Emerging methods for measuring physical activity using accelerometry in children and adolescents with neuromotor disorders: a narrative review.

BACKGROUND: Children and adolescents with neuromotor disorders need regular physical activity to maintain optimal health and functional independence throughout their development. To this end, reliable measures of physical activity are integral to both assessing habitual physical activity and testing the efficacy of the many interventions designed to increase physical activity in these children. Wearable accelerometers have been used for children with neuromotor disorders for decades; however, studies most often use disorder-specific cut points to categorize physical activity intensity, which lack generalizability to a free-living environment. No reviews of accelerometer data processing methods have discussed the novel use of machine learning techniques for monitoring physical activity in children with neuromotor disorders. METHODS: In this narrative review, we discuss traditional measures of physical activity (including questionnaires and objective accelerometry measures), the limitations of standard analysis for accelerometry in this unique population, and the potential benefits of applying machine learning approaches. We also provide recommendations for using machine learning approaches to monitor physical activity. CONCLUSIONS: While wearable accelerometers provided a much-needed method to quantify physical activity, standard cut point analyses have limitations in children with neuromotor disorders. Machine learning models are a more robust method of analyzing accelerometer data in pediatric neuromotor disorders and using these methods over disorder-specific cut points is likely to improve accuracy of classifying both type and intensity of physical activity. Notably, there remains a critical need for further development of classifiers for children with more severe motor impairments, preschool aged children, and children in hospital settings.

Brain-Derived Neurotrophic Factor in Pediatric Acquired Brain Injury and Recovery.

We review emerging preclinical and clinical evidence regarding brain-derived neurotrophic factor (BDNF) protein, genotype, and DNA methylation (DNAm) as biomarkers of outcomes in three important etiologies of pediatric acquired brain injury (ABI), traumatic brain injury, global cerebral ischemia, and stroke. We also summarize evidence suggesting that BDNF is (1) involved in the biological embedding of the psychosocial environment, (2) responsive to rehabilitative therapies, and (3) potentially modifiable. BDNF's unique potential as a biomarker of neuroplasticity and neural repair that is reflective of and responsive to both pre- and post-injury environmental influences separates it from traditional protein biomarkers of structural brain injury with exciting potential to advance pediatric ABI management by increasing the accuracy of prognostic tools and informing clinical decision making through the monitoring of therapeutic effects.

Restoration of sensory feedback from the foot and reduction of phantom limb pain via closed-loop spinal cord stimulation.

Restoring somatosensory feedback in individuals with lower-limb amputations would reduce the risk of falls and alleviate phantom limb pain. Here we show, in three individuals with transtibial amputation (one traumatic and two owing to diabetic peripheral neuropathy), that sensations from the missing foot, with control over their location and intensity, can be evoked via lateral lumbosacral spinal cord stimulation with commercially available electrodes and by modulating the intensity of stimulation in real time on the basis of signals from a wireless pressure-sensitive shoe insole. The restored somatosensation via closed-loop stimulation improved balance control (with a 19-point improvement in the composite score of the Sensory Organization Test in one individual) and gait stability (with a 5-point improvement in the Functional Gait Assessment in one individual). And over the implantation period of the stimulation leads, the three individuals experienced a clinically meaningful decrease in phantom limb pain (with an average reduction of nearly 70% on a visual analogue scale). Our findings support the further clinical assessment of lower-limb neuroprostheses providing somatosensory feedback.

Bilateral symmetry in ankle-muscle activation in transtibial amputees.

By 2020, over 2.2 million people in the United States will be living with an amputated lower limb. The functional impact of amputations presents significant challenges in daily living activities. While significant work has been done to develop smart prosthetics, for the long-term development of effective and robust myoelectric control systems for transtibial amputees, there is still much that needs to be understood regarding how extrinsic muscles of the lower limb are utilized post-amputation. In this study, we examined muscle activity between the intact and residual limbs of three transtibial amputees with the aim of identifying differences in voluntary recruitment patterns during a bilateral motor task. We report that while there is variability across subjects, there are consistencies in the muscle recruitment patterns for the same functional movement between the intact and the residual limb within each subject. These results provide insights for how symmetric activation in residual muscles can be characterized and used to develop myoelectric control strategies for prosthetic devices in transtibial amputees.

A new methodology to record from human primary afferents provides insight for somatosensory neuroprosthetics.

Muscle spindles are integral to proprioception and their behavior is of particular interest for the design of somatosensory neuroprostheses. Prior knowledge about human muscle spindles has been limited to microneurography recordings in peripheral nerves using joint movements that do not disrupt the electrode. Recent studies demonstrate a new methodology for studying the afferent encoding of proprioception during freestanding, providing important information for neural engineering and the broader scientific community (Knellwolf TP, Burton AR, Hammam E, Macefield VG. J Neurophysiol 120: 953-959, 2018; Knellwolf TP, Burton AR, Hammam E, Macefield VG. J Neurophysiol 121: 74-84, 2019; Macefield VG, Knellwolf TP. J Neurophysiol 120: 452-467, 2018).

Phantom limb pain: peripheral neuromodulatory and neuroprosthetic approaches to treatment.

Post-amputation phantom limb pain (PLP) is a widespread phenomenon that can have physical, psychological, and functional impacts on amputees who experience the condition. The varying presentations and mechanisms of PLP make it difficult to effectively provide long-term pain relief. Multiple neuromodulatory approaches to treating PLP have focused on electrical stimulation of the peripheral nervous system, with varying degrees of success. More recently, research has been done to study the effects of neuroprosthetic approaches on PLP. Neuroprosthetics combine the use of a functional prosthetic with stimulation to the peripheral nerves in the residual limb. Although many of the neuroprosthetic studies focus on improving function, several have shown preliminary evidence for the reduction of severity of PLP. In this review we provide an overview of the current understanding of the neurological mechanisms that initiate and sustain PLP, as well as the neuromodulatory and neuroprosthetic approaches under development for treatment of the condition. Muscle Nerve 59:154-167, 2019.

Low load, high repetition resistance training program increases bone mineral density in untrained adults.

BACKGROUND: High load, low repetition resistance training increases BMD in untrained adults; however, many older and untrained adults cannot maintain this type of strenuous program. Our goal was to evaluate whether a low load, high repetition resistance training program would increase BMD in untrained adults. METHODS: Twenty sedentary, but otherwise healthy, adults (6 men and 14 women, age 28-63 yrs) completed a 27-week group exercise program. The participants were randomly assigned to one of two strength groups: one group completed full body, low load, high repetition weight training classes (S-WEIGHT), while the other group completed core focused fusion classes (S-CORE). Both groups also completed indoor cycling classes for cardiovascular conditioning. After a 3-week familiarization period, all participants completed a 12-week block of 5 fitness classes per week (3 cycling + 2 strength) and concluded with another 12-week block of 6 classes per week (3 cycling + 3 strength). We completed iDXA scans at baseline (week 3) and final (week 28). RESULTS: Compared to baseline, BMD significantly increased for S-WEIGHT in the arms (+4%, P<0.001), legs (+8%, P<0.01), pelvis (+6%, P<0.01) and lumbar spine (+4%, P<0.05), whereas BMD did not significantly change for S-CORE at any site. CONCLUSIONS: These results suggest that a low load, high repetition resistance training program may be an effective method to improve bone mass in adults.

Targeting of survivin by nanoliposomal ceramide induces complete remission in a rat model of NK-LGL leukemia.

The natural killer (NK) type of aggressive large granular lymphocytic (LGL) leukemia is a fatal illness that pursues a rapid clinical course. There are no effective therapies for this illness, and pathogenetic mechanisms remain undefined. Here we report that the survivin was highly expressed in both aggressive and chronic leukemic NK cells but not in normal NK cells. In vitro treatment of human and rat NK-LGL leukemia cells with cell-permeable, short-chain C6-ceramide (C6) in nanoliposomal formulation led to caspase-dependent apoptosis and diminished survivin protein expression, in a time- and dose-dependent manner. Importantly, systemic intravenous delivery of nanoliposomal ceramide induced complete remission in the syngeneic Fischer F344 rat model of aggressive NK-LGL leukemia. Therapeutic efficacy was associated with decreased expression of survivin in vivo. These data suggest that in vivo targeting of survivin through delivery of nanoliposomal C6-ceramide may be a promising therapeutic approach for a fatal leukemia.