REDUCED GLUCOSE-METABOLISM IN THE FRONTAL-CORTEX AND BASAL GANGLIA OFMULTIPLE-SCLEROSIS PATIENTS WITH FATIGUE - A F-18 FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY STUDY

To investigate the pathophysiology of fatigue in MS, we assessed cereb ral glucose metabolism (CMRGlu) in 47 MS patients using PET and F-18-f luorodeoxyglucose. Applying the Fatigue Severity Scale (FSS), we first compared MS patients with severe fatigue (MS-FAT, n = 19, FSS > 4.9) and MS patients without fatigue (MS-NOF, n = 16, FSS < 3.7) on a pixel -by-pixel basis using Statistical Parametric Mapping (SPM95). Second, we compared FSS values of all 47 patients covering the whole range of this scale with CMRGlu using an analysis of covariance (SPM95). In add ition, we determined global CMRGlu by region-of-interest analysis. Six teen healthy subjects served as control subjects (CON). Global CMRGlu was significantly lower in both MS groups compared with CON (CON 43.3 +/- 6.9 mu mol/100 mL/min, MS-FAT 34.7 +/- 4.4, MS-NOF 35.4 +/- 4.5) b ut was not related to fatigue severity. Comparing the two MS groups, S PM95 analysis revealed predominant CMRGlu reductions bilaterally in a prefrontal area involving the lateral and medial prefrontal cortex and adjacent white matter, in the premotor cortex, putamen, and in the ri ght supplementary motor area of MS-FAT. In addition, there were CMRGlu reductions in the white matter extending from the rostral putamen tow ard the lateral head of the caudate nucleus. FSS values were inversely related to CMRGlu in the light prefrontal cortex. CMRGlu in the cereb ellar vermis and anterior cingulate was relatively higher in MS-FAT th an in MS-NOF patients. CMRGlu of both regions showed positive correlat ions with FSS values. Our data suggest that fatigue in MS is associate d with frontal cortex and basal ganglia dysfunction that could result from demyelination of the frontal white matter.