Primary motor cortex in stroke: a functional MRI-guided proton MR spectroscopic study.

BACKGROUND AND PURPOSE: Our goal was to investigate whether certain metabolites, specific to neurons, glial cells, or the neuronal-glial neurotransmission system, in primary motor cortices (M1), are altered and correlated with clinical motor severity in chronic stroke. METHODS: Fourteen survivors of a single ischemic stroke located outside the M1 and 14 age-matched healthy control subjects were included. At >6 months after stroke, N-acetylaspartate, myo-inositol, and glutamate/glutamine were measured using proton magnetic resonance spectroscopic imaging (in-plane resolution=5×5 mm(2)) in radiologically normal-appearing gray matter of the hand representation area, identified by functional MRI, in each M1. Metabolite concentrations and analyses of metabolite correlations within M1 were determined. Relationships between metabolite concentrations and arm motor impairment were also evaluated. RESULTS: The stroke survivors showed lower N-acetylaspartate and higher myo-inositol across ipsilesional and contralesional M1 compared with control subjects. Significant correlations between N-acetylaspartate and glutamate/glutamine were found in either M1. Ipsilesional N-acetylaspartate and glutamate/glutamine were positively correlated with arm motor impairment and contralesional N-acetylaspartate with time after stroke. CONCLUSIONS: Our preliminary data demonstrated significant alterations of neuronal-glial interactions in spared M1 with the ipsilesional alterations related to stroke severity and contralesional alterations to stroke duration. Thus, MR spectroscopy might be a sensitive method to quantify relevant metabolite changes after stroke and consequently increase our knowledge of the factors leading from these changes in spared motor cortex to motor impairment after stroke.

Pre-therapy Neural State of Bilateral Motor and Premotor Cortices Predicts Therapy Gain After Subcortical Stroke: A Pilot Study.

OBJECTIVE: The aim of the study was to examine whether neural state of spared motor and premotor cortices captured before a therapy predicts therapy-related motor gains in chronic subcortical stroke. DESIGN: Ten survivors, presenting chronic moderate upper limb impairment, underwent proton magnetic resonance spectroscopy, magnetic resonance imaging, clinical, and kinematics assessments before a 4-wk impairment-oriented training. Clinical/kinematics assessments were repeated after therapy, and motor gain was defined as positive values of clinical upper limb/elbow motion changes and negative values of trunk motion changes. Candidate predictors were N-acetylaspartate-neuronal marker, glutamate-glutamine-indicator of glutamatergic neurotransmission, and myo-inositol-glial marker, measured bilaterally within the upper limb territory in motor and premotor (premotor cortex, supplementary motor area) cortices. Traditional predictors (age, stroke length, pre-therapy upper limb clinical impairment, infarct volume) were also investigated. RESULTS: Poor motor gain was associated with lower glutamate-glutamine levels in ipsilesional primary motor cortex and premotor cortex (r = 0.77, P = 0.01 and r = 0.78, P = 0.008, respectively), lower N-acetylaspartate in ipsilesional premotor cortex (r = 0.69, P = 0.02), higher glutamate-glutamine in contralesional primary motor cortex (r = -0.68, P = 0.03), and lower glutamate-glutamine in contralesional supplementary motor area (r = 0.64, P = 0.04). These predictors outperformed myo-inositol metrics and traditional predictors (P ≈ 0.05-1.0). CONCLUSIONS: Glutamatergic state of bilateral motor and premotor cortices and neuronal state of ipsilesional premotor cortex may be important for predicting motor outcome in the context of a restorative therapy.

Remote motor system metabolic profile and surgery outcome in cervical spondylotic myelopathy.

OBJECTIVE In patients with cervical spondylotic myelopathy (CSM), the motor system may undergo progressive functional/structural changes rostral to the lesion, and these changes may be associated with clinical disability. The extent to which these changes have a prognostic value in the clinical recovery after surgical treatment is not yet known. In this study, magnetic resonance spectroscopy (MRS) was used to test 2 primary hypotheses. 1) Based on evidence of corticospinal and spinocerebellar, rubro-, or reticulospinal tract degeneration/dysfunction during chronic spinal cord compression, the authors hypothesized that the metabolic profile of the primary motor cortices (M1s) and cerebellum, respectively, would be altered in patients with CSM, and these alterations would be associated with the extent of the neurological disabilities. 2) Considering that damage and/or plasticity in the remote motor system may contribute to clinical recovery, they hypothesized that M1 and cerebellar metabolic profiles would predict, at least in part, surgical outcome. METHODS The metabolic profile, consisting of N-acetylaspartate (NAA; marker of neuronal integrity), myoinositol (glial marker), choline (cell membrane synthesis and turnover), and glutamate-glutamine (glutamatergic system), of the M1 hand/arm territory in each hemisphere and the cerebellum vermis was investigated prior to surgery in 21 patients exhibiting weakness of the upper extremities and/or gait abnormalities. Age- and sex-matched controls (n = 16) were also evaluated to estimate the pre-CSM metabolic profile of these areas. Correlation and regression analyses were performed between preoperative metabolite levels and clinical status 6 months after surgery. RESULTS Relative to controls, patients exhibited significantly higher levels of choline but no difference in the levels of other metabolites across M1s. Cerebellar metabolite levels were indistinguishable from control levels. Certain metabolites-myo-inositol and choline across M1s, NAA and glutamate-glutamine in the left M1, and myo-inositol and glutamate-glutamine in the cerebellum-were significantly associated with postoperative clinical status. These associations were greatly improved by including preoperative clinical metrics into the models. Likewise, these models improved the predictive value of preoperative clinical metrics alone. CONCLUSIONS These preliminary findings demonstrate relationships between the preoperative metabolic profiles of two remote motor areas and surgical outcome in CSM patients. Including preoperative clinical metrics in the models significantly strengthened the predictive value. Although further studies are needed, this investigation provides an important starting point to understand how the changes upstream from the injury may influence the effect of spinal cord decompression.

Handgrip-Related Activation in the Primary Motor Cortex Relates to Underlying Neuronal Metabolism After Stroke.

BACKGROUND: Abnormal task-related activation in primary motor cortices (M1) has been consistently found in functional imaging studies of subcortical stroke. Whether the abnormal activations are associated with neuronal alterations in the same or homologous area is not known. OBJECTIVE: Our goal was to establish the relationships between M1 measures of motor-task-related activation and a neuronal marker, N-acetylaspartate (NAA), in patients with severe to mild hemiparesis. METHODS: A total of 18 survivors of an ischemic subcortical stroke (confirmed on T2-weighted images) at more than six months post-onset and 16 age- and sex-matched right-handed healthy controls underwent functional MRI during a handgrip task (impaired hand in patients, dominant hand in controls) and proton magnetic resonance spectroscopy ((1)H-MRS) imaging. Spatial extent and magnitude of blood oxygen level-dependent response (or activation) and NAA levels were measured in each M1. Relationships between activation and NAA were determined. RESULTS: Compared with controls, patients had a greater extent of contralesional (ipsilateral to impaired hand, P < .001) activation and a higher magnitude of activation and lower NAA in both ipsilesional (P = .008 and P < .001, respectively) and contralesional (P < .0001, P < .05) M1. There were significant negative correlations between extent of activation and NAA in each M1 (P = .02) and a trend between contralesional activation and ipsilesional NAA (P = .08) in patients but not in controls. CONCLUSIONS: Our results suggest that after stroke greater neuronal recruitment could be a compensatory response to lower neuronal metabolism. Thus, dual-modality imaging may be a powerful tool for providing complementary probes of post-stroke brain reorganization.

Motor and premotor cortices in subcortical stroke: proton magnetic resonance spectroscopy measures and arm motor impairment.

BACKGROUND: Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies. OBJECTIVE: We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand representation in bilateral motor and premotor areas and correlated with distal and proximal arm motor impairment in hemiparetic persons. METHODS: In 20 participants at >6 months postonset of a subcortical ischemic stroke and 16 age- and sex-matched healthy controls, the concentrations of N-acetylaspartate and myo-inositol were quantified by proton magnetic resonance spectroscopy. Regions of interest identified by functional magnetic resonance imaging included primary (M1), dorsal premotor (PMd), and supplementary (SMA) motor areas. Relationships between metabolite concentrations and distal (hand) and proximal (shoulder/elbow) motor impairment using Fugl-Meyer Upper Extremity (FMUE) subscores were explored. RESULTS: N-Acetylaspartate was lower in M1 (P = .04) and SMA (P = .004) and myo-inositol was higher in M1 (P = .003) and PMd (P = .03) in the injured (ipsilesional) hemisphere after stroke compared with the left hemisphere in controls. N-Acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (P = .04). Significant positive correlations were also found between N-acetylaspartate in ipsilesional M1, PMd, and SMA and in contralesional M1 and shoulder/elbow FMUE subscores (P = .02, .01, .02, and .02, respectively). CONCLUSIONS: Our preliminary results demonstrated that proton magnetic resonance spectroscopy is a sensitive method to quantify relevant neuronal changes in spared motor cortex after stroke and consequently increase our knowledge of the factors leading from these changes to arm motor impairment.

Altered neurochemical profile after traumatic brain injury: (1)H-MRS biomarkers of pathological mechanisms.

Specific neurochemicals measured with proton magnetic resonance spectroscopy ((1)H-MRS) may serve as biomarkers of pathological mechanism in the brain. We used high field in vivo (1)H-MRS to measure a detailed neurochemical profile after experimental traumatic brain injury (TBI) in rats. We characterized neurochemical changes in the contused cortex and the normal-appearing perilesional hippocampus over a time course from 1 hour to 2 weeks after injury. We found significant changes in 19 out of 20 neurochemicals in the cortex, and 9 out of 20 neurochemicals in the hippocampus. These changes provide evidence of altered cellular metabolic status after TBI, with specific compounds proposed to reflect edema, excitotoxicity, neuronal and glial integrity, mitochondrial status and bioenergetics, oxidative stress, inflammation, and cell membrane disruption. Our results support the utility of (1)H-MRS for monitoring cellular mechanisms of TBI pathology in animal models, and the potential of this approach for preclinical evaluation of novel therapies.

Neuronal-glial alterations in non-primary motor areas in chronic subcortical stroke.

Whether functional changes of the non-primary motor areas, e.g., dorsal premotor (PMd) and supplementary motor (SMA) areas, after stroke, reflect reorganization phenomena or recruitment of a pre-existing motor network remains to be clarified. We hypothesized that cellular changes in these areas would be consistent with their involvement in post-stroke reorganization. Specifically, we expected that neuronal and glial compartments would be altered in radiologically normal-appearing, i.e., spared, PMd and SMA in patients with arm paresis. Twenty survivors of a single ischemic subcortical stroke and 16 age-matched healthy controls were included. At more than six months after stroke, metabolites related to neuronal and glial compartments: N-acetylaspartate, myo-inositol, and glutamate/glutamine, were quantified by proton magnetic resonance spectroscopy in PMd and SMA in both injured (ipsilesional) and un-injured (contralesional) hemispheres. Correlations between metabolites were also calculated. Finally, relationships between metabolite concentrations and arm motor impairment (total and proximal Fugl-Meyer Upper Extremity, FMUE, scores) were analyzed. Compared to controls, stroke survivors showed significantly higher ipsilesional PMd myo-inositol and lower SMA N-acetylaspartate. Significantly lower metabolite correlations were found between ipsilesional and contralesional SMA. Ipsilesional N-acetylaspartate was significantly related to proximal FMUE scores. This study provides evidence of abnormalities in metabolites, specific to neuronal and glial compartments, across spared non-primary motor areas. Ipsilesional alterations were related to proximal arm motor impairment. Our results suggest the involvement of these areas in post-stroke reorganization.