Glutamate weighted imaging contrast in gliomas with 7 Tesla magnetic resonance imaging.

INTRODUCTION: Diffuse gliomas are incurable malignancies, which undergo inevitable progression and are associated with seizure in 50-90% of cases. Glutamate has the potential to be an important glioma biomarker of survival and local epileptogenicity if it can be accurately quantified noninvasively. METHODS: We applied the glutamate-weighted imaging method GluCEST (glutamate chemical exchange saturation transfer) and single voxel MRS (magnetic resonance spectroscopy) at 7 Telsa (7 T) to patients with gliomas. GluCEST contrast and MRS metabolite concentrations were quantified within the tumour region and peritumoural rim. Clinical variables of tumour aggressiveness (prior adjuvant therapy and previous radiological progression) and epilepsy (any prior seizures, seizure in last month and drug refractory epilepsy) were correlated with respective glutamate concentrations. Images were separated into post-hoc determined patterns and clinical variables were compared across patterns. RESULTS: Ten adult patients with a histo-molecular (n = 9) or radiological (n = 1) diagnosis of grade II-III diffuse glioma were recruited, 40.3 +/- 12.3 years. Increased tumour GluCEST contrast was associated with prior adjuvant therapy (p = .001), and increased peritumoural GluCEST contrast was associated with both recent seizures (p = .038) and drug refractory epilepsy (p = .029). We distinguished two unique GluCEST contrast patterns with distinct clinical and radiological features. MRS glutamate correlated with GluCEST contrast within the peritumoural voxel (R = 0.89, p = .003) and a positive trend existed in the tumour voxel (R = 0.65, p = .113). CONCLUSION: This study supports the role of glutamate in diffuse glioma biology. It further implicates elevated peritumoural glutamate in epileptogenesis and altered tumour glutamate homeostasis in glioma aggressiveness. Given the ability to non-invasively visualise and quantify glutamate, our findings raise the prospect of 7 T GluCEST selecting patients for individualised therapies directed at the glutamate pathway. Larger studies with prospective follow-up are required.

Stochastic resonance stimulation for upper limb rehabilitation poststroke.

OBJECTIVES: Previous studies have shown that subthreshold electrical or mechanical noise can reduce the sensory threshold and impart short-term improvements in sensorimotor function. We undertook this study to examine the effects of combined subsensory electrical and vibratory stimulation in conjunction with exercise training on long-term motor performance. DESIGN: Thirty subjects were recruited from adult community-dwelling stroke survivors with residual hemiparesis. Subjects were screened for residual motor ability using a functional task, and those who functioned below this level were excluded. All subjects had a history of a single unilateral ischemic or hemorrhagic stroke at least 6 mos before study entry and were not actively receiving occupational or physical therapy. Subjects were stratified by baseline upper extremity Fugl-Meyer (UEFM) (more impaired [28-35] and less impaired [36-55]) and were randomized to one of two groups: treatment (stochastic resonance stimulation [plus over minus sign] exercise: 15 subjects) and control (sham stimulation [plus over minus sign] exercise: 15 subjects). RESULTS: No significant difference was found between the stochastic resonance treatment and control group in the UEFM or in any of the secondary measures. The combined group showed modest improvements in UEFM from baseline to completion of therapy (mean improvement, 2.6 points) (P = 0.004); however, these improvements declined by 1-mo follow-up to 1.5 points (P = 0.055). No change in sensory function was detectable. CONCLUSIONS: Stochastic resonance therapy combined with occupational therapy was no more effective than occupational therapy alone in restoring sensorimotor performance. Other stochastic resonance stimulation montages or protocols might prove more effective.

Correlated change in upper limb function and motor cortex activation after verum and sham acupuncture in patients with chronic stroke.

BACKGROUND: Acupuncture may improve motor function in patients with chronic hemiparetic stroke, yet the neural mechanisms underlying such an effect are unknown. As part of a sham-controlled, randomized clinical trial testing the efficacy of a 10-week acupuncture protocol in patients with chronic hemiparetic stroke, we examined the relationship between changes in function of the affected upper limb and brain activation using functional magnetic resonance imaging (fMRI). METHODS: Seven (7) chronic hemiparetic stroke patients underwent fMRI and testing of function of the affected upper limb (spasticity and range-of-motion) before and after a 10-week period of verum (N=4) or sham (N=3) acupuncture. The correlation between changes in function of the affected upper limb and brain activation after treatment was tested across patients. RESULTS: We found a significant positive correlation between changes in function of the affected upper limb (spasticity and range of motion) and activation in a region of the ipsilesional motor cortex. Patients treated with verum acupuncture showed a trend toward a greater maximum activation change in this motor cortical area as compared to those treated with sham acupuncture. CONCLUSIONS: Acupuncture may improve function of the affected upper limb in chronic hemiparetic stroke patients by increasing activity in the ipsilesional motor cortex.

Acupuncture for upper-extremity rehabilitation in chronic stroke: a randomized sham-controlled study.

OBJECTIVE: To compare the effects of traditional Chinese acupuncture with sham acupuncture on upper-extremity (UE) function and quality of life (QOL) in patients with chronic hemiparesis from stroke. DESIGN: A prospective, sham-controlled, randomized controlled trial (RCT). SETTING: Patients recruited through a hospital stroke rehabilitation program. PARTICIPANTS: Thirty-three subjects who incurred a stroke 0.8 to 24 years previously and had moderate to severe UE functional impairment. INTERVENTIONS: Active acupuncture tailored to traditional Chinese medicine diagnoses, including electroacupuncture, or sham acupuncture. Up to 20 treatment sessions (mean, 16.9) over a mean of 10.5 weeks. MAIN OUTCOME MEASURES: UE motor function, spasticity, grip strength, range of motion (ROM), activities of daily living, QOL, and mood. All outcomes were measured at baseline and after treatment. RESULTS: Intention-to-treat (ITT) analyses found no statistically significant differences in outcomes between active and sham acupuncture groups. Analyses of protocol-compliant subjects revealed significant improvement in wrist spasticity (P<.01) and both wrist (P<.01) and shoulder (P<.01) ROM in the active acupuncture group, and improvement trends in UE motor function (P=.09) and digit ROM (P=.06). CONCLUSIONS: Based on ITT analyses, we conclude that acupuncture does not improve UE function or QOL in patients with chronic stroke symptoms. However, gains in UE function observed in protocol-compliant subjects suggest traditional Chinese acupuncture may help patients with chronic stroke symptoms. These results must be interpreted cautiously because of small sample sizes and multiple, unadjusted, post hoc comparisons. A larger, more definitive RCT using a similar design is feasible and warranted.

Motor recovery strategies after stroke.

Impaired motor function after stroke is a major cause of disability in young stroke survivors. The plasticity of the adult human brain provides opportunities to enhance traditional rehabilitation programs for these individuals. Younger stroke patients appear to have a greater ability to recover from stroke and are likely to benefit substantially from treatments that facilitate plasticity-mediated recovery. The use of new exercise treatments, such as constraint-induced movement therapy, robot-aided rehabilitation, and partial body weight supported treadmill training are being studied intensively and are likely to ultimately be incorporated into standard poststroke rehabilitation. Medications to enhance recovery, growth factors, and stem cells will also be components of rehabilitation for the young stroke survivor in the foreseeable future.