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Alertness dysfunction in MS: structural lesions and functional consequences
Introduction: Recent studies have shown that both grey and white matter lesions contribute to mental dysfunction in MS. The relation between lesion localization and its functional consequences however has not yet been clarified.
Methods: Twenty-two MS patients recruited in two different sites participated in this study. All patients were investigated with a computerized alertness task. MRI data acquisition included T1 and T2 weighted images in all patients. MRI lesion analysis was performed using different methods. In the first site, 12 patients were classified according to an in-house routine (Bochum-Langendreer) with the following categorization: 0=no cerebral lesions; I=single lesions, <12, supratentorial; II=multiple discrete lesions, >12; III=confluent lesions, brain atrophy, ventricular enlargement. In the second site, total T2 lesion load of 10 patients was defined. In addition, T2 lesion volumes were calculated separately for periventricular and cortical/subcortical areas and also calculated for ROI's using the Talairach Reference System and 3D graphic reconstruction to define locations of lesions in frontal, parietal, temporal, and occipital areas. This second group was additionally studied by fMRI while performing the alertness paradigm. SPM2 software package was used for analyses of functional data sets.
Results: Non-parametric analysis revealed for both independently applied approaches, that patients with low alertness performance had higher total and periventricular lesion load compared to good performers. In addition, low performers showed significantly larger lesion volumes in parietal, temporal, and occipital brain regions when compared to high performers while lesions especially in orbitofrontal regions were less frequent. FMRI analyses revealed that patients with high periventricular T2 lesion load showed less recruitment of additional brain regions than patients with low lesion load.
Discussion: Our results, confirmed by two independent methods, support the hypothesis that deficits in alertness are related to extensive lesion distribution. Besides, lesions in periventricular, parietal, temporal, and occipital brain regions correlate strongest with low alertness performance. Moreover, our findings show that in the absence of extensive periventricular lesions, patients are able to recruit additional brain areas while patients with extensive lesion distribution do not.