Do lower limb motor-evoked potentials predict walking outcomes post-stroke?

BACKGROUND: This observational study examined whether lower limb (LL) motor-evoked potentials (MEPs) 1 week post-stroke predict recovery of independent walking, use of ankle-foot orthosis (AFO) or walking aid, at 3 and 6 months post-stroke. METHODS: Non-ambulatory participants were recruited 5 days post-stroke. Transcranial magnetic stimulation was used to determine tibialis anterior MEP status and clinical assessments (age, National Institutes of Health Stroke Scale (NIHSS), ankle dorsiflexion strength, LL motricity index, Berg Balance Test) were completed 1 week post-stroke. Functional Ambulation Category (FAC), use of AFO and walking aid were assessed 3 months and 6 months post-stroke. MEP status, alone and combined with clinical measures, and walking outcomes at 3 and 6 months were analysed with Pearson χ2 and multivariate binary logistic regression. RESULTS: Ninety participants were included (median age 72 years (38-97 years)). Most participants (81%) walked independently (FAC ≥ 4), 17% used an AFO, and 49% used a walking aid 3 months post-stroke with similar findings at 6 months. Independent walking was better predicted by age, LL strength and Berg Balance Test (accuracy 92%, 95% CI 85% to 97%) than MEP status (accuracy 73%, 95% CI 63% to 83%). AFO use was better predicted by NIHSS and MEP status (accuracy 88%, 95% CI 79% to 94%) than MEP status alone (accuracy 76%, 95% CI 65% to 84%). No variables predicted use of walking aids. CONCLUSIONS: The presence of LL MEPs 1-week post-stroke predicts independent walking at 3 and 6 months post-stroke. However, the absence of MEPs does not preclude independent walking. Clinical factors, particularly age, balance and stroke severity, more strongly predict independent walking than MEP status. LL MEP status adds little value as a biomarker for walking outcomes.

Reliability of a TMS-derived threshold matrix of corticomotor function.

Transcranial magnetic stimulation (TMS) studies typically focus on suprathreshold motor evoked potentials (MEPs), overlooking small MEPs representing subthreshold corticomotor pathway activation. Assessing subthreshold excitability could provide insights into corticomotor pathway integrity and function, particularly in neurological conditions like stroke. The aim of the study was to examine the test-retest reliability of metrics derived from a novel compositional analysis of MEP data from older adults. The study also compared the composition between the dominant (D) and non-dominant (ND) sides and explored the association between subthreshold responses and resting motor threshold. In this proof-of-concept study, 23 healthy older adults participated in two identical experimental sessions. Stimulus-response (S-R) curves and threshold matrices were constructed using single-pulse TMS across intensities to obtain MEPs in four upper limb muscles. S-R curves had reliable slopes for every muscle (Intraclass Correlation Coefficient range = 0.58-0.88). Subliminal and suprathreshold elements of the threshold matrix showed good-excellent reliability (D subliminal ICC = 0.83; ND subliminal ICC = 0.79; D suprathreshold ICC = 0.92; ND suprathreshold ICC = 0.94). By contrast, subthreshold elements of the matrix showed poor reliability, presumably due to a floor effect (D subthreshold ICC = 0.39; ND subthreshold ICC = 0.05). No composition differences were found between D and ND sides (suprathreshold BF01 = 3.85; subthreshold BF01 = 1.68; subliminal BF01 = 3.49). The threshold matrix reliably assesses subliminal and suprathreshold MEPs in older adults. Further studies are warranted to evaluate the utility of compositional analyses for assessing recovery of corticomotor pathway function after neurological injury.

Clinical utility of trans-sacral magnetic stimulation-evoked sphincter potentials and high-density electromyography in pelvic floor assessment: Technical evaluation.

AIM: Faecal incontinence is common and of multifactorial aetiologies, yet current diagnostic tools are unable to assess nerve and sphincter function objectively. We developed an anorectal high-density electromyography (HD-EMG) probe to evaluate motor-evoked potentials induced via trans-sacral magnetic stimulation (TSMS). METHOD: Anorectal probes with an 8 × 8 array of electrodes spaced 1 cm apart were developed for recording HD-EMG of the external anal sphincter. These HD-EMG probes were used to map MEP amplitudes and latencies evoked via TSMS delivered through the Magstim Rapid2 (MagStim Company). Patients undergoing pelvic floor investigations were recruited for this IDEAL Stage 2a pilot study. RESULTS: Eight participants (median age 49 years; five female) were recruited. Methodological viability, safety and diagnostic workflow were established. The test was well tolerated with median discomfort scores ≤2.5/10, median pain scores ≤1/10 and no adverse events. Higher Faecal Incontinence Severity Index scores correlated with longer MEP latencies (r = 0.58, p < 0.001) and lower MEP amplitudes (r = -0.32, p = 0.046), as did St. Mark's Incontinence Scores with both MEP latencies (r = 0.49, p = 0.001) and MEP amplitudes (r = -0.47, p = 0.002). CONCLUSION: This HD-EMG probe in conjunction with TSMS presents a novel diagnostic tool for anorectal function assessment. Spatiotemporal assessment of magnetically stimulated MEPs correlated well with symptoms and offers a feasible, safe and patient-tolerable method of evaluating pudendal nerve and external anal sphincter function. Further clinical development and evaluation of these techniques is justified.

Fast Outcome Categorization of the Upper Limb After Stroke.

BACKGROUND AND PURPOSE: The ARAT (Action Research Arm Test) has been used to classify upper limb motor outcome after stroke in 1 of 3, 4, or 5 categories. The COVID-19 pandemic has encouraged the development of assessments that can be performed quickly and remotely. The aim of this study was to derive and internally validate decision trees for categorizing upper limb motor outcomes at the late subacute and chronic stages of stroke using a subset of ARAT tasks. METHODS: This study retrospectively analyzed ARAT scores obtained in-person at 3 months poststroke from 333 patients. In-person ARAT scores were used to categorize patients' 3-month upper limb outcome using classification systems with 3, 4, and 5 outcome categories. Individual task scores from in-person assessments were then used in classification and regression tree analyses to determine subsets of tasks that could accurately categorize upper limb outcome for each of the 3 classification systems. The decision trees developed using 3-month ARAT data were also applied to in-person ARAT data obtained from 157 patients at 6 months poststroke. RESULTS: The classification and regression tree analyses produced decision trees requiring 2 to 4 ARAT tasks. The overall accuracy of the cross-validated decision trees ranged from 87.7% (SE, 1.0%) to 96.7% (SE, 2.0%). Accuracy was highest when classifying patients into one of 3 outcome categories and lowest for 5 categories. The decision trees are referred to as FOCUS (Fast Outcome Categorization of the Upper Limb After Stroke) assessments and they remained accurate for 6-month poststroke ARAT scores (overall accuracy range 83.4%-91.7%). CONCLUSIONS: A subset of ARAT tasks can accurately categorize upper limb motor outcomes after stroke. Future studies could investigate the feasibility and accuracy of categorizing outcomes using the FOCUS assessments remotely via video call.

The modulation of short and long-latency interhemispheric inhibition during bimanually coordinated movements.

Bimanual coordination is essential for the performance of many everyday tasks. There are several types of bimanually coordinated movements, classified according to whether the arms are acting to achieve a single goal (cooperative) or separate goals (independent), and whether the arms are moving symmetrically or asymmetrically. Symmetric bimanual movements are thought to facilitate corticomotor excitability (CME), while asymmetric bimanual movements are thought to recruit interhemispheric inhibition to reduce functional coupling between the motor cortices. The influences of movement symmetry and goal conceptualisation on interhemispheric interactions have not been studied together, and not during bimanually active dynamic tasks. The present study used transcranial magnetic stimulation (TMS) to investigate the modulation of CME and short- and long-latency interhemispheric inhibition (SIHI and LIHI, respectively) during bimanually active dynamic tasks requiring different types of bimanual coordination. Twenty healthy right-handed adults performed four bimanual tasks in which they held a dumbbell in each hand (independent) or a custom device between both hands (cooperative) while rhythmically flexing and extending their wrists symmetrically or asymmetrically. Motor-evoked potentials were recorded from the right extensor carpi ulnaris. We found CME was greater during asymmetric tasks than symmetric tasks, and movement symmetry did not modulate SIHI or LIHI. There was no effect of goal conceptualisation nor any interaction with movement symmetry for CME, SIHI or LIHI. Based on these results, movement symmetry and goal conceptualisation may not modulate interhemispheric inhibition during dynamic bimanual tasks. These findings contradict prevailing thinking about the roles of CME and interhemispheric inhibition in bimanual coordination.

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.

Resting-State Functional Connectivity Magnetic Resonance Imaging and Outcome After Acute Stroke.

Background and Purpose- Physiological effects of stroke are best assessed over entire brain networks rather than just focally at the site of structural damage. Resting-state functional magnetic resonance imaging can map functional-anatomic networks by analyzing spontaneously correlated low-frequency activity fluctuations across the brain, but its potential usefulness in predicting functional outcome after acute stroke remains unknown. We assessed the ability of resting-state functional magnetic resonance imaging to predict functional outcome after acute stroke. Methods- We scanned 37 consecutive reperfused stroke patients (age, 69±14 years; 14 females; 3-day National Institutes of Health Stroke Scale score, 6±5) on day 3 after symptom onset. After imaging preprocessing, we used a whole-brain mask to calculate the correlation coefficient matrices for every paired region using the Harvard-Oxford probabilistic atlas. To evaluate functional outcome, we applied the modified Rankin Scale at 90 days. We used region of interest analyses to explore the functional connectivity between regions and graph-computation analysis to detect differences in functional connectivity between patients with good functional outcome (modified Rankin Scale score ≤2) and those with poor outcome (modified Rankin Scale score >2). Results- Patients with good outcome had greater functional connectivity than patients with poor outcome. Although 3-day National Institutes of Health Stroke Scale score was the most accurate independent predictor of 90-day modified Rankin Scale (84.2%), adding functional connectivity increased accuracy to 94.7%. Preserved bilateral interhemispheric connectivity between the anterior inferior temporal gyrus and superior frontal gyrus and decreased connectivity between the caudate and anterior inferior temporal gyrus in the left hemisphere had the greatest impact in favoring good prognosis. Conclusions- These data suggest that information about functional connectivity from resting-state functional magnetic resonance imaging may help predict 90-day stroke outcome.

Effects of bilateral priming on motor cortex function in healthy adults.

Bilateral priming is a rehabilitation adjuvant that can improve upper limb motor recovery poststroke. It uses a table-top device to couple the upper limbs together such that active flexion and extension of one wrist leads to passive movement of the opposite wrist in a mirror symmetric pattern. Bilateral priming increases corticomotor excitability (CME) in the primary motor cortex (M1) of the passively driven wrist; however, the neurophysiological mechanisms underlying this increase remain unclear. This study explored these mechanisms by using transcranial magnetic stimulation over the right M1 and recording motor-evoked potentials from the passively driven left extensor carpi radialis of healthy adults. Intracortical measures were recorded before and 5 and 35 min after a single 15-min session of priming. One-millisecond short-interval intracortical inhibition, long-interval intracortical inhibition, late cortical disinhibition (LCD), and intracortical facilitation were recorded with a posterior-anterior (PA) intracortical current, whereas CME and short-interval intracortical facilitation (SICF) were recorded with both PA and anterior-posterior (AP) currents. CME with PA stimulation was also recorded ~1 h postpriming. PA CME was elevated 35 min postpriming and remained elevated ~1 h postpriming. LCD decreased, and AP SICF increased at both 5 and 35 min postpriming. However, these changes in LCD and AP SICF are unlikely to be the cause of the increased PA CME because of the differing timelines of their effects and AP and PA currents activating separate interneuron circuits. These results suggest that bilateral priming does not increase CME through alterations of the intracortical circuits investigated here. NEW & NOTEWORTHY This is the first study to measure how bilateral priming modulates corticomotor excitability with posterior-anterior and anterior-posterior intracortical currents, 1-ms short-interval intracortical inhibition, late cortical disinhibition, intracortical facilitation, and short-interval intracortical facilitation. We found corticomotor excitability with a posterior-anterior current increased by 35 min until ~1 h postpriming. Short-interval intracortical facilitation with an anterior-posterior current was greater for at least 35 min postpriming. This provides further insight into the neurophysiological mechanisms underlying bilateral priming.

Proportional Recovery From Lower Limb Motor Impairment After Stroke.

BACKGROUND AND PURPOSE: In people with preserved corticospinal tract (CST) function after stroke, upper limb impairment resolves by ≈70% within 3 months. This is known as the proportional recovery rule. Patients without CST function do not fit this rule and have worse upper limb outcomes. This study investigated resolution of motor impairment in the lower limb (LL). METHODS: Patients with stroke and LL weakness were assessed 3 days and 3 months after stroke with the LL Fugl-Meyer. CST integrity was determined in a subset of patients using transcranial magnetic stimulation to test for LL motor-evoked potentials and magnetic resonance imaging to measure CST lesion load. Linear regression analyses were conducted to predict resolution of motor impairment (ΔFugl-Meyer) including factors initial impairment, motor-evoked potential status, CST lesion load, and LL therapy dose. RESULTS: Thirty-two patients completed 3-month follow-up and recovered 74% (95% confidence interval, 60%-88%) of initial LL motor impairment. Initial impairment was the only significant predictor of resolution of motor impairment. There was no identifiable cluster of patients who did not fit the proportional recovery rule. Measures of CST integrity did not predict proportional LL recovery. CONCLUSIONS: LL impairment resolves by ≈70% within 3 months after stroke. The absence of a nonfitter group may be because of differences in the neuroanatomical organization of descending motor tracts to the upper limb and LL. Proportional recovery of the LL is not influenced by therapy dose providing further evidence that it reflects a fundamental biological process.

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 Δ 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.

Modulation of motor cortex inhibition during motor imagery.

Motor imagery (MI) is similar to overt movement, engaging common neural substrates and facilitating the corticomotor pathway; however, it does not result in excitatory descending motor output. Transcranial magnetic stimulation (TMS) can be used to assess inhibitory networks in the primary motor cortex via measures of 1-ms short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and late cortical disinhibition (LCD). These measures are thought to reflect extrasynaptic GABAA tonic inhibition, postsynaptic GABAB inhibition, and presynaptic GABAB disinhibition, respectively. The behavior of 1-ms SICI, LICI, and LCD during MI has not yet been explored. This study aimed to investigate how 1-ms SICI, LICI, and LCD are modulated during MI and voluntary relaxation (VR) of a target muscle. Twenty-five healthy young adults participated. TMS was used to assess nonconditioned motor evoked potential (MEP) amplitude, 1-ms SICI, 100- (LICI100) and 150-ms LICI, and LCD in the right abductor pollicis brevis (APB) and right abductor digiti minimi during rest, MI, and VR of the hand. Compared with rest, MEP amplitudes were facilitated in APB during MI. SICI was not affected by task or muscle. LICI100 decreased in both muscles during VR but not MI, whereas LCD was recruited in both muscles during both tasks. This indicates that VR modulates postsynaptic GABAB inhibition, whereas both tasks modulate presynaptic GABAB inhibition in a non-muscle-specific way. This study highlights further neurophysiological parallels between actual and imagined movement, which may extend to voluntary relaxation.NEW & NOTEWORTHY This is the first study to investigate how 1-ms short-interval intracortical inhibition, long-interval intracortical inhibition, and late cortical disinhibition are modulated during motor imagery and voluntary muscle relaxation. We present novel findings of decreased 100-ms long-interval intracortical inhibition during voluntary muscle relaxation and increased late cortical disinhibition during both motor imagery and voluntary muscle relaxation.

Diffusion tensor imaging as a prognostic biomarker for motor recovery and rehabilitation after stroke.

PURPOSE: Despite improved acute treatment and new tools to facilitate recovery, most patients have motor deficits after stroke, often causing disability. However, motor impairment varies considerably among patients, and recovery in the acute/subacute phase is difficult to predict using clinical measures alone, particularly in severely impaired patients. Accurate early prediction of recovery would help rationalize rehabilitation goals and improve the design of trials testing strategies to facilitate recovery. METHODS: We review the role of diffusion tensor imaging (DTI) in predicting motor recovery after stroke, in monitoring treatment response, and in evaluating white matter remodeling. We critically appraise DTI studies and discuss their limitations, and we explore directions for future study. RESULTS: Growing evidence suggests that combining clinical scores with information about corticospinal tract (CST) integrity can improve predictions about motor outcome. The extent of CST damage on DTI and/or the overlap between the CST and a lesion are key prognostic factor that determines motor performance and outcome. Three main strategies to quantify stroke-related CST damage have been proposed: (i) measuring FA distal to the stroke area, (ii) measuring the number of fibers that go through the stroke with tractography, and (iii) measuring the overlap between the stroke and a CST map derived from healthy age- and gender-matched controls. CONCLUSION: Recovery of motor function probably involves remodeling of the CST proper and/or a greater reliance on alternative motor tracts through spontaneous and treatment-induced plasticity. DTI-metrics represent promising clinical biomarkers to predict motor recovery and to monitor and predict the response to neurorehabilitative interventions.

Dopamine Gene Profiling to Predict Impulse Control and Effects of Dopamine Agonist Ropinirole.

Dopamine agonists can impair inhibitory control and cause impulse control disorders for those with Parkinson disease (PD), although mechanistically this is not well understood. In this study, we hypothesized that the extent of such drug effects on impulse control is related to specific dopamine gene polymorphisms. This double-blind, placebo-controlled study aimed to examine the effect of single doses of 0.5 and 1.0 mg of the dopamine agonist ropinirole on impulse control in healthy adults of typical age for PD onset. Impulse control was measured by stop signal RT on a response inhibition task and by an index of impulsive decision-making on the Balloon Analogue Risk Task. A dopamine genetic risk score quantified basal dopamine neurotransmission from the influence of five genes: catechol-O-methyltransferase, dopamine transporter, and those encoding receptors D1, D2, and D3. With placebo, impulse control was better for the high versus low genetic risk score groups. Ropinirole modulated impulse control in a manner dependent on genetic risk score. For the lower score group, both doses improved response inhibition (decreased stop signal RT) whereas the lower dose reduced impulsiveness in decision-making. Conversely, the higher score group showed a trend for worsened response inhibition on the lower dose whereas both doses increased impulsiveness in decision-making. The implications of the present findings are that genotyping can be used to predict impulse control and whether it will improve or worsen with the administration of dopamine agonists.

Proportional recovery after stroke depends on corticomotor integrity.

OBJECTIVE: For most patients, resolution of upper limb impairment during the first 6 months poststroke is 70% of the maximum possible. We sought to identify candidate mechanisms of this proportional recovery. We hypothesized that proportional resolution of upper limb impairment depends on ipsilesional corticomotor pathway function, is mirrored by proportional recovery of excitability in this pathway, and is unaffected by upper limb therapy dose. METHODS: Upper limb impairment was measured in 93 patients at 2, 6, 12, and 26 weeks after first-ever ischemic stroke. Motor evoked potentials (MEPs) and motor threshold were recorded from extensor carpi radialis using transcranial magnetic stimulation, and fractional anisotropy (FA) in the posterior limbs of the internal capsules was determined with diffusion-weighted magnetic resonance imaging. RESULTS: Initial impairment score, presence of MEPs and FA asymmetry were the only predictors of impairment resolution, indicating a key role for corticomotor tract function. By 12 weeks, upper limb impairment resolved by 70% in patients with MEPs regardless of their initial impairment, and ipsilesional rest motor threshold also resolved by 70%. Resolution of impairment was insensitive to upper limb therapy dose. INTERPRETATION: These findings indicate that upper limb impairment resolves by 70% of the maximum possible, regardless of initial impairment, but only for patients with intact corticomotor function. Impairment resolution seems to reflect spontaneous neurobiological processes that involve the ipsilesional corticomotor pathway. A better understanding of these mechanisms could lead to interventions that increase resolution of impairment above 70%.

Bilateral priming accelerates recovery of upper limb function after stroke: a randomized controlled trial.

BACKGROUND AND PURPOSE: The ability to live independently after stroke depends on the recovery of upper limb function. We hypothesized that bilateral priming with active-passive movements before upper limb physiotherapy would promote rebalancing of corticomotor excitability and would accelerate upper limb recovery at the subacute stage. METHODS: A single-center randomized controlled trial of bilateral priming was conducted with 57 patients randomized at the subacute stage after first-ever ischemic stroke. The PRIMED group made device-assisted mirror symmetrical bimanual movements before upper limb physiotherapy, every weekday for 4 weeks. The CONTROL group was given intermittent cutaneous electric stimulation of the paretic forearm before physiotherapy. Assessments were made at baseline, 6, 12, and 26 weeks. The primary end point was the proportion of patients who reached their plateau for upper limb function at 12 weeks, measured with the Action Research Arm Test. RESULTS: Odds ratios indicated that PRIMED participants were 3× more likely than controls to reach their recovery plateau by 12 weeks. Intention-to-treat and per-protocol analyses showed a greater proportion of PRIMED participants achieved their plateau by 12 weeks (intention to treat, χ2=4.25; P=0.039 and per protocol, χ2=3.99; P=0.046). ANOVA of per-protocol data showed PRIMED participants had greater rebalancing of corticomotor excitability than controls at 12 and 26 weeks and interhemispheric inhibition at 26 weeks (all P<0.05). CONCLUSIONS: Bilateral priming accelerated recovery of upper limb function in the initial weeks after stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ANZCTR1260900046822.

Predicting and accelerating motor recovery after stroke.

PURPOSE OF REVIEW: This review presents recent developments in the prediction of motor recovery after stroke; explores whether rehabilitation interventions delivered during the spontaneous recovery process can improve outcomes; and identifies the first trials to focus on the rate rather than extent of motor recovery (Supplementary Digital Content 1). RECENT FINDINGS: Two recent studies have attempted to accelerate the rate of motor recovery during the first few weeks after stroke, with neuromodulation techniques designed to facilitate excitability of the ipsilesional motor cortex. One trial using transcranial direct current stimulation was negative, and the other trial using bilateral priming was positive. These contrasting results may be explained by important differences in trial design. This new focus on modifying rate, rather than extent, of motor recovery is in line with accumulating evidence that the motor recovery plateau is largely determined by the extent of damage to descending motor pathways, which is currently untreatable. SUMMARY: Interventions that facilitate neural plasticity and reorganization may accelerate recovery of motor function during the spontaneous recovery period, without affecting final outcome. This may represent a useful new approach for future trials conducted during rehabilitation at the subacute stage of stroke.