Brain plasticity in the motor network is correlated with disease progression in amyotrophic lateral sclerosis

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To test the influence of functional cerebral reorganization in amyotrophic lateral sclerosis (ALS) on disease progression. Nineteen predominantly right-handed ALS patients and 21 controls underwent clinical evaluation, functional Magnetic Resonance Imaging (fMRI), and diffusion tensor imaging. Patients were clinically re-evaluated 1 year later and followed until death. For fMRI, subjects executed and imagined a simple hand-motor task. Between-group comparisons were performed, and correlations were searched with motor deficit arm Medical Research Council (MRC) score, disease progression ALS Functional Rating Scale (ALSFRS), and survival time. By the MRC score, the hand strength was lowered by 12% in the ALS group predominating on the right side in accordance with an abnormal fractional anisotropy (FA) limited to the left corticospinal tract (37.3% reduction vs. controls P < 0.01). Compared to controls, patients displayed overactivations in the controlateral parietal (P < 0.004) and somatosensory (P < 0.004) cortex and in the ipsilateral parietal (P < 0.01) and somatosensory (P < 0.01) cortex to right-hand movement. Movement imagination gave similar results while no difference occurred with left-hand tasks. Stepwise regression analysis corrected for multiple comparisons showed that controlateral parietal activity was inversely correlated with disease progression (R(2) = 0.43, P = 0.001) and ipsilateral somatosensory activations with the severity of the right-arm deficit (R(2) = 0.48, P = 0.001). Cortical Blood Oxygen Level Dependent (BOLD) signal changes occur in the brain of ALS patients during a simple hand-motor task when the motor deficit is still moderate. It is correlated with the rate of disease progression suggesting that brain functional rearrangement in ALS may have prognostic implications.