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From the MS Research Unit (Drs. Blinkenberg, Rune, Ravnborg, and Sørensen) and Neurobiology Research Unit (Drs. Blinkenberg and Paulson, and S. Kyllingsbæk), Departments of Neurology, Neurophysiology (Dr. Ravnborg), Nuclear Medicine (Dr. Holm), Copenhagen University Hospital; the Danish Research Center of Magnetic Resonance (Drs. Jensen and Paulson), Copenhagen University Hospital; the Department of Neurology (Dr. Rune), Næstved County Hospital; and the Department of Psychology (S. Kyllingsbæk), University of Copenhagen, Denmark.
Address correspondence and reprint requests to Dr. Morten Blinkenberg, Neurobiology Research Unit 9201, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.
OBJECTIVE: To study the association between the cortical cerebral metabolic rate of glucose (CMRglc), MRI T2-weighted total lesion area (TLA), cognitive dysfunction, and neurologic disability in MS.
BACKGROUND: MRI lesion load is widely used in the clinical evaluation of the MS patient but little is known about the associated changes in cortical activation.
METHODS: Twenty-three patients with clinically definite MS underwent measurements of CMRglc, TLA, motor evoked potentials (MEPs), and cognitive and neurologic disability. CMRglc was calculated using PET and 18-F-deoxyglucose and compared with nine normal control subjects.
RESULTS: Reductions in CMRglc (p < 0.01) were found in the cortical global and regional lobar measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus, and hippocampus. Global cortical CMRglc correlated with TLA (Spearman rank correlation coefficient [SRCC] = -0.66, p = 0.001), and rCMRglc correlated with regional lesion load in all cerebral lobes (p 
0.05). Global cortical CMRglc and cognitive disability also correlated (SRCC = 0.58, p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the right thalamus and cognitive performance as well as TLA. There was no correlation between CMRglc and neurologic disability (Expanded Disability Status Scale) or MEP.
CONCLUSION: Global and regional cortical CMRglc is reduced significantly in MS patients compared with normal control subjects. Furthermore, the CMRglc reductions correlate with TLA as well as with cognitive dysfunction, which indicates that MRI white matter lesion burden has a deteriorating effect on cortical cerebral neural function.
Key words: MS—PET—MRI—Cognitive dysfunction—Disability—Motor evoked potential
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