N-Acetylaspartate Biomarker of Stroke Recovery: A Case Series Study

Strong experimental neurobehavioral evidence suggests that intensive training improves arm motor disability after stroke. Yet, we still have only limited understanding why some patients recover more completely and others do not. This is in part due to our limited knowledge of the neurobiological principles of recovery from stroke. Mounting evidence suggests that functional and structural remapping of the primary motor cortex (M1) plays a major role in arm recovery after stroke. We used MR Spectroscopy to test the hypothesis that therapy-related arm improvement is associated with changes in levels of a putative marker of neuronal integrity (N-acetylaspartate, NAA) in M1 controlling the paretic arm (ipsilesional M1) in chronic stroke patients (n=5).

Patients (1 female, age, mean ± SD, 58.4 ± 5.8 years) underwent 4-week arm-focused motor training (1080 repetitions of a reach-to-grasp task) at 13.6 ± 5.3 months after stroke onset. NAA levels in the ipsilesional M1 and arm impairment (Fugl-Meyer, FM, 66=normal; proximal FM, FM_p, 30=normal) were assessed prior to and immediately after training.

At baseline, patients exhibited moderate-to-mild arm impairment (FM, 47.2 ± 18.8, FM_p, 22.2 ± 8.6) and showed lower levels of NAA compared with age/sex-matched healthy controls (10.2 ± 0.9 mM in patients vs. 11.6 ± 1.6 mM in controls, p=0.03). After training, arm impairment improved (FM by 7%, 50.6 ± 17.5, p=0.01; FMp, by 5%, 23.4 ± 8.2, p=0.2) and NAA levels increased by 10.5% (11.2 ± 1.2 mM, p=0.1). Changes in NAA positively correlated with changes in FM (r=0.63, p=0.2) and FM_p (r=0.93, p=0.03), suggesting that patients who show greater neuronal changes have a better chance of recovery.

Our data suggest the potential use of M1 NAA as a biomarker of motor recovery after stroke. However, because of our small sample, these preliminary results should be interpreted cautiously. Further work with larger sample sizes is warranted.