Cerebral palsy pain instruments: Recommended tools for clinical research studies by the National Institute of Neurological Disorders and Stroke Cerebral Palsy Common Data Elements project.

AIM: This 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. METHOD: Through 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. RESULTS: Fifteen chronic pain tools met inclusion criteria, representing constructs across all components of the International Classification of Functioning, Disability and Health. INTERPRETATION: This 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.

Gabapentin as part of a multimodal pain protocol for selective dorsal rhizotomy does not impact percentage of rootlets transected.

PURPOSE: We aim to determine whether preoperatively initiated gabapentin for pain control impacts the percentage of rootlets cut during monitored, limited laminectomy selective dorsal rhizotomy (SDR) procedure. METHODS: This retrospective cohort study includes participants with cerebral palsy who had SDR for treatment of spasticity between 2010 and 2019 at a single-institution tertiary care center. One-level laminectomy SDR aimed to evaluate the cauda equina roots from levels L2-S1 with EMG monitoring. Gabapentin titration began 3 weeks prior to SDR. Data was analyzed using simple linear regression. Thirty-one individuals met inclusion criteria. Mean age was 7 years, 4 months. Eighteen participants (58%) identified as male, 12 (39%) female, and one (3%) non-binary. Thirty (97%) had bilateral CP. Sixteen (52%) were GMFCS II, four (13%) GMFCS III, five (16%) GMFCS IV, and six (19%) GMFCS V. RESULTS: Mean percentage of rootlets transected was 50.75% (SD 6.00, range 36.36-60.87). There was no relationship between the dose of gabapentin at time of SDR and percentage of rootlets cut with a linear regression slope of - 0.090 and an R2 of 0.012 (P = 0.56). CONCLUSION: Results indicate that preoperative initiation of gabapentin did not impact the percentage of rootlets transected. Thus, gabapentin can be initiated prior to SDR at moderate dosages without impacting SDR surgical outcomes.

A Critical Evaluation of Current Concepts in Cerebral Palsy.

Spastic cerebral palsy (CP), despite the name, is not consistently identifiable by specific brain lesions. CP animal models focus on risk factors for development of CP, yet few reproduce the diagnostic symptoms. Animal models of CP must advance beyond risk factors to etiologies, including both the brain and spinal cord.

Phrenic motor neuron loss in an animal model of early onset hypertonia.

Phrenic motor neuron (PhMN) development in early onset hypertonia is poorly understood. Respiratory disorders are one of the leading causes of morbidity and mortality in individuals with early onset hypertonia, such as cerebral palsy (CP), but they are largely overshadowed by a focus on physical function in this condition. Furthermore, while the brain is the focus of CP research, motor neurons, via the motor unit and neurotransmitter signaling, are the targets in clinical interventions for hypertonia. Furthermore, critical periods of spinal cord and motor unit development also coincide with the timing that the supposed brain injury occurs in CP. Using an animal model of early-onset spasticity (spa mouse [B6.Cg-Glrbspa/J] with a glycine receptor mutation), we hypothesized that removal of effective glycinergic neurotransmitter inputs to PhMNs during development will result in fewer PhMNs and reduced PhMN somal size at maturity. Adult spa (Glrb-/-), and wild-type (Glrb+/+) mice underwent unilateral retrograde labeling of PhMNs via phrenic nerve dip in tetramethylrhodamine. After three days, mice were euthanized, perfused with 4% paraformaldehyde, and the spinal cord excised and processed for confocal imaging. Spa mice had ~30% fewer PhMNs (P = 0.005), disproportionately affecting larger PhMNs. Additionally, a ~22% reduction in PhMN somal surface area (P = 0.019), an 18% increase in primary dendrites (P < 0.0001), and 24% decrease in dendritic surface area (P = 0.014) were observed. Thus, there are fewer larger PhMNs in spa mice. Fewer and smaller PhMNs may contribute to impaired diaphragm neuromotor control and contribute to respiratory morbidity and mortality in conditions of early onset hypertonia.NEW & NOTEWORTHY Phrenic motor neuron (PhMN) development in early-onset hypertonia is poorly understood. Yet, respiratory disorders are a common cause of morbidity and mortality. In spa mice, an animal model of early-onset hypertonia, we found ~30% fewer PhMNs, compared with controls. This PhMN loss disproportionately affected larger PhMNs. Thus, the number and heterogeneity of the PhMN pool are decreased in spa mice, likely contributing to the hypertonia, impaired neuromotor control, and respiratory disorders.

Impaired neuromuscular transmission of the tibialis anterior in a rodent model of hypertonia.

Early-onset hypertonia is characteristic of developmental neuromotor disorders, including cerebral palsy (CP). The spa transgenic mouse displays early-onset spasticity, abnormal gait, and motor impairments that are remarkably similar to symptoms of human CP. Previously, we showed that spa mice have fewer motor neurons innervating the tibialis anterior (TA). An expanded innervation ratio may result in increased susceptibility to neuromuscular transmission failure (NMTF). We assessed NMTF in an ex vivo TA muscle nerve preparation from spa and wild-type (WT) mice by comparing forces elicited by nerve versus muscle stimulation. TA muscle innervation ratio was assessed by counting the number of muscle fibers and dividing by the number of TA motor neurons. Muscle fiber cross-sectional areas were also assessed in the TA muscle. We observed that NMTF was immediately present in spa mice, increased with repetitive stimulation, and associated with increased innervation ratio. These changes were concomitant with reduced TA muscle fiber cross-sectional area in spa mice compared with WT. Early-onset hypertonia is associated with increased innervation ratio and impaired neuromuscular transmission. These disturbances may exacerbate the underlying gait abnormalities present in individuals with hypertonia.NEW & NOTEWORTHY Nerve-muscle interaction is poorly understood in the context of early-onset spasticity and hypertonia. In an animal model of early-onset spasticity, spa mice, we found a marked impairment of tibialis anterior neuromuscular transmission. This impairment is associated with an increased innervation ratio (mean number of muscle fibers innervated by a single motor neuron). These disturbances may underlie weakness and gait disturbances observed in individual with developmental hypertonia and spasticity.

Differences in lumbar motor neuron pruning in an animal model of early onset spasticity.

Motor neuron (MN) development in early onset spasticity is poorly understood. For example, spastic cerebral palsy (sCP), the most common motor disability of childhood, is poorly predicted by brain imaging, yet research remains focused on the brain. By contrast, MNs, via the motor unit and neurotransmitter signaling, are the target of most therapeutic spasticity treatments and are the final common output of motor control. MN development in sCP is a critical knowledge gap, because the late embryonic and postnatal periods are not only when the supposed brain injury occurs but also are critical times for spinal cord neuromotor development. Using an animal model of early onset spasticity [ spa mouse (B6.Cg- Glrbspa/J) with a glycine (Gly) receptor mutation], we hypothesized that removal of effective glycinergic neurotransmitter inputs to MNs during development will influence MN pruning (including primary dendrites) and MN size. Spa (Glrb-/-) and wild-type (Glrb+/+) mice, ages 4-9 wk, underwent unilateral retrograde labeling of the tibialis anterior muscle MNs via peroneal nerve dip in tetramethylrhodamine. After 3 days, mice were euthanized and perfused with 4% paraformaldehyde, and the spinal cord was excised and processed for confocal imaging. Spa mice had ~61% fewer lumbar tibialis anterior MNs ( P < 0.01), disproportionately affecting larger MNs. Additionally, a ~23% reduction in tibialis anterior MN somal surface area ( P < 0.01) and a 12% increase in primary dendrites ( P = 0.046) were observed. Thus MN pruning and MN somal surface area are abnormal in early onset spasticity. Fewer and smaller MNs may contribute to the spastic phenotype. NEW & NOTEWORTHY Motor neuron (MN) development in early onset spasticity is poorly understood. In an animal model of early onset spasticity, spa mice, we found ~61% fewer lumbar tibialis anterior MNs compared with controls. This MN loss disproportionately affected larger MNs. Thus number and heterogeneity of the MN pool are decreased in spa mice, likely contributing to the spastic phenotype.

A common data language for clinical research studies: the National Institute of Neurological Disorders and Stroke and American Academy for Cerebral Palsy and Developmental Medicine Cerebral Palsy Common Data Elements Version 1.0 recommendations.

To increase the efficiency and effectiveness of clinical research studies, cerebral palsy (CP) specific Common Data Elements (CDEs) were developed through a partnership between the National Institute of Neurological Disorders and Stroke (NINDS) and the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM). International experts reviewed existing NINDS CDEs and tools used in studies of children and young people with CP. CDEs were compiled, subjected to internal review, and posted online for external public comment in September 2016. Guided by the International Classification of Functioning, Disability and Health framework, CDEs were categorized into six domains: (1) participant characteristics; (2) health, growth, and genetics; (3) neuroimaging; (4) neuromotor skills and functional assessments; (5) neurocognitive, social, and emotional assessments; and (6) engagement and quality of life. Version 1.0 of the NINDS/AACPDM CDEs for CP is publicly available on the NINDS CDE and AACPDM websites. Global use of CDEs for CP will standardize data collection, improve data quality, and facilitate comparisons across studies. Ongoing collaboration with international colleagues, industry, and people with CP and their families will provide meaningful feedback and updates as additional evidence is obtained. These CDEs are recommended for NINDS-funded research for CP. WHAT THIS PAPER ADDS: This is the first comprehensive Common Data Elements (CDEs) for children and young people with CP for clinical research. The CDEs for children and young people with CP include common definitions, the standardization of case report forms, and measures. The CDE guides the standardization for data collection and outcome evaluation in all types of studies with children and young people with CP. The CDE ultimately improves data quality and data sharing.

Quantifying passive muscle stiffness in children with and without cerebral palsy using ultrasound shear wave elastography.

AIM: The aim of this study was to compare passive muscle stiffness in children with cerebral palsy (CP) and children with typical development using a novel ultrasound technique: ultrasound shear wave elastography (SWE). METHOD: We conducted a prospective study of 13 children with CP (six females and seven males, median age 5y 1mo [interquartile range 4y 4mo-7y 8mo]) and 13 children with typical development (six females and seven males, median age 5y 3mo [interquartile range 4y 4mo-9y 4mo]). Demographic information and physical exam measurements were obtained in addition to shear modulus measurements (passive muscle stiffness) of the lateral gastrocnemius muscle at 20° plantar flexion, 10° plantar flexion, and 0° plantar flexion using SWE. RESULTS: Children with CP had significantly greater shear modulus measurements at all three foot positions (p<0.050). When the shear modulus values were normalized to the baseline value for each child, there was no significant difference between the two groups. INTERPRETATION: Passive muscle stiffness, measured without the influence of spasticity, is greater in children with CP than in children with typical development when a muscle is at slack and at stretch. When shear modulus was normalized, the results indicate that muscle in children in both groups responds similarly to passive stretch. Further work includes evaluating effect of botulinum toxin on passive muscle properties.

Feasibility and reliability of quantifying passive muscle stiffness in young children by using shear wave ultrasound elastography.

OBJECTIVES: The purpose of this study was to investigate the feasibility and reliability of passive muscle stiffness measurements in children by shear wave ultrasound elastography. METHODS: We conducted a prospective cross-sectional study quantifying the passive stiffness of bilateral lateral gastrocnemius muscles during passive stretching in 20 typically developing children (age range, 2.0-12.6 years). Data collected included passive stiffness of the lateral gastrocnemius muscle (shear modulus in kilopascals) at 4 positions of progressive passive foot dorsiflexion, demographic characteristics of the participants, and comparison of demographic characteristics with the shear modulus. RESULTS: Passive stiffness increased with increasing stretching (mean [SD] range of stiffness, 7.1 [2.0] to 36.2 [22.0] kPa). For all 4 foot positions, no significant difference was found between right and left legs (range, P = .42 to P = .98) or between the sexes (range, P = .28 to P > .99). No correlation of passive muscle stiffness with age, body mass index, or ankle range of motion was found. The reliability of measurements was good to excellent (mean [95% confidence interval] range of reliability, 0.67 [0.44-0.83] to 0.80 [0.63-0.90]). CONCLUSIONS: Measurements of passive stiffness of the lateral gastrocnemius muscle are feasible and reliable in children as young as 2 years. Because this study found no significant difference between sex and the side tested in this age group, future studies involving children of this age range may not need to be stratified on the basis of these parameters. Defining normal passive muscle stiffness in children is critical for identifying and understanding the implications of abnormal passive muscle stiffness in children with neuromuscular disorders.

Ultrasound elastography: the new frontier in direct measurement of muscle stiffness.

The use of brightness-mode ultrasound and Doppler ultrasound in physical medicine and rehabilitation has increased dramatically. The continuing evolution of ultrasound technology has also produced ultrasound elastography, a cutting-edge technology that can directly measure the mechanical properties of tissue, including muscle stiffness. Its real-time and direct measurements of muscle stiffness can aid the diagnosis and rehabilitation of acute musculoskeletal injuries and chronic myofascial pain. It can also help monitor outcomes of interventions affecting muscle in neuromuscular and musculoskeletal diseases, and it can better inform the functional prognosis. This technology has implications for even broader use of ultrasound in physical medicine and rehabilitation practice, but more knowledge about its uses and limitations is essential to its appropriate clinical implementation. In this review, we describe different ultrasound elastography techniques for studying muscle stiffness, including strain elastography, acoustic radiation force impulse imaging, and shear-wave elastography. We discuss the basic principles of these techniques, including the strengths and limitations of their measurement capabilities. We review the current muscle research, discuss physiatric clinical applications of these techniques, and note directions for future research.

Postnatal survival of phrenic motor neurons is promoted by BDNF/TrkB.FL signaling.

The number of motor neurons (MNs) declines precipitously during the final trimester before birth. Thereafter, the number of MNs remains relatively stable, with their connections to skeletal muscle dependent on neurotrophins, including brain-derived neurotrophic factor (BDNF) signaling through its high-affinity full-length tropomyosin-related kinase receptor subtype B (TrkB.FL) receptor. As a genetic knockout of BDNF leads to extensive MN loss and postnatal death within 1-2 days after birth, we tested the hypothesis that postnatal inhibition of BDNF/TrkB.FL signaling is important for postnatal phrenic MN (PhMN) survival. In the present study, we used a 1NMPP1-sensitive TrkBF616A mutant mouse to evaluate the effects of inhibition of TrkB kinase activity on phrenic MN (PhMN) numbers and diaphragm muscle (DIAm) fiber cross-sectional area (CSA). Pups were exposed to 1NMPP1 or vehicle (DMSO) from birth to 21 days old (weaning) via the mother's ingestion in the drinking water. Following weaning, the right phrenic nerve was exposed in the neck and the proximal end dipped in a rhodamine solution to retrogradely label PhMNs. After 24 h, the cervical spinal cord and DIAm were excised. Labeled PhMNs were imaged using confocal microscopy, whereas DIAm strips were frozen at ∼1.5× resting length, cryosectioned, and stained with hematoxylin and eosin to assess CSA. We observed an ∼34% reduction in PhMN numbers and increased primary dendrite numbers in 1NMPP1-treated TrkBF616A mice. The distribution of PhMN size (somal surface area) DIAm fiber cross-sectional areas did not differ. We conclude that survival of PhMNs during early postnatal development is sensitive to BDNF/TrkB.FL signaling.NEW & NOTEWORTHY During early postnatal development, BDNF/TrkB signaling promotes PhMN survival. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact PhMN size. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact the number or CSA of DIAm fibers.

Incidence of Nonsynostotic Plagiocephaly and Developmental Disorders.

Importance: This is the first population-based study quantifying the incidence of nonsynostotic positional plagiocephaly and/or brachycephaly (PPB) in infancy and its association with developmental disorders. Objective: To report the incidence of PPB before age 1 year, the incidence of craniosynostosis, and the percentage of children with PPB diagnosed with a developmental disorder by age 7 years. Design, Setting, and Participants: This was a retrospective, population-based cohort study of children in the Rochester Epidemiology Project (REP) born in Olmsted County, Minnesota, from January 1, 2008, through December 31, 2012, with follow-up through age 7 years. Data were analyzed from March 2021 to April 2024. Exposure: Physical examination detecting cranial deformity. Main Outcomes and Measures: The primary outcome was the incidence of PPB. Secondary outcomes were the incidence of craniosynostosis and the percentage of children with PPB diagnosed with a developmental disorder by age 7 years. Results: Of 9909 infants (5084 [51.3%] male; 9205 [92.9%] born at term and 704 [7.1%] born preterm) included in the study, 575 had PPB, for a PPB incidence of 5.8% (95% CI, 5.3%-6.3%). The incidence of PPB was 5.3% (95% CI, 4.8%-5.8%) in term infants vs 11.8% (95% CI, 9.4%-14.6%) in preterm infants. The incidence of craniosynostosis was 0.16% (95% CI, 0.09%-0.26%). A developmental disorder was known or suspected in 4.2% (95% CI, 2.7%-6.2%) of infants at the time of PPB diagnosis; among 402 infants with PPB and follow-up through age 7 years, 30 (7.5%; 95% CI, 5.0%-10.7%) had a confirmed developmental disorder by 7 years of age. The prevalence of autism spectrum disorder (ASD) in children with a history of PPB who were followed up to age 7 years was 2.2% (9 of 402 children). Conclusions and Relevance: This study found that only a small percentage of the infants had positional head deformity significant enough to be documented and/or referred for subspecialty evaluation, and only a small subset of these children went on to have a developmental disorder in childhood. This information is helpful for counseling families about their child's developmental risk at time of PPB diagnosis.

Is baclofen the least worst option for spasticity management in children?

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.

Spasticity Interventions: Decision-Making and Management.

Spasticity results from an abnormality of the central nervous system and is characterized by a velocity-dependent increase in muscle tone or stiffness. In children, it can cause functional impairments, delays in achieving developmental or motor milestones, participation restrictions, discomfort, and musculoskeletal differences. Unique to children is the ongoing process of a maturing central nervous system and body, which can create the appearance of worsening or changing spasticity. Treatment options include physical interventions such as stretching, serial casting, and bracing; oral and injectable medications; and neurosurgical procedures such as selective dorsal rhizotomy and intrathecal baclofen pump.

Physician distress: Where are we and what can be done.

Depression, suicidal ideation, burnout, and moral injury are on the rise among physicians. Depression and suicidal ideation are mental health disorders that result from multiple interacting factors including biological vulnerabilities and acute stressors. Medical treatment for depression and suicidal ideation is critical to interrupt the potentially deadly progression to suicide that occurs when one's ability to find hope and other solutions is clouded by despair. Yet, stigma and perceived stigma of seeking treatment for mental health disorders still plagues medical providers. Transitions during medical training and practice can be particularly vulnerable time periods, though newer evidence suggests that overall, physicians are not at an increased risk of suicide compared to the general population. While burnout and moral injury are common among rehabilitation physicians, unlike depression, they are not directly associated with suicidal ideation. Opportunities for continued improvement in mental health resources and institutional support exist across the spectrum from medical student to staff physician. With wellness now increasingly supported and promoted by various medical organizations and recognition of the importance of access to effective mental health treatment, regaining hope and positivity while restoring resiliency in physicians, trainees, and medical students is possible.

Diaphragm muscle function in a mouse model of early-onset spasticity.

Spasticity is a common symptom in many developmental motor disorders, including spastic cerebral palsy (sCP). In sCP, respiratory dysfunction is a major contributor to morbidity and mortality, yet it is unknown how spasticity influences respiratory physiology or diaphragm muscle (DIAm) function. To investigate the influence of spasticity on DIAm function, we assessed in vivo transdiaphragmatic pressure (Pdi - measured using intraesophageal and intragastric pressure catheters under conditions of eupnea, hypoxia/hypercapnia and occlusion) including maximum Pdi (Pdimax via bilateral phrenic nerve stimulation), ex vivo DIAm-specific force and fatigue (using muscle strips stimulated with platinum plate electrodes), and type-specific characteristics of DIAm fiber cross sections (using immunoreactivity against myosin heavy chain slow and 2A) in spa and wildtype mice. Spa mice show reduced Pdimax, reduced DIAm specific force, and altered fatigability and atrophy of type IIx/IIb fibers. These findings suggest marked DIAm dysfunction may underlie the respiratory phenotype of sCP.NEW & NOTEWORTHY 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.

A consensus statement on the use of botulinum toxin in pediatric patients.

Botulinum 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.

Diaphragm neuromuscular transmission failure in a mouse model of an early-onset neuromotor disorder.

The spa transgenic mouse displays spasticity and hypertonia that develops during the early postnatal period, with motor impairments that are remarkably similar to symptoms of human cerebral palsy. Previously, we observed that spa mice have fewer phrenic motor neurons innervating the diaphragm muscle (DIAm). We hypothesize that spa mice exhibit increased susceptibility to neuromuscular transmission failure (NMTF) due to an expanded innervation ratio. We retrogradely labeled phrenic motor neurons with rhodamine and imaged them in horizontal sections (70 µm) using confocal microscopy. Phrenic nerve-DIAm strip preparations from wild type and spa mice were stretched to optimal length, and force was evoked by phrenic nerve stimulation at 10, 40, or 75 Hz in 330-ms duration trains repeated each second (33% duty cycle) across a 120-s period. 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 hematoxylin and eosin-stained strips. Compared to wild type, spa mice had over twofold greater NMTF during the first stimulus train that persisted throughout the 120 s period of repetitive activation. In both wild type and spa mice, NMTF was stimulation-frequency dependent. There was no difference in neuromuscular junction morphology or the total number of DIAm fibers between wild type and spa mice, however, there was an increase innervation ratio (39%) in spa mice. We conclude that early-onset developmental neuromotor disorders impair the efficacy of DIAm neuromuscular transmission, likely to contribute to respiratory complications.NEW & NOTEWORTHY 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.

Effects of Selective Dorsal Rhizotomy on Ankle Joint Function in Patients With Cerebral Palsy.

Selective dorsal rhizotomy (SDR) is a neurosurgical technique performed to reduce muscle spasticity and improve motor functions in children with cerebral palsy (CP). In long term, muscle contractures were observed even after SDR. To better understand what is contributing to contracture formation, it is necessary to assess the effects of SDR on joint stiffness. We hypothesized that ankle passive range of motion (ROM) increases and the quasi-stiffness of the ankle joint decreases after SDR in children with CP. This retrospective study included 10 children with diplegic CP (median age 6 years 2 months) who had undergone SDR and for whom gait analysis data were collected 3 months before (Pre-SDR) and 13 months after (Post-SDR) surgery. Additional to clinical measures, ankle quasi-stiffness (the slope of the ankle moment vs. ankle angle plot) was analyzed from gait data. Passive ankle ROM at 0° (p < 0.0001) and 90° knee angles (p < 0.0001) increased after SDR. Dynamic EMG analysis showed improved phasic gastrocnemius activity (p < 0.0001). Equinus gait was improved with the reduction of peak plantar flexion (p < 0.0001), as well as an increase in peak dorsiflexion (p = 0.006) during walking was observed. Ankle joint quasi-stiffness (Pre- and post-SDR median = 0.056 Nm/kg/° and 0.051 Nm/kg/°, and interquartile range: 0.031 Nm/kg/° and 0.019 Nm/kg/°, respectively) decreased significantly (p = 0.0017) after SDR. Moreover, even though the total time of the gait cycle did not change (p = 0.99), the time interval from maximum dorsiflexion to maximum plantar flexion (Pre- and post-SDR median = 0.125 s and 0.156 s, and interquartile range: 0.153 and 0.253 s, respectively) increased significantly (p = 0.0068) after SDR. In conclusion, the decreased ankle quasi-stiffness and the enhanced time interval in the gait cycle due to SDR indicate better motor control and joint stability. Our findings suggest that the long-term contracture formation occurring even after surgical interventions may be related to the stiffening of non-contractile structures.

Growth and survival characteristics of spa mice.

Characterization of growth and survival of mice displaying early onset hypertonic symptoms is critical as these animals are important for research investigating mechanisms and treatments of pediatric conditions associated with hypertonia, such as cerebral palsy. Currently, most animal models of cerebral palsy reproduce risk factors for developing this condition, with most failing to develop the physical symptoms or failing to survive in the postnatal period. The B6.Cg-Glrbspa /J (Gly receptor mutation) transgenic mouse (spa mouse), displays symptoms of early onset hypertonia, though little has been reported on growth and survival, with no reports of growth and survival since genotyping became available. We found that the majority of spa mice display symptoms by P14-P16. Of mice surviving to weaning, only ~9% were spa mice. By weaning age, spa mice had significantly lower weights than their heterozygote and wild-type littermates. Of mice that died after weaning and prior to use in experiments or being culled, 48% were spa mice. The poor growth and decreased survival of spa mice across multiple developmental and adult ages resembled the varied survival rates observed in humans with mild or severe cerebral palsy. The understanding of the expected survival of these mice is helpful for planning breeding and animal numbers for experiments. Due to the symptoms and timing of symptom onset, spa mice will be valuable in uncovering mechanisms and long-term effects of early onset hypertonia in order to move toward interventions for these conditions.