Brandenburg, Joline E.

AbstractAimThis study describes the process of updating the cerebral palsy (CP) common data elements (CDEs), specifically identifying tools that capture the impact of chronic pain on children's functioning.MethodThrough a partnership between the American Academy for Cerebral Palsy and Developmental Medicine and the National Institute of Neurological Disorders and Stroke (NINDS), the CP CDEs were developed as data standards for clinical research in neuroscience. Chronic pain was underrepresented in the NINDS CP CDEs version 1.0. A multi‐step methodology was applied by an interdisciplinary professional team. Following an adapted CP chronic pain tools' rating system, and a review of psychometric properties, clinical utility, and compliance with inclusion/exclusion criteria, a set of recommended pain tools was posted online for external public comment in May 2022.ResultsFifteen chronic pain tools met inclusion criteria, representing constructs across all components of the International Classification of Functioning, Disability and Health.InterpretationThis paper describes the first condition‐specific pain CDEs for a pediatric population. The proposed set of chronic pain tools complement and enhance the applicability of the existing pediatric CP CDEs. The novel CP CDE pain tools harmonize the assessment of chronic pain, addressing not only intensity of chronic pain, but also the functional impact of experiencing it in everyday activities.

During embryonic development, the number of phrenic motor neurons (PhMNs) declines precipitously during the final trimester and continues into the early postnatal period. When BDNF/TrkB signaling is absent in utero, animals do not survive after birth, most likely due to excessive loss of vital motor neurons (e.g., PhMNs). Far less is known about the early postnatal effect of BDNF/TrkB signaling. We have shown that BDNF/TrkB signaling is important in promoting PhMN neuroplasticity in mature rodents. Taken together, we hypothesized that inhibition of BDNF/TrkB signaling during early postnatal development results in fewer PhMNs. Chemo-genetic TrkBF616A mutant mice were used to induce inhibition of TrkB kinase activity in response to oral administration (via drinking water) of a phosphoprotein phosphatase 1 inhibitor derivative (1NMPP1). 1NMPP1-induced TrkB kinase inhibition was initiated at P0 and continued until P21 and compared to untreated control mice. At P28, PhMNs were retrogradely labeled via rhodamine phrenic nerve dip. One day later, mice were euthanized, perfused with 4% paraformaldehyde, and the cervical spinal cord was excised and processed for longitudinal cryosectioning (70 μm). Labeled PhMNs were imaged by 3D high resolution confocal microscopy. The number of PhMNs were counted. PhMN somal surface area and number of primary dendrites were also determined. 1NMPP1-induced inhibition of TrkB kinase resulted in 24% fewer PhMNs (P=0.01) and 21% more primary dendrites (P=0.0002) than control mice. The distribution of PhMN somal surface areas was not affected. We conclude that BDNF/TrkB signaling is essential in promoting survival of PhMNs in the early postnatal period. BDNF/TrkB signaling during postnatal development also plays a role in paring primary dendrites. While inhibition of TrkB kinase did not significantly alter the distribution of PhMN somal surface areas at P28, it is possible that further growth of PhMNs into maturity might have been altered as larger PhMNs emerge as a result of disproportionate growth beyond this age in mice. Supported by National Institutes of Health grants R01-AG044615 (GCS), R01-HL96750 (GCS). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Baclofen is often considered a first-line treatment option for spasticity management in children. However, adverse effects, administration, and dosing can be barriers to effectiveness. In my practice, other medications for spasticity management are often used prior to initiating baclofen. In this article, baclofen use for spasticity management in children is briefly reviewed along with discussion of approaches using other medications as first-line treatment options. I will present a rationale for medication selection for spasticity management and discuss the approaches I take in medication selection that incorporate spasticity severity, patient goals, and medication side effect profiles.

Developmental motor control dysfunctions, including spastic cerebral palsy (sCP) often have respiratory components. Spa mutant mice exhibit a spastic phenotype closely resembling sCP symptoms. Using the spa mouse model of spastic cerebral palsy (sCP), we quantified transdiaphragmatic pressure deficits, diaphragm muscle weakness, and fiber type-specific atrophy, improving our understanding of respiratory dysfunctions in sCP.

In rats, there is a strong association between the expansion of phrenic motor neuron (PhMN) size (from ~21‐28 days postnatal), the emergence of mature diaphragm muscle (DIAm) myosin heavy chain (MyHC 2X and MyHC 2B ) isoform expression, alongside the manifestation of mature morphological and functional properties. Despite mice models being de rigueur for developmental investigations, the postnatal development of mouse PhMN and DIAm properties have not been comprehensively characterized. Using wildtype C57 mice at ages P7, P14, P21, P28, and >3 months (maturity) we evaluated PhMN and DIAm physiologic properties. PhMNs were labelled via rhodamine phrenic nerve dip, processed for longitudinal cryosectioning (70 µm) and prepared for confocal imaging and PhMN assessment. Ex vivo DIAm strips were used for functional assessments of maximum specific force (P o ) and fatigue. DIAm strips were also fresh‐frozen, with 8 µm cross‐sections immuno‐labelled for MyHC slow , MyHC 2A , MyHC 2X and MyHC 2X and processed for fluorescent assessment. The number of PhMNs remained stable throughout postnatal life (~195), while PhMN surface area increased steadily, ~10% from P14 to P21, P21 to P28, and P28 to maturity, with overall ~30% increase from P14 to maturity. The biggest changes in number of primary dendrites occurred between P14 and P28 and between P28 and maturity, 25% decrease in primary dendrites between each group. DIAm maximum P o increased in two phases, 3.5‐fold from P7 to P14 and remained similar until P21. The second large increase was ~3‐fold from P21 to P28 and remained steady to maturity. The fatiguability of the DIAm increased with age in two phases, with fatigability being similar from P7 and P14 and increasing by ~20% at P21. Following, fatigability of the DIAm was similar from P21 to P28 and increased by ~35% at maturity. These major PhMN and DIAm changes coincide with the steady growth of PhMN and the emergence of MyHC 2X and MyHC 2B expression in DIAm from P14 to P21 onwards. The maturation of orderly PhMN recruitment likely depends on an interplay between PhMN size properties and network inputs to a refined dendritic tree. We show that DIAm muscle fiber maturation in mice hinges on the expression of MyHC 2X and MyHC 2B isoforms that is associated with an ~10 fold increase in DIAm force‐generation capacity.

AbstractBotulinum toxin has been used in medicine for the past 30 years. However, there continues to be controversy about the appropriate uses and dosing, especially in the pediatric population. A panel of nine pediatric physiatrists from different regions and previous training programs in the United States were nominated based on institutional reputation and botulinum toxin (BoNT) experience. Based on a review of the current literature, the goal was to provide the rationale for recommendations on the administration of BoNT in the pediatric population. The goal was not only to review safety, dosing, and injection techniques but also to develop a consensus on the appropriate uses in the pediatric population. In addition to upper and lower limb spasticity, the consensus also provides recommendations for congenital muscular torticollis, cervical dystonia, sialorrhea, and brachial plexus palsies.

Glycine (Gly) is a key inhibitory neurotransmitter at phrenic motor neurons (PhMN). In development, Gly is excitatory, transitioning to inhibitory action in the postnatal period. In adult conditions such as amyotrophic lateral sclerosis (ALS), excessive excitatory signaling onto motor neurons results in excitotoxic motor neuron death. However, it is not known how an imbalance of neurotransmission early in development impacts PhMNs at maturity. This is a knowledge gap, as some congenital hypertonia conditions exhibit an imbalance in neurotransmitter signaling, with these individuals suffering significant morbidity and mortality from respiratory disorders. Using an animal model of congenital hypertonia ( spa mouse [B6.Cg‐ Glrb spa /J] with a Gly receptor mutation), we evaluated PhMN and motor unit physiology. Similar to previous work in other Gly mutants, we hypothesized that spa mice will have excessive developmental PhMN loss with preserved PhMNs having a smaller somal size compared to wildtype (WT) mice. We also hypothesized that fewer PhMNs in spa mice will result in an increased diaphragm (DIAm) innervation ratio (number of DIAm fibers innervated by a PhMN) and increased DIAm neuromuscular transmission failure (NMTF). S pa and WT mice from our colony, ages 6 to 16 weeks, underwent unilateral retrograde labeling of PhMNs via rhodamine phrenic nerve dip. After three days, mice were euthanized, perfused with 4% paraformaldehyde, cervical spinal cord excised and processed for longitudinal cryosectioning (70 µm) and prepared for confocal imaging. Absolute PhMN counts were obtained using mosaic images of adjacent serial sections. Somal size measurements (i.e. surface area) were obtained using ImageJ. DIAm force was determined from DIAm strip preparations stretched to optimal length, and force was evoked by phrenic nerve stimulation at 40 Hz in 330 ms duration trains repeated each s (33% duty cycle) for 120 s. To assess NMTF, force evoked by phrenic nerve stimulation was compared to force evoked by direct DIAm stimulation superimposed every 15 s. Total DIAm fiber number was estimated in H&E stained cross‐sections. S pa mice had 30% fewer PhMNs compared to WT ( P =0.005) with somal size being 22% smaller in spa mice ( P =0.019). Spa mice had 20% NMTF during the initial stimulus train compared to 8% in WT mice with spa mice having 82% NMTF and WT having 40% NMTF at end of stimulation. Spa mice had a 39% greater innervation ratio of DIAm motor units compared to WT. Developmental PhMN loss and somal size is significantly disrupted in congenital hypertonia due to impaired Gly signaling and may impact performance of high‐force expulsive DIAm activities. In addition, the increased innervation ratio of DIAm motor units in spa mice, likely contributes to the NMTF due to branch point failure. Overall, this results in less effective airway defense and straining behaviors in congenital hypertonia. Our next step is to identify crucial developmental milestones when excessive PhMN loss occurs and the impact on large versus small PhMNs.

Individuals with motor control deficits, including cerebral palsy (CP) often have respiratory impairments. Glycine-receptor mutant spa mice have early-onset hypertonia, and limb motor impairments, similar to individuals with CP. We hypothesized that in the diaphragm of spa mice, disruption of glycinergic inputs to MNs would result in increased phrenic–DIAm neuromuscular transmission failure. Pathophysiologic abnormalities in neuromuscular transmission may contribute to respiratory dysfunction in conditions where early developmental MN loss or motor control deficits are apparent.

Over 80% of the children in the world have had their education impacted by COVID-19. For children with disabilities who receive special education services, access to in-person education and other resources at school is particularly important. The American Academy of Pediatrics advocates for students to attend school in person, without specifics for how children with disabilities can safely return to school. To appropriately plan and accommodate children with disabilities we must prioritize safety, allow for adherence to the Individuals with Disabilities Education Act, and preserve essential school staff. The less cumbersome default of confining students with disabilities to home is not acceptable. We provide an outline describing why Individual Education Plans and 504 plans are important, how they are related to the COVID-19 pandemic, and recommendations for measures to help with safe return to school for children with disabilities.

The COVID-19 pandemic has accelerated many changes in medicine including the transition from providing care in person to providing care via technology enabled telemedicine. The benefits of telemedicine visits with a Pediatric Rehabilitation Medicine (PRM) provider, also known as telerehabilitation medicine visits, are numerous. Telerehabilitation medicine provides an opportunity to deliver timely, patient and family-centric rehabilitation care while maintaining physical distance and reducing potential COVID-19 exposure for our patients, their caregivers and medical providers. Telerehabilitation medicine also allows for access to PRM care in rural areas or areas without medical specialty, virtual in-home equipment evaluation, and reduced travel burden. Because of these and many other benefits, telerehabilitation medicine will likely become part of our ongoing model of care if barriers to telemedicine continue to be lowered or removed. This paper is intended to establish a foundation for pediatric telerehabilitation medicine visit efficiency and effectiveness in our current environment and into the future.