Remote ischaemic conditioning combined with bimanual task training to enhance bimanual skill learning and corticospinal excitability in children with unilateral cerebral palsy: a study protocol of a single centre, phase II randomised controlled trial.

INTRODUCTION: Children with unilateral cerebral palsy (UCP) have difficulty in bimanual coordination that restricts the child's independence in daily activities. Although several efficacious interventions to improve bimanual coordination exist, these interventions often require higher training doses and have modest effect sizes. Thus, there is a critical need to find an effective priming agent that, when paired with task-specific training, will facilitate neurobiological processes to enhance the magnitude of training effects and subsequently improve functional capabilities of children with UCP. The aim of this study is to determine the effects of a novel priming agent, remote ischaemic conditioning (RIC), combined with bimanual training on bimanual skill learning and corticospinal excitability in children with UCP. METHODS AND ANALYSES: 46 children, aged 8-16 years, will be randomly assigned to receive RIC or sham conditioning combined with 5 days of bimanual skill (cup stacking) training (15 trials per session). RIC or sham conditioning will be performed with a standard conditioning protocol of five cycles of alternative inflation and deflation of a pressure cuff on the affected arm with the pressure of at least 20 mm Hg above systolic blood pressure for RIC and 25 mm Hg for sham conditioning. Primary outcomes will be movement time and corticospinal excitability measures determined with a single-pulse transcranial magnetic stimulation (TMS). Secondary outcomes include Assisting Hand Assessment, spatio-temporal kinematic variables and paired pulse TMS measures. All measures will be conducted before and immediately after the intervention. A mixed model analysis of variance will test the group×time interaction for all outcomes with group (RIC and sham) as between-subject and time (preintervention, postintervention) as within-subject factors. ETHICS AND DISSEMINATION: The study has been approved by the University Medical Centre Institutional Review Board (UMCIRB #21-001913). We will disseminate the study findings via peer-reviewed publications and presentations at professional conferences. TRIAL REGISTRATION NUMBER: NCT05777070.

Bimanual Movement Characteristics and Real-World Performance Following Hand-Arm Bimanual Intensive Therapy in Children with Unilateral Cerebral Palsy.

The purpose of this study was to quantify characteristics of bimanual movement intensity during 30 h of hand-arm bimanual intensive therapy (HABIT) and bimanual performance (activities and participation) in real-world settings using accelerometers in children with unilateral cerebral palsy (UCP). Twenty-five children with UCP participated in a 30 h HABIT program. Data were collected from bilateral wrist-worn accelerometers during 30 h of HABIT to quantify the movement intensity and three days pre- and post-HABIT to assess real-world performance gains. Movement intensity and performance gains were measured using six standard accelerometer-derived variables. Bimanual capacity (body function and activities) was assessed using standardized hand function tests. We found that accelerometer variables increased significantly during HABIT, indicating increased bimanual symmetry and intensity. Post-HABIT, children demonstrated significant improvements in all accelerometer metrics, reflecting real-world performance gains. Children also achieved significant and clinically relevant changes in hand capacity following HABIT. Therefore, our findings suggest that accelerometers can objectively quantify bimanual movement intensity during HABIT. Moreover, HABIT enhances hand function as well as activities and participation in real-world situations in children with UCP.

Corticomuscular Coherence in Children with Unilateral Cerebral Palsy: A Feasibility and Preliminary Protocol Study.

Objective This study assessed the feasibility of corticomuscular coherence measurement during a goal-directed task in children with unilateral cerebral palsy while establishing optimal experimental parameters. Methods Participants (Manual Ability Classification System levels I-III) completed a submaximal isometric goal-directed grip task during simultaneous electroencephalography and electromyography (EMG) acquisition. Results All participants (n = 11, 6 females, mean age 11.3 ±2.4 years) completed corticomuscular coherence procedures. Of the 40 trials obtained per extremity, an average of 29 (n = 9) and 27 (n = 10) trials were retained from the more- and less-affected extremities, respectively. Obtaining measurement stability required an average of 28 trials per extremity. Conclusion Findings from this work support the feasibility of corticomuscular coherence measurement in children with unilateral cerebral palsy. Acquiring 28 to 40 corticomuscular coherence trials per extremity is ideal. The experimental parameters established in this work will inform future corticomuscular coherence application in pediatric unilateral cerebral palsy.

Hand-Arm Bimanual Intensive Training in Virtual Reality: A Feasibility Study.

OBJECTIVE: The aim of the study was to evaluate the feasibility of virtual reality (VR) software built using the core concepts of hand-arm bimanual intensive training (HABIT) for improving upper extremity motor function in children with cerebral palsy (CP). METHODS: Eight children with CP participated in a 10-day, 40-hour HABIT program. Half of the time custom VR software, HABIT-VR was used. The children's motor skills were assessed pre- and postintervention with the Assisting Hand Assessment, Box and Blocks Test, and Nine-Hole Peg Test. RESULTS: The children had significant and clinically relevant changes in the Assisting Hand Assessment and Box and Blocks Test; however, Nine-Hole Peg Test scores did not change with intervention. CONCLUSION: These data suggest that combining traditional HABIT strategies with HABIT-VR games improve upper extremity function and gross motor skills but not fine motor skills.

Exploration of a novel physical therapy protocol that uses a sensory substitution device to improve the standing postural balance of children with balance disorders.

OBJECTIVE: To explore if an intensive balance training protocol that incorporated the BrainPort sensory substitution device improves the standing postural balance of children with balance disorders. METHODS: Eight children with balance disorders received 8-weeks of balance training while using the BrainPort device. Pre- and post-intervention changes in the Bruininks-Oseretsky Test of Motor Proficiency balance subtest (BOT-2) scores, standing duration on an unstable surface, and center of pressure (COP) sway were assessed. RESULTS: Post-intervention, the BOT-2 balance subtest scores increased by 29.6% and demonstrated clinically meaningful improvements. Overall, the standing duration with vision increased. The standing duration on the unstable surface without vision increased significantly from pre- to post-intervention. However, anterior-posterior (AP) and medial-lateral (ML) sway did not change post-intervention. The children also reported new functional activities (i.e. riding a bike, standing on unsteady or narrow surfaces). CONCLUSION: Balance training with the BrainPort sensory substitution device has the potential to result in clinically relevant improvements in the standing postural balance of children with balance disorders.

Cognitive-Motor Interference Heightens the Prefrontal Cortical Activation and Deteriorates the Task Performance in Children With Hemiplegic Cerebral Palsy.

OBJECTIVE: To compare the prefrontal cortex (PFC) activation and task performance during single- and dual-task conditions between typically developing (TD) children and children with hemiplegic cerebral palsy (HCP). DESIGN: A prospective, comparative design. SETTING: Research laboratory. PARTICIPANTS: Participants (N=21) included 12 TD children (age, 6.0±1.1y) and 9 children with HCP (age, 7.2±3.1). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: PFC activation was assessed by measuring the concentration of oxygenated hemoglobin while the children performed a shape-matching task with their more affected arm while sitting on a stable (single task) vs dynamic surface (dual task). The task performance was assessed with the total number of shapes matched, dual-task cost, and reaction time (RT). RESULTS: For both conditions, the children with HCP exhibited greater PFC activation, matched a fewer shapes, and had slower RT than the TD children. These differences were accentuated during the dual-task condition and the dual-task cost was greater. An increase in the PFC activation during the dual-task condition was tightly correlated with a higher dual-task cost in children with HCP (r=0.77, P=.01). CONCLUSIONS: Children with HCP appear to have a heightened amount of PFC activity while performing a dual task. The greater cortical activity may be a result of the finite attentional resources that are shared between both the motor as well as cognitive demands of the task. The cognitive-motor interference is likely exacerbated in children with HCP because of the structural and functional brain changes as a result of an insult to the developing brain.

Effects of remote limb ischemic conditioning on muscle strength in healthy young adults: A randomized controlled trial.

Remote limb ischemic conditioning (RLIC) is a clinically feasible method in which brief, sub-lethal bouts of ischemia protects remote organs or tissues from subsequent ischemic injury. A single session of RLIC can improve exercise performance and increase muscle activation. The purpose of this study, therefore, was to assess the effects of a brief, two-week protocol of repeated RLIC combined with strength training on strength gain and neural adaptation in healthy young adults. Participants age 18-40 years were randomized to receive either RLIC plus strength training (n = 15) or sham conditioning plus strength training (n = 15). Participants received RLIC or sham conditioning over 8 visits using a blood pressure cuff on the dominant arm with 5 cycles of 5 minutes each alternating inflation and deflation. Visits 3-8 paired conditioning with wrist extensors strength training on the non-dominant (non-conditioned) arm using standard guidelines. Changes in one repetition maximum (1 RM) and electromyography (EMG) amplitude were compared between groups. Both groups were trained at a similar workload. While both groups gained strength over time (P = 0.001), the RLIC group had greater strength gains (9.38 ± 1.01 lbs) than the sham group (6.3 ± 1.08 lbs, P = 0.035). There was not a significant group x time interaction in EMG amplitude (P = 0.231). The RLIC group had larger percent changes in 1 RM (43.8% vs. 26.1%, P = 0.003) and EMG amplitudes (31.0% vs. 8.6%, P = 0.023) compared to sham conditioning. RLIC holds promise for enhancing muscle strength in healthy young and older adults, as well as clinical populations that could benefit from strength training.

Dose of remote limb ischemic conditioning for enhancing learning in healthy young adults.

Remote limb ischemic conditioning (RLIC) is a technique in which tissues distant from the target organ are exposed to brief, sub-lethal bouts of ischemia. The effects of remotely applied ischemic conditioning are systemically transferred to the target organ, and typically manifested as protection from subsequent ischemic injury. Previous studies in our lab have found and confirmed that RLIC enhances learning and retention during motor training on a balance task. The current study tested the effect of RLIC dose (number of cycles) on learning enhancement in young, healthy adults. Forty healthy participants age 18-40 years were randomized to receive 5 cycles of sham conditioning (n = 9), 3 cycles of RLIC (n = 11), 4 cycles of RLIC (n = 10), or 5 cycles of RLIC (n = 10) using a blood pressure cuff around the upper arm once a day for 7 consecutive weekdays (Days 1-7). Participants concurrently trained on a balance task, bimanual cup stacking task, and a discrete sequence production task on Days 3-7. Change in performance on each of the three tasks was compared across groups. Participants in all four groups improved their performance on each of the three tasks over time. However, RLIC at any dose did not enhance learning on any of the three tasks. While RLIC is safe, inexpensive, and clinically feasible, reproducibility may be challenged by unidentified factors, raising critical challenges to the straightforward translation of RLIC for improving rehabilitation outcomes in individuals recovering from neurological injury.

Sequencing of Chemotherapy and Radiotherapy for Newly Diagnosed Anaplastic Oligodendroglioma and Oligoastrocytoma.

INTRODUCTION: Adjuvant management of anaplastic oligodendrogliomas (AOs) and anaplastic oligoastrocytomas (AOAs) is guided by 2 seminal phase III trials, one of which utilized radiotherapy (RT) followed by chemotherapy (CT) (RT-CT), and the other in which CT was followed by RT (CT-RT). Both paradigms are endorsed by the National Comprehensive Cancer Network because no direct comparison in the first-line (nonprogressive) setting has been performed to date. This study of a contemporary national database sought to evaluate practice patterns and outcomes between both approaches. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for newly diagnosed AO/AOA treated with postoperative sequential CT-RT or RT-CT. Multivariable logistic regression ascertained factors independently associated with delivery of a particular paradigm. Overall survival (OS) between cohorts was compared using Kaplan-Meier methodology. Univariate and multivariate Cox proportional hazards modeling evaluated factors associated with OS. RESULTS: Of 225 patients, 19 (8.4%) received CT-RT and 206 (91.6%) underwent RT-CT. Groups were well-balanced, although CT-RT was more often administered to men (P=0.009) and AOs (P=0.037). Median follow-up was 58 months. Median OS in the CT-RT cohort was 93 months (95% confidence interval, 37-150 mo), and 107 months (95% confidence interval, 72-142 mo) in the RT-CT group (P=0.709). Therapy sequence was not associated with OS on univariate (P=0.709) or multivariate (P=0.257) assessment. CONCLUSIONS: In the United States, most AO/AOA patients receiving sequential therapy undergo RT followed by CT. No differences in survival were observed with either approach; this addresses a knowledge gap and confirms that both paradigms are appropriate in the first-line setting.

Remote Limb Ischemic Conditioning and Motor Learning: Evaluation of Factors Influencing Response in Older Adults.

Remote limb ischemic conditioning (RLIC) is a clinically feasible method of promoting tissue protection against subsequent ischemic insult. Recent findings from our lab demonstrated that RLIC robustly enhances motor learning in young, healthy humans. The next step is to determine which individuals would receive maximum benefit from RLIC before applying these findings to clinical rehabilitation populations such as stroke. Numerous factors, such as age, sex, body mass index (BMI), and cardiovascular comorbidities may influence the response. Sixty-nine participants aged 40-80 were randomized to receive either RLIC (n = 33) or sham (n = 36) conditioning. Participants underwent seven consecutive sessions consisting of RLIC or sham conditioning with a blood pressure cuff on the upper extremity and motor training on a stability platform balance task, with two follow-up sessions. Balance change (post-test-pre-test) was compared across participants, groups, and the factors of age, sex, BMI, and comorbidities. Participants in both groups improved their performance on the balance task from pre- to post-test. Overall balance change was independently associated with age and BMI. There was no difference in balance change between RLIC and Sham groups. However, RLIC significantly enhanced balance performance in participants with no comorbidities. Compared with our previous study in young adults, middle-aged and older adults demonstrated smaller improvements on the balance task. RLIC enhanced learning in middle-aged and older adults only in the absence of pre-defined comorbidities. RLIC may be a promising tool for enhancing motor recovery, but the accumulation of comorbidity with age may decrease its effectiveness.

Impaired anticipatory vision and visuomotor coordination affects action planning and execution in children with hemiplegic cerebral palsy.

BACKGROUND: Action-planning and execution deficits in children with hemiplegic cerebral palsy (HCP) are potentially due to deficits in the integration of sensory information, such as vision, with motor output. AIMS: To determine differences in anticipatory visual patterns in children with HCP compared to typically developing (TD) children, and to assess visuomotor coordination in children with HCP. METHODS AND PROCEDURES: We included 13 children with HCP (Age = 6.8 + 2.9 yrs) and 15 TD children (Age = 5.8 + 1.1 yrs). The experimental task used in this study is a valid action-planning task, which consisted of initially reaching and grasping an object placed at a fixed position, followed by placing the object in a random target position. Visual patterns were recorded using a head-mounted eye-tracker system and arm movements were recorded using motion capture (120 Hz). OUTCOMES AND RESULTS: Children with HCP had delayed anticipatory gaze time and longer latency than TD children during the planning and execution phases. Children with HCP also had a higher frequency of gaze shifts, longer reaction times (RT) and movement times (MT) than TD children. CONCLUSIONS AND IMPLICATIONS: Children with HCP may have deficits in anticipatory vision, which potentially affected planning and executing a goal-directed action. Therapeutic interventions focusing on improving visuomotor coordination may improve the motor performance in children with HCP.

Practice patterns and outcomes of chemoradiotherapy versus radiotherapy alone for older patients with nasopharyngeal cancer.

Older patients are at increased risk of toxicities from aggressive oncologic therapy and of nononcologic death. A meta-analysis of non-nasopharyngeal head and neck cancers showed no statistical benefit in adding chemotherapy to radiotherapy (RT) in older patients; another meta-analysis of RT versus chemoradiotherapy (CRT) in NPC found advantages to CRT, but vastly under-represented patients ≥70 years old. This is the largest study to date evaluating outcomes of CRT versus RT alone in this population. The National Cancer Data Base (NCDB) was queried for primary nasopharyngeal cancer cases (2004-2013) in patients ≥70 years old receiving RT alone or CRT. Patients with unknown RT/chemotherapy and T1N0 or M1 disease were excluded. Logistic regression analysis ascertained factors associated with CRT delivery. Kaplan-Meier analysis evaluated overall survival (OS) between both cohorts. Cox proportional hazards modeling determined variables associated with OS. In total, 930 patients were analyzed (n = 713 (77%) CRT, n = 217 (23%) RT). Groups were relatively balanced; CRT was less frequently delivered in patients with advancing age, lower nodal burden, and females (P < 0.05 for all). Median OS in the CRT and RT groups were 35.3 versus 20.0 months, respectively (P = 0.002). On multivariate analysis, independent predictors of OS included age, comorbidities, income and insurance status, tumor grade, and stage (P < 0.05 for all). Notably, receipt of chemotherapy independently predicted for improved OS (P = 0.036). CRT, compared to RT alone, was independently associated with improved survival in NPC patients ≥70 years old. CRT appears to be a promising approach in this population, but treatment-related toxicity risks should continue to be weighed against potential oncologic benefits.

Neural activation within the prefrontal cortices during the goal-directed motor actions of children with hemiplegic cerebral palsy.

The primary aim of the study was to explore the prefrontal cortical (PFC) activation while performing a shape-matching motor task in children with hemiplegic cerebral palsy (HCP) as compared with typically developing (TD) children. Fifteen TD children ([Formula: see text]) and 12 children with HCP ([Formula: see text]) were included. We assessed the PFC activation while performing an ecologically valid upper extremity shape-matching task of different complexities by measuring the concentration of oxygenated hemoglobin (HbO) using functional near-infrared spectroscopy. The motor task performance was assessed by quantifying the average number of shapes matched, reaction time (RT), task errors, nine-hole peg test (NHPT), and the box and block test (BBT). Overall, there was a systematic increase in the HbO in the PFC across the shape-matching complexity conditions. Our results also revealed that the children with HCP had an increased amount of PFC activation while performing all of the shape-matching tasks. The increased PFC activation paralleled the differences in the number of shapes matched, RT, task errors, NHPT, and BBT. The atypical motor actions seen in children with HCP may be partially related to the greater cognitive demands placed on the PFC.

Hand-Arm Bimanual Intensive Therapy Improves Prefrontal Cortex Activation in Children With Hemiplegic Cerebral Palsy.

PURPOSE: To determine the changes in the prefrontal cortical (PFC) activation following hand-arm bimanual intensive therapy (HABIT) in children with hemiplegic cerebral palsy (HCP). METHODS: Nine children with HCP and 15 children who were developing typically participated in the study. Children with HCP received 50 hours of HABIT. We assessed pre- and post-HABIT PFC activation using functional near-infrared spectroscopy neuroimaging. Bimanual coordination and motor task performance were assessed using the Assisting Hand Assessment (AHA), the average number of shapes matched, the shape matching errors, the reaction time, the 9-hole peg test, and the box and blocks test. RESULTS: The PFC activation decreased following HABIT and became similar to what was seen in the children who were developing typically. Post-HABIT PFC activation improvements paralleled with the improvements seen in the AHA and the behavioral outcomes. CONCLUSION: HABIT potentially improves the PFC's involvement in the action planning of the upper extremity movements in children with HCP.

Chemoradiotherapy Versus Chemotherapy Alone for Unresected Nonmetastatic Gallbladder Cancer: National Practice Patterns and Outcomes.

Purpose: Current guidelines recommend chemotherapy (CT) with or without radiotherapy for unresected nonmetastatic gallbladder cancer (GC), with little consensus. However, several small-volume, single-institution studies have documented the efficacy of local therapy for this population. This is the largest study to date evaluating outcomes of chemoradiotherapy (CRT) versus CT alone in unresected nonmetastatic GC. Methods: The National Cancer Database was queried for primary GC cases (2004-2013) receiving CT alone or CRT. Patients receiving resection or lack of CT were excluded, as were those with metastatic disease or unknown M classification. Logistic regression analysis ascertained factors associated with CRT delivery. Kaplan-Meier analysis evaluated overall survival (OS) between both cohorts. Cox proportional hazards modeling determined variables associated with OS. Results: In total, 1,199 patients were analyzed (CRT: n=327, 27%; CT: n=872, 73%). Groups were evenly balanced, with no factor on multivariate logistic regression analysis statistically predicting for receipt of a particular paradigm. Median OS in the CRT and CT groups was 12.9 versus 7.8 months, respectively (P=.001). On multivariate analysis, OS was associated with age and years of treatment (P=.001 each). Notably, receipt of CRT independently predicted for improved OS (P=.001). Conclusions: CRT, compared with CT alone, was independently associated with improved survival in unresected nonmetastatic GC. Although causation is not implied, these results support the necessity for prospective CRT evaluation.

Sitting postural control affects the development of focused attention in children with cerebral palsy.

PURPOSE: To investigate whether focused attention (FA) changes over time as sitting postural control improves and whether an impairment in sitting postural control affects the development of FA in children with cerebral palsy (CP). METHODS: Nineteen children with CP, mean ages 21.47 months, were assessed for FA and sitting scores pre- and postintervention. RESULTS: Longest, total, and global FA increased and frequency of FA decreased in children who achieved independent sitting. However, children who achieved mobility postintervention exhibited a decrease in longest FA and an increase in frequency of FA. CONCLUSION: Sitting postural control and the development of FA appear associated in children with CP. The increase in FA may signal a key opportunity for learning and attending to objects. However, the time of early mobility may interrupt these long periods of attention, resulting in less sustained attention to objects.

Delayed onset neuropathy along with recurrent laryngeal nerve palsy due to organophosphate poisoning and the role of physiotherapy rehabilitation.

Organophosphorus poisoning is a major global cause of health problems and the leading cause of mortality and morbidity in the developing countries. In this, the inhibition of acetyl-choline esterase and neurotoxic esterase along with nicotinic receptor involvement produces three well-identified and documented clinical phases: The initial cholinergic phase, which is a medical emergency often requiring management in an intensive care unit; the intermediate syndrome, during which prolonged ventilator care is necessary; and finally delayed neurotoxicity. Vocal cord paralysis is rare and leads to aphonia. Role of physiotherapy rehabilitation is substantial in all three stages and aims at early weaning off from mechanical ventilator until the functional independence and community integration of the patient.