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

BACKGROUND AND PURPOSE: 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). METHODS: 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, FMp, 30=normal) were assessed prior to and immediately after training. RESULTS: At baseline, patients exhibited moderate-to-mild arm impairment (FM, 47.2 ± 18.8, FMp, 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 FMp (r=0.93, p=0.03), suggesting that patients who show greater neuronal changes have a better chance of recovery. CONCLUSIONS: 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.

Ipsilateral primary motor cortex and behavioral compensation after stroke: a case series study.

Arm motor recovery after stroke is mainly attributed to reorganization of the primary motor cortex (M1). While M1 contralateral to the paretic arm (cM1) is critical for recovery, the role of ipsilateral M1 (iM1) is still inconclusive. Whether iM1 activity is related to recovery, behavioral compensation, or both is still far from settled. We hypothesized that the magnitude of iM1 activity in chronic stroke survivors will increase or decrease in direct proportion to the degree that movements of the paretic arm are compensated. Movement kinematics (VICON, Oxford Metrics) and functional MRI data (3T MR system) were collected in 11 patients before and after a 4-week training designed to improve motor control of the paretic arm and decrease compensatory trunk recruitment. Twelve matched controls underwent similar evaluations and training. Relationships between iM1 activity and trunk motion were analyzed. At baseline, patients exhibited increased iM1 activity (p = 0.001) and relied more on trunk movement (p = 0.02) than controls. These two variables were directly and significantly related in patients (r = 0.74, p = 0.01) but not in controls (r = 0.28, p = 0.4). After training, patients displayed a significant reduction in iM1 activity (p = 0.008) and a trend toward decreased trunk use (p = 0.1). The relationship between these two variables remained significant (r = 0.66, p = 0.03) and different from controls (r = 0.26, p = 0.4). Our preliminary results suggest that iM1 may play a role in compensating for brain damage rather than directly gaining control of the paretic arm. However, we recommend caution in interpreting these results until more work is completed.

Post-stroke motor recovery and cortical organization following Constraint-Induced Movement Therapies: a literature review.

[Purpose] This review synthesizes findings from studies on two forms of Constraint-Induced Movement Therapies: the original Constraint-Induced Movement Therapy and the modified Constraint-Induced Movement Therapy, in adult stroke patients including the evidence, current limitations and future directions. [Methods] We critically reviewed studies evaluating the effectiveness of Constraint-Induced Movement Therapies in chronic stoke focusing on the functional (i.e. motor recovery) and the neural (i.e. cortical organization) levels. [Results] Constraint-Induced Movement Therapies seemed to improve the upper limb functional usage in chronic stoke with no reliable neurophysiological underlying mechanisms. The Motor Activity Log was the common outcome measuring motor recovery. The work that has been done on modified Constraint-Induced Movement Therapy was far less than the work done on the original Constraint-Induced Movement Therapy. [Conclusion] Evident lack of understanding of the association between changes in motor recovery and the underlying neural mechanisms in-terms of measures of assessing and defining functional recovery (i.e Motor Activity Log) that lacks sufficient sensitivity to characterize changes in movement strategies and thereby lack of distinction between recovery and behavioral compensation. Future studies should employ using kinematic metrics to quantify and explain the training-related changes in behavior following Constraint-Induced Movement Therapies in chronic stroke.

The evidence for prolonged muscle stretching in ankle joint management in upper motor neuron lesions: considerations for rehabilitation - a systematic review.

BACKGROUND: As clinicians, muscles stretching approaches are one of the most commonly used interventions in rehabilitation. However, there is a need for an in-depth evaluation of research on prolonged stretching in terms of the features of the stretching approaches, such as duration and frequency, as well as the compatible measures of a successful stretching approach. OBJECTIVE: This review is an effort to synthesize findings from studies on "prolonged" stretching approaches in patients with UMNs including stroke, spinal cord injuries, and traumatic brain injuries. We investigated the compatible features of successful stretching regimens in terms of reducing spasticity, improving the Active Range of Motion (AROM), Passive Range of Motion (PROM), and gait training of spastic patient with upper motor neuron lesions. METHODS: Studies evaluating the effectiveness of "prolonged" stretching on spastic ankle planterflexor muscles and its complications were critically reviewed, and the level of evidence was analyzed. RESULTS: There is a sufficient level of evidence to support the use of stretching as and effective techniques in rehabilitation. However, more research is yet to be done to objectively examine the ideal parameters of a successful stretching approach using functional assessments, such as walking, speed, walking capacity, and balance. CONCLUSION: The review adds stronger understanding with regard to stretching considerations in rehabilitation following UMNs. The ideal approach, as well as the functional implications on motor performance are yet to be further studied.

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.

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.

Age-related changes in vestibular evoked myogenic potentials using a modified blood pressure manometer feedback method.

PURPOSE: To collect age-specific vestibular evoked myogenic potential (VEMP) data and to characterize age-related differences in VEMP parameters using a modified blood pressure manometer (BPM) method of sternocleidomastoid (SCM) muscle monitoring. METHODS: VEMPs were recorded on healthy adults ranging in age from 23 to 84 years with no history of dizziness, neuromuscular pathologies, or cervical complaints. Participants were assigned to 3 groups using a nonprobability static group assignment based on their age. VEMP P1 and N1 latency, threshold, peak-to-peak amplitude, and interamplitude difference (IAD) ratios were obtained at 130 dB SPL. RESULTS: Statistical differences were detected in peak-to-peak mean amplitude and threshold measures among groups. Post hoc analysis revealed that differences shown were between the young group and both older groups. No significant differences were noted in P1 and N1 latencies or IAD ratios. CONCLUSIONS: This study confirmed a significant decline in VEMP amplitude and increase in VEMP thresholds in healthy older persons. Normative age-related data may be necessary to properly interpret VEMP recordings in a clinical setting when evaluating aging populations. The BPM method utilized for controlling SCM muscle may be a valuable alternative to control SCM muscle contraction when electromyography equipment is not available.