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Objectives: The aim of the study were to (1) investigate what physical and physiological parameters are most important for Frame Running capacity, a parasport for individuals with ambulatory difficulties, and (2) determine whether Frame Running capacity can be predicted in athletes with cerebral palsy., Design: Athletes with cerebral palsy ( N = 62, Gross Motor Classification System I-V; 2/26/11/21/2) completed a 6-min Frame Running test. Before the 6-min Frame Running test, muscle thickness, passive range of motion (hip, knee, ankle), selective motor control, and spasticity (hip, knee, ankle) were measured in both legs. In total, 54 variables per individual were included. Data were analyzed using correlations, principal component analysis, orthogonal partial least square regression, and variable importance in projection analysis., Results: The mean 6-min Frame Running test distance was 789 ± 335 m and decreased with motor function severity. The orthogonal partial least square analysis revealed a modest degree of covariance in the variables analyzed and that the variance in the 6-min Frame Running test distance could be predicted with 75% accuracy based on all the variables measured. Variable importance in projection analysis indicated hip and knee extensor spasticity (negative effect), and muscle thickness (positive effect) arose as the most important factors contributing to Frame Running capacity., Conclusions: These results are an important resource to enable optimization of training regimes to improve Frame Running capacity and contribute to evidence-based and fair classification for this parasport., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to explore the feasibility of using time-matched uniaxial accelerometers for measuring movement in daily life in children with cerebral palsy (CP) before and after botulinum toxin injections., Methods: This observational study of clinical care with a pre-post design was set in the home and school environment. Participants included eleven children (4-13 years of age) with CP (GMFCS I-III). The children wore uniaxial accelerometers (ActiGraph, model GT1M) for 4 days on both wrists, the right ankle and around the waist before, 3 weeks and 3 months after BoNT-A injections in the legs. Five children also got BoNT-A in the most affected arm. All injections were given according to clinical indications and routine. The accelerometers were all time-matched to define ambulation, arm swing, voluntary activity of arms, and bimanual activity. The feasibility of wearing accelerometers with this setup was evaluated. A linear mixed model was used for analysis of the percentage time and at which intensity the different activities were performed. The confidence interval demonstrated any difference between the dominant and non-dominant arm., Results: Time-matching of accelerometers placed on both wrists, the waist, and one ankle is a feasible method of registering ambulation, arm swing during gait, and arm movements while not ambulating. Before injections, the children spent 5.6% of their time ambulating. This value declined to 3.9% at 3 months. Contrary to clinical goals, arm movement did not increase after injecting the most affected arm with BoNT-A, however, injections may have decreased mirror movements, which are often bothersome for the child., Conclusion: A time-matched 4-accelerometer set-up is feasible in children with cerebral palsy. A future study including time-matched multi-axial accelerometers on all four limbs, could provide important information on the effect of BoNT-A in daily life.

In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling ( n = 10; TD EX) or were enrolled as controls with no exercise ( n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (∼25%, p < 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD ( p < 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise ( p < 0.05). Interestingly, miR-486 was upregulated ∼2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with a miR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with CP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vechetti, Norrbom, Alkner, Hjalmarsson, Palmcrantz, Pontén, Pingel, von Walden and Fernandez-Gonzalo.)

Purpose: To determine the physiological response and association to peak oxygen uptake of the 6-minute Frame Running test (6-MFRT) in persons with cerebral palsy (CP)., Methods: Twenty-four participants with CP, Gross Motor Function Classification System II/III/IV, performed the 6-MFRT. Distance, peak heart rate (HR peak ), peak respiratory exchange ratio (RER peak ), and peak oxygen uptake ( O 2peak ) were measured., Results: HR peak ranged from 146 to 201 beats per minute, RER peak from 0.94 to 1.49, 6-MFRT distance from 179 to 1220 m and O 2peak from 0.62 to 2.18 L/min. HR peak was achieved in 63%, RER peak in 71%. A strong correlation was observed between 6-MFRT and O 2peak ., Conclusions: The 6-MFRT represented a (near) maximum effort for 75% of the participants and the 6-MFRT can be used to estimate oxygen consumption on an individual basis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

Aim: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP)., Method: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were analyzed with a focused query investigating metabolism- and mitochondria-related gene networks., Results: The mtDNA to genomic DNA ratio was lower in the children with CP compared to the typically developing group (-23%, p=0.002). Out of five investigated complexes in the mitochondrial respiratory chain, we observed lower protein levels of all complexes (I, III, IV, V, -20% to -37%; p<0.05) except complex II. Total peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) messenger RNA (p<0.004), isoforms PGC1α1 (p=0.05), and PGC1α4 (p<0.001) were reduced in CP. Transcriptional similarities were observed between CP, aging, and 90 days' bed rest., Interpretation: Mitochondrial biogenesis, mtDNA, and oxidative phosphorylation protein content are reduced in CP muscle compared with typically developing muscle. Transcriptional pathways shared between aging and long-term unloading suggests metabolic dysregulation in CP, which may guide therapeutic strategies for combatting CP muscle pathology. What this paper adds Cerebral palsy (CP) muscle contains fewer energy-generating organelles than typically developing muscle. Gene expression in CP muscle is similar to aging and long-term bed rest., (© 2021 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Peripheral nerve injuries (PNI) of the upper limb are a common event in the paediatric population, following both fractures and soft tissues injuries. Open injuries should in theory be easier to identify and the repair of injured structures performed as soon as possible in order to obtain a satisfying outcome. Conversely, due to the reduced compliance of younger children during clinical assessment, the diagnosis of a closed nerve injury may sometimes be delayed. As the compliance of patients is influenced by pain, anxiety and stress, the execution of the clinical manoeuvres intended to identify a loss of motor function or sensibility, can be impaired. Although the majority of PNI are neuroapraxias resulting in spontaneous recovery, there are open questions regarding certain aspects of closed PNI, e.g. when to ask for electrophysiological exams, when and how long to wait for a spontaneous recovery and when a surgical approach becomes mandatory. The aim of the article is therefore to analyse the main aspects of the different closed PNI of the upper limb in order to provide recommendations for timely and correct management, and to determine differences in the PNI treatment between children and adults., (Copyright © 2020, The author(s).)

Introduction: Cerebral palsy (CP) is the most common motor impairment in children. Skeletal muscles in individuals with CP are typically weak, thin, and stiff. Whether epigenetic changes at the ribosomal DNA (rDNA) promoter are involved in this dysregulation remains unknown. Methods: Skeletal muscle samples were collected from 19 children with CP and 10 typically developed (TD) control children. Methylation of the rDNA promoter was analyzed using the Agena Epityper Mass array and gene expression by qRT-PCR. Results: Biceps brachii muscle ribosome biogenesis was suppressed in CP as compared to TD. Average methylation of the rDNA promoter was not different between CP and TD but negatively correlated to elbow flexor contracture in the CP group. Discussions: We observed a negative correlation between rDNA promoter methylation and degree of muscle contracture in the CP group. Children with CP with more severe motor impairment had less methylation of the rDNA promoter compared to less affected children. This finding suggests the importance of neural input and voluntary muscle movements for promoter methylation to occur in the biceps muscle., (Copyright © 2020 von Walden, Fernandez-Gonzalo, Pingel, McCarthy, Stål and Pontén.)

Introduction: The development of efficient resistance exercise protocols to counteract muscle dysfunction in cerebral palsy is warranted. Whether individuals with cerebral palsy are able to perform iso-inertial resistance (flywheel) exercise in a comparable manner to typically developed subjects has never been experimentally tested., Design: A comparative, controlled study., Subjects: Eight young ambulatory adults with cerebral palsy (mean age 19 years; Gross Motor Function Classification System (GMFCS) I-III) and 8 typically developed control subjects (mean age 21 years)., Methods: Subjects performed acute bouts on the weight-stack and flywheel leg-press device, respectively. Range of motion, electromyography, power, work and muscle thickness (ultrasound) data were collected., Results: Subjects with cerebral palsy were able to produce a greater eccentric/concentric peak power ratio on the flywheel (p < 0.05 vs ratio in weight-stack), however absolute values were lower (p < 0.05 vs weight-stack). Typically developed subjects produced more power per mm of thigh muscle than the cerebral palsy group, independent of leg, device and action., Discussion: Subjects with cerebral palsy could not elicit the eccentric overload seen in typically developed subjects. Furthermore, peak power production per mm muscle was markedly reduced in both legs in subjects with cerebral palsy. In conclusion, this comparative study of weight-stack and flywheel exercise does not support the implementation of the current iso-inertial protocol for young adults with cerebral palsy.

Background: Individuals with cerebral palsy (CP) are less physically active, spend more time sedentary and have lower cardiorespiratory endurance as compared to typically developed individuals. RaceRunning enables high-intensity exercise in individuals with CP with limited or no walking ability, using a three-wheeled running bike with a saddle and a chest plate for support, but no pedals. Training adaptations using this type of exercise are unknown., Methods: Fifteen adolescents/young adults (mean age 16, range 9-29, 7 females/8 males) with CP completed 12 weeks, two sessions/week, of RaceRunning training. Measurements of cardiorespiratory endurance (6-min RaceRunning test (6-MRT), average and maximum heart rate, rate of perceived exertion using the Borg scale (Borg-RPE)), skeletal muscle thickness (ultrasound) of the thigh (vastus lateralis and intermedius muscles) and lower leg (medial gastrocnemius muscle) and passive range of motion (pROM) of hip, knee and ankle were collected before and after the training period., Results: Cardiorespiratory endurance increased on average 34% (6-MRT distance; pre 576 ± 320 m vs. post 723 ± 368 m, p < 0.001). Average and maximum heart rate and Borg-RPE during the 6-MRT did not differ pre vs. post training. Thickness of the medial gastrocnemius muscle increased 9% in response to training (p < 0.05) on the more-affected side. Passive hip flexion increased (p < 0.05) on the less-affected side and ankle dorsiflexion decreased (p < 0.05) on the more affected side after 12 weeks of RaceRunning training., Conclusions: These results support the efficacy of RaceRunning as a powerful and effective training modality in individuals with CP, promoting both cardiorespiratory and peripheral adaptations.

Objective: To investigate the potential of an acute bout of transcranial electrical stimulation to induce anabolic signalling., Design: Experimental intervention on healthy subjects., Subjects: Ten healthy subjects, 5 women and 5 men (mean age (standard deviation (SD) 32 years (SD 4))., Methods: The quadriceps muscle was stimulated at a frequency of 10 Hz for 10 s, followed by 20 s of rest, repeated 40 times over 20 min. Electromyography and force data were collected for all transcranial electrical stimulation sequences. Muscle biopsies were obtained from the vastus lateralis muscle before and 1 and 3 h after stimulation., Results: One bout of transcranial electrical stimulation decreased phosphorylation of AKT at Thr308 (1 h: -29%, 3 h: -38%; p < 0.05) and mTOR phosphorylation at Ser2448 (1 h: -10%; ns, 3 h: -21%; p < 0.05), both in the anabolic pathway. Phosphorylation of AMPK, ACC and ULK1 were not affected. c-MYC gene expression was unchanged following transcranial electrical stimulation, but rDNA transcription decreased (1 h: -28%, 3 h: -19%; p < 0.05). PGC1α-ex1b mRNA increased (1 h: 2.3-fold, 3 h: 2.6-fold; p < 0.05), which also correlated with vastus lateralis electromyography activity, while other PGC-1α variants were unchanged., Conclusion: Acute transcranial electrical stimulation of skeletal muscle in weight-bearing healthy individuals did not induce anabolic signalling, and some signs of impaired muscle anabolism were detected, suggesting limited potential in preventing muscle wasting.

Arthrogryposis multiplex congenita (AMC) has been described and defined in thousands of articles, but the terminology used has been inconsistent in clinical and research communities. A definition of AMC was recently developed using a modified Delphi consensus method involving 25 experts in the field of AMC from 8 countries. Participants included health care professionals, researchers, and individuals with AMC. An annotation of the definition provides more in-depth explanations of the different sentences of the AMC definition and is useful to complement the proposed definition. The aim of this study was to provide an annotation of the proposed consensus-based AMC definition. For the annotation process, 17 experts in AMC representing 10 disciplines across 7 countries participated. A paragraph was developed for each sentence of the definition using an iterative process involving multiple authors with varied and complementary expertise, ensuring all points of view were taken into consideration. The annotated definition provides an overview of the different topics related to AMC and is intended for all stakeholders, including youth and adults with AMC, their families, and clinicians and researchers, with the hopes of unifying the understanding of AMC in the international community., (© 2019 The Authors American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals, Inc.)

The aim of this study was to evaluate whether short-term positive effects on bimanual function after surgery of the paretic arm in cerebral palsy are maintained long term. Assisting Hand Assessment (AHA) and active range of motion was tested before surgery and at 7 month and 9-year follow-up (n=18). AHA improved significantly from 50 to 52 U at 7 months, but was not different from before surgery at the 9-year follow-up, 49 U. Surgery of wrist and elbow flexors significantly improved active extension. Improvement in wrist and elbow extension was maintained at the 9-year follow-up, but usefulness of the hand measured with AHA had returned to the same level as before surgery.

Introduction: Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested., Methods: The biceps muscles of children and adolescents with CP/ABI (n = 20) and typically developing controls (n = 10) were investigated. We used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting to assess gene expression relevant to growth and size homeostasis., Results: Classical pro-inflammatory cytokines and genes involved in extracellular matrix (ECM) production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase I transcription factors, 45s pre-rRNA and 28S rRNA., Discussion: The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures, possibly underlying stunted growth and perimysial ECM expansion. Muscle Nerve 58: 277-285, 2018., (© 2018 Wiley Periodicals, Inc.)

Muscle and joint contact force influence stresses at the proximal growth plate of the femur and thus bone growth, affecting the neck shaft angle (NSA) and femoral anteversion (FA). This study aims to illustrate how different muscle groups' activation during gait affects NSA and FA development in able-bodied children. Subject-specific femur models were developed for three able-bodied children (ages 6, 7, and 11 years) using magnetic resonance images. Contributions of different muscle groups-hip flexors, hip extensors, hip adductors, hip abductors, and knee extensors-to overall hip contact force were computed. Specific growth rate for the growth plate was computed, and the growth was simulated in the principal stress direction at each element in the growth front. The predicted growth indicated decreased NSA and FA (of about [Formula: see text] over a four-month period) for able-bodied children. Hip abductors contributed the most, and hip adductors, the least, to growth rate. All muscles groups contributed to a decrease in predicted NSA ([Formula: see text]0.01[Formula: see text]-0.04[Formula: see text] and FA ([Formula: see text]0.004[Formula: see text]-[Formula: see text]), except hip extensors and hip adductors, which showed a tendency to increase the FA ([Formula: see text]0.004[Formula: see text]-[Formula: see text]). Understanding influences of different muscle groups on long bone growth tendency can help in treatment planning for growing children with affected gait.

Lower extremity deformities of patients with arthrogryposis multiplex congenita present a wide spectrum of severity and deformity combinations. Treatment goals range from merely ensuring comfortable seating and shoe wear, to fully independent and active ambulation, but the overarching intention is to help realize the patient's greatest potential for independence and function. Treatment of hip and knee contractures and dislocations has become more interventional, whereas treatment of foot deformities has paradoxically become much less surgical. This article synopsizes the treatment strategies presented in September 2014 in Saint Petersburg, Russia at the second international symposium on arthrogryposis.

Arthrogryposis multiplex congenital is a relatively uncommon condition, with little consensus on treatment. In 2007, the 1st International Symposium on Arthrogryposis was held in Birmingham, United Kingdom, to bring together patients, their families, and a multinational group of health care experts in the field of arthrogryposis, to discuss various aspects of the care of patients with arthrogryposis multiplex congenital. From that meeting, there was a coalescence of thought on diagnosis and classification, a sharing of practices on treatments and their outcomes, and an agreement on future directions. At the beginning of the 2nd International Symposium on Arthrogryposis held in Saint Petersburg in September 2014, Russia, these "lessons learnt" were synopsized to set the tone for the new meeting.

Children with cerebral palsy (CP) often develop reduced passive range of motion with age. The determining factor underlying this process is believed to be progressive development of contracture in skeletal muscle that likely changes the biomechanics of the joints. Consequently, to identify the underlying mechanisms, we modeled the mechanical characteristics of the forearm flexors acting across the wrist joint. We investigated skeletal muscle strength (Grippit®) and passive stiffness and viscosity of the forearm flexors in 15 typically developing (TD) children (10 boys/5 girls, mean age 12 years, range 8-18 yrs) and nine children with CP Nine children (6 boys/3 girls, mean age 11 ± 3 years (yrs), range 7-15 yrs) using the NeuroFlexor® apparatus. The muscle stiffness we estimate and report is the instantaneous mechanical response of the tissue that is independent of reflex activity. Furthermore, we assessed cross-sectional area of the flexor carpi radialis (FCR) muscle using ultrasound. Age and body weight did not differ significantly between the two groups. Children with CP had a significantly weaker (-65%, p < 0.01) grip and had smaller cross-sectional area (-43%, p < 0.01) of the FCR muscle. Passive stiffness of the forearm muscles in children with CP was increased 2-fold ( p < 0.05) whereas viscosity did not differ significantly between CP and TD children. FCR cross-sectional area correlated to age ( R 2 = 0.58, p < 0.01), body weight ( R 2 = 0.92, p < 0.0001) and grip strength ( R 2 = 0.82, p < 0.0001) in TD children but only to grip strength ( R 2 = 0.60, p < 0.05) in children with CP. We conclude that children with CP have weaker, thinner, and stiffer forearm flexors as compared to typically developing children.

Background: Arthrogryposis Multiplex Congenita (AMC) is a heterogeneous condition characterized by multiple joint contractures at birth. Greater movements in the trunk and pelvis during walking have been observed in children with AMC using orthoses compared to those wearing only shoes. This study investigated gait dynamics in children with AMC and identified compensatory mechanisms that accommodate walking., Methods: Twenty-six children with AMC who walked with orthoses or shoes and a control group consisting of 37 typically-developing children were evaluated in 3D gait analysis. Children with AMC were divided into subgroups based on which joints needed to be stabilized in the sagittal plane; AMC1 used knee-ankle-foot orthoses (KAFOs) with locked knee joints, AMC2 used KAFOs with open knee joints or ankle-foot orthoses, and AMC3 used shoes., Results: The Gait Deviation Index was lower in AMC groups than in the control group, with the lowest in AMC1. Excessive trunk movements in frontal and transverse planes were observed in AMC2 and especially in AMC1. Lower hip flexion moment was found in AMC1, while AMC2 and AMC3 showed similar hip flexion moments as the control group. Knee extension moments were similar between the groups. In the frontal plane there were only small differences between the groups in hip abduction moment. A joint work analysis indicated greater contribution from the hip muscles to overall positive work in AMC groups, particularly in AMC1, than in the control group., Conclusion: All AMC groups showed less hip extension than the control group, but hip flexion moment was significantly lower only in AMC1, which can be attributed to their gait strategy with bilateral locked KAFOs. AMC1, who had weak knee extensors, were helped by their locked KAFOs and therefore showed similar knee extension moment as the other groups. This finding, together with their gait patterns, demonstrates the children's high reliance on hip muscles and presumably trunk muscles to provide propulsion. Our study shows that with adequate orthotic support, children with AMC and even with severe weakness and contractures can achieve walking.

Arthrogryposis is defined as limited range of motion in three or more joints in two or more body parts. This article will describe treatment options for the arthrogrypotic knee. In all types of arthrogryposis, and in both extension and flexion deformities, very early treatment is favorable. Just after birth, traction and mobilization followed by serial casting could often greatly improve the range of motion. In the hyperextended knee, surgical lengthening of the extensor apparatus may be needed. Flexion deformities could be improved with temporary physeal arrest of the anterior distal femur by fixing two-hole plates over the physis on both sides of patella. The plates will result in a constrained growth of the anterior physis, and thus a very slow extension of the knee, which will give the nerves and vessels time to adjust. Pterygium, webbing of the knee joint, is a special subgroup that in selected mild cases could be treated with extensive surgical release of the webbing and orthotics. Arthrogrypotic knees can be treated with early reduction and maintenance with orthotics.

Background: Children with cerebral palsy (CP) use their paretic arm less than normal but have a relative overactivity of wrist flexors, causing an impairing flexed position of the wrist. Voluntary use of a muscle downregulates myosin heavy chain (MyHC) IIx, but it is unclear whether the relative overactivity of wrist flexors and extensors in children with CP affects MyHC expression compared to normal subjects., Questions/purposes: We therefore asked whether MyHC expression composition differs in wrist flexors compared to extensors in children with CP and in controls and whether it is related to clinical findings., Methods: We took muscle biopsies from wrist flexors and extensors during hand surgery in children with CP (n = 9) and during open reduction of forearm fractures in control children (n = 5). The expression of the MyHC I, IIa, and IIx isoforms were determined on silver-stained 6% SDS-PAGE., Results: CP flexors showed a higher proportion of MyHC IIx (40%) than control flexors (16%) and CP extensors (20%). MyHC IIa isoform proportion was lower in CP flexors (27%) than in control flexors (46%) and in CP extensors (45%). MyHC I expression was lower in CP (36%) than in controls (46%) for wrist extensors only., Conclusions: Both the brain injury in CP and the different demands on flexors and extensors affect the expression of MyHCs. The higher amount of MyHC IIx in CP could be caused by a decreased voluntary use of the hemiplegic arm., Clinical Relevance: More information on the structural difference between flexors and extensors in normal and spastic muscle could improve the understanding of strain of wrist extensors and possibly the development of flexion contractures in CP.

The present study was performed to investigate if, in a short term perspective, bimanual hand function in children with brain damage improves as an effect of hand surgery. Assisting Hand Assessment (AHA), Goal Achievement Scale, consolidated House Functional Classification, Zancolli Classification, and the active range of motion were measured before surgery and 5-14 months after surgery in 18 children, aged 6-16 years, mean of 11 years. AHA improved from 44.5 AHA units (range 20-66) to 52.5 AHA units (range 25-69) (P<0.005) on a 0-100 AHA unit scale. Active motion improved (P<0.005). Rating of selected goals improved from 2.6 to 6.4, on a 10-grade scale. On a short term, hand surgery improved not only the grip, but also the ability to use the hemiplegic hand in bimanual activities.

Background: Cerebral palsy (CP) is an upper motor neuron disease that results in a progressive movement disorder. Secondary to the neurological insult, muscles from CP patients often become spastic. Spastic muscle is characterized by an increased resistance to stretch, but often develops the further complication of contracture which represents a prominent disability in children with CP. This study's purpose is to characterize alterations of spastic muscle on the transcriptional level. Increased knowledge of spastic muscle may lead to novel therapies to improve the quality of life for children with CP., Method: The transcriptional profile of spastic muscles were defined in children with cerebral palsy and compared to control patients using Affymetrix U133A chips. Expression data were verified using quantitative-PCR (QPCR) and validated with SDS-PAGE for select genes. Significant genes were determined using a 2 x 2 ANOVA and results required congruence between 3 preprocessing algorithms., Results: CP patients clustered independently and 205 genes were significantly altered, covering a range of cellular processes. Placing gene expression in the context of physiological pathways, the results demonstrated that spastic muscle in CP adapts transcriptionally by altering extracellular matrix, fiber type, and myogenic potential. Extracellular matrix adaptations occur primarily in the basal lamina although there is increase in fibrillar collagen components. Fiber type is predominately fast compared to normal muscle as evidenced by contractile gene isoforms and decrease in oxidative metabolic gene transcription, despite a paradoxical increased transcription of slow fiber pathway genes. We also found competing pathways of fiber hypertrophy with an increase in the anabolic IGF1 gene in parallel with a paradoxical increase in myostatin, a gene responsible for stopping muscle growth. We found evidence that excitation-contraction coupling genes are altered in muscles from patients with CP and may be a significant component of disease., Conclusion: This is the first transcriptional profile performed on spastic muscle of CP patients and these adaptations were not characteristic of those observed in other disease states such as Duchenne muscular dystrophy and immobilization-induced muscle atrophy. Further research is required to understand the mechanism of muscle adaptation to this upper motor neuron lesion that could lead to the development of innovative therapies.

The objective of the study was to investigate the feasibility of modified constraint-induced (CI) therapy provided in a 2-week day-camp model with and without intramuscular botulinum toxin type A (BoNT-A) injections for children with congenital cerebral palsy. Sixteen children with congenital hemiplegia, Manual Ability Classification System (MACS) level I and II, aged 8-17 years, participated in a CI therapy day camp; of whom five participants (aged 11-16 years) received intramuscular BoNT-A prior to CI therapy. Assessments were conducted 4 months and 2 weeks before (baselines 1 and 2), immediately after, and 6 months after the day camp. For the children who received BoNT-A, no statistical analyses were conducted due to the small size of the sample. In this group, consistent improvement was only found according to the Melbourne Unilateral Limb Assessment. The children who received only the CI therapy demonstrated improvements in the Jebsen-Taylor Hand Function Test (p =. 04) at posttest, but improvements were not sustained at 6-month follow-up. No significant improvement was obtained for the Melbourne Assessment or the Assisting Hand Assessment. Children in both groups improved on specially trained tasks: frisbee golf, stacking blocks, and in-hand manipulation. Feedback from the participants suggests that the day-camp model is a feasible intervention following intramuscular BoNT-A injections. The results suggest that children with congenital hemiplegia with varying severity of impairment in hand function may benefit from CI therapy, but not every child demonstrates improvements in hand function. The characteristics of children who respond the best to CI therapy are not clear.

Spastic cerebral palsy can be divided into diagnostic groups by the relative severity of the arm impairment. This study investigates if hemiplegic, tetraplegic or diplegic cerebral palsy (CP) results in different patterns of myosin heavy chain (MyHC) expression in the flexor carpi ulnaris muscle from 17 young patients with CP. Using enzyme-immunohistochemistry and gel electrophoresis techniques we found a higher percentage of fibers expressing fast MyHC IIx (52%) in tetraplegic CP compared to hemiplegic patients (32%), (p<0.05). Tetraplegic CP also resulted in a lower amount of fibers expressing slow MyHC I (18%) compared to hemiplegic CP (40%), (p<0.005). The proportion of muscle fibers containing fetal MyHC was higher in tetraplegic CP compared to other groups, (p<0.005). Taken together theses results indicate that tetraplegic CP is associated with a shift from slow to fast myosins and that regenerative events are more prominent in tetraplegic CP compared with milder brain damage.

Rabbits were immobilized for 3 weeks with the ankle in plantar flexion, midrange position or dorsal extension (n=15). The left leg was used as control. Sarcomere lengths were measured by laser diffraction in vivo in the tibialis anterior (TA) muscle. Legs immobilized in the midrange position showed coherent diffraction patterns through the range of motion, but in those immobilized with TA in the stretched position no diffraction patterns in vivo could be obtained. Morphological analyses revealed increased fibrosis and occurrence of whorled fibers in these muscles. On 15 more likewise immobilized rabbits, a technique of measuring sarcomere lengths in vitro by first digesting the collagen in nitric acid was developed. These in vitro measurements showed shorter sarcomeres in the muscles immobilized in a lengthened position compared to the control, indicating an addition of sarcomeres in series.

Children with cerebral palsy often have spasticity of both the extensors and flexors, but how and why a flexion contracture of the wrist will develop during growth is not thoroughly understood. In order to understand the muscle adaptations that occur during contracture formation, the relationship between intraoperative sarcomere length and the extent of contracture was measured in 23 children (average age, 14.3 +/- 2.9 years) undergoing tendon transfers involving the flexor carpi ulnaris (FCU) or extensor carpi radialis brevis (ECRB) muscles. For both ECRB and FCU, sarcomere lengths measured intraoperatively were longer compared to sarcomere lengths predicted from a regression relationship obtained from "control" patients with radial nerve injury (P < 0.001). The most interesting aspect of the long FCU sarcomere lengths measured was that there was a highly significant correlation between the degree of contracture formation and intraoperative sarcomere length (r2 = 0.5, P < 0.005). These data clearly show that greater contracture severity is associated with longer intraoperative FCU sarcomere length. No such correlation was observed for the ECRB. The data suggest that the clinical presentation of the contracture is related to degree of FCU, but not ECRB adaptation, to the central nervous system lesion.

Morphological properties of skeletal muscle were compared between wrist flexors and extensors within the same children (n = 8, six females, two males; age range 4 to 9y, median age 7 y) with wrist muscle imbalance secondary to spastic cerebral palsy (CP). Five patients had hemiplegic CP, two diplegic CP, and one patient had tetraplegic CP. Muscle biopsies were taken during either tendon transfer or tendon lengthening procedures. Analyses included distribution of muscle fibre types, fibre sizes, and expression of developmental myosins. Extensor fibre area was significantly greater than flexor fibre area for type 2A fibres and type 2B fibres but not for type 1 fibres. Coefficient of variation (CV) of fibre size for all three fibre types was greater for flexors compared with extensors. The greatest CV was observed for the type 2A fibres in flexors (39.5 [3.6%]). A wide variation was observed for expression of developmental myosin with the magnitude of the expression being greater, but not statistically significant, in flexors compared with extensors (5.4/mm2 vs 0.53/mm2). These data demonstrate that significant secondary myopathy of wrist flexor muscles results from CP.