PII: S0022-510X(05)00019-5

Abstract

We appreciate the opportunity provided by Hardmeier et al. to comment on the rate of short-term brain atrophy progression in relapsing–remitting (RR) multiple sclerosis (MS) found in a recent study from our group [ [1] Zivadinov R. Bagnato F. Nasuelli D. Bastianello S. Bratina A. Locatelli L. et al. Short-term brain atrophy changes in relapsing-remitting multiple sclerosis. J Neurol Sci. 2004; 223: 185-193 Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar ]. Longitudinal natural history studies and therapeutic trials of patients treated with placebo suggest that brain atrophy is common in patients with RRMS from the earliest stages of the disease [ 2 Zivadinov R. Bakshi R. Role of MRI in multiple sclerosis: II. Brain and spinal cord atrophy. Front Biosci. 2004; 9: 647-664 Crossref PubMed Scopus (66) Google Scholar , 3 Zivadinov R. Bakshi R. Central nervous system atrophy and clinical status in multiple sclerosis. J Neuroimaging. 2004; 14: 27S-35S Crossref PubMed Scopus (84) Google Scholar , 4 Zivadinov R. Zorzon M. Bakshi R. Central nervous system atrophy in multiple sclerosis: introduction. in: Zivadinov R. Bakshi R. Brain and spinal cord atrophy in multiple sclerosis. Nova Biomedical Books, 2004: 1-4 Google Scholar , 5 Zivadinov R. Bakshi R. Neurologic disability and central nervous system atrophy in multiple sclerosis. in: Zivadinov R. Bakshi R. Brain and spinal cord atrophy in multiple sclerosis. Nova Biomedical Books, 2004: 137-166 Google Scholar ]. The estimated annual rate of whole-brain atrophy varies across studies and methods but is slightly higher in patients with early-stage RRMS (range, −0.7% to 1.33%) than in those with advanced stages of RRMS (range, −0.61% to 1.2%) [ 3 Zivadinov R. Bakshi R. Central nervous system atrophy and clinical status in multiple sclerosis. J Neuroimaging. 2004; 14: 27S-35S Crossref PubMed Scopus (84) Google Scholar , 5 Zivadinov R. Bakshi R. Neurologic disability and central nervous system atrophy in multiple sclerosis. in: Zivadinov R. Bakshi R. Brain and spinal cord atrophy in multiple sclerosis. Nova Biomedical Books, 2004: 137-166 Google Scholar ]. A few studies have monitored the development of brain atrophy over the short term [ 1 Zivadinov R. Bagnato F. Nasuelli D. Bastianello S. Bratina A. Locatelli L. et al. Short-term brain atrophy changes in relapsing-remitting multiple sclerosis. J Neurol Sci. 2004; 223: 185-193 Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar , 6 Hardmeier M. Wagenpfeil S. Freitag P. Fisher E. Rudick R.A. Kooijmans-Coutinho M. et al. Atrophy is detectable within a 3-month period in untreated patients with active relapsing remitting multiple sclerosis. Arch Neurol. 2003; 60: 1736-1739 Crossref PubMed Scopus (33) Google Scholar , 7 Redmond I.T. Barbosa S. Blumhardt L.D. Roberts N. Short-term ventricular volume changes on serial MRI in multiple sclerosis. Acta Neurol Scand. 2000; 102: 99-105 Crossref PubMed Scopus (24) Google Scholar , 8 Rovaris M. Comi G. Rocca M.A. Wolinsky J.S. Filippi M. Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications. Brain. 2001; 124: 1803-1812 Crossref PubMed Scopus (147) Google Scholar ]. Brain volume changes in the short term may be affected by factors other than tissue loss, mainly changes in hydration, steroid treatment, and edema caused by acute inflammation [ 2 Zivadinov R. Bakshi R. Role of MRI in multiple sclerosis: II. Brain and spinal cord atrophy. Front Biosci. 2004; 9: 647-664 Crossref PubMed Scopus (66) Google Scholar , 9 Gasperini C. Whole-brain atrophy measurement and short-term brain volume changes. in: Zivadinov R. Bakshi R. Brain and spinal cord atrophy in multiple sclerosis. Nova Biomedical Books, 2004: 29-38 Google Scholar ]. Two studies have demonstrated that patients with MS develop significant brain atrophy within 6 to 12 months [ 7 Redmond I.T. Barbosa S. Blumhardt L.D. Roberts N. Short-term ventricular volume changes on serial MRI in multiple sclerosis. Acta Neurol Scand. 2000; 102: 99-105 Crossref PubMed Scopus (24) Google Scholar , 8 Rovaris M. Comi G. Rocca M.A. Wolinsky J.S. Filippi M. Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications. Brain. 2001; 124: 1803-1812 Crossref PubMed Scopus (147) Google Scholar ]. Recently, a group of very active patients with RRMS were monitored monthly for 3 months during a run-in phase preceding entry into a clinical trial [ [10] Clanet M. Radue E.W. Kappos L. Hartung H.P. Hohlfeld R. Sandberg-Wollheim M. et al. A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS. Neurology. 2002; 59: 1507-1517 Crossref PubMed Scopus (202) Google Scholar ]. The study determined that detectable brain volume loss can be shown in this short time period [ [6] Hardmeier M. Wagenpfeil S. Freitag P. Fisher E. Rudick R.A. Kooijmans-Coutinho M. et al. Atrophy is detectable within a 3-month period in untreated patients with active relapsing remitting multiple sclerosis. Arch Neurol. 2003; 60: 1736-1739 Crossref PubMed Scopus (33) Google Scholar ]. The authors reported a significant decrease in BPF from baseline scan to month 3 (−0.229%; P<0.001). In our short-term study of a smaller sample, we did not observe significant brain atrophy progression in a group of patients with early RRMS at any time point over 3 months [ [1] Zivadinov R. Bagnato F. Nasuelli D. Bastianello S. Bratina A. Locatelli L. et al. Short-term brain atrophy changes in relapsing-remitting multiple sclerosis. J Neurol Sci. 2004; 223: 185-193 Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar ]. We contended that some differences in demographic (age and disease duration), clinical (EDSS and relapse rate), and MRI (number of Gd+lesions at baseline) characteristics of patients with RRMS may help to explain the divergent findings in the 2 studies.