Self-Reported Cancer-Related Cognitive Impairment in Patients With Breast Cancer Is Associated With Potassium Channel Gene Polymorphisms.

OBJECTIVES: To evaluate for associations of polymorphisms for potassium channel genes in patients with breast cancer who were classified as having high or low-moderate levels of cancer-related cognitive impairment (CRCI). SAMPLE & SETTING: 397 women who were scheduled to undergo surgery for breast cancer on one breast were recruited from breast care centers located in a comprehensive cancer center, two public hospitals, and four community practices. METHODS & VARIABLES: CRCI was assessed using the Attentional Function Index prior to and for six months after surgery. The attentional function classes were identified using growth mixture modeling. RESULTS: Differences between patients in the high versus low-moderate attentional function classes were evaluated. Six single nucleotide polymorphisms for potassium channel genes were associated with low-moderate class membership. IMPLICATIONS FOR NURSING: The results contribute to knowledge of the mechanisms for CRCI. These findings may lead to the identification of high-risk patients and the development of novel therapeutics.

Neuroprosthesis for Decoding Speech in a Paralyzed Person with Anarthria.

BACKGROUND: Technology to restore the ability to communicate in paralyzed persons who cannot speak has the potential to improve autonomy and quality of life. An approach that decodes words and sentences directly from the cerebral cortical activity of such patients may represent an advancement over existing methods for assisted communication. METHODS: We implanted a subdural, high-density, multielectrode array over the area of the sensorimotor cortex that controls speech in a person with anarthria (the loss of the ability to articulate speech) and spastic quadriparesis caused by a brain-stem stroke. Over the course of 48 sessions, we recorded 22 hours of cortical activity while the participant attempted to say individual words from a vocabulary set of 50 words. We used deep-learning algorithms to create computational models for the detection and classification of words from patterns in the recorded cortical activity. We applied these computational models, as well as a natural-language model that yielded next-word probabilities given the preceding words in a sequence, to decode full sentences as the participant attempted to say them. RESULTS: We decoded sentences from the participant's cortical activity in real time at a median rate of 15.2 words per minute, with a median word error rate of 25.6%. In post hoc analyses, we detected 98% of the attempts by the participant to produce individual words, and we classified words with 47.1% accuracy using cortical signals that were stable throughout the 81-week study period. CONCLUSIONS: In a person with anarthria and spastic quadriparesis caused by a brain-stem stroke, words and sentences were decoded directly from cortical activity during attempted speech with the use of deep-learning models and a natural-language model. (Funded by Facebook and others; ClinicalTrials.gov number, NCT03698149.).

Management of chronic spinal cord dysfunction.

PURPOSE OF REVIEW: Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. RECENT FINDINGS: Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. SUMMARY: The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life.

Long-Term Follow-up to a Randomized Controlled Trial Comparing Peroneal Nerve Functional Electrical Stimulation to an Ankle Foot Orthosis for Patients With Chronic Stroke.

BACKGROUND: Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle foot orthoses (AFO) for treatment of foot drop poststroke, but few long-term, randomized controlled comparisons exist. OBJECTIVE: Compare changes in gait quality and function between FES and AFOs in individuals with foot drop poststroke over a 12-month period. METHODS: Follow-up analysis of an unblinded randomized controlled trial (ClinicalTrials.gov #NCT01087957) conducted at 30 rehabilitation centers comparing FES to AFOs over 6 months. Subjects continued to wear their randomized device for another 6 months to final 12-month assessments. Subjects used study devices for all home and community ambulation. Multiply imputed intention-to-treat analyses were utilized; primary endpoints were tested for noninferiority and secondary endpoints for superiority. Primary endpoints: 10 Meter Walk Test (10MWT) and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test (6MWT), GaitRite Functional Ambulation Profile, and Modified Emory Functional Ambulation Profile (mEFAP). RESULTS: A total of 495 subjects were randomized, and 384 completed the 12-month follow-up. FES proved noninferior to AFOs for all primary endpoints. Both FES and AFO groups showed statistically and clinically significant improvement for 10MWT compared with initial measurement. No statistically significant between-group differences were found for primary or secondary endpoints. The FES group demonstrated statistically significant improvements for 6MWT and mEFAP Stair-time subscore. CONCLUSIONS: At 12 months, both FES and AFOs continue to demonstrate equivalent gains in gait speed. Results suggest that long-term FES use may lead to additional improvements in walking endurance and functional ambulation; further research is needed to confirm these findings.

Poststroke upper limb recovery.

Upper limb recovery after a stroke is suboptimal. Only a few individuals achieve full functional use of the hemiparetic arm. Complex primary and secondary impairments may affect recovery of upper limb function in stroke survivors. In addition, multiple personal, social, behavioral, economic, and environmental factors may interact to positively or negatively influence recovery during the different stages of rehabilitation. The current management of upper limb dysfunction poststroke has become more evidence based. In this article, we review the standard of care for upper limb poststroke rehabilitation, the evidence supporting the treatment modalities that currently exist and the exciting new developments in the therapeutic pipeline.

The effects of peroneal nerve functional electrical stimulation versus ankle-foot orthosis in patients with chronic stroke: a randomized controlled trial.

BACKGROUND: Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle-foot orthoses (AFO) for treatment of foot drop poststroke, but few randomized controlled comparisons exist. OBJECTIVE: To compare changes in gait and quality of life (QoL) between FES and an AFO in individuals with foot drop poststroke. METHODS: In a multicenter randomized controlled trial (ClinicalTrials.gov #NCT01087957) with unblinded outcome assessments, 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months. Primary endpoints: 10-Meter Walk Test (10MWT), a composite of the Mobility, Activities of Daily Living/Instrumental Activities of Daily Living, and Social Participation subscores on the Stroke Impact Scale (SIS), and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test, GaitRite Functional Ambulation Profile (FAP), Modified Emory Functional Ambulation Profile (mEFAP), Berg Balance Scale (BBS), Timed Up and Go, individual SIS domains, and Stroke-Specific Quality of Life measures. Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority. RESULTS: A total of 399 subjects completed the study. FES proved noninferior to the AFO for all primary endpoints. Both the FES and AFO groups improved significantly on the 10MWT. Within the FES group, significant improvements were found for SIS composite score, total mFEAP score, individual Floor and Obstacle course time scores of the mEFAP, FAP, and BBS, but again, no between-group differences were found. CONCLUSIONS: Use of FES is equivalent to the AFO. Further studies should examine whether FES enables better performance in tasks involving functional mobility, activities of daily living, and balance.

Associations between cytokine gene variations and severe persistent breast pain in women following breast cancer surgery.

UNLABELLED: Persistent pain following breast cancer surgery is a significant clinical problem. Although immune mechanisms may play a role in the development and maintenance of persistent pain, few studies have evaluated for associations between persistent breast pain following breast cancer surgery and variations in cytokine genes. In this study, associations between previously identified extreme persistent breast pain phenotypes (ie, no pain vs severe pain) and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. In unadjusted analyses, the frequency of 13 SNPs and 3 haplotypes in 7 genes differed significantly between the no pain and severe pain classes. After adjustment for preoperative breast pain and the severity of average postoperative pain, 1 SNP (ie, interleukin [IL] 1 receptor 2 rs11674595) and 1 haplotype (ie, IL10 haplotype A8) were associated with pain group membership. These findings suggest a role for cytokine gene polymorphisms in the development of persistent breast pain following breast cancer surgery. PERSPECTIVE: This study evaluated for associations between cytokine gene variations and the severity of persistent breast pain in women following breast cancer surgery. Variations in 2 cytokine genes were associated with severe breast pain. The results suggest that cytokines play a role in the development of persistent postsurgical pain.

Chronic stroke survivors achieve comparable outcomes following virtual task specific repetitive training guided by a wearable robotic orthosis (UL-EXO7) and actual task specific repetitive training guided by a physical therapist.

Survivors post stroke commonly have upper limb impairments. Patients can drive neural reorganization, brain recovery and return of function with task specific repetitive training (TSRT). Fifteen community independent stroke survivors (25-75 years, >6 months post stroke, Upper Limb Fugl Meyer [ULFM] scores 16-39) participated in this randomized feasibility study to compare outcomes of upper limb TSRT guided by a robotic orthosis (bilateral or unilateral) or a physical therapist. After 6 weeks of training (18 h), across all subjects, there were significant improvements in depression, flexibility, strength, tone, pain and voluntary movement (ULFM) (p < 0.05; effect sizes 0.49-3.53). Each training group significantly improved ULFM scores and range of motion without significant group differences. Virtual or actual TSRT performed with a robotic orthosis or a physical therapist significantly reduced arm impairments around the shoulder and elbow without significant gains in fine motor hand control, activities of daily living or independence.

Effect of a foot-drop stimulator and ankle-foot orthosis on walking performance after stroke: a multicenter randomized controlled trial.

BACKGROUND: Studies have demonstrated the efficacy of functional electrical stimulation in the management of foot drop after stroke. OBJECTIVE: To compare changes in walking performance with the WalkAide (WA) foot-drop stimulator and a conventional ankle-foot orthosis (AFO). METHODS: Individuals with stroke within the previous 12 months and residual foot drop were enrolled in a multicenter, randomized controlled, crossover trial. Subjects were assigned to 1 of 3 parallel arms for 12 weeks (6 weeks/device): arm 1 (WA-AFO), n = 38; arm 2 (AFO-WA), n = 31; arm 3 (AFO-AFO), n = 24. Primary outcomes were walking speed and Physiological Cost Index for the Figure-of-8 walking test. Secondary measures included 10-m walking speed and perceived safety during this test, general mobility, and device preference for arms 1 and 2 for continued use. Walking tests were performed with (On) and without a device (Off) at 0, 3, 6, 9, and 12 weeks. RESULTS: Both WA and AFO had significant orthotic (On-Off difference), therapeutic (change over time when Off), and combined (change over time On vs baseline Off) effects on walking speed. An AFO also had a significant orthotic effect on Physiological Cost Index. The WA had a higher, but not significantly different therapeutic effect on speed than an AFO, whereas an AFO had a greater orthotic effect than the WA (significant at 12 weeks). Combined effects on speed after 6 weeks did not differ between devices. Users felt as safe with the WA as with an AFO, but significantly more users preferred the WA. CONCLUSIONS: Both devices produce equivalent functional gains.

Neurorehabilitation: motor recovery after stroke as an example.

The field of neurorehabilitation aims to translate neuroscience research toward the goal of maximizing functional recovery after neurological injury. A growing body of research indicates that the fundamental principles of neurological rehabilitation are applicable to a broad range of congenital, degenerative, and acquired neurological disorders. In this perspective, we will focus on motor recovery after acquired brain injuries such as stroke. Over the past few decades, a large body of basic and clinical research has created an experimental and theoretical foundation for approaches to neurorehabilitation. Recent randomized clinical trials all emphasize the requirement for intense progressive rehabilitation programs to optimally enhance recovery. Moreover, advances in multimodal assessment of patients with neuroimaging and neurophysiological tools suggest the possibility of individualized treatment plans based on recovery potential. There are also promising indications for medical as well as noninvasive brain stimulation paradigms to facilitate recovery. Ongoing or planned clinical studies should provide more definitive evidence. We also highlight unmet needs and potential areas of research. Continued research built upon a robust experimental and theoretical foundation should help to develop novel treatments to improve recovery after neurological injury.

Kinematic data analysis for post-stroke patients following bilateral versus unilateral rehabilitation with an upper limb wearable robotic system.

Robot-assisted stroke rehabilitation has become popular as one approach to helping patients recover function post-stroke. Robotic rehabilitation requires four important elements to match the robot to the patient: realistic biomechanical robotic elements, an assistive control scheme enabled through the human-robot interface, a task oriented rehabilitation program based on the principles of plasticity, and objective assessment tools to monitor change. This paper reports on a randomized clinical trial utilizing a complete robot-assisted rehabilitation system for the recovery of upper limb function in patients post-stroke. In this study, a seven degree-of-freedom (DOF) upper limb exoskeleton robot (UL-EXO7) is applied in a rehabilitation clinical trial for patients stable post-stroke (greater than six months). Patients had a Fugl-Meyer Score between 16-39, were mentally alert (> 19 on the VA Mini Mental Status Exam) and were between 27 and 70 years of age. Patients were randomly assigned to three groups: bilateral robotic training, unilateral robotic training, and usual care. This study is concerned with the changes in kinematics in the two robotic groups. Both patient groups played eight therapeutic video games over 12 sessions (90 min, two times a week). In each session, patients intensively played the different combination of video games that directly interacted with UL-EXO7 under the supervision of research assistant. At each session, all of the joint angle data was recorded for the evaluation of therapeutic effects. A new assessment metric is reported along with conventional metrics. The experimental result shows that both groups of patients showed consistent improvement with respect to the proposed and conventional metrics.

Management of chronic myelopathy symptoms and activities of daily living.

Many disorders can injure the spinal cord resulting in long-term chronic myelopathy. Spinal cord dysfunction influences the homeostasis of multiple organ systems ranging from the heart or lung to the integument, thus presenting a wide variety of challenges for medical management. Although most of our knowledge about the consequences of myelopathies derives from the study of traumatic spinal cord injuries, similar complications occur in myelopathies of all etiologies. The authors survey some of the important clinical issues that the general neurologist needs to consider in caring for patients with chronic spinal cord disease.

Combat-related headache and traumatic brain injury.

Post-traumatic headache is a commonly described complication of traumatic brain injury. Recent studies highlight differences between headache features of combat veterans who suffered traumatic brain injury compared to civilians. Not surprisingly, there is a higher rate of associated PTSD and sleep disturbances among veterans. Factors of lower socioeconomic status, rank, and multiple head injuries appear to have a similar effect on post-traumatic headache in combat-related traumatic brain injury. Areas of discordance in the literature include the effect of prolonged loss of consciousness and the prevalence of specific headache phenotypes following head trauma. To date, there have been no randomized trials of treatment for post-traumatic headache. This may be related to the variability of headache features and uncertainty of pathophysiologic mechanisms. Given this lack of data, many practitioners follow treatment guidelines for primary headaches. Additionally, because of mounting data linking PTSD to post-traumatic headache in combat veterans, it may be crucial to choose multimodal agents and take a multidisciplinary approach to combat-related headache.

Redundancy resolution of the human arm and an upper limb exoskeleton.

The human arm has 7 degrees of freedom (DOF) while only 6 DOF are required to position the wrist and orient the palm. Thus, the inverse kinematics of an human arm has a nonunique solution. Resolving this redundancy becomes critical as the human interacts with a wearable robot and the inverse kinematics solution of these two coupled systems must be identical to guarantee an seamless integration. The redundancy of the arm can be formulated by defining the swivel angle, the rotation angle of the plane defined by the upper and lower arm around a virtual axis that connects the shoulder and wrist joints. Analyzing reaching tasks recorded with a motion capture system indicates that the swivel angle is selected such that when the elbow joint is flexed, the palm points to the head. Based on these experimental results, a new criterion is formed to resolve the human arm redundancy. This criterion was implemented into the control algorithm of an upper limb 7-DOF wearable robot. Experimental results indicate that by using the proposed redundancy resolution criterion, the error between the predicted and the actual swivel angle adopted by the motor control system is less then 5°.

Training of goal-directed attention regulation enhances control over neural processing for individuals with brain injury.

Deficits in attention and executive control are some of the most common, debilitating and persistent consequences of brain injuries. Understanding neural mechanisms that support clinically significant improvements, when they do occur, may help advance treatment development. Intervening via rehabilitation provides an opportunity to probe such mechanisms. Our objective was to identify neural mechanisms that underlie improvements in attention and executive control with rehabilitation training. We tested the hypothesis that intensive training enhances modulatory control of neural processing of perceptual information in patients with acquired brain injuries. Patients (n=12) participated either in standardized training designed to target goal-directed attention regulation, or a comparison condition (brief education). Training resulted in significant improvements on behavioural measures of attention and executive control. Functional magnetic resonance imaging methods adapted for testing the effects of intervention for patients with varied injury pathology were used to index modulatory control of neural processing. Pattern classification was utilized to decode individual functional magnetic resonance imaging data acquired during a visual selective attention task. Results showed that modulation of neural processing in extrastriate cortex was significantly enhanced by attention regulation training. Neural changes in prefrontal cortex, a candidate mediator for attention regulation, appeared to depend on individual baseline state. These behavioural and neural effects did not occur with the comparison condition. These results suggest that enhanced modulatory control over visual processing and a rebalancing of prefrontal functioning may underlie improvements in attention and executive control.

Development and validation of the Function In Sitting Test in adults with acute stroke.

BACKGROUND AND PURPOSE: Research studies indicate that sitting balance ability is a substantial predictor of functional recovery after stroke. There are no gold standards for sitting balance assessment, and commonly used balance measures do not isolate sitting balance abilities. This study was designed to develop, pilot test, and analyze reliability and validity of a short test of functional sitting balance in patients following acute stroke. METHODS: The Function In Sitting Test (FIST) was constructed after reviewing balance measures and interviewing 15 physical therapists. A written survey regarding the FIST items and scoring scales was designed, pilot tested, and sent to 12 additional physical therapists with expertise in measurement construction, balance assessment, and/or research. Thirty-one adults who were within 3 months following stroke participated in this study. RESULTS: The expert panel survey was returned by 83.3% of the participants. Survey feedback and weighted rank analysis reduced the number of FIST items from 26 to 17. After subject testing, Item Response Theory analysis eliminated 3 additional items. The person separation index was 0.978 and the coefficient alpha was 0.98, indicating high internal consistency of the FIST. The Item Response Theory analysis confirmed content and construct validity. Concurrent validity was supported by high correlations to the modified Rankin Scale, static balance indices, and dynamic balance grades. DISCUSSION AND CONCLUSIONS: The 14-item FIST is reliable and valid in adults following acute stroke. Studies of intra- or intertester reliability and evaluative validity studies including applications to other patient populations with sitting balance dysfunction are now necessary.

Epilepsy, sleep disturbances, and psychiatric consequences.

Neurologic impairment after TBI causes serious morbidity for patients and their families. Prior articles have discussed headache and memory impairment. In this article, epilepsy, sleep disturbances, and psychiatric consequences will be covered. People who have suffered traumatic brain injury are at risk for any of these disturbances, and each person will have a constellation of neurologic symptoms spanning the spectrum from no difficulty in any area to symptoms in each of these areas.

Functional outcomes can vary by dose: learning-based sensorimotor training for patients stable poststroke.

OBJECTIVE: This study aimed to determine whether the dose of learning-based sensorimotor training (LBSMT) significantly enhances gains in upper limb function in patients stable post stroke. METHODS: A total of 45 subjects stable poststroke participated in a 6-8-week LBSMT program of varied dosage: group I (n = 18; 1x/week, 1.5 hours/visit); group II (n = 19, 3x/week, 0.75 hours/visit); and group III (n = 8; 4x/week, 3 hours/visit). All subjects reinforced their training with home-based practice. The primary outcome measures were functional independence, strength, sensory discrimination, and fine motor skills. RESULTS: Across all individual subjects, significant gains were measured on the 4 dependent variables (improvement ranging from 9.0% to 38.9%; P < .001). Group III made greater gains than groups I and II on functional independence, sensory discrimination, and fine motor skills, with a significant linear trend by dose for functional independence (P < .001). Only 2-3 subjects in groups I and II, respectively, would need to be treated at the high dosage of group III for one more subject to achieve >50% gain in functional independence. CONCLUSIONS: Learning-based sensorimotor training based on the principles of neuroplasticity was associated with improved function in patients stable poststroke. The gains were dose specific with the greatest change measured in subjects participating in the high-intensity treatment group.

A comprehensive analysis of gait impairment after experimental stroke and the therapeutic effect of environmental enrichment in rats.

Although gait changes are considered as reliable indices of stroke severity and efficacy of rehabilitative therapies in humans, data from animal models of focal ischemia are lacking. To determine the effect of stroke on gait function in adult rats with distal middle cerebral artery occlusion (MCAO), we assessed the longitudinal changes in gait using an automated computer-assisted gait analysis system. Four days after MCAO, intensity, maximal area of contact, and paw angle were significantly decreased in the affected forepaw whereas the double support time using ipsilateral paws increased. Relative print positions between the fore and hindpaws and limb coupling were also altered, suggesting that stroke affected sensorimotor status and reduced limb coordination. Except for paw angle, these impairments persisted for at least 5 weeks. However, unlike human stroke patients, stride length and stance were not affected in rats with MCAO. Environmental enrichment for 4 weeks improved paw contact area and relative print position of the affected limb and reduced double support time in ischemic rats compared with controls. Our results indicate that gait analysis provides great insight into various aspects of motor function changes in ischemic quadrupeds, and that environmental enrichment is beneficial in reducing a variety of poststroke gait impairments possibly through enhanced structural plasticity mechanisms within injured cortical neuronal networks underlying locomotor function.