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272 results on '"Freedman, M. S."'

1. A Proposed Method for Measuring the Electric Dipole Moment of the Neutron Using Acceleration in an Electric-Field Gradient and Ultracold Neutron Interferometry

Author

Freedman, M. S., Ringo, G. R., and Dombeck, T. W.

Subjects
Nuclear Experiment, High Energy Physics - Experiment
Abstract

The use of an ultracold neutron interferometer incorporating an electrostatic accelerator having a strong electric field gradient to accelerate neutrons by their possible electric moments is proposed as a method of measuring the neutron electric dipole moment. Such electrical acceleration, followed by an amplifier and a generator of phase difference, could develop relatively large phase differences and these could be measured by a Mach-Zehnder interferometer. This method might extend the sensitivity of the measurement by several orders of magnitude beyond the current limit of 10^{-25} e.cm. Furthermore the systematic errors in such a measurement could be significantly different from those of the current EDM experiments., Comment: 33 pages, now including figures. REVTEX

Published
1998
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8. Autologous haematopoietic stem cell transplantation as a first-line disease-modifying therapy in patients with 'aggressive' multiple sclerosis

Author

Das, J., Snowden, J. A., Burman, Joachim, Freedman, M. S., Atkins, H., Bowman, M., Burt, R. K., Saccardi, R., Innocenti, C., Mistry, S., Laud, P. J., Jessop, H., Sharrack, B., Das, J., Snowden, J. A., Burman, Joachim, Freedman, M. S., Atkins, H., Bowman, M., Burt, R. K., Saccardi, R., Innocenti, C., Mistry, S., Laud, P. J., Jessop, H., and Sharrack, B.

Abstract

Background: Autologous haematopoietic stem cell transplantation (AHSCT) is an effective treatment for patients with multiple sclerosis (MS) who have highly active disease, despite the use of standard disease-modifying therapies (DMTs). However, the optimal time for offering AHSCT to patients with ‘aggressive’ MS is yet to be established. Objectives: The objective was to explore the safety and efficacy of AHSCT as a first-line DMT in patients with ‘aggressive’ MS. Methods: All patients with ‘aggressive’ MS who received AHSCT as a first-line DMT in five European and North American centres were retrospectively evaluated. Results: Twenty patients were identified. The median interval between diagnosis and AHSCT was 5 (1–20) months. All had multiple poor prognostic markers with a median pre-transplant Expanded Disability Status Scale (EDSS) score of 5.0 (1.5–9.5). After a median follow-up of 30 (12–118) months, the median EDSS score improved to 2.0 (0–6.5, p < 0.0001). No patient had further relapses. Three had residual magnetic resonance imaging (MRI) disease activities in the first 6 months post-transplant, but no further new or enhancing lesions were observed in subsequent scans. Conclusion: AHSCT is safe and effective as a first-line DMT in inducing rapid and sustained remission in patients with ‘aggressive’ MS.

Published
2021
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9. High or increasing serum NfL is predictive of impending multiple sclerosis relapses

Author

Thebault, S., Reaume, M., Marrie, R. A., Marriott, J. J., Furlan, R., Laroni, A., Booth, R. A., Uccelli, A., and Freedman, M. S.

Subjects
Canada, Cross-Sectional Studies, Multiple Sclerosis, Neurology, Recurrence, biomarkers, multiple sclerosis, Neurofilament light chain, Biomarkers, Humans, Neurology (clinical), General Medicine
Abstract

One-off serum levels of neurofilament light chain (sNfL) is an established predictor of emerging disease activity in multiple sclerosis (MS). However, the importance of longitudinal increases in sNfL is yet to be enumerated, an important consideration as this test is translated for serial monitoring. Glial Fibrillary Acidic Protein (sGFAP) is another biomarker of predictive interest. Our objective was to assess the association between longitudinal changes sNfL and prediction of future relapses, as well as a possible role for sGFAP.Participants with active MS were prospectively monitored for one year as part of a clinical trial testing mesenchymal stem cells. Visits every three months or less included clinical assessments, MRI scans and serum draws. sNfL and sGFAP concentrations were quantified with Single Molecule Array immunoassay. We used Kaplan-Meier estimates and Anderson-Gill Cox regression models with and without adjustment for age, sex, disease subtype, disease duration and expanded disability status score (EDSS) to estimate the rate of relapse predicted by baseline and longitudinal changes in biomarker.58 Canadian and Italian participants with MS were enrolled in this study. Higher baseline sNfL was future relapse (Log-rank p = 0.0068), MRI lesions (p=0.0096), composite-relapse associated worsening (p=0.01) and progression independent of relapse activity (p=0.0096). Conversely, baseline sGFAP was only weakly associated with MRI lesions (0.044). Cross-sectional analyses of baseline sNfL revealed that a two-fold difference in baseline sNfL, e.g. from 10 to 20 pg/mL, was associated with a 2.3-fold increased risk of relapse during follow-up (95% confidence interval 1.65-3.17). Longitudinally, a two-fold increase in sNfL level from the first measurement was associated with an additional 1.46 times increased risk of relapse (1.07-2.00). The impact of longitudinal increases in sNfL on the risk of relapse were most pronounced for patients with lower baseline values of sNfL (10 pg/mL: HR = 1.54, 1.06-2.24). These associations remained significant after adjustment for potential confounders.We enumerate the risk of relapse associated with dynamic changes in sNfL. Both baseline and longitudinal change in sNfL may help identify patients who would benefit from early treatment optimisation.Canada:NCT02239393, Italy:NCT01854957EudraCT, 2011-001295-19 CLASSIFICATION OF EVIDENCE: This study provides class 1 evidence that high baseline and longitudinal increases in sNfL are predictive of impending relapses in patients with active MS.

Published
2022
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18. Vitamin D and the development and evolution of permanent black holes among patients with clinically isolated syndrome

Author

Fitzgerald, K. C., Munger, K., Freedman, M. S., Hartung, H. -P., Montalban, X., Edan, Gilles, Barkhof, F., Sandbrink, R., Kappos, L., Suarez, G., Pohl, C., Ascherio, A, Harvard University, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Vrije Universiteit Amsterdam [Amsterdam] (VU), University Hospital Basel [Basel], Harvard University [Cambridge], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2015

19. Predicting conversion to clinically definite multiple sclerosis using machine learning on the basis of cerebral grey matter segmentations

Author

Bendfeldt, K., Taschler, B., Gaetano, L., Madoerin, P., Kuster, P., Mueller-Lenke, N., Amann, M., Vrenken, H., Barkhof, F., Stefan Borgwardt, Kloeppel, S., Nichols, T. E., Suarez, G., Kappos, L., Edan, G., Freedman, M. S., Montalban, X., Hartung, H. -P, Pohl, C., Sandbrink, R., Wuerfel, J., Radue, E. -W, Sprenger, T., University Hospital Basel [Basel], Vrije Universiteit Amsterdam [Amsterdam] (VU), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2015

20. MRI results in patients with CIS treated with interferon beta-1b: 11-year follow up in BENEFIT (BENEFIT 11)

Author

Barkhof, F., Wattjes, M. P., Edan, Gilles, Freedman, M. S., Montalban, X., Hartung, H. -P., Hemmer, B., Fox, E. J., Schippling, S., Koelbach, R., Pleimes, D., Pohl, C., Sandbrink, R., Suarez, G., Wicklein, E. -M., Kappos, Ludwig, Jonchère, Laurent, Vrije Universiteit Amsterdam [Amsterdam] (VU), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital universitaire de Zurich, University Hospital Basel [Basel], and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2015

21. Impact of early treatment of MS with interferon beta-1b: cognitive outcomes at the 11-year follow-up of BENEFIT (BENEFIT 11)

Author

Foley, F., Penner, I. -K., Edan, Gilles, Freedman, M. S., Montalban, X., Hartung, H. -P., Hemmer, B., Fox, E. J., Barkhof, F., Schippling, S., Koelbach, R., Pleimes, D., Pohl, C., Sandbrink, R., Suarez, G., Wicklein, E. -M., Kappos, L., Jonchère, Laurent, Yeshiva University, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Vrije Universiteit Amsterdam [Amsterdam] (VU), Hôpital universitaire de Zurich, University Hospital Basel [Basel], and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2015

22. Optical coherence tomography and ophthalmological findings in patients with CIS treated with interferon beta-1b: 11-year follow-up in BENEFIT (BENEFIT 11)

Author

Lukas, S., Hanson, J. V. M., Edan, Gilles, Freedman, M. S., Montalban, X., Hartung, H. -P., Hemmer, B., Fox, E. J., Barkhof, F., Koelbach, R., Pleimes, D., Pohl, C., Sandbrink, R., Suarez, G., Wicklein, E. -M., Kappos, L., Schippling, S., Jonchère, Laurent, Hôpital universitaire de Zurich, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Vrije Universiteit Amsterdam [Amsterdam] (VU), University Hospital Basel [Basel], Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2015

23. Disability outcome measures in multiple sclerosis clinical trials: current status and future prospects

Author

Cohen, Jeffrey A., Reingold, Stephen C., Polman, Chris H., International Advisory Committee On Clinical Trials In Multiple Sclerosis Polman, Wolinsky Js C. H., Barkhof, F., Balcer, L. J., Banwell, B., Calabresi, P., Clanet, M., Cohen, J. A., Comi, G., Cutter, G. R., Freedman, M. S., Goodman, A. D., Kappos, L., Kieseier, B. C., Lubetzki, C., Lublin, F. D., Miller, A., Montalban, X., O'Connor, P., Petkau, J., Pozzilli, Carlo, Reingold, S. C., Sørensen, P. S., Sormani, M. P., Stuve, O., Thompson, A. J., Wolinsky, Jerry S., Neurology, and NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases

Subjects
medicine.medical_specialty, Activities of daily living, Multiple Sclerosis, MEDLINE, Alternative medicine, Retina, Disability Evaluation, Quality of life (healthcare), Activities of Daily Living, Medicine, Humans, Intensive care medicine, Randomized Controlled Trials as Topic, Neurologic Examination, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Brain, medicine.disease, Magnetic Resonance Imaging, Clinical trial, Multiple sclerosis functional composite, Physical therapy, Disease Progression, Neurology (clinical), business, Biomarkers, Tomography, Optical Coherence
Abstract

Many of the available disability outcome measures used in clinical trials of multiple sclerosis are insensitive to change over time, inadequately validated, or insensitive to patient-perceived health status or quality of life. Increasing focus on therapies that slow or reverse disability progression makes it essential to refine existing measures or to develop new tools. Major changes to the expanded disability status scale should be avoided to prevent the loss of acceptance by regulators as a measure for primary outcomes in trials that provide substantial evidence of effectiveness. Rather, we recommend practical refinements. Conversely, although substantial data support the multiple sclerosis functional composite as an alternative measure, changes to its component tests and scoring method are needed. Novel approaches, including the use of composite endpoints, patient-reported outcomes, and measurement of biomarkers, show promise as adjuncts to the current disability measures, but are insufficiently validated to serve as substitutes. A collaborative approach that involves academic experts, regulators, industry representitives, and funding agencies is needed to most effectively develop disability outcome measures.

Published
2012
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24. Defining the clinical course of multiple sclerosis: The 2013 revisions

Author

Lublin, F. D., primary, Reingold, S. C., additional, Cohen, J. A., additional, Cutter, G. R., additional, Sorensen, P. S., additional, Thompson, A. J., additional, Wolinsky, J. S., additional, Balcer, L. J., additional, Banwell, B., additional, Barkhof, F., additional, Bebo, B., additional, Calabresi, P. A., additional, Clanet, M., additional, Comi, G., additional, Fox, R. J., additional, Freedman, M. S., additional, Goodman, A. D., additional, Inglese, M., additional, Kappos, L., additional, Kieseier, B. C., additional, Lincoln, J. A., additional, Lubetzki, C., additional, Miller, A. E., additional, Montalban, X., additional, O'Connor, P. W., additional, Petkau, J., additional, Pozzilli, C., additional, Rudick, R. A., additional, Sormani, M. P., additional, Stuve, O., additional, Waubant, E., additional, and Polman, C. H., additional

Published
2014
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26. A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper

Author

Saccardi, R, Freedman, M S, Sormani, M P, Atkins, H, Farge, D, Griffith, L M, Kraft, G, Mancardi, G L, Nash, R, Pasquini, M, Martin, R; https://orcid.org/0000-0002-0982-1329, Muraro, P A, Saccardi, R, Freedman, M S, Sormani, M P, Atkins, H, Farge, D, Griffith, L M, Kraft, G, Mancardi, G L, Nash, R, Pasquini, M, Martin, R; https://orcid.org/0000-0002-0982-1329, and Muraro, P A

Abstract

BACKGROUND: Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of them having been recruited in small, single-centre, phase 1-2 uncontrolled trials. Clinical and magnetic resonance imaging outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted during the relapsing-remitting phase than in those in the secondary progressive stage. OBJECTIVES: An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of discussing a controlled clinical trial, to be designed within the new scenarios of evolving MS treatments. CONCLUSIONS: Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.

Published
2012

27. Efficacy of subcutaneous interferon -1a on MRI outcomes in a randomised controlled trial of patients with clinically isolated syndromes

Author

De Stefano, N., primary, Comi, G., additional, Kappos, L., additional, Freedman, M. S., additional, Polman, C. H., additional, Uitdehaag, B. M. J., additional, Hennessy, B., additional, Casset-Semanaz, F., additional, Lehr, L., additional, Stubinski, B., additional, Jack, D. L., additional, and Barkhof, F., additional

Published
2013
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30. Validation of anti-GAGA4 IgM antibodies for predicting the development of relapsing-remitting MS after the first neurological event

Author

UCL - Cliniques universitaires Saint-Luc, UCL, Freedman, M. S., Sindic, Christian, Laks, J., Dotan, N., Altstock, R. T., Dukler, A., 11th Annual Meeting of the Americas-Committee-for-Treatment-and-Research-in- Multiple-Sclerosis, UCL - Cliniques universitaires Saint-Luc, UCL, Freedman, M. S., Sindic, Christian, Laks, J., Dotan, N., Altstock, R. T., Dukler, A., and 11th Annual Meeting of the Americas-Committee-for-Treatment-and-Research-in- Multiple-Sclerosis

Published
2007

35. TLR-mediated B cell activation results in ectopic CLIP expression that promotes B cell-dependent inflammation

Author

Newell, M K, primary, Tobin, R P, additional, Cabrera, J H, additional, Sorensen, M B, additional, Huckstep, A, additional, Villalobos-Menuey, E M, additional, Burnett, M, additional, McCrea, E, additional, Harvey, C P, additional, Buddiga, A, additional, Bar-Or, A, additional, Freedman, M S, additional, Nalbantoglu, J, additional, Arbour, N, additional, Zamvil, S S, additional, and Antel, J P, additional

Published
2010
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37. Ethics of placebo-controlled clinical trials in multiple sclerosis: A reassessment

Author

Polman, C. H., primary, Reingold, S. C., additional, Barkhof, F., additional, Calabresi, P. A., additional, Clanet, M., additional, Cohen, J. A., additional, Cutter, G. R., additional, Freedman, M. S., additional, Kappos, L., additional, Lublin, F. D., additional, McFarland, H. F., additional, Metz, L. M., additional, Miller, A. E., additional, Montalban, X., additional, O'Connor, P. W., additional, Panitch, H., additional, Richert, J. R., additional, Petkau, J., additional, Schwid, S. R., additional, Sormani, M. P., additional, Thompson, A. J., additional, Weinshenker, B. G., additional, and Wolinsky, J. S., additional

Published
2008
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40. Progressive multiple sclerosis exhibits decreasing glutamate and glutamine over two years.

Author

MacMillan, E. L., Tam, R., Zhao, Y., Vavasour, I. M., Li, D. K. B., Oger, J., Freedman, M. S., Kolind, S. H., and Traboulsee, A. L.

Subjects
GLUTAMINE, DEMYELINATION, EXCITATORY amino acid agents, NUCLEAR magnetic resonance spectroscopy, METABOLITES, CEREBRAL atrophy
Abstract

Background: Few biomarkers of progressive multiple sclerosis (MS) are sensitive to change within the two-year time frame of a clinical trial. Objective: To identify biomarkers of MS disease progression with magnetic resonance spectroscopy (MRS) in secondary progressive MS (SPMS). Methods: Forty-seven SPMS subjects were scanned at baseline and annually for two years. Concentrations of N-acetylaspartate, total creatine, total choline, myo-inositol, glutamate, glutamine, and the sum glutamate+glutamine were measured in a single white matter voxel. Results: Glutamate and glutamine were the only metabolites to show an effect with time: with annual declines of (95% confidence interval): glutamate −4.2% (−6.2% to −2.2%, p < 10−4), glutamine −7.3% (−11.8% to −2.9%, p = 0.003), and glutamate+glutamine −5.2% (−7.6% to −2.8%, p < 10−4). Metabolite rates of change were more apparent than changes in clinical scores or brain atrophy measures. Conclusions: The high rates of change of both glutamate and glutamine over two years suggest they are promising new biomarkers of MS disease progression. [ABSTRACT FROM AUTHOR]

Published
2016
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42. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes

Author

Koch, M. W., primary, Mostert, J. P., additional, de Vries, J. J., additional, De Keyser, J., additional, Kappos, L ., additional, Polman, C .H., additional, Freedman, M .S., additional, Edan, G ., additional, Hartung, H .-P., additional, Miller, D .H., additional, Montalban, X ., additional, Barkhof, F ., additional, Bauer, L ., additional, Pohl, C ., additional, and Sandbrink, R ., additional

Published
2007
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43. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials.

Author

Goodman, Andrew D., Bethoux, Francois, Brown, Theodore R., Schapiro, Randall T., Cohen, Ron, Marinucci, Lawrence N., Henney, Herbert R., Blight, Andrew R., Agius, M., Arnason, B. G. W., Bethoux, F. A., Bever, C. T., Bowen, J. D., Brown, T. R., Dietrich, D. W., Edwards, K., Freedman, M. S., Freedman, M., Kachuck, N. J., and Kaufman, M. D.

Subjects
MULTIPLE sclerosis, WALKING speed, DRUGS, VIRUS diseases, SPEED
Abstract

Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. [ABSTRACT FROM AUTHOR]

Published
2015
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47. Book Reviews

Author

Freedman, M. S., primary, Turnbull, O., additional, and Hawley, R. J., additional

Published
2003
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