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Articles
October 9, 2001

Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS

October 9, 2001 issue
57 (7) 1239-1247

Abstract

Background: IV methylprednisolone (IVMP) has been used to treat relapses in patients with relapsing-remitting (RR) MS, but its effect on disease progression is not known. Furthermore, there are no data on the impact of IVMP on T1 black holes or whole-brain atrophy. Objective: To determine the effect of IVMP on MRI measures of the destructive pathology in patients with RR-MS and secondarily to determine the effect of IVMP on disability progression in patients with RR-MS. Methods: The authors conducted a randomized, controlled, single-blind, phase II clinical trial of IVMP in patients with RR-MS. Eighty-eight patients with RR-MS with baseline Expanded Disability Status Scale (EDSS) scores of ≤5.5 were randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral prednisone taper) or IVMP at the same dose schedule only for relapses (IVMP for relapses) and followed without other disease-modifying drug therapy for 5 years. Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the subsequent 2 years. Patients had quantitative cranial MRI scans at study entry and after 5 years and standardized clinical assessments every 4 to 6 months. Results: Eighty-one of 88 patients completed the trial as planned, and treatment was well tolerated. Baseline demographic, clinical, and MRI measures were well matched in the two study arms. Patients on the pulsed IVMP arm received more MP than patients on the control arm of the study (p < 0.0001). Mean change in T1 black hole volume favored pulsed IVMP therapy (+1.3 vs +5.2 mL; p < 0.0001), as did mean change in brain parenchymal volume (+2.6 vs −74.5 mL; p = 0.003). There was no significant difference between treatment arms in the change in T2 volume or annual relapse rate during the study. However, there was significantly more EDSS score worsening in the control group, receiving IVMP only for relapses. There was a 32.2% reduction (p ≤ 0.0001) in the probability of sustained EDSS score worsening in the pulsed MP arm compared with the relapse treatment arm. At the end of the study, EDSS was better in the pulsed MP group (1.7 vs 3.4; p < 0.0001). Prolonged treatment with pulsed IVMP was safe and well tolerated; only two patients dropped out for toxic side effects over 5 years. Conclusions: In patients with RR-MS, treatment with pulses of IVMP slows development of T1 black holes, prevents or delays whole-brain atrophy, and prevents or delays disability progression. A phase III study of IVMP pulses is warranted.

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Information & Authors

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Published In

Neurology®
Volume 57Number 7October 9, 2001
Pages: 1239-1247
PubMed: 11591843

Publication History

Received: October 31, 2000
Accepted: May 15, 2001
Published online: October 9, 2001
Published in print: October 9, 2001

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Authors

Affiliations & Disclosures

R. Zivadinov, MD
From the Departments of Clinical Medicine and Neurology (Drs. Zivadinov, De Masi, Nasuelli, Cazzato, and Zorzon), Radiology (Drs. Ukmar and Pozzi–Mucelli), and Electrical, Electronics, and Computer Science (A. Grop), University of Trieste, Italy; and Mellen Center (Dr. Rudick), Department of Neurology, Cleveland Clinic Foundation, OH.
R. A. Rudick, MD
From the Departments of Clinical Medicine and Neurology (Drs. Zivadinov, De Masi, Nasuelli, Cazzato, and Zorzon), Radiology (Drs. Ukmar and Pozzi–Mucelli), and Electrical, Electronics, and Computer Science (A. Grop), University of Trieste, Italy; and Mellen Center (Dr. Rudick), Department of Neurology, Cleveland Clinic Foundation, OH.
R. De Masi, MD
From the Departments of Clinical Medicine and Neurology (Drs. Zivadinov, De Masi, Nasuelli, Cazzato, and Zorzon), Radiology (Drs. Ukmar and Pozzi–Mucelli), and Electrical, Electronics, and Computer Science (A. Grop), University of Trieste, Italy; and Mellen Center (Dr. Rudick), Department of Neurology, Cleveland Clinic Foundation, OH.
D. Nasuelli, MD
From the Departments of Clinical Medicine and Neurology (Drs. Zivadinov, De Masi, Nasuelli, Cazzato, and Zorzon), Radiology (Drs. Ukmar and Pozzi–Mucelli), and Electrical, Electronics, and Computer Science (A. Grop), University of Trieste, Italy; and Mellen Center (Dr. Rudick), Department of Neurology, Cleveland Clinic Foundation, OH.
M. Ukmar, MD
From the Departments of Clinical Medicine and Neurology (Drs. Zivadinov, De Masi, Nasuelli, Cazzato, and Zorzon), Radiology (Drs. Ukmar and Pozzi–Mucelli), and Electrical, Electronics, and Computer Science (A. Grop), University of Trieste, Italy; and Mellen Center (Dr. Rudick), Department of Neurology, Cleveland Clinic Foundation, OH.
R. S. Pozzi–Mucelli, MD
From the Departments of Clinical Medicine and Neurology (Drs. Zivadinov, De Masi, Nasuelli, Cazzato, and Zorzon), Radiology (Drs. Ukmar and Pozzi–Mucelli), and Electrical, Electronics, and Computer Science (A. Grop), University of Trieste, Italy; and Mellen Center (Dr. Rudick), Department of Neurology, Cleveland Clinic Foundation, OH.
A. Grop, BSc
From the Departments of Clinical Medicine and Neurology (Drs. Zivadinov, De Masi, Nasuelli, Cazzato, and Zorzon), Radiology (Drs. Ukmar and Pozzi–Mucelli), and Electrical, Electronics, and Computer Science (A. Grop), University of Trieste, Italy; and Mellen Center (Dr. Rudick), Department of Neurology, Cleveland Clinic Foundation, OH.
G. Cazzato, MD
From the Departments of Clinical Medicine and Neurology (Drs. Zivadinov, De Masi, Nasuelli, Cazzato, and Zorzon), Radiology (Drs. Ukmar and Pozzi–Mucelli), and Electrical, Electronics, and Computer Science (A. Grop), University of Trieste, Italy; and Mellen Center (Dr. Rudick), Department of Neurology, Cleveland Clinic Foundation, OH.
M. Zorzon, MD
From the Departments of Clinical Medicine and Neurology (Drs. Zivadinov, De Masi, Nasuelli, Cazzato, and Zorzon), Radiology (Drs. Ukmar and Pozzi–Mucelli), and Electrical, Electronics, and Computer Science (A. Grop), University of Trieste, Italy; and Mellen Center (Dr. Rudick), Department of Neurology, Cleveland Clinic Foundation, OH.

Notes

Address correspondence and reprint requests to Dr. R. Zivadinov, Neurological Clinic, Cattinara Hospital, Strada di Fiume, 447-34149 Trieste, Italy; e-mail: [email protected]

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