Functional magnetic resonance imaging in multiple sclerosis patients with fatigue before and after neurorehabilitation therapy

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1 Functional magnetic resonance imaging in multiple sclerosis patients with fatigue before and after neurorehabilitation therapy Poster No.: C-2496 Congress: ECR 2010 Type: Topic: Authors: Keywords: DOI: Scientific Exhibit Neuro M. Ukmar, E. Trincia, M. Naccarato, M. Catalan, S. Mezzarobba, M. A. Cova; Trieste/IT fmri, multiple sclerosis, fatigue /ecr2010/C-2496 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 9

2 Purpose Fatigue is a common symptom in patients with multiple sclerosis (MS), reported in over 80% of cases and associated with a high degree of disability and a reduced quality of life [1]. The pathogenesis of fatigue in MS is still unclear, but electrophysiological and neuroimaging studies recently supported a central origin. In fact, fatigue may be correlated to motor dysfunction of circuits involving the thalamus, the basal ganglia and the frontal cortex [2,3,4]. Moreover in MS patient the f-mri demonstrates an abnormal cortical and subcortical activation while performing a nmotor task, due to functionally adaptive changes as a consequence of white and gray matter [4,5,6]. Rehabilitation treatment could modify this activation [7]. According to the evidence that fatigue is the consequence of motor planning and execution dysfunction we supposed that a specific neurorehabilitation therapy could modify the cortical activation reducing the fatigue symptoms. The aim of our study was to evaluate the pattern of activation during a motor task by f-mri in patients with MS and fatigue, without motor impairment, before and after neurorehabilitation therapy. Methods and Materials In our study we enorolled 10 female patients right handed, with relapsing-remitting MS and fatigue. The mean age was years (range years) and the mean disease duration was 5 years (range 2-10 years). EDSS (Expanded Disability Status Scale) score was low (<3.5). The fatigue score was measured by Fatigue Severity Scale (FSS) and was higher than 4.5 points. Criteria for excluding patients were ongoing clinical relapse, major depression, cognitive impairment, traeatment with immunosupressive drugs, and common contraindication to MR examination. All MR examination were performed by using 1.5 T magnet: SE PD/T2 weighted and FLAIR sequences were performed in order to calculate the lesion load. The functional evaluation was performed by an EPI sequence (TR/TE=2158/ 45 msec, 25 slices, 4 mm, no gap, 160 dynamics) during the execution of a simple finger tapping task with the right hand. Page 2 of 9

3 The neurological evaluation (disability, fatigue) and the MR examination were performed before and after the neurorehabilitation therapy. This therapy lasted three months and consisted of exercises in order to modify specifically cognitive processes during movement planning and subsequently movement control. The statistical analysis concerning disability and fatigue scale was performed using non parametric Wilcoxon test. The lesion load was calculated by using the software Analyze 5. The functional data were processed using the SPM package version 2. Single subjects SPM-maps were generated (p<0.001 corrected for multiple comparisons). Then a group analysis was performed comparing activations maps of patients before and after treatment (p<0.05 corrected for multiple comparisons). The statistical analysis, concerning functional evaluation, was performed by using Student's t-test. Results After treatment, a significant decrease in fatigue scale (FSS) was detected, while no differences were detected in disability scores (tab.1). Baseline mean±sd Follow-up mean±sd p EDSS 1.63± ±0.37 ns FSS 5.56± ± TAB: 1- Clinical evaluation before and after treatment EDSS: expanded disability status scale FSS: fatigue severity scale No differences were found regarding the total lesion load (tab.2). pre post p Page 3 of 9

4 T2 Lesion load 4.24± ±4.96 ns TAB. 2: Conventional MRI: Lesion load before and after treatment The fmri analysis performed after neurorehabilitation therapy showed a reduction in activations of both bilateral sensorimotor cortex, mainly the ipsilateral one, cerebellum and thalami (p<0.05) (Fig. 1A-B) on page 5 (Fig. 2). on page 5 Fig.: Fig 1 A-B: f-mri - cortical activation before (A) and after neurorehabiliation therapy (B). After therapy there are a reduced activation mainly in the ipsilateral sensori-motor area and in the cerebellum bilaterally. References: M. Ukmar; Department of Radiology, University of Trieste, Trieste, ITALY Page 4 of 9

5 Images for this section: Fig. 1: Fig 1 A-B: f-mri - cortical activation before (A) and after neurorehabiliation therapy (B). After therapy there are a reduced activation mainly in the ipsilateral sensori-motor area and in the cerebellum bilaterally. Page 5 of 9

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7 Fig. 2: Fig 2: f-mri - Pre vs post treatment analysis: reduction in activation of thalami after rehabilitation treatment. Page 7 of 9

8 Conclusion Our results confirm that there is an abnormal activation during the execution of a motor task in patients with MS and fatigue. Neurorehabilitation therapy could reduce the grade of fatigue improving the quality of life of the patients by modifying cortical and subcortical activation. The fmri could be an objective tool to evaluate the efficacy of rehabilitation treatment in MS patients with fatigue. References 1) Krupp LB, Alvarez LA, LaRocca NG, Scheinberg LC (1988) Clinical characteristics of fatigue in multiple sclerosis. Arch Neurol. 45: ) Filippi M, Rocca MA, Colombo B, Falini A, Codella M, Scotti G, Comi G. (2002) Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis. Neuroimage 15: ) De Luca J, Genova HM, Hillary FG, Wylie G (2008) Neural correlates of cognitive fatigue in multiple sclerosis using functional MRI. Journal Neurol Sci 270: ) Tartaglia MC, Narayanan S, Arnold DL (2008) Mental fatigue alters the pattern and increase the volume of cerebral activation required for a motor task in multiple sclerosis patients with fatigue. Eur J Neurol 15: Page 8 of 9

9 5) Rocca MA, Filippi M (2007) Functional MRI in multiple sclerosis. J neuroimaging 17: 36S-41S. 6) Lee M, Reddy H, Johansen-Berg H, Pendlebury S, Jenkinson M, Smith S, Palace J, Matthews PM (2000) The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis. Ann Neuro 47: ) Carey LM, Seitz RJ: Functional neuroimaging in stroke recovery and neurorehabilitation: conceptual issues and perspectives (2007) Int J Stroke 2: Personal Information Maja Ukmar, MD Department of Radiology University of Trieste Italy majaukmar@alice.it Page 9 of 9