Arm Motor Recovery After Ischemic Stroke: A Focus on Clinically Distinct Trajectory Groups.

BACKGROUND AND PURPOSE: Recovery of arm function poststroke is highly variable with some people experiencing rapid recovery but many experiencing slower or limited functional improvement. Current stroke prediction models provide some guidance for clinicians regarding expected motor outcomes poststroke but do not address recovery rates, complicating discharge planning. This study developed a novel approach to defining recovery groups based on arm motor recovery trajectories poststroke. In addition, between-group differences in baseline characteristics and therapy hours were explored. METHODS: A retrospective cohort analysis was conducted where 40 participants with arm weakness were assessed 1 week, 6 weeks, 3 months, and 6 months after an ischemic stroke. Arm recovery trajectory groups were defined on the basis of timing of changes in the Fugl-Meyer Assessment Upper Extremity (FMA-UE), at least the minimal clinically important difference (MCID), 1 week to 6 weeks or 6 weeks to 6 months. Three recovery trajectory groups were defined: Fast (n = 19), Extended (n = 12), and Limited (n = 9). Between-group differences in baseline characteristics and therapy hours were assessed. Associations between baseline characteristics and group membership were also determined. RESULTS: Three baseline characteristics were associated with trajectory group membership: FMA-UE, NIH Stroke Scale, and Barthel Index. The Fast Recovery group received the least therapy hours 6 weeks to 6 months. No differences in therapy hours were observed between Extended and Limited Recovery groups at any time points. DISCUSSION AND CONCLUSIONS: Three clinically relevant recovery trajectory groups were defined using the FMA-UE MCID. Baseline impairment, overall stroke severity, and dependence in activities of daily living were associated with group membership and therapy hours differed between groups. Stratifying individuals by recovery trajectory early poststroke could offer additional guidance to clinicians in discharge planning.(See Supplemental Digital Content 1 for Video Abstract, available at: http://links.lww.com/JNPT/A337.).

Stepping Up to Rethink the Future of Rehabilitation: IV STEP Considerations and Inspirations.

BACKGROUND AND PURPOSE: The IV STEP conference challenged presenters and participants to consider the state of science in rehabilitation, highlighting key area of progress since the previous STEP conference related to prediction, prevention, plasticity, and participation in rehabilitation. KEY POINTS: Emerging from the thought-provoking discussions was recognition of the progress we have made as a profession and a call for future growth. In this summary article, we present a recap of the key points and call for action. We review the information presented and the field at large as it relates to the 4 Ps: prediction, prevention, plasticity, and participation. RECOMMENDATIONS FOR PRACTICE: Given that personalized medicine is an increasingly important approach that was clearly woven throughout the IV STEP presentations, we took the liberty of adding a fifth "P," Personalized, in our discussion of the future direction of the profession.

Stepping Up to Rethink the Future of Rehabilitation: IV STEP Considerations and Inspirations.

BACKGROUND AND PURPOSE: The IV STEP conference challenged presenters and participants to consider the state of science in rehabilitation, highlighting key area of progress since the previous STEP conference related to prediction, prevention, plasticity, and participation in rehabilitation. KEY POINTS: Emerging from the thought-provoking discussions was recognition of the progress we have made as a profession and a call for future growth. In this summary article, we present a recap of the key points and call for action. We review the information presented and the field at large as it relates to the 4 Ps: prediction, prevention, plasticity, and participation. RECOMMENDATIONS FOR PRACTICE: Given that personalized medicine is an increasingly important approach that was clearly woven throughout the IV STEP presentations, we took the liberty of adding a fifth "P," Personalized, in our discussion of the future direction of the profession.

Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation.

OBJECTIVES: To examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); to present the method for determining optimal stimulation to increase inhibition in a given patient; and to examine individual responses to prolonged intervention. DESIGN: Single-subject design to determine optimal parameters to increase inhibition for a given subject and to use the selected parameters once per week for 6 weeks, with 1-week follow-up, to determine response. SETTING: Clinical research laboratory. PARTICIPANTS: A volunteer sample of subjects with FHD (N = 2). One participant had transcranial magnetic stimulation responses indicating impaired inhibition, and the other had responses within normative limits. INTERVENTIONS: There were 1200 pulses of 1-Hz rTMS delivered using 4 different stimulation sites/intensity combinations: primary motor cortex at 90% or 110% of resting motor threshold (RMT) and dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as the intervention. MAIN OUTCOME MEASURES: Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short latency intracortical inhibition and facilitation. RESULTS: The individual with baseline transcranial magnetic stimulation responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, an increase in the CSP, and subjective report of moderate symptom improvement at 1-week follow-up. The individual with normative baseline responses failed to respond to the intervention. In both subjects, 90% of RMT to the PMd produced the greatest lengthening of the CSP and was used as the intervention. CONCLUSIONS: An individualized understanding of neurophysiological measures can be an indicator of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine likely responders versus nonresponders.

Both sleep and wakefulness support consolidation of continuous, goal-directed, visuomotor skill.

Sleep has been shown to benefit memory consolidation for certain motor skills, but it remains unclear if this relationship exists for motor skills with direct rehabilitation applications. We aimed to determine the neurobehavioral relationship between finger-tracking skill development and sleep following skill training in young, healthy subjects. Forty subjects received tracking training in the morning (n = 20) or the evening (n = 20). Measures of tracking skill and cortical excitability were collected before and after training. Following training, tracking skill and measures of cortical excitability were assessed at two additional follow-up visits (12 and 24 h post-training) for each subject following an episode of sleep or waking activity. Two-way repeated-measures ANOVAs with Bonferroni-adjusted post hoc tests were conducted for tracking accuracy and measures of cortical excitability. Skill performance improved after training and continued to develop offline during the first post-training interval (12 h). This development was not further enhanced by sleep during this interval. Level of skill improvement was maintained for at least one day in both training groups. Cortical excitability was reduced following training and was related to level of skill performance at follow-up assessment. These data suggest offline memory consolidation of a continuous, visuospatial, finger-tracking skill is not dependent on sleep. These findings are in agreement with recent literature, indicating characteristics of a motor skill may be sensitive to the beneficial effect of sleep on post-training information processing.

Lasting effects of repeated rTMS application in focal hand dystonia.

PURPOSE: Focal hand dystonia (FHD) is a rare but potentially devastating disorder involving involuntary muscle spasms and abnormal posturing that impairs functional hand use. Increased cortical excitability and lack of inhibitory mechanisms have been associated with these symptoms. This study investigated the short- and long-term effects of repeated administrations of repetitive-transcranial magnetic stimulation (rTMS) on cortical excitability and handwriting performance. METHODS: Six subjects with FHD and nine healthy controls were studied. All subjects with FHD received rTMS (1Hz) to the premotor cortex (PMC) for five consecutive days; of those, three subjects received five days of sham rTMS completed ten days prior to real treatment. Healthy subjects received one real rTMS session. Cortical silent period (CSP) and measures of handwriting performance were compared before and after treatment and at ten-day post-treatment follow-up. RESULTS: At baseline, significant differences in CSP and pen pressure were observed between subjects with FHD and healthy controls. Differences in CSP and pen velocity between subjects in real and sham rTMS groups were observed across treatment sessions and maintained at follow-up. CONCLUSIONS: After five days of rTMS to PMC, reduced cortical excitability and improved handwriting performance were observed and maintained at least ten days following treatment in subjects with FHD. These preliminary results support further investigation of the therapeutic potential of rTMS in FHD.

Motor and cognitive outcomes in children after functional hemispherectomy.

PURPOSE: Medically intractable epilepsy is a chronic recurrence of seizures that often requires surgery to reduce or eliminate them. Although a reduction of seizures is the primary goal of hemispherectomy, the effect of surgery on motor and cognitive skills is also of importance. This review will provide a discussion of (1) evidence regarding motor and cognitive outcomes, (2) predictors of these outcomes, and (3) neural mechanisms responsible for preservation of function after hemispherectomy. SUMMARY OF KEY POINTS: Motor and cognitive outcomes after hemispherectomy are variable and depend on many predictors including etiology and duration of seizure disorder, age at the time of surgery, premorbid status, and postsurgical seizure control. A refined ipsilateral pathway may explain the preservation of motor function in some children. CONCLUSIONS: A clear understanding of outcome predictors is important for planning effective rehabilitative programs after surgery.

An Exploratory Study of Predictors of Response to Vagus Nerve Stimulation Paired with Upper-Limb Rehabilitation After Ischemic Stroke.

We have previously shown the safety and feasibility of vagus nerve stimulation (VNS) paired with upper-limb rehabilitation after ischemic stroke. In this exploratory study, we assessed whether clinical and brain MRI variables predict response to treatment. We used data from two completed randomised and blinded clinical trials (N = 35). All participants had moderate to severe upper-limb weakness and were randomised to 6-weeks intensive physiotherapy with or without VNS. Participants had 3 T brain MRI at baseline. The primary outcome was change in Fugl-Meyer Assessment, upper-extremity score (FMA-UE) from baseline to the first day after therapy completion. We used general linear regression to identify clinical and brain MRI predictors of change in FMA-UE. VNS-treated participants had greater improvement in FMA-UE at day-1 post therapy than controls (8.63 ± 5.02 versus 3.79 ± 5.04 points, t = 2.83, Cohen's d = 0.96, P = 0.008). Higher cerebrospinal fluid volume was associated with less improvement in FMA-UE in the control but not VNS group. This was also true for white matter hyperintensity volume but not after removal of an outlying participant from the control group. Responders in the VNS group had more severe arm impairment at baseline than responders to control. A phase III trial is now underway to formally determine whether VNS improves outcomes and will explore whether these differ in people with more severe baseline upper-limb disability and cerebrovascular disease.

fMRI reliability in subjects with stroke.

Functional MRI (fMRI) has become one of the most commonly used neuroimaging tools to assess the cortical effects associated with rehabilitation, learning, or disease recovery in subjects with stroke. Despite this, there has been no systematic study of the reliability of the fMR signal in this population. The purpose of this study was to examine the within- and between-session reliability of fMRI in cortical and cerebellar structures in subjects with stroke during a complex, continuous visual motor task performed with the less affected hand. Nine subjects with stroke underwent four testing trials during two sessions separated by three weeks. Subjects performed a drawing task using an MRI compatible joystick while in the MRI. Methods of analysis evaluated included: percent signal intensity change, active voxel count and a voxel by voxel stat value analysis within and between testing sessions. Reliability was determined with Interclass correlation coefficients (ICC) in the following regions of interest: primary motor (M1), primary sensory (S1), premotor cortex (PMC), medial cerebellum (MCB), and lateral cerebellum (LCB). Results indicate that intensity change has superior reliability to the other methods of analysis (Average ICC across brain regions and trials: intensity change: 0.73, voxel count: 0.58, voxel by voxel: 0.67) and that generally with any analysis method, within-session reliability was higher than between-session, as indicated by higher ICC values across brain regions. Overall, when comparing between-session results, moderate to good reliability was obtained with intensity change (ICC: M1: 0.52, S1: 0.80, SMA: 0.78, PMC: 0.94, MCB: 0.86, and LCB: 0.59). These results show good reliability in subjects with stroke when performing a continuous motor task. These findings give confidence for interpreting fMRI test/retest research in subjects with stroke.

Reliability of fMRI during a continuous motor task: assessment of analysis techniques.

The purpose of this study was to determine which method of functional magnetic resonance image analysis had the highest reliability in cortical and cerebellar areas during a continuous motor task. Fourteen subjects underwent 4 testing trials during 2 testing sessions separated by 3 weeks. Subjects performed a joystick task. Methods of analysis evaluated included: percent signal intensity change, active voxel count, and percent contribution. Two types of activation thresholds were evaluated: P< or = .05 and false discovery rate = .05. Reliability was determined with intraclass correlation coefficients and a repeated measure ANOVA was used to determine whether there was a significant difference between trials. A group analysis was assessed with coefficient of variation. Results indicate within session reliability was higher than between session and that signal intensity is more reliable than voxel count analysis. The intraclass correlation coefficients across different regions of interest varied depending on analysis technique. The data did not support a clear difference between thresholds. The group analysis also found less variability with intensity measures than voxel count. A stabilization effect was seen after the first trial of the experiment, suggesting that in pretest/posttest designs, a more stable result may be obtained by performing a test trial prior to actual data collection.

Understanding neuroimaging.

Neuroimaging is an emergent method of investigation for studying the human brain in healthy and impaired populations. An increasing number of these investigations involve topics important to rehabilitation. Thus, a basic understanding of the more commonly used neuroimaging techniques is important for understanding and interpreting this growing area of research. Included in this article is a description of the signal source, the advantages and limitations of each technique, considerations for study design, and how to interpret cortical imaging data. Particular emphasis is placed on functional magnetic resonance imaging because of its ubiquitous presence in rehabilitation research.

Cortical Silent Period Reveals Differences Between Adductor Spasmodic Dysphonia and Muscle Tension Dysphonia.

BACKGROUND: The pathophysiology of adductor spasmodic dysphonia (AdSD), like other focal dystonias, is largely unknown. OBJECTIVE: The purposes of this study were to determine (a) cortical excitability differences between AdSD, muscle tension dysphonia (MTD), and healthy controls; (b) distribution of potential differences in cranial or skeletal muscle; and (c) if cortical excitability measures assist in the differential diagnosis of AdSD and MTD. METHODS: Ten participants with adductor spasmodic dysphonia, 8 with muscle tension dysphonia, and 10 healthy controls received single and paired pulse transcranial magnetic stimulation (TMS) to the primary motor cortex contralateral to tested muscles, first dorsal interosseus (FDI), and masseter. We tested the hypothesis that cortical excitability measures in AdSD would be significantly different from those in MTD and healthy controls. In addition, we hypothesized that there would be a correlation between cortical excitability measures and clinical voice severity in AdSD. RESULTS: Cortical silent period duration in masseter and FDI was significantly shorter in AdSD than MTD and healthy controls. Other measures failed to demonstrate differences. CONCLUSION: There are differences in cortical excitability between AdSD, MTD, and healthy controls. These differences in the cortical measure of both the FDI and masseter muscles in AdSD suggest widespread dysfunction of the GABAB mechanism may be a pathophysiologic feature of AdSD, similar to other forms of focal dystonia. Further exploration of the use of TMS to assist in the differential diagnosis of AdSD and MTD is warranted.

Shortened cortical silent period in adductor spasmodic dysphonia: evidence for widespread cortical excitability.

The purpose of this study was to compare cortical inhibition in the hand region of the primary motor cortex between subjects with focal hand dystonia (FHD), adductor spasmodic dysphonia (AdSD), and healthy controls. Data from 28 subjects were analyzed (FHD n=11, 53.25 ± 8.74 y; AdSD: n=8, 56.38 ± 7.5 y; and healthy controls: n=941.67 ± 10.85 y). All subjects received single pulse TMS to the left motor cortex to measure cortical silent period (CSP) in the right first dorsal interosseus (FDI) muscle. Duration of the CSP was measured and compared across groups. A one-way ANCOVA with age as a covariate revealed a significant group effect (p<0.001). Post hoc analysis revealed significantly longer CSP duration in the healthy group vs. AdSD group (p<0.001) and FHD group (p<0.001). These results suggest impaired intracortical inhibition is a neurophysiologic characteristic of FHD and AdSD. In addition, the shortened CSP in AdSD provides evidence to support a widespread decrease in cortical inhibition in areas of the motor cortex that represent an asymptomatic region of the body. These findings may inform future investigations of differential diagnosis as well as alternative treatments for focal dystonias.

Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia: clinical and physiological effects.

PURPOSE: The ability of low-frequency repetitive transcranial magnetic stimulation (rTMS) to enhance intracortical inhibition has motivated its use as a potential therapeutic intervention in focal hand dystonia (FHD). In this preliminary investigation, we assessed the physiologic and behavioral effects of multiple sessions of rTMS in FHD. METHODS: 12 patients with FHD underwent five daily-sessions of 1 Hz rTMS to contralateral dorsal premotor cortex (dPMC). Patients held a pencil and made movements that did not elicit dystonic symptoms during rTMS. We hypothesized that an active but non-dystonic motor state would increase beneficial effects of rTMS. Five additional patients received sham-rTMS protocol. The area under curve (AUC) of the motor evoked potentials and the cortical silent period (CSP) were measured to assess changes in corticospinal excitability and intracortical inhibition, respectively. Behavioral measures included pen force and velocity during handwriting and subjective report. RESULTS: Multiple-session rTMS strengthened intracortical inhibition causing a prolongation of CSP after 3 days of intervention and pen force was reduced at day 1 and 5, leaving other measures unchanged. 68% of patients self-reported as 'responders' at day 5, and 58% at follow-up. Age predicted responders. CONCLUSIONS: A strong therapeutic potential of this rTMS paradigm in FHD was not supported but findings warrant further investigation.

Using actigraphy and transcranial magnetic stimulation to assess the relationship between sleep and visuomotor skill learning.

PURPOSE: Sleep following training can enhance motor skill memory consolidation while chronic sleep disruption can have the converse effect. The aim of this investigation was to explore the relationship between sleep measured by wrist actigraphy, motor skill consolidation and primary motor cortex excitability in young, healthy individuals. METHODS: Training was a visuospatial finger-tracking task. Dependent measures included tracking skill performance, cortical excitability, measures of sleep, and level of arousal. Assessments occurred pre-training, post-training and at 12 h and 24 h retention. An activity monitor was worn on the wrist during the nights preceding and following training. RESULTS: Results indicate that sleep during the night following training was predictive of 1) offline skill consolidation following training (R² = 0.34) and 2) cortical excitability at 24 h follow-up (R² = 0.35) with less time spent awake associated with better skill performance and lower cortical excitability at 24 h follow-up. No difference in measures of sleep was observed between nights of sleep (p > 0.05). Sleep the night before training did not influence skill performance, skill acquisition during training, nor measures of cortical excitability at pre-training assessment. CONCLUSIONS: These findings suggest a relationship between motor skill development, cortical excitability and sleep following training. These results invite further investigation into the utility of actigraphy as a low-cost, easy-to-administer alternative to polysomnography for short and long-term evaluation of the relationship between sleep, cortical excitability and motor skill learning in healthy and patient populations.

Goal-directed visuomotor skill learning: off-line enhancement and the importance of the primary motor cortex.

PURPOSE: The time course and neural substrates of motor skill learning are not well-understood in healthy or neurologic patient populations. Certain motor skills undergo off-line skill enhancement following training and the primary motor cortex (M1) may be involved. It is unknown if goal-directed visuomotor skill undergoes off-line enhancement or if M1 is associated with that enhancement. METHODS: 32 right-handed, healthy subjects were randomly assigned to two groups: real repetitive transcranial magnetic stimulation (rTMS) or sham rTMS applied to the contralateral M1 immediately following one 20-minute finger tracking training session. Tracking performance and cortical excitability were assessed before and after training, following rTMS and 24 hours post-training. RESULTS: Results demonstrate that skill performance continues to develop for at least 30 minutes after training completion, is maintained for 24 hours post-training, and is not affected by inhibitory rTMS applied to M1. Level of skill improvement was associated with the degree of intracortical inhibition increase. CONCLUSIONS: These results suggest dispersed information processing for goal-directed visuomotor skill learning following training and a relationship between cortical excitability and skill development in healthy individuals. These findings invite further investigation of the neural mechanisms underlying motor skill learning and may have rehabilitation implications for patients with neurologic injury.

Visualizing the effects of rTMS in a patient sample: small N vs. group level analysis.

The use of transcranial magnetic stimulation (TMS) to assess changes in cortical excitability is a tool used with increased prevalence in healthy and impaired populations. One factor of concern with this technique is how to achieve adequate statistical power given constraints of a small number of subjects and variability in responses. This paper compares a single pulse excitability measure using traditional group-level statistics vs single subject analyses in a patient population of subjects with focal hand dystonia, pre and post repetitive TMS (rTMS). Results show significant differences in cortical excitability for 4/5 subjects using a split middle line analysis on plots of individual subject data. Group level statistics (ANOVA), however, did not detect any significant findings. The consideration of single subject statistics for TMS excitability measures may assist researchers in describing the variably of rTMS outcome measures.

Comparison of amounts and types of practice during rehabilitation for traumatic brain injury and stroke.

Patients with acquired neurological deficits may capitalize on cortical reorganization to recover functional skills that have been lost. Research in neuroplasticity proposes that a high number of repetitions may lead to cortical reorganization. The purposes of this study were to quantify the number and type of activities performed by patients with traumatic brain injury (TBI) and stroke in physical and occupational therapy sessions to determine whether (1) the number of repetitions approaches the numbers in neuroplasticity research, (2) there were differences based on patient diagnosis, and (3) patient or therapist characteristics affected the type or amount of activities performed. Forty-eight patient and forty provider subjects participated. One hundred seven therapy sessions were observed. Data from therapy sessions were counted and categorized. Neither patient group approached the total number of repetitions neuroplasticity research suggests may be required for neuroplastic change. Repetitions per session did not differ between groups. Subjects with TBI performed more repetitions per minute in three categories (total upper-limb repetitions, gait steps, and transfers) than subjects with stroke. Therapists with <1 year or >15 years of neurological therapy experience instructed patients in fewer functional repetitions per minute than did therapists with 5 to 15 years of experience.