Our concept of multiple sclerosis (MS) as
|
|
- Anne Blake
- 7 years ago
- Views:
Transcription
1 MEASURING AND ASSESSING NEURODEGENERATION AND NEUROPROTECTION: THE ROLE OF MRI * Nancy Richert, MD, PhD ABSTRACT Multiple sclerosis is a complex disease involving inflammatory and neurodegenerative processes. Imaging techniques that can quantitate the nature and the extent of tissue damage as well as reversible changes (eg, remyelination and repair) will be essential for therapeutic trials with neuroprotective agents. Newer magnetic resonance imaging (MRI) measures that visualize the pathology of the disease also may improve the modest correlation between MRI and clinical disability. Conventional MRI (cmri), using T1- and T2-weighted imaging sequences, can accurately determine the number of new contrastenhancing lesions (acute blood-brain barrier disruptions) and total burden of disease (T2 lesion load); however, these methods lack pathologic specificity. cmri also fails to measure microscopic disease in the normal-appearing white matter and gray matter structures. To address this limitation, techniques that measure diffuse disease are being implemented. These include cerebral atrophy measures, proton magnetic resonance spectroscopy (MRS), magnetization transfer imaging, and diffusion tensor imaging. With the exception of MRS, which estimates axonal density by measuring the neuronal-specific marker, N-acetyl aspartate, none of these imaging measures are specific for axonal loss. However, they have provided valuable insights into the extent of tissue damage and the pathology of this complex disease process. (Adv Stud Med. 2007;7(8): ) *Based on a presentation given by Dr Richert at the 4th Annual Johns Hopkins MS Symposium held on March 17, 2007, in New York City. Staff Clinician, Neuroimmunology Branch, National Institutes of Health, Bethesda, Maryland. Address correspondence to: Nancy Richert, MD, PhD, Staff Clinician, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Building 10 Room B1N 256, National Institutes of Health, Bethesda, MD richertn@helix.nih.gov. Our concept of multiple sclerosis (MS) as a purely demyelinating disease was revolutionized when immunohistochemistry studies using confocal microscopy showed axonal transection in acute and chronic lesions in pathologic specimens of MS brains. 1 The number of transected axons in MS lesions is estimated at ovoids/mm 3. As a result of these findings, it is currently believed that axonal damage rather than demyelination is responsible for permanent neurologic impairment. The disease process in MS is considered as having 2 distinct pathologic phases. In early disease or relapsing-remitting MS (RRMS), the disease is characterized by inflammation and clinical relapses. Focal inflammatory events, causing blood-brain barrier breakdown, are imaged on magnetic resonance imaging (MRI) as contrast-enhancing lesions (CEL), which generally persist for 1 month or less. Although enhancement will cease, CELs persist as hyperintense focal lesions on T2-weighted images. Patients with RRMS generally evolve into a secondary progressive (SPMS) stage of disease within 10 to 15 years. In SPMS the predominant disease pathology is neurodegeneration. New inflammatory lesions are reduced, but the disease becomes more diffuse involving normalappearing white matter (NAWM) and grey matter (GM) structures. On conventional MRI (cmri), the best techniques for measuring neurodegeneration are T1 black holes and cerebral atrophy. Newer MRI techniques (eg, proton magnetic resonance spectroscopy [MRS], magnetization transfer imaging [MTI], and diffusion tensor imaging [DTI]) also are being used to measure focal and diffuse disease. The relationship between the inflammatory lesions and subsequent neurodegeneration is unclear. Axonal loss and cerebral atrophy can be detected at even the earliest stages of the disease, which leads some to suggest that the disease is primarily a diffuse process Johns Hopkins Advanced Studies in Medicine 233
2 throughout the white matter, and inflammatory lesions are inconsequential. Others believe inflammatory lesions are the inciting events that precede the eventual axonal damage. Evidence for the latter hypothesis is provided again by confocal microscopy studies, which demonstrated that the axonal loss in NAWM (17 axonal transections/mm 3 ) is miniscule compared to the axonal damage within visible lesions. 1 To address the question of which MRI methods are useful measures of neuroprotection and repair, we need to consider and quantitate 3 events. First, we need to demonstrate that ongoing inflammation is halted. Second, the extent of tissue damage must be assessed. Third, new axonal growth and/or remyelination must be measurable. The MRI technique should therefore be capable of measuring reversible changes in axonal and myelin content and ideally should measure these changes in focal lesions and the diffuse lesions in white matter and GM. This review will consider some newer nonconventional MRI techniques, including MRS, MTI, and DTI, as tools to measure neuronal and axonal repair. LESION MEASURES OF TISSUE DAMAGE The initial event of lesion evolution (ie, bloodbrain barrier breakdown and influx of inflammatory T cells) is documented on MRI by the presence of CELs on T1-weighted images. These active lesions persist as focal areas of hyperintense signal on T2-weighted scans, and the T2 lesion volume estimates the total burden of disease. However, T2 lesions are pathologically nonspecific and represent an entire spectrum of tissue damage, including lesions with inflammation, lesions with demyelination, gliotic scars, or lesions with severe axonal loss. Even remyelinating lesions appear hyperintense on T2 imaging sequences. Approximately 30% of CELs and T2 lesions will evolve into T1 black holes (ie, lesions with severe axonal loss and matrix destruction). This subset of hyperintense T2 lesions, which are hypointense on T1-weighted scans, is of particular interest because the axonal loss in these lesions is most likely responsible for clinical disability. In fact, T1 lesion volume correlates more closely with clinical disability than other lesion measures. Because T1 black holes are end-stage lesions, they are useful estimates of irreversible tissue damage but will not be useful as measures of tissue repair. Nevertheless, the evolution of CELs into T1 black holes has been used to measure neuroprotection. In a large multicenter, placebo-controlled trial, Filippi et al demonstrated a neuroprotective effect of glatiramer acetate by showing a significant reduction in the percentage of CELs evolving into T1 black holes. 2 A large sample (1276 lesions) was analyzed in this trial, making it a labor-intensive process. T1 black hole evolution is also subject to a high degree of interobserver variability and does not account for disease in the NAWM or GM. MRS Proton MRS is the most specific measure of axonal damage because it quantitates the neuronal-specific metabolite, N-acetyl aspartate (NAA), and expresses it as a ratio to the stable brain metabolite creatine (Cr). 3 A reduction in NAA/Cr ratio has been demonstrated in lesions and in NAWM and GM of patients with MS compared to healthy control subjects (Figure 1). 4 The decrease in NAA is progressive with disease duration and correlates with cerebral atrophy, although the rate of decrease in NAA (5%/year) is higher in patients with RRMS than in those with SPMS. 5 A robust correlation between lesion and NAWM NAA and clinical disability also has been observed. Because the reduction in NAA is partially reversible, this measure probably Figure 1. MRS Measures Axonal Loss in NAWM Left panel, normal brain with measure of NAA from the voxel indicated; Right panel, MS brain with measure of NAA from NAWM (upper voxel) and from MS lesion (lower voxel). MRS = magnetic resonance spectroscopy; MS = multiple sclerosis; NAA = N-acetyl aspartate; NAWM = normal-appearing white matter. Reprinted with permission from Matthews et al. Semin Neurol. 1998;18: Vol. 7, No. 8 August 2007
3 reflects irreversible axonal damage and a reversible axonal dysfunction. Thus MRS could potentially be used as a measure of neuroprotection and neuronal repair. Proton MRS has been used in several small studies to demonstrate axonal recovery in patients with MS treated with disease-modifying therapies. In a study of 10 patients with RRMS treated with high-dose interferon (IFN) β-1b, Narayanan et al demonstrated an 11% increase in NAA over a 12-month period of time, using a volume of interest (VOI) measure centered over the corpus callosum. 6 Other studies in patients with RRMS using a lower-dose IFN, shorter period of observation, or patients with RRMS with a longer disease duration have not been able to confirm these findings. 7,8 However, a recent study with glatiramer acetate also showed 10% increase in NAA in the VOI over a 2-year period of time in 18 glatiramer acetate-treated patients with RRMS compared to 4 untreated patients. 9 The interpretation of this study, however, is confounded by the significantly higher T2 lesion load in the untreated patients at entry to the study. Although MRS as a measure of neuroprotection and repair is promising, further clinical trials with larger patient groups will be necessary to assess its use. CEREBRAL ATROPHY Cerebral atrophy is a sensitive, accurate, and highly reproducible measure of irreversible brain parenchymal tissue loss, well suited to multicenter trials with neuroprotective agents. Because 75% of brain tissue is composed of axons and myelin, a decrease in brain volume most likely reflects irreversible neuroaxonal degeneration. In fact, a strong correlation between axonal density, NAA, and cerebral atrophy has been confirmed histopathologically. 10,11 The rate of atrophy in RRMS is generally estimated at 0.5% to 1% per year, approximately 10-fold higher than in agematched healthy control subjects. Atrophy is progressive with the course of the disease and correlates with clinical disability at all time points. 12 Atrophy can be used as a global measure of tissue damage or regional measure of axonal loss, if segmentation techniques are used to isolate deep GM structures or the cortical ribbon. Although brain atrophy measures have been used in several clinical trials to demonstrate a therapeutic effect in slowing atrophy rate, this will most likely not be a useful technique for demonstrating tissue repair because it represents irreversible change. MTI Magnetization transfer imaging is an indirect measure of tissue damage that reflects primarily myelin loss but also correlates with axonal density on histopathologic specimens. 13 The technique is based on the principle that protons bound to macromolecular structures (eg, myelin) are in equilibrium with the free protons responsible for the signal intensity of the image. If a radiofrequency pulse is used to selectively saturate myelin-bound protons, the signal intensity of the image decreases. The ratio of the signal intensity of images obtained with and without the saturation pulse is expressed as the magnetization transfer ratio (MTR; MTR = T1W-MT/T1W). Myelinated white matter has a relatively high MTR (0.4), GM has a lower MTR (0.32), and MS lesions have a spectrum of MTR values depending on the extent of demyelination. T1 black holes with severe axonal loss and tissue destruction have very low MTR values some approach pure fluid values (MTR = 0) that are similar to cerebrospinal fluid. Thus, MTR can stratify T2 lesions based on myelin and axonal content. Increases and decreases in myelin content can be observed over time. 14 Demyelination has been demonstrated by MTR in animal models of experimental allergic encephalomyelitis and toxic demyelination 15 and in Wallerian degeneration of the feline visual system. 16 Remyelination in MS lesions causes an increase in MTR values, a finding that has been confirmed on postmortem specimens. Surprisingly, 84% of MS lesions undergo remyelination to some extent. 13 Magnetization transfer ratio can be used as a global measurement of tissue destruction and/or to follow the evolution of individual CELs over time. Lesion MTR measurements confirm the heterogeneity of MS lesions. MTR values generally decrease dramatically at the time of contrast enhancement and MTR recovery (remyelination) occurs in some but not all lesions over the next 12 months. To evaluate the effect of treatment on lesion recovery, we examined 225 CELs from patients with RRMS over 24 months during a baseline versus treatment trial with IFNβ-1b. 17 Compared to untreated baseline lesions, CELs that occurred during IFN treatment, or those that occurred during a clinical relapse requiring methylprednisolone (1 g/day for 5 days), showed significantly higher MTR values at all time points after the initial enhancement, indicating improved recovery (Figure 2). 17 Because MTR reflects damage and repair, this imag- Johns Hopkins Advanced Studies in Medicine 235
4 ing technique will be useful for evaluating therapies aimed at neuroprotection and repair. Global measurements of whole-brain MTR also can be obtained if MTR values for each brain voxel are calculated and plotted as a histogram. In patients with MS, the accumulation of voxels with abnormally low MTR values causes a shift in the histogram metrics compared to healthy controls. Whole-brain histograms in patients with MS have a decrease in peak height, a leftward shift of the histogram, and a lower mean (average) histogram compared to healthy control subjects. The limitation of this method of analysis is that it is relatively insensitive to change over a short period of time. Compared to lesion analysis, wholebrain MTR histogram analysis for neuroprotection trials will require a large number of patients over a long period of time to produce statistically significant data. DTI Like MTR, DTI is an indirect measure of tissue integrity. Diffusion imaging measures the random Figure 2. Effect of Treatment on MTR Recovery of CELs Lesion MTR, % NAWM 105% 100% 95% 90% 85% 80% 75% 70% Gd enhancement P <.001 B-CEL (n = 109) S-CEL (n = 76) IFN CEL (n = 40) P =.01 65% Months from enhancement Four patients with MS were monitored monthly for a period of 2 years. During the time period to the left of time 0, the patients were untreated. After the Gd enhancement some patients remained untreated and their CEL followed (B-CEL). Other lesions were treated with IFNβ-1b (IFN CEL) or with methylprednisolone (S CEL). MTR is expressed as percent NAWM. CEL = contrast-enhancing lesion; Gd = gadolinium; IFN = interferon; MS = multiple sclerosis; MTR = magnetization transfer ratio; NAWM = normal-appearing white matter. Reprinted with permission from Richert et al. Mult Scler. 2001;7: motion of protons in tissue. In MS lesions and in NAWM, the average diffusion coefficient (ADC) is increased because of the loss of structural barriers. The directionality of diffusion, expressed as fractional anisotropy, is decreased in MS because of the loss of highly aligned structures (eg, axons) or because of gliotic scar tissue. Although there are no histopathologic correlates of diffusion measurements, ADC correlates well with MTR measures and with T1 black hole hypointensity. 18 Serial monthly diffusion measurements of CELs in 5 patients with MS were obtained over a period of 12 months. 19 Interestingly, in the area of the lesions, prelesional increases in ADC were detected 6 months prior to gadolinium enhancement. Similar prelesional changes have been noted using MTR and MRS. This suggests that nonconventional MRI is more sensitive than cmri in detecting early changes in tissue architecture. Moreover, these results may suggest that gadolinium enhancement may not indicate the inciting event in lesion formation. CONCLUSIONS Imaging of axonal damage is critical for assessing disease progression and treatment efficacy of neuroprotective agents. cmri techniques using T1- or T2- weighted sequences (with the exception of T1 black holes) lack the specificity for neuronal axonal damage but can evaluate whether inflammation is halted. MRS is the most specific measure of axonal damage but may be difficult to implement in multicenter clinical trials. Cerebral atrophy is currently considered the best in vivo marker of axonal damage and a useful measure of neuroprotection. Because MTR can measure reversible changes in myelin content, repair strategies would need to include a measure such as lesion MTR. DTI is a promising new technique that will improve MRI correlation with clinical deficits. DISCUSSION Dr Bar-Or: I was curious about a couple of the slides in which you showed the serial studies with MTR and the suggestion that the MTR dropped significantly before the time point of seeing the gadolinium enhancement. Can you comment on that? Is that, do you think, just a relative insensitivity of picking up the gadolinium abnormality, or an abnormality that might be initiated at the myelin level before gadolinium enhancement? 236 Vol. 7, No. 8 August 2007
5 Dr Richert: That is a fascinating question. I did not really dwell on it, but before the enhancement, up to 12 to 24 months beforehand, we see very small changes in MTR in the region of the lesion, if we go backwards in time rather than forwards in time. The changes are very small, maybe 5% or so, but they are definitely there. What this represents, whether this is an event that is occurring that we are not able to detect on cmri, or whether this is purely edema, we are not really certain. I think it would be fascinating to go back even further. We have 10 years of MTR data at this point. Now, I do not think it represents lesions that we would see, for example, with triple-dose contrast. And it would not represent lesions that we would see with delayed scanning, because we are now doing delayed scanning routinely with a 20-minute delay, and we are not seeing it there. Thus I do not think that it is just a matter of not being able to detect an enhancing lesion. I think there are really changes there. We also see them with MRS. You see very subtle changes in the area where lesions will ultimately develop. Therefore, there clearly are events before gadolinium enhancement that we just are only beginning to detect. REFERENCES 1. Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998;338: Filippi M, Grossman RI. MRI techniques to monitor MS evolution: the present and the future. Neurology. 2002;58: Criste GA, Trapp BD. N-acetyl-L-aspartate in multiple sclerosis. Adv Exp Med Biol. 2006;576: ; discussion Matthews PM, De Stefano N, Narayanan S, et al. Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis. Semin Neurol. 1998;18: Fu L, Matthews PM, De Stefano N, et al. Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain. 1998;121: Narayanan S, De Stefano N, Francis GS, et al. Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol. 2001;248: Parry A, Corkill R, Blamire AM, et al. Beta-Interferon treatment does not always slow the progression of axonal injury in multiple sclerosis. J Neurol. 2003;250: Sarchielli P, Presciutti O, Tarducci R, et al. 1H-MRS in patients with multiple sclerosis undergoing treatment with interferon beta-1a: results of a preliminary study. J Neurol Neurosurg Psychiatry. 1998;64: Khan O, Shen Y, Caon C, et al. Axonal metabolic recovery and potential neuroprotective effect of glatiramer acetate in relapsing-remitting multiple sclerosis. Mult Scler. 2005;11: Evangelou N, Esiri MM, Smith S, et al. Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol. 2000;47: Wylezinska M, Cifelli A, Jezzard P, et al. Thalamic neurodegeneration in relapsing-remitting multiple sclerosis. Neurology. 2003;60: Fisher E, Rudick RA, Simon JH, et al. Eight-year follow-up study of brain atrophy in patients with MS. Neurology. 2002;59: Barkhof F, Bruck W, De Groot CJ, et al. Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch Neurol. 2003;60: Inglese M, Grossman RI, Filippi M. Magnetic resonance imaging monitoring of multiple sclerosis lesion evolution. J Neuroimaging. 2005;15:22S-29S. 15. Brochet B, Dousset V. Pathological correlates of magnetization transfer imaging abnormalities in animal models and humans with multiple sclerosis. Neurology. 1999;53:S12-S Lexa FJ, Grossman RI, Rosenquist AC. Detection of early axonal degeneration in the mammalian central nervous system by magnetization transfer techniques in magnetic resonance imaging. Ann N Y Acad Sci. 1993;679: Richert ND, Ostuni JL, Bash CN, et al. Interferon beta-1b and intravenous methylprednisolone promote lesion recovery in multiple sclerosis. Mult Scler. 2001;7: Iannucci G, Rovaris M, Giacomotti L, et al. Correlation of multiple sclerosis measures derived from T2-weighted, T1- weighted, magnetization transfer, and diffusion tensor MR imaging. AJNR Am J Neuroradiol. 2001;22: Werring DJ, Brassat D, Droogan AG, et al. The pathogenesis of lesions and normal-appearing white matter changes in multiple sclerosis: a serial diffusion MRI study. Brain. 2000;123: Johns Hopkins Advanced Studies in Medicine 237
Chapter 10. Summary & Future perspectives
Summary & Future perspectives 123 Multiple sclerosis is a chronic disorder of the central nervous system, characterized by inflammation and axonal degeneration. All current therapies modulate the peripheral
More informationMRI in drug development: Lessons from MS
MRI in drug development: Lessons from MS Douglas L. Arnold MD McConnel Brain Imaging Center, MNI, McGill NeuroRx Research Inc Drug development Pre-clinical Phase I Phase II Phase III Phase IV Candidate
More informationSensitive and reproducible clinical rating
CLINICAL AND MRI MARKERS OF MS DISEASE PROGRESSION * Richard A. Rudick, MD ABSTRACT Sensitive and reproducible measures of multiple sclerosis (MS) severity and progression are important in the treatment
More informationUpdate: MRI in Multiple sclerosis
Nyt indenfor MS ved MR Update: MRI in Multiple sclerosis Hartwig Roman Siebner Danish Research Centre for Magnetic Resonance (DRCMR) Copenhagen University Hospital Hvidovre Dansk Radiologisk Selskabs 10.
More informationORIGINAL CONTRIBUTION. Effects of Interferon Beta-1b on Black Holes in Multiple Sclerosis Over a 6-Year Period With Monthly Evaluations
ORIGINAL CONTRIBUTION Effects of Interferon Beta-1b on Black Holes in Multiple Sclerosis Over a 6-Year Period With Monthly Evaluations Francesca Bagnato, MD; Shiva Gupta, BA; Nancy D. Richert, MD, PhD;
More informationReversibility of Acute Demyelinating Lesions in relapsingremitting
Reversibility of Acute Demyelinating Lesions in relapsingremitting Multiple Sclerosis Omar A. Khan ( Division of Neuroimmunology, Department of Neurology, Neurology and Research Services. Veterans Affairs
More informationNancy D. Richert, John L. Ostuni, Craig N. Bash, Jeff H. Duyn, Henry F. McFarland, and Joseph A. Frank
AJNR Am J Neuroradiol 19:1705 1713, October 1998 Serial Whole-Brain Magnetization Transfer Imaging in Patients with Relapsing-Remitting Multiple Sclerosis at Baseline and during Treatment with Interferon
More informationCharacterization of Differences between Multiple Sclerosis and Normal Brain: A Global Magnetization Transfer Application
AJR Am J euroradiol 20:50 507, March 999 Characterization of Differences between Multiple Sclerosis and ormal Brain: A Global Magnetization Transfer Application John L. Ostuni, ancy D. Richert, Bobbi K.
More informationThe role of MRI in modern management of and treatment decisions in MS
The role of MRI in modern management of and treatment decisions in MS franz.fazekas@medunigraz.at Vienna, September 25, 2013 Department of Neurology, http://neurologie.uniklinikumgraz.at Disclosures 8
More informationBrain Atrophy in Relapsing-Remitting Multiple Sclerosis: Fractional Volumetric Analysis of Gray Matter and White Matter 1
Neuroradiology Yulin Ge, MD Robert I. Grossman, MD Jayaram K. Udupa, PhD James S. Babb, PhD László G. Nyúl, MSc Dennis L. Kolson, MD, PhD Index terms: Brain, gray matter, 10.88 Brain, MR, 10.121411, 10.121419
More informationRational basis for early treatment in MS. Bonaventura Casanova Estruch Unitat d Esclerosi Múltiple Hospital Universitari la Fe València
Rational basis for early treatment in MS Bonaventura Casanova Estruch Unitat d Esclerosi Múltiple Hospital Universitari la Fe València Bonaventura Casanova Department of Neurology University Hospital La
More informationDisease Management Consensus Statement
Expert Opinion Paper National Medical Advisory Board Disease Management Consensus Statement Treatment Recommendations for Clinicians This paper is currently undergoing updates from 2008 content. Visit
More informationFastTest. You ve read the book... ... now test yourself
FastTest You ve read the book...... now test yourself To ensure you have learned the key points that will improve your patient care, read the authors questions below. The answers will refer you back to
More informationDirectional Diffusion in Relapsing-Remitting Multiple Sclerosis: A Possible In Vivo Signature of Wallerian Degeneration
JOURNAL OF MAGNETIC RESONANCE IMAGING 18:420 426 (2003) Original Research Directional Diffusion in Relapsing-Remitting Multiple Sclerosis: A Possible In Vivo Signature of Wallerian Degeneration Roland
More informationOHTAC Recommendation
OHTAC Recommendation Multiple Sclerosis and Chronic Cerebrospinal Venous Insufficiency Presented to the Ontario Health Technology Advisory Committee in May 2010 May 2010 Issue Background A review on the
More informationEVOLVING CONCEPTS IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS AND THEIR THERAPEUTIC IMPLICATIONS
EVOLVING CONCEPTS IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS AND THEIR THERAPEUTIC IMPLICATIONS Richard A. Rudick, M.D. Cleveland, Ohio INTRODUCTION In recent years, concepts of MS pathogenesis have evolved
More informationMR imaging is a sensitive tool for visualizing the characteristic
ORIGINAL RESEARCH I.J. van den Elskamp D.L. Knol B.M.J. Uitdehaag F. Barkhof Modeling MR Imaging Enhancing-Lesion Volumes in Multiple Sclerosis: Application in Clinical Trials BACKGROUND AND PURPOSE: Although
More informationORIGINAL CONTRIBUTION. Progressive Gray Matter Damage in Patients With Relapsing-Remitting Multiple Sclerosis
ORIGINAL CONTRIBUTION Progressive Gray Matter Damage in Patients With Relapsing-Remitting Multiple Sclerosis A Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study Celia Oreja-Guevara, MD; Marco
More informationManaging Relapsing Remitting MS Risks & benefits of emerging therapies. Dr Mike Boggild The Walton Centre
Managing Relapsing Remitting MS Risks & benefits of emerging therapies Dr Mike Boggild The Walton Centre MS: Facts and figures Affects 1 in 800 in the UK Commonest cause of acquired neurological disability
More informationMultiple Sclerosis. Matt Hulvey BL A - 615
Multiple Sclerosis Matt Hulvey BL A - 615 Multiple Sclerosis Multiple Sclerosis (MS) is an idiopathic inflammatory disease of the central nervous system (CNS) MS is characterized by demyelination (lesions)
More informationAward Number: W81XWH-10-1-0739
AD Award Number: W81XWH-10-1-0739 TITLE: Voxel-Wise Time-Series Analysis of Quantitative MRI in Relapsing-Remitting MS: Dynamic Imaging Metrics of Disease Activity Including Prelesional Changes PRINCIPAL
More informationPicturing Multiple Sclerosis: Conventional and Diffusion Tensor Imaging
Picturing Multiple Sclerosis: Conventional and Diffusion Tensor Imaging Robert J. Fox, M.D. 1 ABSTRACT Magnetic resonance imaging (MRI) has provided an unparalleled window into understanding multiple sclerosis
More informationThe role of focal white matter lesions on magnetic resonance
ORIGINAL ARTICLE Treatment Effect on Brain Atrophy Correlates with Treatment Effect on Disability in Multiple Sclerosis Maria Pia Sormani, PhD, 1 Douglas L. Arnold, MD, 2 and Nicola De Stefano, MD 3 Objective:
More information3.1. Persistent T1 Hypointensity as an MRI Marker for Treatment Ef cacy in Multiple Sclerosis
3.1 Persistent T1 Hypointensity as an MRI Marker for Treatment Ef cacy in Multiple Sclerosis I.J. van den Elskamp J. Lembcke, V. Dattola K. Beckmann C. Pohl W. Hong R. Sandbrink K. Wagner D. L. Knol B.M.J
More informationHow To Use A Drug In Multiple Sclerosis
Revised (2009) guidelines for prescribing in multiple sclerosis INTRODUCTION In January 2001, the (ABN) first published guidelines for the use of licensed disease modifying treatments (ß-interferon and
More informationDemyelinating Plaques in Relapsing-remitting and Secondary-progressive Multiple Sclerosis: Assessment with Diffusion MR Imaging
AJNR Am J Neuroradiol 21:862 868, May 2000 Demyelinating Plaques in Relapsing-remitting and Secondary-progressive Multiple Sclerosis: Assessment with Diffusion MR Imaging Alessandro Castriota Scanderbeg,
More informationIn 1868, Jean-Martin Charcot first described
CURRENT THERAPIES AND CLINICAL TRIALS * Benjamin Greenberg, MD, MHS ABSTRACT Although Charcot and others described many of the clinical and histopathologic features of multiple sclerosis (MS) as early
More informationClinical Trials of Disease Modifying Treatments
MS CENTER CLINICAL RESEARCH The UCSF MS Center is an internationally recognized leader in multiple sclerosis clinical research. We conduct clinical trials involving the use of experimental treatments,
More informationSerial Contrast-Enhanced MR in Patients with Multiple Sclerosis and Varying Levels of Disability
Serial Contrast-Enhanced MR in Patients with Multiple Sclerosis and Varying Levels of Disability Massimo Filippi, Paolo Rossi, Adriana Campi, Bruno Colombo, Clodoaldo Pereira, and Giancarlo Comi PURPOSE:
More informationMultiple Sclerosis - Relapsing and Remissioning
DISEASE-MODIFYING THERAPIES IN RELAPSING-REMITTING MULTIPLE SCLEROSIS* Benjamin M. Greenberg, MD, MHS ABSTRACT Four major disease-modifying therapies are discussed within the context of relapsing and remitting
More informationProgress in MS: Current and Emerging Therapies
Progress in MS: Current and Emerging Therapies Presented by: Dr. Kathryn Giles, MD MSc FRCPC The MS Society gratefully acknowledges the grant received from Biogen Idec Canada, which makes possible the
More informationQuantitative Assessment of MRI Features in Patients with Relapsing-Remitting Multiple Sclerosis
BIOSCIENCES BIOTECHNOLOGY RESEARCH ASIA, August 2014. Vol. 11(2), 863-868 Quantitative Assessment of MRI Features in Patients with Relapsing-Remitting Multiple Sclerosis Babak Shekarchi 1, Samaneh Fartook
More informationMedication Policy Manual. Topic: Aubagio, teriflunomide Date of Origin: November 9, 2012
Medication Policy Manual Policy No: dru283 Topic: Aubagio, teriflunomide Date of Origin: November 9, 2012 Committee Approval Date: December 12, 2014 Next Review Date: December 2015 Effective Date: January
More informationNeuroimaging Christopher Bever, MD, MBA (MODERATOR) Use of MRI in Diagnosing and Monitoring MS Jack H. Simon, Portland, OR
Neuroimaging Christopher Bever, MD, MBA (MODERATOR) Use of MRI in Diagnosing and Monitoring MS Jack H. Simon, Portland, OR What MRI Taught Us about Neurodegeneration and MS Matilde Inglese, NewYork MRI
More informationß-interferon and. ABN Guidelines for 2007 Treatment of Multiple Sclerosis with. Glatiramer Acetate
ABN Guidelines for 2007 Treatment of Multiple Sclerosis with ß-interferon and Glatiramer Acetate Published by the Association of British Neurologists Ormond House, 27 Boswell Street, London WC1N 3JZ Contents
More informationMRI for Paediatric Surgeons
MRI for Paediatric Surgeons Starship David Perry Paediatric Radiologist Starship Children s Hospital CHILDREN S HEALTH What determines the brightness of a pixel in MRI? i.e. What determines the strength
More informationMedication Policy Manual. Topic: Gilenya, fingolimod Date of Origin: November 22, 2010
Medication Policy Manual Policy No: dru229 Topic: Gilenya, fingolimod Date of Origin: November 22, 2010 Committee Approval Date: December 11, 2015 Next Review Date: December 2016 Effective Date: January
More informationInterferon-β-1a in relapsing-remitting multiple sclerosis: evect on hypointense lesion volume on T1 weighted images
J Neurol Neurosurg Psychiatry 1999;67:579 584 579 Interferon-β-1a in relapsing-remitting multiple sclerosis: evect on hypointense lesion volume on T1 weighted images Claudio Gasperini, Carlo Pozzilli,
More informationInforming Decisions to Improve the Continuum of Care in Relapsing-Remitting Multiple Sclerosis
Informing Decisions to Improve the Continuum of Care in Relapsing-Remitting Multiple Sclerosis Mirla Avila, MD Texas Tech University Health Sciences Center, Lubbock, Texas Abstract Disease-modifying therapy
More informationPredictive Value of Lesions for Relapses in Relapsingremitting
AJNR Am J Neuroradiol :8 9, February Predictive Value of Lesions for Relapses in Relapsingremitting Multiple Sclerosis James A. Koziol, Simone Wagner, David F. Sobel, Lloyd S. Slivka, John S. Romine, Jack
More informationDisease Modifying Therapies for MS
Disease Modifying Therapies for MS The term disease-modifying therapy (DMT) means a drug that can modify or change the course of a disease. In other words a DMT should be able to reduce the number of attacks
More informationAn introduction to modern MS treatments
BETAFERON is a Prescription Medicine. Use strictly as directed. Consult your pharmacist or other health professional in case of side effects. BETAFERON is reimbursed for some patients. See your neurologist
More informationApplication of Interferon Beta-1b in Multiple Sclerosis. Francesca Bagnato, MD, PhD
Application of Interferon Beta-1b in Multiple Sclerosis Francesca Bagnato, MD, PhD Visiting Assistant Professor of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science
More informationThe Burden of Disease
The Burden of Disease A closer look at the consequences of living with multiple sclerosis 2011 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by www.msatrium.com, MS.US.PO83.0711E
More informationUse of imaging in multiple sclerosis
CHAPTER 3 Use of imaging in multiple sclerosis M. Filippi, 1 M. A. Rocca, 1 D. L. Arnold,2 R. Bakshi,3 F. B ar khof, 4 5 N. De Stefano, F. Fazekas,6 E. Frohman,7 D. H. Mil le r, 8 9 J. S. Wolinsky 1 Institute
More informationIssues Regarding Use of Placebo in MS Drug Trials. Peter Scott Chin, MD Novartis Pharmaceuticals Corporation
Issues Regarding Use of Placebo in MS Drug Trials Peter Scott Chin, MD Novartis Pharmaceuticals Corporation Context of the Guidance The draft EMA Guidance mentions placebo as a comparator for superiority
More informationThe Prospect of Stem Cell Therapy in Multiple Sclerosis. Multiple sclerosis is a multifocal inflammatory disease of the central
The Prospect of Stem Cell Therapy in Multiple Sclerosis Multiple sclerosis is a multifocal inflammatory disease of the central nervous system that generally affects young individuals, causing paralysis
More informationLesional magnetization transfer ratio: a feasible outcome for remyelinating treatment trials in multiple sclerosis
Research Paper Lesional magnetization transfer ratio: a feasible outcome for remyelinating treatment trials in multiple sclerosis Multiple Sclerosis 16(6) 660 669! The Author(s) 010 Reprints and permissions:
More informationAccuracy in Space and Time: Diagnosing Multiple Sclerosis. 2012 Genzyme Corporation, a Sanofi company.
Accuracy in Space and Time: Diagnosing Multiple Sclerosis 2012 Genzyme Corporation, a Sanofi company. Brought All rights to reserved. you by www.msatrium.com, MS.US.PO876.1012 your gateway to MS knowledge.
More informationDisease Modifying Therapies for MS
Disease Modifying Therapies for MS The term disease-modifying therapy means a drug that can modify or change the course of a disease. In other words a DMT should be able to reduce the number of attacks
More informationThree Subsequent Single Doses of Gadolinium Chelate for Brain MR Imaging in Multiple Sclerosis
AJNR Am J Neuroradiol 24:658 662, April 2003 Three Subsequent Single Doses of Gadolinium Chelate for Brain MR Imaging in Multiple Sclerosis Francesco Sardanelli, Andrea Iozzelli, Caterina Losacco, Alessandra
More informationClinical trials of multiple sclerosis monitored with enhanced MRI: new sample size calculations based on large data sets
494 J Neurol Neurosurg Psychiatry 21;7:494 499 Clinical trials of multiple sclerosis monitored with enhanced MRI: new sample size calculations based on large data sets M P Sormani, D H Miller, G Comi,
More informationSummary HTA. Interferons and Natalizumab for Multiple Sclerosis Clar C, Velasco-Garrido M, Gericke C. HTA-Report Summary
Summary HTA HTA-Report Summary Interferons and Natalizumab for Multiple Sclerosis Clar C, Velasco-Garrido M, Gericke C Health policy background Multiple sclerosis (MS) is a chronic inflammatory disease
More informationBenign versus Secondary-Progressive Multiple Sclerosis: The Potential Role of Proton MR Spectroscopy in Defining the Nature of Disability
AJNR Am J Neuroradiol 19:223 229, February 1998 Benign versus Secondary-Progressive Multiple Sclerosis: The Potential Role of Proton MR Spectroscopy in Defining the Nature of Disability A. Falini, G. Calabrese,
More informationMultiple Sclerosis in Practice. An Expert Commentary With Jeffrey Cohen, MD, PhD A Clinical Context Report
Multiple Sclerosis in Practice An Expert Commentary With Jeffrey Cohen, MD, PhD A Clinical Context Report Clinical Context: Multiple Sclerosis in Practice Expert Commentary Jointly Sponsored by: and Clinical
More informationTwo-Year Phase III Data Presented at AAN 61st Annual Meeting Show Positive Outcome of Cladribine Tablets in Patients with Multiple Sclerosis
Your contact News Release Barbara Fry Phone +1 905 919 0163 April 29/30, 2009 Two-Year Phase III Data Presented at AAN 61st Annual Meeting Show Positive Outcome of Cladribine Tablets in Patients with Multiple
More informationMULTIPLE SCLEROSIS Update. Disclosures. Multiple Sclerosis. I do not have any disclosures. E. Torage Shivapour, M.D.
MULTIPLE SCLEROSIS Update E. Torage Shivapour, M.D. Clinical Professor Department of Neurology University of Iowa Hospitals & Clinics Disclosures I do not have any disclosures. Multiple Sclerosis Most
More informationMULTIMODAL THERAPY FOR MS- ASSOCIATED COGNITIVE DYSFUNCTION
MULTIMODAL THERAPY FOR MS- ASSOCIATED COGNITIVE DYSFUNCTION Michael K. Racke, MD Professor and Chairman in Neurology The Helen C. Kurtz Chair in Neurology Department of Neurology Ohio State University
More informationApparent Diffusion Coefficients in the Evaluation of High-grade Cerebral Gliomas
AJNR Am J Neuroradiol 22:60 64, January 2001 Apparent Diffusion Coefficients in the Evaluation of High-grade Cerebral Gliomas Mauricio Castillo, J. Keith Smith, Lester Kwock, and Kathy Wilber BACKGROUND
More informationIF YOU ARE RECEIVING TREATMENT WITH TYSABRI FOR RELAPSING-REMITTING MS (NATALIZUMAB)
IF YOU ARE RECEIVING (NATALIZUMAB) TREATMENT WITH TYSABRI FOR RELAPSING-REMITTING MS Read the patient information leaflet that accompanies the medicine carefully. 1 This brochure is a supplement to the
More informationAcute demyelinating optic neuritis Rod Foroozan, MD, Lawrence M. Buono, MD, Peter J. Savino, MD, and Robert C. Sergott, MD
Acute demyelinating optic neuritis Rod Foroozan, MD, Lawrence M. Buono, MD, Peter J. Savino, MD, and Robert C. Sergott, MD Acute demyelinating optic neuritis associated with multiple sclerosis (MS) is
More informationApproved Beta Interferons in Relapsing-Remitting Multiple sclerosis: Is There an Odd One Out?
Journal of Central Nervous System Disease Review Open Access Full open access to this and thousands of other papers at http://www.la-press.com. Approved Beta Interferons in Relapsing-Remitting Multiple
More informationAdvances in the Use of MRI in the Management of MS. The Role of MRI in MS Management. Jack H. Simon Portland, Oregon
Advances in the Use of MRI in the Management of MS The Role of MRI in MS Management Jack H. Simon Portland, Oregon Disclosures Dr. Simon has nothing to disclose. This continuing education activity is managed
More informationHeld, Heigenhauser, Shang, Kappos, Polman: Predicting the On-Study Relapse Rate for Multiple Sclerosis Patients in Clinical Trials
Held, Heigenhauser, Shang, Kappos, Polman: Predicting the On-Study Relapse Rate for Multiple Sclerosis Patients in Clinical Trials Sonderforschungsbereich 386, Paper 430 (2005) Online unter: http://epub.ub.uni-muenchen.de/
More informationVersion History. Previous Versions. Drugs for MS.Drug facts box fingolimod Version 1.0 Author
Version History Policy Title Drugs for MS.Drug facts box fingolimod Version 1.0 Author West Midlands Commissioning Support Unit Publication Date Jan 2013 Review Date Supersedes/New (Further fields as required
More informationNew Treatment Options for MS Patients: Understanding risks versus benefits
New Treatment Options for MS Patients: Understanding risks versus benefits By Michael A. Meyer, MD Department of Neurology, Sisters Hospital, Buffalo, NY Objectives: 1. to understand fundamentals of MS
More informationMANAGED CARE CONSULTANTM
MANAGED CARE CONSULTANTM MEDICAL EDUCATION FOR THE CLINICAL DECISION MAKER VOL. 4, NO. 1, MARCH 2005 New Frontiers in the Treatment of Multiple Sclerosis: An Evidence-Based Approach Multiple Sclerosis
More informationDrug Class Review Disease-modifying Drugs for Multiple Sclerosis
Drug Class Review Disease-modifying Drugs for Multiple Sclerosis Final Update 3 Report May 2016 The purpose of reports is to make available information regarding the comparative clinical effectiveness
More informationMS: The Treatment Paradigm, A Pathway to Success for Improved Patient Outcomes
MS: The Treatment Paradigm, Pathway to Success for Improved Patient Outcomes Jack Burks, MD For a CME/CEU version of this article please go to www.namcp.org/cmeonline.htm, and then click the activity title.
More informationLife with MS: Striving for Maximal Independence & Fulfillment
Life with MS: Striving for Maximal Independence & Fulfillment St. Louis, May 7, 2005 Florian P. Thomas, MA, MD, PhD MS Center, Department of Neurology Associate Professor, Saint Louis University Brain
More informationNew Approaches to Neuroimaging of Progressive Multifocal Leukoencephalopathy. Alexandra Binnie, HMS III Gillian Lieberman, M.D.
New Approaches to Neuroimaging of Progressive Multifocal Leukoencephalopathy Alexandra Binnie, HMS III Gillian Lieberman, M.D. What is Progressive Multifocal Leukoencephalopathy (PML)? A demyelinating
More informationTechnological Innovation: High Field Open Magnetic Resonance Spectroscopy
Technological Innovation: High Field Open Magnetic Resonance Spectroscopy Student Investigator: Thomas R. Pace UVM COM Class of 2012 Faculty Mentor: Christopher Filippi Department of Radiology Fletcher
More informationOntario Reimburses CIS Indication for REBIF, a First-Line Treatment for Multiple Sclerosis
May 25, 2015 Contact: Shikha Virdi 905-919-0200 ext. 5504 Ontario Reimburses CIS Indication for REBIF, a First-Line Treatment for Multiple Sclerosis Rebif now reimbursed under Ontario Drug Benefit Program
More informationCommittee Approval Date: December 12, 2014 Next Review Date: December 2015
Medication Policy Manual Policy No: dru299 Topic: Tecfidera, dimethyl fumarate Date of Origin: May 16, 2013 Committee Approval Date: December 12, 2014 Next Review Date: December 2015 Effective Date: January
More informationMedication Policy Manual. Topic: Aubagio, teriflunomide Date of Origin: November 9, 2012
Medication Policy Manual Policy No: dru283 Topic: Aubagio, teriflunomide Date of Origin: November 9, 2012 Committee Approval Date: December 11, 2015 Next Review Date: December 2016 Effective Date: January
More informationCAMBRIDGE UNIVERSITY CENTRE FOR BRAIN REPAIR A layman's account of our scientific objectives What is Brain Damage? Many forms of trauma and disease affect the nervous system to produce permanent neurological
More informationNATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE. Proposed Health Technology Appraisal
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE Proposed Health Technology Appraisal Daclizumab for treating relapsing-remitting multiple Draft scope (pre-referral) Draft remit/appraisal objective To
More informationPersonalised Medicine in MS
Personalised Medicine in MS Supportive Evidence from Therapeutic Trials Ludwig Kappos Neurology and Department of Biomedicine University Hospital CH-4031 Basel LKappos@uhbs.ch Established partially effective
More informationThe New England Journal of Medicine
The New England Journal of Medicine Copyright, 2, by the Massachusetts Medical Society VOLUME 343 N OVEMBER 16, 2 NUMBER 2 RELAPSES AND PROGRESSION OF DISABILITY IN MULTIPLE SCLEROSIS CHRISTIAN CONFAVREUX,
More informationT 1 hypointense lesions in secondary progressive multiple sclerosis: effect of interferon beta-1b treatment
Brain (2001), 124, 1396 1402 T 1 hypointense lesions in secondary progressive multiple sclerosis: effect of interferon beta-1b treatment Frederik Barkhof, 1 Jan-Hein T. M. van Waesberghe, 1 Massimo Filippi,
More informationWith the development of effective therapies for multiple sclerosis (MS), therapeutic
SECTION EDITOR: IRA SHOULSON, MD Disease-Modifying Drugs for Relapsing-Remitting Multiple Sclerosis and Future Directions for Multiple Sclerosis Therapeutics Richard A. Rudick, MD NEUROTHERAPEUTICS With
More informationLaquinimod Polman, C. et al. Neurology 2005;64:987-991
Laquinimod Polman, C. et al. Neurology 2005;64:987-991 Multicenter, double-blind, randomized trial, patients with RR MS received 0.1 mg or 0.3 mg laquinimod or placebo as three daily tablets for 24 weeks
More informationVersion History. Previous Versions. Policy Title. Drugs for MS.Drug facts box Glatiramer Acetate Version 1.0 Author
Version History Policy Title Drugs for MS.Drug facts box Glatiramer Acetate Version 1.0 Author West Midlands Commissioning Support Unit Publication Date Jan 2013 Review Date Supersedes/New (Further fields
More informationfingolimod (as hydrochloride), 0.5mg hard capsules (Gilenya ) SMC No. (763/12) Novartis Pharmaceuticals UK Ltd
fingolimod (as hydrochloride), 0.5mg hard capsules (Gilenya ) SMC No. (763/12) Novartis Pharmaceuticals UK Ltd 10 February 2012 The Scottish Medicines Consortium (SMC) has completed its assessment of the
More informationDiffusione e perfusione in risonanza magnetica. E. Pagani, M. Filippi
Diffusione e perfusione in risonanza magnetica E. Pagani, M. Filippi DW-MRI DIFFUSION-WEIGHTED MRI Principles Diffusion results from a microspic random motion known as Brownian motion THE RANDOM WALK How
More informationProgress in the field: therapeutic improvements for all patients?
Progress in the field: therapeutic improvements for all patients? Krzysztof Selmaj, Department of Neurology, Medical University of Lodz, PL Warsaw 15 May, 2015 Main features of MS Inflammation Demyelination
More informationCHAPTER Hyperbaric Oxygen Therapy in Multiple Sclerosis
CHAPTER Hyperbaric Oxygen Therapy in Multiple Sclerosis 20 D.J.D. Perrins, R.A. Neubauer and P.B. James 1 INTRODUCTION Multiple sclerosis (MS) is a disease associated with clinical evidence of disability
More informationImmunex Corporation Novantrone (Mitoxantrone HCL) P&CNS Advisory Committee Briefing Document. Page 020
Page 020 4.0 Efficacy of Mitoxantrone in Multiple Sclerosis The efficacy of mitoxantrone in MS was demonstrated in two well-designed, randomized trials: Studies 901 and 902. The study design and efficacy
More informationNeuroimaging module I: Modern neuroimaging methods of investigation of the human brain in health and disease
1 Neuroimaging module I: Modern neuroimaging methods of investigation of the human brain in health and disease The following contains a summary of the content of the neuroimaging module I on the postgraduate
More informationMultiple Sclerosis: An imaging review and update on new treatments.
Multiple Sclerosis: An imaging review and update on new treatments. Dr Marcus Likeman Consultant Neuroradiologist North Bristol NHS Trust Bristol Royal Hospital for Children MRI appearances - White Matter
More informationMultifocal Motor Neuropathy. Jonathan Katz, MD Richard Lewis, MD
Multifocal Motor Neuropathy Jonathan Katz, MD Richard Lewis, MD What is Multifocal Motor Neuropathy? Multifocal Motor Neuropathy (MMN) is a rare condition in which multiple motor nerves are attacked by
More informationTreatment Optimization in MS: When to Start, When to Shift, when to Stop
Treatment Optimization in MS: When to Start, When to Shift, when to Stop Mark S. Freedman MSc MD FAAN FANA FRCPC Director, Multiple Sclerosis Research Unit University of Ottawa Sr. Scientist, Ottawa Hospital
More informationCalming microglia: a future method for treating multiple sclerosis Jarred Younger, PhD University of Alabama at Birmingham
Calming microglia: a future method for treating multiple sclerosis Jarred Younger, PhD University of Alabama at Birmingham Sonja Paetau, University of Helsinki Disclosures Will be discussing off-label
More informationAUBMC Multiple Sclerosis Center
AUBMC Multiple Sclerosis Center 1 AUBMC Multiple Sclerosis Center The vision of the American University of Beirut Medical Center (AUBMC) is to be the leading academic medical center in Lebanon and the
More informationRelapsing-remitting multiple sclerosis Ambulatory with or without aid
AVONEX/BETASERON/COPAXONE/EXTAVIA/GILENYA/REBIF/TYSABRI Applicant must be covered on an Alberta Government sponsored drug program. Page 1 of 5 PATIENT INFMATION Surname First Name Middle Initial Sex Date
More informationCollaborative Network Award Planning Grants Project Summaries
Collaborative Network Award Planning Grants Project Summaries PRIORITY AREA: Projects that will drive development of one or more pre-clinical drug candidates through identification and validation of molecular
More informationMultiple sclerosis (MS) is an immune-mediated demyelinating
JAMES R. MILLER, MD ABSTRACT OBJECTIVE: To describe the current understanding of the diagnosis and treatment of multiple sclerosis (MS) and to explore the use of magnetic resonance imaging (MRI) assessment
More informationCOMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP)
European Medicines Agency London, 16 November 2006 Doc. Ref. CPMP/EWP/561/98 Rev. 1 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) GUIDELINE ON CLINICAL INVESTIGATION OF MEDICINAL PRODUCTS FOR THE
More informationClinically isolated syndrome (CIS)
Clinically isolated syndrome (CIS) Spirella Building, Letchworth, SG6 4ET 01462 476700 www.mstrust.org.uk reg charity no. 1088353 We hope you find the information in this factsheet helpful. If you would
More informationAdvanced MRI methods in diagnostics of spinal cord pathology
Advanced MRI methods in diagnostics of spinal cord pathology Stanisław Kwieciński Department of Magnetic Resonance MR IMAGING LAB MRI /MRS IN BIOMEDICAL RESEARCH ON HUMANS AND ANIMAL MODELS IN VIVO Equipment:
More information