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.

Reliability of quantitative magnetic resonance imaging methods in the assessment of spinal canal stenosis and cord compression in cervical myelopathy.

STUDY DESIGN: Prospective, blinded reliability study of quantitative magnetic resonance imaging (MRI) measures in patients with cervical myelopathy. OBJECTIVE: To assess the intra- and interobserver reliability of commonly used quantitative MRI measures such as transverse area (TA) of spinal cord, compression ratio (CR), maximum canal compromise (MCC), and maximum spinal cord compression (MSCC). SUMMARY OF BACKGROUND DATA: There is no consensus on an optimal quantitative MRI method(s) in assessing canal stenosis and cord compression. METHODS: Seven surgeons performed measurements on 17 digital MR images, on 4 separate occasions. The degree of stenosis was evaluated by measuring TA and CR on axial T2, MCC, and MSCC on midsagittal T1- and T2-weighted MRI sequences, respectively. Statistical analyses included repeated-measures analysis of variance and intraclass correlation coefficients (ICCs). RESULTS: The mean ± SD for intraobserver ICC was 0.88 ± 0.1 for MCC, 0.76 ± 0.08 for MSCC, 0.92 ± 0.07 for TA, and 0.82 ± 0.13 for CR. In addition, the interobserver ICC was 0.75 ± 0.04 for MCC, 0.79 ± 0.09 for MSCC, 0.80 ± 0.05 for CR, and 0.86 ± 0.03 for TA. Higher degree of canal compromise (MCC) was associated with lower modified version of Japanese Orthopaedic Association Scale score (P = 0.05). Also, a strong association was found between MSCC and lower modified version of Japanese Orthopaedic Association Scale score, greater number of steps, and longer walking time (P < 0.05). CONCLUSION: All 4 measurement techniques demonstrated a good to moderately high degree of intra- and interobserver reliability. Highest reliability was noted in the assessment of T2-weighted sequences and axial MRI. Our results show that the measurements of MCC, MSCC, and CR are sufficiently reliable and correlate well with clinical severity of cervical myelopathy.

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.

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.

Accuracy and reliability of MRI quantitative measurements to assess spinal cord compression in cervical spondylotic myelopathy: a prospective study.

STUDY TYPE: Reliability study Introduction: Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder in persons more than 55 years old. Despite multiple neuroimaging approaches proposed to quantify the spinal cord compromise in CSM patients, magnetic resonance imaging (MRI) remains the procedure of choice by providing helpful information for clinical decision making, determining optimal subpopulations for treatment, and selecting the optimal treatment strategies. However, the validity, reliability, and accuracy of the MRI quantitative measurements have not yet been addressed. OBJECTIVE: To assess the intra- and inter-observer reliability of MRI quantitative measurements of the spinal cord compromise in CSM patients. METHODS: Seventeen CSM patients (13 male) of mean age 54.5 years old were selected from the AOSpine North America database. The patients had different combinations of stenotic levels (1-4 levels) and the clinical severity (range mJOA baseline: 8-18). Asymptomatic or previous surgically treated CSM, active infection, neoplastic disease, rheumatoid arthritis, ankylosing spondylitis, trauma, or concomitant lumbar stenosis were excluded. The patients underwent preoperative MRI using 1.5T (15 patients) and 3T (two patients) scanner, including mid-sagittal T1-weighted, axial and mid-sagittal T2-weighted series. MRI data were analyzed (Mango 2.0 software; Multi-Image Analysis GUI) by four blind raters in three different sessions. Four measurements were analysed: transverse area (TA) (Figure 1), compression ratio (CR) (Figure 2), maximal canal compromise (MCC), and maximal spinal cord compression (MSCC) (Figure 3). The differences for each measurement were evaluated using mixed-effect ANOVA models (ratter, session, ratter x session). The intra- and inter-rater reliability was evaluated with intraclass correlation coefficients (ICC) (Figure 4). Figure 1 Transverse area (TA)Figure 2 Compression ratio (CR = AP/W)Figure 3 Maximal canal compromise (MCC), and maximal spinal cord compression (MSCC). MCC(%) = 1-[Dx/(Da+Db)/2] × 100%; MSCC(%) = 1-[dx/(da+db)/2] × 100%Figure 4 Intraclass correlation coefficients (ICC) Results: The principal findings were: (i) for TA (71.48 ± 12.99mm2), the intra-rater agreement was 0.97 (95% CI, range 0.94-0.99) and the inter-rater agreement was 0.76 (95% CI, range 0.49-0.90); (ii) for CR (0.35 ± 0.04%), 0.94 (95% CI, range 0.88-0.98), and 0.79 (95% CI, range 0.57-0.91) respectively; (iii) for MCC (83.21 ± 2.08%), 0.95 (95% CI, range 0.89-0.98), and 0.64 (95% CI, range 0.28-0.85) respectively; and (iv) for MSCC (82.87 ± 1.52%), 0.93 (95% CI, range 0.86-0.97), and 0.84 (95% CI, range 0.65-0.93) respectively. CONCLUSIONS: Our data suggest that three out of four measurements (TA, CR and MSCC) have acceptable intra- and interreliability coefficients (ICC > 0.75). However, for the maximal canal compromise measure, although the intrareliability was acceptable, the inter-rater reliability was not acceptable (0.64). Based on this study, we recommend that three MRI measures: transverse area, compression ratio and maximal spinal cord compression should be used in the imaging assessment of the spinal cord in CSM patients.