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Multiple Sclerosis, Vol. 11, No. 4, 433-440 (2005)
DOI: 10.1191/1352458505ms1196oa

MRI results from the European Study on Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS)

F Fazekas

Departments of Neurology and Neuroradiology, Medical University, Graz, Austria, franz.fazekas{at}meduni-graz.at

P S Sørensen

Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

M Filippi

Neuroimaging Research Unit and Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy

S Ropele

Departments of Neurology and Neuroradiology, Medical University, Graz, Austria

X Lin

Queens Medical Centre, Nottingham, UK

H W Koelmel

Department of Neurology, Klinikum Erfurt, Erfurt, Germany

O Fernandez

Department of Neurology, Hospital Regional Carlos Haya, Malaga, Spain

C Pozzilli

Clinica Neurologica I, Universita la Sapienza, Rome, Italy

P O'Connor

St Michael’s Hospital,; Toronto, Canada

M Maas Enriquez

Bayer Vital, Leverkusen, Germany

O R Hommes

European Charcot Foundation, Nijmegen, The Netherlands

ESIMS trialists

Background: Monthly application of high-dose intravenous immunoglobulin (IVIG) to patients with secondary progressive multiple sclerosis (MS) showed no clinical benefit in the European Study on Immunoglobulin in MS (ESIMS). Magnetic resonance imaging (MRI) results may provide insights into the morphologic consequences of such treatment. Methods: A total of 318 patients (mean age 44± 7 years) were enrolled in 31 European and Canadian centres and treated monthly with 1 g/kg body weight of IVIG or equivalent amounts of albumin 0.1% for 27 months. MRI was performed at baseline and after 12 and 24 months and comprised of conventional dual-echo T2-weighted and T1-weighted scans before and after application of 0.1 mmol/kg Gd-DTPA. Results: Similar to clinical variables, MRI measures at baseline were well comparable between treatment groups except for a somewhat lower mean number of contrast-enhancing lesions and number of active scans in IVIG-treated patients. Over the trial period there was almost no change of the T2-lesion load and the ‘black hole’ volume in both treatment groups and the cumulative number of contrast-enhancing lesions were similar. There was only a trend for fewer new or enlarged T2-lesions in IVIG patients, which disappeared after correction for the imbalance in the number of contrast-enhancing lesions at baseline. Brain volume in terms of a partial cerebral fraction decreased significantly less with IVIG than placebo treatment (final visit:-0.62± 0.88% versus-0.88± 0.91%; P= 0.009). This difference remained statistically significant with correction for active lesions at baseline (P= 0.02) and was seen primarily in male patients and those with an Expanded Disability Status Scale score ≥ 6 and no relapses in the two years before the study. Conclusion: The absence of significant differences in conventional MRI measures between both treatment groups parallels the negative clinical results of ESIMS. The causes for and possible long-term clinical effects of a lower rate of brain volume loss in IVIG patients should be explored further.

Key Words: brain atrophy • contrast enhancement • intravenous immunoglobulin • lesion load • magnetic resonance imaging • secondary progressive MS • treatment trial


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