lukas C, Rovira A, Meesen B, Chard D, Comabella M, Palace J, Trojano M. The clinical perspective: How to personalise treatment in MS and how may biomarkers including imaging contribute to this? Mult Scler 2018; 22:18-33. [PMID: 27465613 DOI: 10.1177/1352458516650739] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 04/23/2016] [Indexed: 01/17/2023]
Abstract
BACKGROUND Multiple sclerosis (MS) is a highly heterogeneous disease, both in its course and in its response to treatments. Effective biomarkers may help predict disability progression and monitor patients' treatment responses. OBJECTIVE The aim of this review was to focus on how biomarkers may contribute to treatment individualisation in MS patients. METHODS This review reflects the content of presentations, polling results and discussions on the clinical perspective of MS during the first and second Pan-European MS Multi-stakeholder Colloquia in Brussels in May 2014 and 2015. RESULTS In clinical practice, magnetic resonance imaging (MRI) measures play a significant role in the diagnosis and follow-up of MS patients. Together with clinical markers, the rate of MRI-visible lesion accrual once a patient has started treatment may also help to predict subsequent treatment responsiveness. In addition, several molecular (immunological, genetic) biomarkers have been established that may play a role in predictive models of MS relapses and progression. To reach personalised treatment decisions, estimates of disability progression and likely treatment response should be carefully considered alongside the risk of serious adverse events, together with the patient's treatment expectations. CONCLUSION Although biomarkers may be very useful for individualised decision making in MS, many are still research tools and need to be validated before implementation in clinical practice.
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Affiliation(s)
- Patrick Vermersch
- University of Lille, CHRU de Lille, Lille International Research Inflammation Center (LIRIC), INSRRM U995, FHU Imminent, Lille, France
| | - Thomas Berger
- Neuroimmunology and Multiple Sclerosis Clinic, Medical University of Innsbruck (MUI), Innsbruck, Austria
| | - Ralf Gold
- Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany
| | - Carsten Lukas
- Department of Diagnostic and Interventional Radiology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany
| | - Alex Rovira
- Department of Radiology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Bianca Meesen
- Managing Director at Ismar Healthcare, Lier, Belgium
| | - Declan Chard
- NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, University College London, London, UK/Biomedical Research Centre, University College London Hospitals (UCLH), National Institute for Health Research (NIHR), London, UK
| | - Manuel Comabella
- Department of Clinical Neuroimmunology, Multiple Sclerosis Center of Catalonia (Cemcat), Vall d'Hebron University Hospital, Barcelona, Spain
| | - Jacqueline Palace
- Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
| | - Maria Trojano
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy
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Do MRI Structured Reports for Multiple Sclerosis Contain Adequate Information for Clinical Decision Making? AJR Am J Roentgenol 2018; 210:24-29. [DOI: 10.2214/ajr.17.18451] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Dahan A, Wang W, Gaillard F. Computer-Aided Detection Can Bridge the Skill Gap in Multiple Sclerosis Monitoring. J Am Coll Radiol 2018; 15:93-96. [DOI: 10.1016/j.jacr.2017.06.030] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 06/17/2017] [Accepted: 06/29/2017] [Indexed: 11/25/2022]
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Wang W, van Heerden J, Tacey MA, Gaillard F. Neuroradiologists Compared with Non-Neuroradiologists in the Detection of New Multiple Sclerosis Plaques. AJNR Am J Neuroradiol 2017; 38:1323-1327. [PMID: 28473341 DOI: 10.3174/ajnr.a5185] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 02/09/2017] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE Multiple sclerosis monitoring is based on the detection of new lesions on brain MR imaging. Outside of study populations, MS imaging studies are reported by radiologists with varying expertise. The aim of this study was to investigate the accuracy of MS reporting performed by neuroradiologists (someone who had spent at least 1 year in neuroradiology subspecialty training) versus non-neuroradiologists. MATERIALS AND METHODS Patients with ≥2 MS studies with 3T MR imaging that included a volumetric T2 FLAIR sequence performed between 2009 and 2011 inclusive were recruited into this study. The reports for these studies were analyzed for lesions detected, which were categorized as either progressed or stable. The results from a previous study using a semiautomated assistive software for lesion detection were used as the reference standard. RESULTS There were 5 neuroradiologists and 5 non-neuroradiologists who reported all studies. In total, 159 comparison pairs (ie, 318 studies) met the selection criteria. Of these, 96 (60.4%) were reported by a neuroradiologist. Neuroradiologists had higher sensitivity (82% versus 42%), higher negative predictive value (89% versus 64%), and lower false-negative rate (18% versus 58%) compared with non-neuroradiologists. Both groups had a 100% positive predictive value. CONCLUSIONS Neuroradiologists detect more new lesions than non-neuroradiologists in reading MR imaging for follow-up of MS. Assistive software that aids in the identification of new lesions has a beneficial effect for both neuroradiologists and non-neuroradiologists, though the effect is more profound in the non-neuroradiologist group.
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Affiliation(s)
- W Wang
- From the Department of Radiology (W.W., F.G.)
| | - J van Heerden
- Perth Radiological Clinic (J.v.H.), Subiaco, Western Australia, Australia
| | - M A Tacey
- Melbourne Epicentre (M.A.T.), the Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - F Gaillard
- From the Department of Radiology (W.W., F.G.)
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11
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Abstract
Due to its sensitivity to the different multiple sclerosis (MS)-related abnormalities, magnetic resonance imaging (MRI) has become an established tool to diagnose MS and to monitor its evolution. MRI has been included in the diagnostic workup of patients with clinically isolated syndromes suggestive of MS, and ad hoc criteria have been proposed and are regularly updated. In patients with definite MS, the ability of conventional MRI techniques to explain patients' clinical status and progression of disability is still suboptimal. Several advanced MRI-based technologies have been applied to estimate overall MS burden in the different phases of the disease. Their use has allowed the heterogeneity of MS pathology in focal lesions, normal-appearing white matter and gray matter to be graded in vivo. Recently, additional features of MS pathology, including macrophage infiltration and abnormal iron deposition, have become quantifiable. All of this, combined with functional imaging techniques, is improving our understanding of the mechanisms associated with MS evolution. In the near future, the use of ultrahigh-field systems is likely to provide additional insight into disease pathophysiology. However, the utility of advanced MRI techniques in clinical trial monitoring and in assessing individual patients' response to treatment still needs to be assessed.
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Affiliation(s)
- Massimo Filippi
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
| | - Paolo Preziosa
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Maria A Rocca
- Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
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12
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van Heerden J, Rawlinson D, Zhang AM, Chakravorty R, Tacey MA, Desmond PM, Gaillard F. Improving Multiple Sclerosis Plaque Detection Using a Semiautomated Assistive Approach. AJNR Am J Neuroradiol 2015; 36:1465-71. [PMID: 26089318 DOI: 10.3174/ajnr.a4375] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2014] [Accepted: 02/03/2015] [Indexed: 01/02/2023]
Abstract
BACKGROUND AND PURPOSE Treating MS with disease-modifying drugs relies on accurate MR imaging follow-up to determine the treatment effect. We aimed to develop and validate a semiautomated software platform to facilitate detection of new lesions and improved lesions. MATERIALS AND METHODS We developed VisTarsier to assist manual comparison of volumetric FLAIR sequences by using interstudy registration, resectioning, and color-map overlays that highlight new lesions and improved lesions. Using the software, 2 neuroradiologists retrospectively assessed MR imaging MS comparison study pairs acquired between 2009 and 2011 (161 comparison study pairs met the study inclusion criteria). Lesion detection and reading times were recorded. We tested inter- and intraobserver agreement and comparison with original clinical reports. Feedback was obtained from referring neurologists to assess the potential clinical impact. RESULTS More comparison study pairs with new lesions (reader 1, n = 60; reader 2, n = 62) and improved lesions (reader 1, n = 28; reader 2, n = 39) were recorded by using the software compared with original radiology reports (new lesions, n = 20; improved lesions, n = 5); the difference reached statistical significance (P < .001). Interobserver lesion number agreement was substantial (≥1 new lesion: κ = 0.87; 95% CI, 0.79-0.95; ≥1 improved lesion: κ = 0.72; 95% CI, 0.59-0.85), and overall interobserver lesion number correlation was good (Spearman ρ: new lesion = 0.910, improved lesion = 0.774). Intraobserver agreement was very good (new lesion: κ = 1.0, improved lesion: κ = 0.94; 95% CI, 0.82-1.00). Mean reporting times were <3 minutes. Neurologists indicated retrospective management alterations in 79% of comparative study pairs with newly detected lesion changes. CONCLUSIONS Using software that highlights changes between study pairs can improve lesion detection. Neurologist feedback indicated a likely impact on management.
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Affiliation(s)
- J van Heerden
- From the Department of Radiology (J.v.H., P.M.D., F.G.), The Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria, Australia
| | - D Rawlinson
- Department of Electrical and Electronic Engineering (D.R., A.M.Z.), School of Engineering, University of Melbourne, Parkville, Victoria, Australia
| | - A M Zhang
- Department of Electrical and Electronic Engineering (D.R., A.M.Z.), School of Engineering, University of Melbourne, Parkville, Victoria, Australia
| | | | - M A Tacey
- Melbourne EpiCentre (M.A.T.), The Royal Melbourne Hospital and Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - P M Desmond
- From the Department of Radiology (J.v.H., P.M.D., F.G.), The Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria, Australia
| | - F Gaillard
- From the Department of Radiology (J.v.H., P.M.D., F.G.), The Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria, Australia
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Gajofatto A, Benedetti MD. Treatment strategies for multiple sclerosis: When to start, when to change, when to stop? World J Clin Cases 2015; 3:545-555. [PMID: 26244148 PMCID: PMC4517331 DOI: 10.12998/wjcc.v3.i7.545] [Citation(s) in RCA: 183] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Revised: 03/02/2015] [Accepted: 05/06/2015] [Indexed: 02/05/2023] Open
Abstract
Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies.
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Matthews PM, Edison P, Geraghty OC, Johnson MR. The emerging agenda of stratified medicine in neurology. Nat Rev Neurol 2013; 10:15-26. [DOI: 10.1038/nrneurol.2013.245] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Luo J, Yablonskiy DA, Hildebolt CF, Lancia S, Cross AH. Gradient echo magnetic resonance imaging correlates with clinical measures and allows visualization of veins within multiple sclerosis lesions. Mult Scler 2013; 20:349-55. [PMID: 23836876 DOI: 10.1177/1352458513495935] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Conventional magnetic resonance imaging (MRI) methods do not quantify the severity of multiple sclerosis (MS) white matter lesions or measure pathology within normal-appearing white matter (NAWM). OBJECTIVE Gradient Echo Plural Contrast Imaging (GEPCI), a fast MRI technique producing inherently co-registered images for qualitative and quantitative assessment of MS, was used to 1) correlate with disability; 2) distinguish clinical MS subtypes; 3) determine prevalence of veins co-localized within lesions in WM. METHODS Thirty subjects representing relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS) subtypes were scanned with clinical and GEPCI protocols. Standard measures of physical disability and cognition were correlated with magnetic resonance metrics. Lesions with central veins were counted for RRMS subjects. RESULTS Tissue damage load (TDL-GEPCI) and lesion load (LL-GEPCI) derived with GEPCI correlated better with MS functional composite (MSFC) measures and most other neurologic measures than lesion load derived with FLAIR (LL-FLAIR). GEPCI correctly classified clinical subtypes in 70% subjects. A central vein could be identified in 76% of WM lesions in RRMS subjects on GEPCI T2*-SWI images. CONCLUSION GEPCI lesion metrics correlated better with neurologic disability than lesion load derived using FLAIR imaging, and showed promise in classifying clinical subtypes of MS. These improvements are likely attributable to the ability of GEPCI to quantify tissue damage.
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Affiliation(s)
- Jie Luo
- Department of Radiology, Washington University, St. Louis MO, USA
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Kolasinski J, Stagg CJ, Chance SA, Deluca GC, Esiri MM, Chang EH, Palace JA, McNab JA, Jenkinson M, Miller KL, Johansen-Berg H. A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology. ACTA ACUST UNITED AC 2013; 135:2938-51. [PMID: 23065787 PMCID: PMC3470716 DOI: 10.1093/brain/aws242] [Citation(s) in RCA: 114] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a ‘tract-specific’ pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies.
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Affiliation(s)
- James Kolasinski
- Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), University of Oxford, Oxford, OX3 9DU, UK
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Abstract
Over the past 2 decades, MRI has been integrated into the diagnosis of multiple sclerosis (MS), the study of MS pathobiology, and the development and monitoring of MS treatments. This integration has irrevocably changed the way we think about the disease. New treatments, advanced through early stages of development using MRI outcome measures, have revolutionized the treatment of MS. Although MS remains a clinical diagnosis, conventional MRI is now a requisite adjunct to that diagnosis. Early in the disease, MRI monitoring of a patient on immunomodulatory therapy is helpful in identifying breakthrough disease activity that may predict long-term outcome. Advanced MRI technologies, although currently relegated to the research realm, are improving the detection of previously underappreciated aspects of MS pathology and may help lead to the evaluation of new therapeutic strategies.
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La Mantia L, Vacchi L, Di Pietrantonj C, Ebers G, Rovaris M, Fredrikson S, Filippini G. Interferon beta for secondary progressive multiple sclerosis. Cochrane Database Syst Rev 2012; 1:CD005181. [PMID: 22258960 PMCID: PMC11627149 DOI: 10.1002/14651858.cd005181.pub3] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Therapy with either recombinant beta-1a or beta-1b interferons (IFNs) is worldwide approved for Relapsing Remitting Multiple Sclerosis (RRMS). A major unanswered question is whether this treatment is able to safely reverse or retard the progressive phase of the disease. OBJECTIVES The main objective was to verify whether IFNs treatment in Secondary Progressive Multiple Sclerosis (SPMS) is more effective than placebo in reducing the number of patients who experience disability progression. SEARCH METHODS We searched the Cochrane Multiple Sclerosis Group's Trials Register (1995 to 15 February 2011), the reference lists of relevant articles and conference proceedings. Regulatory agencies were used as additional sources of information. SELECTION CRITERIA We included all randomised, double or single blind, placebo-controlled trials (RCTs) evaluating the efficacy of IFNs versus placebo in SPMS patients. DATA COLLECTION AND ANALYSIS Two review authors independently assessed all reports retrieved from the search. They independently extracted clinical, safety and MRI data, using a predefined data extraction form, resolving disagreements after discussion with a third reviewer. Risk of bias was evaluated to assess the quality of the studies. Treatment effect was measured using Risk Ratio (RR) with 95% confidence intervals (CI) for the binary outcomes and Standard Mean Difference with 95% CI for the continuous outcomes. MAIN RESULTS Five RCTs met the inclusion criteria, from which 3122 (1829 IFN and 1293 placebo) treated patients contributed to the analysis. Included population was heterogeneous in terms of baseline clinical characteristics of the disease, in particular the percentage of patients affected by secondary progression with superimposed relapse ranging from 72% to 44%. IFN beta 1a and 1b did not decrease the risk of progression sustained at 6 months (RR, 95% CI: 0.98, [0.82-1.16]) after three years of treatment. A significant decrease of the risk of progression sustained at 3 months (RR, 95% CI: 0.88 [0.80, 0.97]) and of the risk of developing new relapses at three years (RR 0.91, [0.84-0.97]) were found. The risk of developing new active brain lesions decreased over time but this data was obtained from single studies on Magnetic Resonance Imaging (MRI), performed in subgroups of patients; in spite of no effect on progression, the radiological data supported an effect on MRI parameters. The safety profile reflects what is commonly reported in MS IFN-treated patients. AUTHORS' CONCLUSIONS Well designed RCTs, evaluating a high number of patients were included in the review. Recombinant IFN beta does not prevent the development of permanent physical disability in SPMS. We were unable to verify the effect on cognitive function for the lack of comparable data. This treatment significantly reduces the risk of relapse and of short -term relapse-related disability.Overall, these results show that IFNs' anti-inflammatory effect is unable to retard progression, when established. In the future, no new RCTs for IFNs versus placebo in SPMS will probably be undertaken, because research is now focusing on innovative drugs. We believe that this review gives conclusive evidence on the clinical efficacy of IFNs versus placebo in SPMS.
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Affiliation(s)
- Loredana La Mantia
- Unit of Neurology - Multiple Sclerosis Center, I.R.C.C.S. Santa Maria Nascente FondazioneDon Gnocchi, Via Capecelatro 66, Milano, 20148, Italy.
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Abstract
Owing to its ability to depict the pathologic features of multiple sclerosis (MS) in exquisite detail, conventional magnetic resonance (MR) imaging has become an established tool in the diagnosis of this disease and in monitoring its evolution. MR imaging has been formally included in the diagnostic work-up of patients who present with a clinically isolated syndrome suggestive of MS, and ad hoc diagnostic criteria have been proposed and are updated on a regular basis. In patients with established MS and in those participating in treatment trials, examinations performed with conventional MR pulse sequences provide objective measures to monitor disease activity and progression; however, they have a limited prognostic role. This has driven the application of newer MR imaging technologies, including higher-field-strength MR units, to estimate overall MS burden and mechanisms of recovery in patients at different stages of the disease. These techniques have allowed in vivo assessment of the heterogeneity of MS pathologic features in focal lesions and in normal-appearing tissues. More recently, some of the finer details of MS, including macrophage infiltration and abnormal iron deposition, have become quantifiable with MR imaging. The utility of these modern MR techniques in clinical trial monitoring and in the assessment of the individual patient's response to treatment still need to be evaluated.
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Affiliation(s)
- Massimo Filippi
- Neuroimaging Research Unit, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
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Prosperini L, Kouleridou A, Petsas N, Leonardi L, Tona F, Pantano P, Pozzilli C. The relationship between infratentorial lesions, balance deficit and accidental falls in multiple sclerosis. J Neurol Sci 2011; 304:55-60. [DOI: 10.1016/j.jns.2011.02.014] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2010] [Revised: 02/14/2011] [Accepted: 02/14/2011] [Indexed: 11/26/2022]
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Sicotte NL. Magnetic Resonance Imaging in Multiple Sclerosis: The Role of Conventional Imaging. Neurol Clin 2011; 29:343-56. [DOI: 10.1016/j.ncl.2011.01.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Abstract
Recent years have witnessed impressive advances in the use of magnetic resonance imaging (MRI) for the assessment of patients with multiple sclerosis (MS). Complementary to the clinical evaluation, conventional MRI provides crucial pieces of information for the diagnosis of MS. However, the correlation between the burden of lesions observed on conventional MRI scans and the clinical manifestations of the disease remains weak. The discrepancy between clinical and conventional MRI findings in MS is explained, at least partially, by the limited ability of conventional MRI to characterize and quantify the heterogeneous features of MS pathology. Other quantitative MR-based techniques, however, have the potential to overcome such a limitation of conventional MRI. Indeed, magnetization transfer MRI, diffusion tensor MRI, proton MR spectroscopy, and functional MRI are contributing to elucidate the mechanisms that underlie injury, repair, and functional adaptation in patients with MS. Such techniques are likely to benefit from the use of high-field MR systems and thus allow in the near future providing additional insight into all these aspects of the disease. This review summarizes how MRI is dramatically changing our understanding of the factors associated with the accumulation of irreversible disability in MS and highlights the reasons why they should be used more extensively in studies of disease evolution and clinical trials.
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Affiliation(s)
- M Filippi
- Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Milan, Italy.
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Goldman MD. Possible clinical outcome measures for clinical trials in patients with multiple sclerosis. Ther Adv Neurol Disord 2010; 3:229-39. [PMID: 21179614 PMCID: PMC3002657 DOI: 10.1177/1756285610374117] [Citation(s) in RCA: 119] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease with both clinical and pathological heterogeneity. The complexity of the MS population has offered challenges to the measurement of MS disease progression in therapeutic trials. The current standard clinical outcome measures are relapse rate, Expanded Disability Severity Scale (EDSS), and the MS Functional Composite (MSFC). These measures each have strengths and some weakness. Two additional measures, the six-minute walk and accelerometry, show promise in augmenting current measures. MS therapeutics is a quickly advancing field which requires sensitive clinical outcome measures that can detect small changes in disability that reliably reflect long-term changes in sustained disease progression in a complex population. A single clinical outcome measure of sustained disease progression may remain elusive. Rather, an integration of current and new outcome measures may be most appropriate and utilization of different measures depending on the MS population and stage of the disease may be preferred.
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Affiliation(s)
- Myla D. Goldman
- University of Virginia, Department of Neurology, PO Box 800394, Charlottesville, VA 22908, USA
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Dobson R, Miller RF, Palmer HE, Feldmann M, Thompson EJ, Thompson AJ, Miller DH, Giovannoni G. Increased urinary free immunoglobulin light chain excretion in patients with multiple sclerosis. J Neuroimmunol 2010; 220:99-103. [PMID: 20171744 DOI: 10.1016/j.jneuroim.2010.01.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2009] [Revised: 01/04/2010] [Accepted: 01/20/2010] [Indexed: 10/19/2022]
Abstract
BACKGROUND Plasma and B cells are implicated in multiple sclerosis (MS) and produce free light chains (FLC) that are excreted in urine. OBJECTIVE To confirm that demyelinating diseases (DD) cause increased urinary FLCs. METHOD Urinary FLC in 50 patients with DD were compared to 20 patients with posterior uveitis (PU), 19 with AIDS, 34 with rheumatoid arthritis (RA) and 19 normal controls (NC). RESULT Subjects with DD, PU, RA and AIDS have higher urinary FLCs than NC (p<0.01). Urinary FLCs did not correlate with gadolinium-enhancing lesions on MRI. CONCLUSIONS Urinary FLCs are raised in DD. Further studies are required to see if they correlate with disease activity.
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Affiliation(s)
- Ruth Dobson
- Neuroimmunology Unit, Queen Mary University of London, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, 4 Newark Street, Whitechapel, London E1 2AT, United Kingdom.
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