Neurochemical balance and inhibition at the subacute stage after stroke.

Stroke is a leading cause of death and disability worldwide with many people left with impaired motor function. Evidence from experimental animal models of stroke indicates that reducing motor cortex inhibition may facilitate neural plasticity and motor recovery. This study compared primary motor cortex (M1) inhibition measures over the first 12 wk after stroke with a cohort of age-similar healthy controls. The excitation-inhibition ratio and gamma-aminobutyric acid (GABA) neurotransmission within M1 were assessed using magnetic resonance spectroscopy and threshold hunting paired-pulse transcranial magnetic stimulation respectively. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Patients with a functional corticospinal pathway had motor-evoked potentials on the paretic side and exhibited better recovery from upper limb impairment and recovery of function than patients without a functional corticospinal pathway. Compared with age-similar controls, the neurochemical balance in terms of the excitation-inhibition ratio was greater within contralesional M1 in patients with a functional corticospinal pathway. There was evidence for elevated long-interval inhibition in both ipsilesional and contralesional M1 compared with controls. Short-interval inhibition measures differed between the first and second phases, with evidence for elevation of the former only in ipsilesional M1 and no evidence of disinhibition for the latter. Overall, findings from transcranial magnetic stimulation indicate an upregulation of GABA-mediated tonic inhibition in M1 early after stroke. Therapeutic approaches that aim to normalize inhibitory tone during the subacute period warrant further investigation.NEW & NOTEWORTHY Magnetic resonance spectroscopy indicated higher excitation-inhibition ratios within motor cortex during subacute recovery than age-similar healthy controls. Measures obtained from adaptive threshold hunting paired-pulse transcranial magnetic stimulation indicated greater tonic inhibition in patients compared with controls. Therapeutic approaches that aim to normalize motor cortex inhibition during the subacute stage of recovery should be explored.

The Influence of Primary Motor Cortex Inhibition on Upper Limb Impairment and Function in Chronic Stroke: A Multimodal Study.

BACKGROUND: Stroke is a leading cause of adult disability owing largely to motor impairment and loss of function. After stroke, there may be abnormalities in γ-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. OBJECTIVE: To quantify GABA neurotransmission and concentration within ipsilesional and contralesional M1 and determine if they relate to upper limb impairment and function at the chronic stage of stroke. METHODS: Twelve chronic stroke patients and 16 age-similar controls were recruited for the study. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Threshold tracking paired-pulse transcranial magnetic stimulation protocols were used to examine short- and long-interval intracortical inhibition and late cortical disinhibition. Magnetic resonance spectroscopy was used to evaluate GABA concentration. RESULTS: Short-interval intracortical inhibition was similar between patients and controls ( P = .10). Long-interval intracortical inhibition was greater in ipsilesional M1 compared with controls ( P < .001). Patients who did not exhibit late cortical disinhibition in ipsilesional M1 were those with greater upper limb impairment and worse function ( P = .002 and P = .017). GABA concentration was lower within ipsilesional ( P = .009) and contralesional ( P = .021) M1 compared with controls, resulting in an elevated excitation-inhibition ratio for patients. CONCLUSION: These findings indicate that ipsilesional and contralesional M1 GABAergic inhibition are altered in this small cohort of chronic stroke patients. Further study is warranted to determine how M1 inhibitory networks might be targeted to improve motor function.

An assessment of the Hua Oranga outcome instrument and comparison to other outcome measures in an intervention study with Maori and Pacific people following stroke.

AIM: Health outcomes research for Maori has been hampered by the lack of adequately validated instruments that directly address outcomes of importance to Maori, framed by a Maori perspective of health. Hua Oranga is an outcome instrument developed for Maori with mental illness that uses a holistic view of Maori health to determine improvements in physical, mental, spiritual and family domains of health. Basic psychometric work for Hua Oranga is lacking. We sought to explore the psychometric properties of the instrument and compare its responsiveness alongside other, more established tools in an intervention study involving Maori and Pacific people following acute stroke. METHODS: Randomised 2x2 controlled trial of Maori and Pacific people following acute stroke with two interventions aimed at facilitating self-directed rehabilitation, and with follow-up at 12 months after randomisation. Primary outcome measures were the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Short Form 36 (SF36) at 12 months. Hua Oranga was used as a secondary outcome measure for participants at 12 months and for carers and whanau (extended family). Psychometric properties of Hua Oranga were explored using plots and correlation coefficients, principal factors analysis and scree plots. RESULTS: 172 participants were randomised, of whom 139 (80.8%) completed follow-up. Of these, 135 (97%) completed the Hua Oranga and 117 (84.2%) completed the PCS and MCS of the SF36. Eighty-nine carers completed the Hua Oranga. Total Hua Oranga scores and PCS improved significantly for one intervention group but not the other. Total Hua Oranga scores for carers improved significantly for both interventions. Total Hua Oranga score correlated moderately with the PCS (correlation coefficient 0.55, p<0.001). Factor analysis suggested that Hua Oranga measures two and not four factors; one 'physical-mental' and one 'spiritual-family'. CONCLUSION: The Hua Oranga instrument, developed for Maori people with mental illness, showed good responsiveness and adequate psychometric properties in Maori and Pacific people after stroke. Its simplicity, relative brevity, minimal cost and adequate psychometric properties should favour its use in future studies with both Maori and Pacific people. Suggestions are made for refinements to the measure. These should be tested in a new population before Hua Oranga is recommended for general use in a clinical setting.

Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial.

OBJECTIVE: To determine the effect of calcium supplementation on myocardial infarction, stroke, and sudden death in healthy postmenopausal women. DESIGN: Randomised, placebo controlled trial. SETTING: Academic medical centre in an urban setting in New Zealand. PARTICIPANTS: 1471 postmenopausal women (mean age 74): 732 were randomised to calcium supplementation and 739 to placebo. MAIN OUTCOME MEASURES: Adverse cardiovascular events over five years: death, sudden death, myocardial infarction, angina, other chest pain, stroke, transient ischaemic attack, and a composite end point of myocardial infarction, stroke, or sudden death. RESULTS: Myocardial infarction was more commonly reported in the calcium group than in the placebo group (45 events in 31 women v 19 events in 14 women, P=0.01). The composite end point of myocardial infarction, stroke, or sudden death was also more common in the calcium group (101 events in 69 women v 54 events in 42 women, P=0.008). After adjudication myocardial infarction remained more common in the calcium group (24 events in 21 women v 10 events in 10 women, relative risk 2.12, 95% confidence interval 1.01 to 4.47). For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group (relative risk 1.47, 0.97 to 2.23). When unreported events were added from the national database of hospital admissions in New Zealand the relative risk of myocardial infarction was 1.49 (0.86 to 2.57) and that of the composite end point was 1.21 (0.84 to 1.74). The respective rate ratios were 1.67 (95% confidence intervals 0.98 to 2.87) and 1.43 (1.01 to 2.04); event rates: placebo 16.3/1000 person years, calcium 23.3/1000 person years. For stroke (including unreported events) the relative risk was 1.37 (0.83 to 2.28) and the rate ratio was 1.45 (0.88 to 2.49). CONCLUSION: Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates. This potentially detrimental effect should be balanced against the likely benefits of calcium on bone. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN 012605000242628.

Lateralization of motor imagery following stroke.

OBJECTIVE: Motor imagery may activate the primary motor cortex (M1) and promote functional recovery following stroke. We investigated whether the hemisphere affected by stroke affects performance and M1 activity during motor imagery. METHODS: Twelve stroke patients (6 left, 6 right hemisphere) and eight healthy age-matched adults participated. Experiment 1 assessed the speed and ease of actual and imagined motor performance. Experiment 2 measured corticomotor excitability during imagined movement of each hand separately, and both hands together, using transcranial magnetic stimulation. RESULTS: For control participants, imagined movements were performed more slowly than actual movements, and right-hand MEPs were facilitated when they imagined moving their right hand or both hands together. Patients reported being able to imagine movements with either hand, despite no measurable facilitation of MEPs in the stroke-affected hand. In left hemisphere patients, MEPs were facilitated in the left hand during imagery of the right hand and both hands together. In right hemisphere patients, motor imagery did not facilitate MEPs in either hand. CONCLUSIONS: Motor imagery does not appear to facilitate the ipsilesional M1 following stroke. SIGNIFICANCE: Motor imagery may play a role in rehabilitating movement planning, but its role in directly facilitating corticomotor output appears limited.