Marie-Claire Smith

Mirror Symmetric Bimanual Movement Priming Can Increase Corticomotor Excitability and Enhance Motor Learning

Repetitive mirror symmetric bilateral upper limb may be a suitable priming technique for upper limb rehabilitation after stroke. Here we demonstrate neurophysiological and behavioural after-effects in healthy participants after priming with 20 minutes of repetitive active-passive bimanual wrist flexion and extension in a mirror symmetric pattern with respect to the body midline (MIR) compared to an control priming condition with alternating flexion-extension (ALT). Transcranial magnetic stimulation (TMS) indicated that corticomotor excitability (CME) of the passive hemisphere remained elevated compared to baseline for at least 30 minutes after MIR but not ALT, evidenced by an increase in the size of motor evoked potentials in ECR and FCR. Short and long-latency intracortical inhibition (SICI, LICI), short afferent inhibition (SAI) and interhemispheric inhibition (IHI) were also examined using pairs of stimuli. LICI differed between patterns, with less LICI after MIR compared with ALT, and an effect of pattern on IHI, with reduced IHI in passive FCR 15 minutes after MIR compared with ALT and baseline. There was no effect of pattern on SAI or FCR H-reflex. Similarly, SICI remained unchanged after 20 minutes of MIR. We then had participants complete a timed manual dexterity motor learning task with the passive hand during, immediately after, and 24 hours after MIR or control priming. The rate of task completion was faster with MIR priming compared to control conditions. Finally, ECR and FCR MEPs were examined within a pre-movement facilitation paradigm of wrist extension before and after MIR. ECR, but not FCR, MEPs were consistently facilitated before and after MIR, demonstrating no degradation of selective muscle activation. In summary, mirror symmetric active-passive bimanual movement increases CME and can enhance motor learning without degradation of muscle selectivity. These findings rationalise the use of mirror symmetric bimanual movement as a priming modality in post-stroke upper limb rehabilitation.

Proportional Motor Recovery after Stroke: Implications for Trial Design

Background and Purpose— Recovery of upper-limb motor impairment after first-ever ischemic stroke is proportional to the degree of initial impairment in patients with a functional corticospinal tract (CST). This study aimed to investigate whether proportional recovery occurs in a more clinically relevant sample including patients with intracerebral hemorrhage and previous stroke. Methods— Patients with upper-limb weakness were assessed 3 days and 3 months poststroke with the Fugl–Meyer scale. Transcranial magnetic stimulation was used to test CST function, and patients were dichotomized according to the presence of motor evoked potentials in the paretic wrist extensors. Linear regression modeling of &Dgr; Fugl–Meyer score between 3 days and 3 months was performed, with predictors including initial impairment (66 − baseline Fugl–Meyer score), age, sex, stroke type, previous stroke, comorbidities, and upper-limb therapy dose. Results— One hundred ninety-two patients were recruited, and 157 completed 3-month follow-up. Patients with a functional CST made a proportional recovery of 63% (95% confidence interval, 55%–70%) of initial motor impairment. The recovery of patients without a functional CST was not proportional to initial impairment and was reduced by greater CST damage. Conclusions— Recovery of motor impairment in patients with intact CST is proportional to initial impairment and unaffected by previous stroke, type of stroke, or upper-limb therapy dose. Novel interventions that interact with the neurobiological mechanisms of recovery are needed. The generalizability of proportional recovery is such that patients with intracerebral hemorrhage and previous stroke may usefully be included in interventional rehabilitation trials. Clinical Trial Registration— URL: http://www.anzctr.org.au. Unique identifier: ANZCTR12611000755932.

Predicting Recovery Potential for Individual Stroke Patients Increases Rehabilitation Efficiency

Background and Purpose— Several clinical measures and biomarkers are associated with motor recovery after stroke, but none are used to guide rehabilitation for individual patients. The objective of this study was to evaluate the implementation of upper limb predictions in stroke rehabilitation, by combining clinical measures and biomarkers using the Predict Recovery Potential (PREP) algorithm. Methods— Predictions were provided for patients in the implementation group (n=110) and withheld from the comparison group (n=82). Predictions guided rehabilitation therapy focus for patients in the implementation group. The effects of predictive information on clinical practice (length of stay, therapist confidence, therapy content, and dose) were evaluated. Clinical outcomes (upper limb function, impairment and use, independence, and quality of life) were measured 3 and 6 months poststroke. The primary clinical practice outcome was inpatient length of stay. The primary clinical outcome was Action Research Arm Test score 3 months poststroke. Results— Length of stay was 1 week shorter for the implementation group (11 days; 95% confidence interval, 9–13 days) than the comparison group (17 days; 95% confidence interval, 14–21 days; P=0.001), controlling for upper limb impairment, age, sex, and comorbidities. Therapists were more confident (P=0.004) and modified therapy content according to predictions for the implementation group (P<0.05). The algorithm correctly predicted the primary clinical outcome for 80% of patients in both groups. There were no adverse effects of algorithm implementation on patient outcomes at 3 or 6 months poststroke. Conclusions— PREP algorithm predictions modify therapy content and increase rehabilitation efficiency after stroke without compromising clinical outcome. Clinical Trial Registration— URL: http://anzctr.org.au. Unique identifier: ACTRN12611000755932.

Transcranial magnetic stimulation (TMS) in stroke: Ready for clinical practice?

The use of transcranial magnetic stimulation (TMS) in stroke research has increased dramatically over the last decade with two emerging and potentially useful functions identified. Firstly, the use of single pulse TMS as a tool for predicting recovery of motor function after stroke, and secondly, the use of repetitive TMS (rTMS) as a treatment adjunct aimed at modifying the excitability of the motor cortex in preparation for rehabilitation. This review discusses recent advances in the use of TMS in both prediction and treatment after stroke. Prediction of recovery after stroke is a complex process and the use of TMS alone is not sufficient to provide accurate prediction for an individual after stroke. However, when applied in conjunction with other tools such as clinical assessment and MRI, accuracy of prediction using TMS is increased. rTMS temporarily modulates cortical excitability after stroke. Very few rTMS studies are completed in the acute or sub-acute stages after stroke and the translation of altered cortical excitability into gains in motor function are modest, with little evidence of long term effects. Although gains have been made in both of these areas, further investigation is needed before these techniques can be applied in routine clinical care.

PREP2: A biomarker-based algorithm for predicting upper limb function after stroke

Recovery of motor function is important for regaining independence after stroke, but difficult to predict for individual patients. Our aim was to develop an efficient, accurate, and accessible algorithm for use in clinical settings. Clinical, neurophysiological, and neuroimaging biomarkers of corticospinal integrity obtained within days of stroke were combined to predict likely upper limb motor outcomes 3 months after stroke.

Effects of non-target leg activation, TMS coil orientation, and limb dominance on lower limb motor cortex excitability

Transcranial magnetic stimulation (TMS) is used to examine corticospinal tract integrity after stroke, however, generating motor-evoked potentials (MEPs) in the lower limb (LL) can be difficult. Previous studies have used activation of the target leg to facilitate MEPs in the LL but this may not be possible after stroke due to hemiplegia. The dominance of the target limb may also be important, however the neurophysiological effects of LL dominance are not known. We investigated whether voluntary activation of the non-target leg combined with optimal TMS coil orientation increases corticomotor excitability in healthy adults, and whether limb dominance influences these results. TMS was delivered to induce a posterior-anterior (PA) and a medial-lateral (ML) cortical current in 22 healthy adults. MEPs were recorded in tibialis anterior (TA) with the participant at rest and when activating the non-target leg. We found that non-target leg activation increased corticomotor excitability in the target leg (reduced rest motor threshold (RMT) and MEP latency, and increased recruitment curve slope). ML cortical current also reduced RMT and MEP latency. The degree of footedness correlated with the degree of RMT asymmetry, with a PA but not ML cortical current direction. In summary, cross-facilitation by activating the non-target leg in a task requiring postural stabilisation and inducing ML current increase corticomotor excitability regardless of limb dominance. This protocol may have practical application in testing CST integrity after stroke when paretic limb thresholds are high, by increasing the likelihood of eliciting a MEP.

The TWIST Algorithm Predicts Time to Walking Independently After Stroke

Background and Objective. The likelihood of regaining independent walking after stroke is of concern to patients and their families and influences hospital discharge planning. The objective of this study was to explore factors that could be combined in an algorithm for predicting whether and when a patient will walk independently after stroke. Methods. Adults with new lower limb weakness were recruited within 3 days of having a stroke. Clinical assessment, transcranial magnetic stimulation, and magnetic resonance imaging were completed 1 to 2 weeks poststroke. Classification and regression tree (CART) analysis was used to identify factors that predicted whether a patient achieved independent walking by 6 or 12 weeks, or remained dependent at 12 weeks. Results. We recruited 41 patients (24 women; median age 72 years, range 43-96 years). The CART analysis results were used to create the Time to Walking Independently after STroke (TWIST) algorithm, which made accurate predictions for 95% of patients. Patients with a trunk control test score >40 at 1 week walked independently within 6 weeks. Patients with a trunk control test score <40 only achieved independent walking by 12 weeks if they also had hip extension strength of Medical Research Council grade 3 or more. Neurophysiological and neuroimaging measures did not predict independent walking after stroke. Conclusions. In this exploratory study, the TWIST algorithm accurately predicted whether and when an individual patient walked independently after stroke using simple bedside measures 1 week poststroke. Further work is required to develop and validate this algorithm in a larger study.