Motor Activated Auricular Vagus Nerve Stimulation as a Potential Neuromodulation Approach for Post-Stroke Motor Rehabilitation: A Pilot Study.

BACKGROUND: Implanted vagus nerve stimulation (VNS), when synchronized with post-stroke motor rehabilitation improves conventional motor rehabilitation training. A non-invasive VNS method known as transcutaneous auricular vagus nerves stimulation (taVNS) has emerged, which may mimic the effects of implanted VNS. OBJECTIVE: To determine whether taVNS paired with motor rehabilitation improves post-stroke motor function, and whether synchronization with movement and amount of stimulation is critical to outcomes. METHODS: We developed a closed-loop taVNS system for motor rehabilitation called motor activated auricular vagus nerve stimulation (MAAVNS) and conducted a randomized, double-blind, pilot trial investigating the use of MAAVNS to improve upper limb function in 20 stroke survivors. Participants attended 12 rehabilitation sessions over 4-weeks, and were assigned to a group that received either MAAVNS or active unpaired taVNS concurrently with task-specific training. Motor assessments were conducted at baseline, and weekly during rehabilitation training. Stimulation pulses were counted for both groups. RESULTS: A total of 16 individuals completed the trial, and both MAAVNS (n = 9) and unpaired taVNS (n = 7) demonstrated improved Fugl-Meyer Assessment upper extremity scores (Mean ± SEM, MAAVNS: 5.00 ± 1.02, unpaired taVNS: 3.14 ± 0.63). MAAVNS demonstrated greater effect size (Cohen's d = 0.63) compared to unpaired taVNS (Cohen's d = 0.30). Furthermore, MAAVNS participants received significantly fewer stimulation pulses (Mean ± SEM, MAAVNS: 36 070 ± 3205) than the fixed 45 000 pulses unpaired taVNS participants received (P < .05). CONCLUSION: This trial suggests stimulation timing likely matters, and that pairing taVNS with movements may be superior to an unpaired approach. Additionally, MAAVNS effect size is comparable to that of the implanted VNS approach.

Different aspects of hand grip performance associated with structural connectivity of distinct sensorimotor networks in chronic stroke.

Knowledge regarding the neural origins of distinct upper extremity impairments may guide the choice of interventions to target neural structures responsible for specific impairments. This cross-sectional pilot study investigated whether different brain networks explain distinct aspects of hand grip performance in stroke survivors. In 22 chronic stroke survivors, hand grip performance was characterized as grip strength, reaction, relaxation times, and control of grip force magnitude and direction. In addition, their brain structural connectomes were constructed from diffusion tensor MRI. Prominent networks were identified based on a two-step factor analysis using the number of streamlines among brain regions relevant to sensorimotor function. We used regression models to estimate the predictive value of sensorimotor network connectivity for hand grip performance measures while controlling for stroke lesion volumes. Each hand grip performance measure correlated with the connectivity of distinct brain sensorimotor networks. These results suggest that different brain networks may be responsible for different aspects of hand grip performance, which leads to varying clinical presentations of upper extremity impairment following stroke. Understanding the brain network correlates for different hand grip performances may facilitate the development of personalized rehabilitation interventions to directly target the responsible brain network for specific impairments in individual patients, thus improving outcomes.

Case report: unique failure of a Synthes TFNA fenestrated lag screw in a peritrochanteric nonunion.

Background: Intertrochanteric femur fractures are a common orthopaedic injury that are often treated surgically. Cephalomedullary nails (CMN) are frequently the implant of choice for intertrochanteric femur fractures, resulting in low complication rates. Implant failure is a rare but reported complication. Common locations of failure include the proximal nail aperture, distal screw holes, and implant shaft. In this case report, we describe a CMN failure pattern through fenestrated cephalic screw holes. Case: A 70-year-old female sustained an OTA 31A-2.2 peritrochanteric fracture during a motor vehicle collision. She was treated the following day with a Synthes Trochanteric Fixation Nail-Advanced CMN utilizing a fenestrated cephalic screw. There were no intraoperative complications. She was made non-weight bearing for 8 weeks after the procedure due to ipsilateral foot fractures. At 6 months follow-up she was noted to have a delayed union. 11 months postoperatively she suffered a ground level fall and the cephalic lag screw failed through its fenestrations, resulting in varus collapse of her fracture at the femoral neck. The patient then underwent nail extraction and salvage total hip arthroplasty. Conclusion: Cephalomedullary nail implant failure is presented with implant fracture propagation through a fenestrated cephalic screw. Cephalomedullary lag screw failure is rare and can be difficult to manage. It is important to monitor new implants for unique failure mechanisms.

A feasibility study of objective outcome measures used in clinical trials of freezing of gait.

BACKGROUND: Freezing of gait (FOG) is notoriously difficult to quantify, which has led to the use of multiple markers as outcomes for clinical trials. The instrumented timed up and go (TUG) and the many parameters that can be derived from it are commonly used as objective markers of FOG severity in clinical trials; however, it is unknown if they represent actual FOG severity. OBJECTIVE: To determine the specificity and responsiveness of objective surrogate markers of FOG severity commonly utilized in FOG studies. METHODS: Study design: We compared the specificity and responsiveness of commonly used markers in FOG clinical trials. Markers compared included velocity, step/stride length, step/stride length variability, TUG, and turn duration. Data was collected in four conditions (ON and OFF dopaminergic drugs, with and without a dual task). Unified Parkinson's Disease Rating Scale (UPDRS) was administered in the ON and OFF states. RESULTS: Thirty-three subjects were recruited (17 PD subjects without FOG (PD-control) and 16 subjects with PD and dopa-responsive FOG PD-FOG). The UPDRS motor scores were 24.9 for the PD-control group in the ON state, 24.8 for the FOG group in the ON state, and 42.4 for the FOG group in the OFF state. Significant mean differences between the ON and OFF conditions were observed with all surrogate markers (p < 0.01). However, only dual task turn duration and step variability showed trends toward significance when comparing PD-control and ON-FOG (p = 0.08). Test-retest reliability was high (ICC > 0.90) for all markers except standard deviations. Step length variability was the only marker to show an area under the ROC curve analysis > 0.70 comparing ON-FOG vs. PD-control. CONCLUSIONS: Multiple candidate surrogate markers for FOG severity showed responsiveness to levodopa challenge; however, most were not specific for FOG severity.

From adults to pediatrics: A review noninvasive brain stimulation (NIBS) to facilitate recovery from brain injury.

Stroke is a major problem worldwide that impacts over 100 million adults and children annually. Rehabilitation therapy is the current standard of care to restore functional impairments post-stroke, however its effects are limited and many patients suffer persisting functional impairments and life-long disability. Noninvasive Brain Stimulation (NIBS) has emerged as a potential rehabilitation treatment option in both adults and children with brain injury. In the last decade, Transcranial Magnetic Stimulation (TMS), Transcranial Direct Current Stimulation (tDCS) and Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) have been investigated to improve motor recovery in adults post-stroke. These promising adult findings using NIBS, however, have yet to be widely translated to the area of pediatrics. The limited studies exploring NIBS in children have demonstrated safety, feasibility, and utility of stimulation-augmented rehabilitation. This chapter will describe the mechanism of NIBS therapy (cortical excitability, neuroplasticity) that underlies its use in stroke and motor function and how TMS, tDCS, and taVNS are applied in adult stroke treatment paradigms. We will then discuss the current state of NIBS in early pediatric brain injury and will provide insight regarding practical considerations and future applications of NIBS in pediatrics to make this promising treatment option a viable therapy in children.

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation.

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans and can be assessed using transcranial magnetic stimulation (TMS). Given the role of distal leg muscles in upright postural and dynamic tasks, such as walking, a growing research interest in the assessment and modulation of the corticospinal tracts relative to the function of these muscles has emerged in the last decade. However, methodological parameters used in previous work have varied across studies making the interpretation of results from cross-sectional and longitudinal studies less robust. Therefore, use of a standardized TMS protocol specific to the assessment of leg muscles' corticomotor response (CMR) will allow for direct comparison of results across studies and cohorts. The objective of this paper is to present a protocol that provides the flexibility to simultaneously assess the bilateral CMR of two main ankle antagonistic muscles, the tibialis anterior and soleus, using single pulse TMS with a neuronavigation system. The present protocol is applicable while the examined muscle is either fully relaxed or isometrically contracted at a defined percentage of maximum isometric voluntary contraction. Using each subject's structural MRI with the neuronavigation system ensures accurate and precise positioning of the coil over the leg cortical representations during assessment. Given the inconsistency in CMR derived measures, this protocol also describes a standardized calculation of these measures using automated algorithms. Though this protocol is not conducted during upright postural or dynamic tasks, it can be used to assess bilaterally any pair of leg muscles, either antagonistic or synergistic, in both neurologically intact and impaired subjects.

Preclinical and Clinical Evidence on Ipsilateral Corticospinal Projections: Implication for Motor Recovery.

Motor impairment is the most common complication after stroke, and recovery of motor function has been shown to be dependent on the extent of lesion in the ipsilesional corticospinal tract (iCST) and activity within ipsilesional primary and secondary motor cortices. However, work from neuroimaging research has suggested a role of the contralesional hemisphere in promoting recovery after stroke potentially through the ipsilateral uncrossed CST fibers descending to ipsilateral spinal segments. These ipsilateral fibers, sometimes referred to as "latent" projections, are thought to contribute to motor recovery independent of the crossed CST. The aim of this paper is to evaluate using cumulative evidence from animal models and human patients on whether an uncrossed CST component is present in mammals and conserved through primates and humans, and whether iCST fibers have a functional role in hemiparetic/hemiplegic human conditions. This review highlights that an ipsilateral uncrossed CST exists in human during development, but the evidence on a functionally relevant iCST component in adult humans is still elusive. In addition, this review argues that whereas activity within the ipsilesional cortex is essential for enhancing motor recovery after stroke, the role of iCST projections specifically is still controversial. Finally, conclusions from current literature emphasize the importance of activity in the ipsilesional cortex and the integrity of crossed CST fibers as major determinants of motor recovery after brain injury.

Changes in muscle coordination patterns induced by exposure to a viscous force field.

BACKGROUND: Robotic neurorehabilitation aims at promoting the recovery of lost function after neurological injury by leveraging strategies of motor learning. One important aspect of the rehabilitation process is the improvement of muscle coordination patterns, which can be drastically altered after stroke. However, it is not fully understood if and how robotic therapy can address these deficits. The aim of our study was to find how muscle coordination, analyzed from the perspective of motor modules, could change during motor adaptation to a dynamic environment generated by a haptic interface. METHODS: In our experiment we employed the traditional paradigm of exposure to a viscous force field to subjects that grasped the handle of an actuated joystick during a reaching movement (participants moved directly forward and back by 30 c m). EMG signals of ten muscles of the tested arm were recorded. We extracted motor modules from the pooled EMG data of all subjects and analyzed the muscle coordination patterns. RESULTS: We found that the participants reacted by using a coordination strategy that could be explained by a change in the activation of motor modules used during free motion and by two complementary modules. These complementary modules aggregated changes in muscle coordination, and evolved throughout the experiment eventually maintaining a comparable structure until the late phase of re-adaptation. CONCLUSIONS: This result suggests that motor adaptation induced by the interaction with a robotic device can lead to changes in the muscle coordination patterns of the subject.

Pilot study of atomoxetine in patients with Parkinson's disease and dopa-unresponsive Freezing of Gait.

BACKGROUND: Freezing of gait (FoG) is a common and debilitating condition in Parkinson's disease (PD) associated with executive dysfunction. A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency. This pilot study explores the effects of atomoxetine on gait in PD patients with dopa-unresponsive FoG using a novel paradigm for objective gait assessment. FINDINGS: Ten patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study. Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning, while performing a dual task. Clinical, and subjective assessments of gait, quality of life, and safety were also administered. The primary outcome was a validated subjective assessment for FoG (FOG-Q). Atomoxetine was well tolerated, however, no significant change was observed in the primary outcome. The gait analysis protocol correlated well with clinical scales, but not with subjective assessments. DBS patients were more likely to increase gait velocity (p = 0.033), and improved in other clinical assessments. CONCLUSIONS: Objective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population, and may be superior correlates of FoG severity than subjective measures. These findings can inform future trials in this population.

Effects of trunk restraint combined with intensive task practice on poststroke upper extremity reach and function: a pilot study.

BACKGROUND: Poststroke reaching is characterized by excessive trunk motion and abnormal shoulder-elbow coordination. Little attention is typically given to arm-trunk kinematics during task practice. Preventing compensatory trunk motion during short-term practice immediately improves kinematics, but effects of longer-term practice are unknown. OBJECTIVE: This study compared the effects of intensive task practice with and without trunk restraint on poststroke reaching kinematics and function. METHODS: A total of 11 individuals with chronic stroke, baseline Fugl-Meyer Upper Extremity Assessment scores 26 to 54, were randomized to 2 constraint-therapy intervention groups. All participants wore a mitt on the unaffected hand for 90% of waking hours over 14 days and participated in 10 days/6 hours/day of supervised progressive task practice. During supervised sessions, one group trained with a trunk restraint (preventing anterior trunk motion) and one group did not. Tasks for the trunk-restraint group were located to afford repeated use of a shoulder flexion-elbow extension reaching pattern. Outcome measures included kinematics of unrestrained targeted reaching and tests of functional arm ability. RESULTS: Posttraining, the trunk-restraint group demonstrated straighter reach trajectories (P=.000) and less trunk displacement (P=.001). The trunk-restraint group gained shoulder flexion (P=.006) and elbow extension (P=.022) voluntary ranges of motion, the nonrestraint group did not. Posttraining angle-angle plots illustrated that individuals from the trunk-restraint group transitioned from elbow flexion to elbow extension during mid-reach; individuals in the nonrestraint group retained pretraining movement strategies. Both groups gained functional arm ability (P<.05 all tests). CONCLUSION: Intensive task practice structured to prevent compensatory trunk movements and promote shoulder flexion-elbow extension coordination may reinforce development of "normal" reaching kinematics.

Effects of stroke severity and training duration on locomotor recovery after stroke: a pilot study.

BACKGROUND: Locomotor training using partial body weight-supported treadmill (BWST) walking has been widely investigated for people after stroke, yet there remains a lack of evidence concerning the optimal training duration and the effect of locomotor impairment severity. Previous protocols have not emphasized the transfer of locomotor skills from the BWST environment to overground. OBJECTIVES: To assess the feasibility of a program combining locomotor training using BWST with task-specific overground training and to obtain pilot data on the effects of severity and training duration on recovery of locomotion. METHODS: Seven adults with chronic poststroke hemiparesis and gait speed less than 0.8 m/s were recruited to participate in a 12-week (36 session) locomotor training program. Each session comprised 20 to 30 minutes of training using BWST with manual assistance, followed by 10 to 15 minutes of overground training to transfer the skills trained in the BWST environment. Gait speed was the primary outcome measure. RESULTS: Six out of the 7 enrolled individuals completed the intervention program; 1 was withdrawn due to transportation difficulties affecting compliance with the training schedule. Four of the 6 participants had a functionally significant improvement in walking speed after 36 sessions, defined as having achieved a 0.4 m/s gait speed or greater for those with initial severe gait speed impairment (<0.4 m/s) or as having achieved a 0.8 m/s gait speed or greater for persons with initial moderate gait speed impairment (>or=0.4 m/s and <0.8 m/s). All participants improved in balance and distance walked over 6 minutes, and 5 of the 6 participants showed increases in their daily home and community step activity. CONCLUSIONS: A locomotor training program combining walking using BWST and manual assistance with overground practice is feasible for people with chronic poststroke hemiparesis and moderate or severe gait speed impairment. This intervention shows promise for achieving functionally significant improvements in walking speed.