Suzanne J. Ackerley

Combining Theta Burst Stimulation With Training After Subcortical Stroke

Background and Purpose— Repetitive transcranial magnetic stimulation of the primary motor cortex (M1) may improve outcomes after stroke. The aim of this study was to determine the effects of M1 theta burst stimulation (TBS) and standardized motor training on upper-limb function of patients with chronic stroke. Methods— Ten patients with chronic subcortical stroke and upper-limb impairment were recruited to this double-blind, crossover, sham-controlled study. Intermittent TBS of the ipsilesional M1, continuous TBS of the contralesional M1, and sham TBS were delivered in separate sessions in conjunction with standardized training of a precision grip task using the paretic upper limb. Results— Training after real TBS improved paretic-hand grip-lift kinetics, whereas training after sham TBS resulted in deterioration of grip-lift. Ipsilesional M1 excitability increased after intermittent TBS of the ipsilesional M1 but decreased after continuous TBS of the contralesional M1. Action Research Arm Test scores deteriorated when training followed continuous TBS of the contralesional M1, and this was correlated with reduced ipsilesional corticomotor excitability. Conclusions— Generally, TBS and training led to task-specific improvements in grip-lift. Specifically, continuous TBS of the contralesional M1 led to an overall decrement in upper-limb function, indicating that the contralesional hemisphere may play a pivotal role in recovery after stroke.

Proportional recovery after stroke depends on corticomotor integrity

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.

Rehabilitation is Initiated Early After Stroke, but Most Motor Rehabilitation Trials Are Not A Systematic Review

Stroke is the third most common cause of death and the most common cause of acquired adult disability in developed countries.1 Motor impairment is common after stroke, and a critical factor influencing the patient’s ability to live independently.2,3 The neurobiological mechanisms of plasticity and spontaneous recovery during the initial days and weeks after stroke have been reasonably well characterized using animal models.4,5 These mechanisms include cell genesis, functional plasticity, and structural adaptations, such as axonal sprouting and synaptogenesis. The nature and time course of these mechanisms map onto the trajectory of motor recovery observed in human patients, most of whom reach their recovery plateau within 3 months of stroke.6,7 Rehabilitation is primarily delivered in this time period, to capitalize on the unique physiological conditions that prevail, and shape the spontaneous recovery process for the patient’s benefit. Recovery of function is likely to be enhanced by novel treatments that interact with and facilitate the underlying mechanisms of spontaneous recovery. A variety of neurorehabilitation techniques aimed at improving motor recovery after stroke have been developed and trialed over the past 3 decades. These include repetitive task training, biofeedback, constraint-induced movement therapy, robotics, virtual reality, motor imagery, noninvasive brain stimulation, and pharmacological agents.8,9 However, despite almost 1000 randomized control trials (RCTs) in stroke rehabilitation,10 there is very little translation of this evidence base into clinical practice.11,12 Research efforts to develop the evidence base are challenged by difficulties in recruiting patients, resulting in small sample sizes; the heterogeneity of impairments after stroke and the complexity of their interactions with factors affecting recovery; and limited collaboration between scientists, clinicians, patient groups, and industry.11 Even when the research evidence base supports the development of clinical guidelines, significant barriers …

Promoting use-dependent plasticity with externally-paced training

OBJECTIVE To evaluate use-dependent plasticity (UDP) before and after training under metronome-paced and self-paced conditions. METHODS Twelve healthy adults were recruited to this cross-over, pseudo-randomized, repeated measures study. Participants performed wrist extension training that was either self-paced, or externally-paced to an auditory metronome at their preferred movement frequency or at a more demanding frequency. Motor evoked potentials from transcranial magnetic stimulation of left primary motor cortex were recorded in right extensor carpi radialis (ECR) and flexor carpi radialis (FCR) to assess corticomotor excitability. The direction and velocity of TMS-evoked wrist movement (stimulus-evoked velocity, SEV) were measured before and after training to evaluate UDP. RESULTS The most persistent UDP occurred when training was metronome-paced at the participants preferred movement frequency. This training protocol produced spatially selective modulation of resting ECR and FCR corticomotor excitability and directional tuning of TMS-evoked wrist movement toward the trained direction. Metronome-paced training at a more demanding frequency resulted in nonspecific facilitation of resting corticomotor excitability, and did not alter TMS-evoked wrist movement. CONCLUSIONS These novel findings indicate that externally-paced training at the individuals preferred frequency facilitates UDP. SIGNIFICANCE UDP underpins motor recovery after stroke. Externally-paced training may be a useful adjunct to movement rehabilitation therapy.

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.

Assessment of quality of life and participation within an outpatient rehabilitation setting

Purpose. To evaluate the use of quality of life and participation measures in routine rehabilitation practice, determine the relationship between two scales and investigate their ability to evaluate change in a general outpatient population over a time of rehabilitation. Methods. This cohort study consisted of 55 patients admitted consecutively to an outpatient rehabilitation centre. All participants completed the WHOQOL-BREF and the London Handicap Scale (LHS) at admission and discharge. Results. Non-parametric statistical analysis demonstrated a significant change in the total scores of both the WHOQOL-BREF and LHS over time (Z = −4.33, P < 0.001 and Z = −4.40, P < 0.001 respectively) with ‘better’ scores on completion of rehabilitation. A strong correlation existed between the total WHOQOL-BREF and LHS scores both cross-sectionally (admission and discharge ρ > 0.7), and longitudinally (ρ = 0.63). Conclusions. Our study demonstrated a strong relationship between quality of life and participation, with change shown using both scales over a period of outpatient rehabilitation. Given the findings, it seems appropriate to use only one of these measures. The WHOQOL-BREF has a wider scope, being useful both to evaluate service delivery in a diverse outpatient population or when measuring an individual over time.

Priming sensorimotor cortex to enhance task-specific training after subcortical stroke

OBJECTIVE This double-blind sham-controlled crossover study investigated the interactions between primary sensory and motor cortex after stroke and their response to Theta Burst Stimulation (TBS). METHODS Thirteen chronic subcortical stroke patients with upper limb impairment performed standardised dexterity training primed with ipsilesional M1 intermittent TBS (iTBSiM1), contralesional M1 continuous TBS (cTBScM1) or sham TBS. The effects on sensorimotor integration, corticomotor excitability, sensation and grip-lift kinetics were examined. RESULTS After iTBSiM1, improvements in paretic grip-lift performance were accompanied by an immediate facilitation of ipsilesional M1 excitability and a subsequent increase in ipsilesional short latency afferent inhibition (SAI) during training. Precision grip-lift performance improved after cTBScM1 and training, alongside increased ipsilesional M1 excitability with no effect on ipsilesional SAI. There were no effects on sensory performance. CONCLUSION Primary motor cortex iTBS not only modulates M1 corticospinal excitability but also increases M1 receptiveness to sensory input. SIGNIFICANCE Priming with iTBSiM1 may enhance ipsilesional sensorimotor integration and facilitate better quality sensorimotor training after subcortical stroke.

Primed Physical Therapy Enhances Recovery of Upper Limb Function in Chronic Stroke Patients

Background. Recovery of upper limb function is important for regaining independence after stroke. Objective. To test the effects of priming upper limb physical therapy with intermittent theta burst stimulation (iTBS), a form of noninvasive brain stimulation. Methods. Eighteen adults with first-ever chronic monohemispheric subcortical stroke participated in this randomized, controlled, triple-blinded trial. Intervention consisted of priming with real or sham iTBS to the ipsilesional primary motor cortex immediately before 45 minutes of upper limb physical therapy, daily for 10 days. Changes in upper limb function (Action Research Arm Test [ARAT]), upper limb impairment (Fugl-Meyer Scale), and corticomotor excitability, were assessed before, during, and immediately, 1 month and 3 months after the intervention. Functional magnetic resonance images were acquired before and at one month after the intervention. Results. Improvements in ARAT were observed after the intervention period when therapy was primed with real iTBS, but not sham, and were maintained at 1 month. These improvements were not apparent halfway through the intervention, indicating a dose effect. Improvements in ARAT at 1 month were related to balancing of corticomotor excitability and an increase in ipsilesional premotor cortex activation during paretic hand grip. Conclusions. Two weeks of iTBS-primed therapy improves upper limb function at the chronic stage of stroke, for at least 1 month postintervention, whereas therapy alone may not be sufficient to alter function. This indicates a potential role for iTBS as an adjuvant to therapy delivered at the chronic stage.

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.