The Effect of Selective Dorsal Rhizotomy on Hip Displacement in Children With Cerebral Palsy: A Long-term Follow-up Study.

BACKGROUND: Hip displacement is common in children with cerebral palsy (CP). Spasticity in the hip adductor muscles, hip flexors, and medial hamstrings has been identified as a possible cause of progressive hip displacement. Selective dorsal rhizotomy (SDR) aims to reduce lower extremity spasticity in children with CP. Here, we investigate the influence of SDR on hip displacement in children with CP at long-term follow-up, a minimum of 5 years post-SDR. METHODS: A retrospective review of children undergoing SDR at a Canadian pediatric hospital was completed. Migration percentage (MP) was measured on pelvis radiographs taken in the 6 months before SDR and minimum 5 years post-SDR or before hip surgery. The number of hips with displacement, defined as MP >30%, and the number of children with at least 1 hip displaced were determined. A linear mixed-effects model was used to assess potential risk factors for poor outcome post-SDR, defined as having MP >40% or surgical intervention for hip displacement. RESULTS: Ninety children [50 males, 40 females, Gross Motor Function Classification System (GMFCS) levels I to V: 1/13/24/43/9] with a mean follow-up of 8.5 years (SD 5.1) were included. The mean age at SDR was 4.9 years (SD 1.5); more than half of children (52%) had hip displacement at the time of SDR. Post-SDR, MP exceeded 30% in 0 (0%) of children at GMFCS level I, 1 (8%) at II, 11 (46%) at III, 31 (72%) at IV, and 7 (78%) at V. A poor outcome was associated with preoperative MP, age, and GMFCS level. CONCLUSIONS: The incidence of hip displacement post-SDR was consistent with population-based studies when evaluated by GMFCS. Our findings suggest that SDR has neither a positive nor negative effect on hip displacement when assessed at least 5 years postintervention. LEVEL OF EVIDENCE: Level IV.

Combined therapy of bilateral transcranial direct current stimulation and ocular occlusion improves visual function in adults with amblyopia, a randomized pilot study.

Background: Amblyopia is the interocular visual acuity difference of two lines or more with the best correction in both eyes. It is treated with ocular occlusion therapy, but its success depends on neuroplasticity, and thus is effective in children but not adults. Transcranial Direct Current Stimulation (tDCS) is suggested to increase neuroplasticity. Objective: To determine if combined intervention of bilateral tDCS and ocular occlusion improves visual function in adults with amblyopia. Methods: A double-blind randomized, controlled pilot trial was conducted in 10 volunteers with amblyopia. While applying ocular occlusion and performing a reading task, participants received bilateral tDCS (n = 5) or sham stimulation (n = 5), with the anodal tDCS electrode in the contralateral visual cortex and the cathodal in the ipsilateral visual cortex in relation to the amblyopic eye. Visual function (through visual acuity, stereopsis, and contrast sensitivity tests) and visual evoked potential (with checkerboard pattern stimuli presentation) were evaluated immediately after. Results: A total of 30 min after treatment with bilateral tDCS, visual acuity improved by 0.16 (± 0.025) LogMAR in the treatment group compared with no improvement (-0.02 ± 0.02) in five controls (p = 0.0079), along with a significant increase in the amplitude of visual evoked potentials of the amblyopic eye response (p = 0.0286). No significant changes were observed in stereopsis and contrast sensitivity. No volunteer reported any harm derived from the intervention. Conclusion: Our study is the first to combine anodal and cathodal tDCS for the treatment of amblyopia, showing transient improved visual acuity in amblyopic adults.

Unilateral versus bilateral reconstructive hip surgery in children with cerebral palsy: A survey of pediatric orthopedic surgery practice and decision-making.

Purpose: This study explored whether surgeons favor unilateral or bilateral reconstructive hip surgery in children with cerebral palsy who have unilateral hip displacement. Methods: An invitation to participate in an anonymous, online survey was sent to 44 pediatric orthopedic surgeons. The case of an 8 year old at Gross Motor Function Classification System level IV with migration percentages of 76% and 22% was described. Surgeons selected their surgical treatment of choice and provided their rationale. Respondents were also asked to list and rank radiographic parameters used for decision-making and multidisciplinary team members involved in decision-making. Results: Twenty-eight orthopedic surgeons from nine countries with a mean 21.3 years (range, 5-40 years) of experience completed the survey. A "bilateral VDROs with a right pelvic osteotomy (PO) was selected by 68% (19/28) of respondents; risk of contralateral subluxation (9/19; 47%) and maintaining symmetry (7/19; 37%) were the most common rationales for bilateral surgery. The remaining 32% (9/28) chose a 'right VDRO with a right PO'" with most of these (8/9; 89%) stating the left hip was sufficiently covered. Of 31 radiographic parameters identified, migration percentage, acetabular angle/index, Shenton line, neck shaft angle, and presence of open/closed triradiate growth plates were the most common. Physical therapists (68%) and physiatrists (43%) were most likely to be involved in pre-operative surgical consultation. Conclusion: There is a lack of agreement on management of the contralateral hip in children with unilateral hip displacement. Further studies comparing patient important outcomes following unilateral and bilateral surgery are required. Level of Evidence: V.

Late Hip Displacement Identified in Children at Gross Motor Function Classification System II and III With Asymmetric Diplegia and Fixed Pelvic Obliquity.

Risk of hip displacement in children with cerebral palsy is directly related to a child's level of motor function as classified by the Gross Motor Function Classification System (GMFCS) and is reported to be greatest at a young age. In this study, we present a series of four children with asymmetric diplegic cerebral palsy at GMFCS levels II and III, with the more involved hip showing rapid, progressive displacement at a later age. Current hip surveillance guidelines may not adequately identify hip displacement in children with asymmetric diplegia and pelvic obliquity; modifications to surveillance guidelines may be warranted. Additional investigation of hip displacement in this subset of children is required to determine whether the incidence of displacement is higher than anticipated based on the GMFCS level alone.

Variability in Postoperative Immobilization and Rehabilitation Following Reconstructive Hip Surgery in Nonambulatory Children With Cerebral Palsy.

BACKGROUND: Despite being a common procedure, there are no standard protocols for postoperative immobilization and rehabilitation following reconstructive hip surgery in children with cerebral palsy (CP). The purpose of this study was to investigate variability in postoperative management and physical therapy (PT) recommendations among orthopaedic surgeons treating hip displacement in children with CP. METHODS: An invitation to participate in an anonymous, online survey was sent to 44 pediatric orthopaedic surgeons. The case of a child undergoing bilateral femoral varus derotation osteotomies and adductor tenotomies was presented. Surgeons were asked to consider their typical practice and the case scenario when answering questions related to immobilization, weight-bearing, and rehabilitation. Recommendations with increasingly complex surgical interventions and different age or level of motor function were also assessed. RESULTS: Twenty-eight orthopaedic surgeons from 9 countries with a mean 21.3 years (range: 5 to 40 y) of experience completed the survey. Postoperative immobilization was recommended by 86% (24/28) of respondents with 7 different methods of immobilization identified. All but 1 (23/24) reported immobilizing full time. Most (20/23) reported using immobilization for 4 to 6 weeks. Return to weight-bearing varied from 0 to 6 weeks for partial weight-bearing and 0 to 12 weeks for full weight-bearing. PT in the first 1 to 2 weeks postoperatively was reported as unnecessary by 29% (8/28) of surgeons. PT for range of motion, strengthening, and return to function was recommended by 96% (27/28) of surgeons, starting at a mean of 2.6 weeks postoperatively (range: 0 to 16 wk). Only 48% (13/27) reported all of their patients would receive PT for these goals in their practice setting. Inpatient rehabilitation was available for 75% (21/28) but most surgeons (17/21) reported this was accessed by 20% or fewer of their patients. CONCLUSIONS: Postoperative immobilization and PT recommendations were highly variable among surgeons. This variability may influence surgical outcomes and complication rates and should be considered when evaluating procedures. Further study into the impact of postoperative immobilization and rehabilitation is warranted.

Non-conventional Axonal Organelles Control TRPM8 Ion Channel Trafficking and Peripheral Cold Sensing.

TRPM8 is the main ion channel responsible for cold transduction in the somatosensory system. Nerve terminal availability of TRPM8 determines cold sensitivity, but how axonal secretory organelles control channel delivery remains poorly understood. Here we examine the distribution of TRPM8 and trafficking organelles in cold-sensitive peripheral axons and disrupt trafficking by targeting the ARF-GEF GBF1 pharmacologically or the small GTPase RAB6 by optogenetics. In axons of the sciatic nerve, inhibition of GBF1 interrupts TRPM8 trafficking and increases association with the trans-Golgi network, LAMP1, and Golgi satellites, which distribute profusely along the axonal shaft. Accordingly, both TRPM8-dependent ongoing activity and cold-evoked responses reversibly decline upon GBF1 inhibition in nerve endings of corneal cold thermoreceptors. Inhibition of RAB6, which also associates to Golgi satellites, decreases cold-induced responses in vivo. Our results support a non-conventional axonal trafficking mechanism controlling the availability of TRPM8 in axons and cold sensitivity in the peripheral nervous system.

Prevention of hip displacement in children with cerebral palsy: a systematic review.

AIM: To conduct a systematic review and evaluate the quality of evidence for interventions to prevent hip displacement in children with cerebral palsy (CP). METHOD: A systematic review was performed using American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were completed in seven electronic databases. Studies were included if participants had CP and the effectiveness of the intervention was reported using a radiological measure. Results of orthopaedic surgical interventions were excluded. RESULTS: Twenty-four studies fulfilled the inclusion criteria (4 botulinum neurotoxin A; 2 botulinum neurotoxin A and bracing; 1 complementary and alternative medicine; 1 intrathecal baclofen; 1 obturator nerve block; 8 positioning; 7 selective dorsal rhizotomy). There was significant variability in treatment dosages, participant characteristics, and duration of follow-up among the studies. Overall, the level of evidence was low. No intervention in this review demonstrated a large treatment effect on hip displacement. INTERPRETATION: The level and quality of evidence for all interventions aimed at slowing or preventing hip displacement is low. There is currently insufficient evidence to support or refute the use of the identified interventions to prevent hip displacement or dislocation in children and young people with CP. WHAT THIS PAPER ADDS: High-quality evidence on prevention of hip displacement is lacking. No recommendations can be made for preventing hip displacement in children with cerebral palsy because of poor-quality evidence. High-quality, prospective, longitudinal studies investigating the impact of interventions on hip displacement are required.

Salsolinol and isosalsolinol: condensation products of acetaldehyde and dopamine. Separation of their enantiomers in the presence of a large excess of dopamine.

Dopamine (DA) condenses, at least in vitro, with acetaldehyde, the primary metabolite of ethanol, to form the regioisomers salsolinol (SAL) and isosalsolinol (isoSAL). An alternative in vivo route to SAL, requiring a decarboxylation step, has been suggested via condensation of DA with pyruvic acid. SAL has been proposed as a mediator of the rewarding effects of ethanol in the brain. We have now shown by HPLC, nuclear magnetic resonance (NMR) and mass spectrometry (MS) that the commercially available SAL contains about 10% of isoSAL, whose biological activity is unknown. If SAL is indeed the biologically active metabolite, rather than isoSAL, it is also unknown whether the rewarding molecule is (S)- or (R)-SAL. We have developed methodologies for the quantitative determination of DA, SAL and isoSAL using ion-pair reversed-phase HPLC, and for the separation of DA from (S)- and (R)-SAL and an isoSAL enantiomer on a ß-cyclodextrin-modified column, in both cases with electrochemical detection. A significant advance over earlier methods was achieved for the analysis of (S)- and (R)-SAL in the presence of a large excess of DA (100:1 DA-SAL ratio), as expected to occur in vivo, by suppressing the DA peak by selective derivatization with 2,3-naphthalenedicarboxaldehyde into a molecule that is electrochemically silent at the electrode potential used. The methodologies developed will allow the separation and determination of the pharmacological activity of these two products of condensation of acetaldehyde with DA. Further, the techniques for (S)- and (R)-SAL separation at a high DA:SA ratio will allow the existence of a putative (R)-SAL synthase to be determined and, if it exists, its role in alcoholism.