Positive Effect of Impairment-Oriented Training on N-Acetylaspartate Levels of Ipsilesional Motor Cortex in Subcortical Stroke: A Case Study.

Abstract

BACKGROUND AND PURPOSE We investigated the effects of an intensive impairment-oriented training on neuronal state (assessed by proton MR spectroscopy, 1H-MRS) of the spared motor and premotor cortices in the injured (ipsilesional) hemisphere and clinical impairment in a patient with chronic subcortical stroke. METHODS One survivor of a single ischemic stroke located outside of the motor and premotor cortices (assessed on T1-weighted MRI) was studied at six months after stroke. We used functional MRI-guided 1H-MRS to quantify the levels of N-acetylaspartate (NAA - a putative neuronal marker) in the hand representation within ipsilesional primary motor cortex (M1), dorsal premotor cortex (dPM) and supplementary motor area (SMA), and Fugl-Meyer (normal=66 points) test to assess the arm motor impairment immediately before and after a motor training paradigm. Training comprised intensive variable practice (1080 repetitions over 12 day-period) of a reach-to-grasp task with the impaired hand while focusing the learner's attention on an altered movement component, i.e., decreased elbow extension. RESULTS At baseline, the patient was severely impaired (Fugl-Meyer score=25 points) and exhibited lower level of NAA in all areas (M1, 9.2 mM vs. 11.6 ± 2.0 mM in healthy controls; dPM, 8.9 mM vs. 12.2 ± 1.9 mM; SMA, 7.4 mM vs. 11.0 ± 2.3 mM). After training, the patient improved clinically (by 6 points) and displayed higher levels of NAA across all areas (by 0.6-3.3 mM). CONCLUSIONS Our data demonstrated that the radiologically normal-appearing ipsilesional motor and premotor areas have the resources to boost behavioral output in response to an intervention. We hope that these data will act as a starting point for further research to test the potential of 1H-MRS measures to provide a biomarker of neuroplasticity in response to restorative therapies in chronic stroke.