Inactivating TDP2 missense mutation in siblings with congenital abnormalities reminiscent of fanconi anemia.

Mutations in TDP2, encoding tyrosyl-DNA phosphodiesterase 2, have been associated with a syndromal form of autosomal recessive spinocerebellar ataxia, type 23 (SCAR23). This is a very rare and progressive neurodegenerative disorder described in only nine patients to date, and caused by splice site or nonsense mutations that result in greatly reduced or absent TDP2 protein. TDP2 is required for the rapid repair of DNA double-strand breaks induced by abortive DNA topoisomerase II (TOP2) activity, important for genetic stability in post-mitotic cells such as neurons. Here, we describe a sibship that is homozygous for the first TDP2 missense mutation (p.Glu152Lys) and which presents with clinical features overlapping both SCAR23 and Fanconi anemia (FA). We show that in contrast to previously reported SCAR23 patients, fibroblasts derived from the current patient retain significant levels of TDP2 protein. However, this protein is catalytically inactive, resulting in reduced rates of repair of TOP2-induced DNA double-strand breaks and cellular hypersensitivity to the TOP2 poison, etoposide. The TDP2-mutated patient-derived fibroblasts do not display increased chromosome breakage following treatment with DNA crosslinking agents, but both TDP2-mutated and FA cells exhibit increased chromosome breakage in response to etoposide. This suggests that the FA pathway is required in response to TOP2-induced DNA lesions, providing a possible explanation for the clinical overlap between FA and the current TDP2-mutated patients. When reviewing the relatively small number of patients with SCAR23 that have been reported, it is clear that the phenotype of such patients can extend beyond neurological features, indicating that the TDP2 protein influences not only neural homeostasis but also other tissues as well.

Reliability of 3D freehand ultrasound to assess lower limb muscles in children with spastic cerebral palsy and typical development.

This study investigated the reliability of 3-dimensional freehand ultrasound (3DfUS) to quantify the size (muscle volume [MV] and anatomical cross-sectional area [aCSA]), length (muscle length [ML], tendon length [TL], and muscle tendon unit length [MTUL]), and echo-intensity (EI, whole muscle and 50% aCSA), of lower limb muscles in children with spastic cerebral palsy (SCP) and typical development (TD). In total, 13 children with SCP (median age 14.3 (7.3) years) and 13 TD children (median age 11.1 (1.7) years) participated. 3DfUS scans of rectus femoris, semitendinosus, medial gastrocnemius, and tibialis anterior were performed by two raters in two sessions. The intra- and inter-rater and intra- and inter-session reliability were defined with relative and absolute reliability measures, that is, intra-class correlation coefficients (ICCs) and absolute and relative standard error of measurement (SEM and SEM%), respectively. Over all conditions, ICCs for muscle size measures ranged from 0.818 to 0.999 with SEM%s of 12.6%-1.6%. For EI measures, ICCs varied from 0.233 to 0.967 with SEM%s of 15.6%-1.7%. Length measure ICCs ranged from 0.642 to 0.999 with SEM%s of 16.0%-0.5%. In general, reliability did not differ between the TD and SCP cohort but the influence of different muscles, raters, and sessions was not constant for all 3DfUS parameters. Muscle length and muscle tendon unit length were the most reliable length parameters in all conditions. MV and aCSA showed comparable SEM%s over all muscles, where tibialis anterior MV was most reliable. EI had low-relative reliability, but absolute reliability was better, with better reliability for the distal muscles in comparison to the proximal muscles. Combining these results with earlier studies describing muscle morphology assessed in children with SCP, 3DfUS seems sufficiently reliable to determine differences between cohorts and functional levels. The applicability on an individual level, for longitudinal follow-up and after interventions is dependent on the investigated muscle and parameter. Moreover, the semitendinosus, the acquisition, and processing of multiple sweeps, and the definition of EI and TL require further investigation. In general, it is recommended, especially for longitudinal follow-up studies, to keep the rater the same, while standardizing acquisition settings and positioning of the subject.

Muscle synergy structure and gait patterns in children with spastic cerebral palsy.

AIM: To determine if muscle synergy structure (activations and weights) differs between gait patterns in children with spastic cerebral palsy (CP). METHOD: In this cross-sectional study, we classified 188 children with unilateral (n=82) or bilateral (n=106) spastic CP (mean age: 9y 5mo, SD: 4y 3mo, range: 3y 9mo-17y 7mo; 75 females; Gross Motor Function Classification System [GMFCS] level I: 106, GMFCS level II: 55, GMFCS level III: 27) into a minor deviations (n=34), drop foot (n=16), genu recurvatum (n=26), apparent equinus (n=53), crouch (n=39), and jump gait pattern (n=20). Surface electromyography recordings from eight lower limb muscles of the most affected side were used to calculate synergies with weighted non-negative matrix factorization. We compared synergy activations and weights between the patterns. RESULTS: Synergy structure was similar between gait patterns, although weights differed in the more impaired children (crouch and jump gait) when compared to the other patterns. Variability in synergy structure between participants was high. INTERPRETATION: The similarity in synergy structure between gait patterns suggests a generic motor control strategy to compensate for the brain lesion. However, the differences in weights and high variability between participants indicate that this generic motor control strategy might be individualized and dependent on impairment level.

Proximal femoral derotation osteotomy in children with CP : long term outcome and the role of age at time of surgery.

The femoral derotation osteotomy (FDO) is seen as the golden standard treatment in children with cerebral palsy and internal rotated gait. This study provides quantitative evidence in support of the beneficial effect of FDO after long term follow up. Retrospective clinical and kinematic evaluation of 31 CP patients (55 operated limbs) pre-, 1 and 3 years postoperatively after proximal FDO was conducted for a minimal follow-up of 3 years. This group con- sisted of 20 men and 11 women, aged 10.68±3.31 years at the time of surgery. Minimum follow up was 3 years (3.16±0.53 years), with 22 patients (38 operated limbs) having an additional follow up at 5 years (5.02±0.49 years). Age at FU3 and FU5 was 14.06±3.52 years and 15.39±3.08 years respectively. A set of clinical and kinematic parameters were ana- lyzed and showed a significant correction of mean hip rotation and femoral anteversion after FDO. Further plotting of individual data comparing 3 or 5 year postoperative values to 1 year postoperative values showed no further significant changes, indicating sustained correction of internally rotted gait until end of our follow up. Plotting mean hip rotation in stance as well as kinematic knee parameters according to age grouped cohorts could not show age at time of surgery to be a significant factor in recurrence of internally rotated gait or preoperative disturbances of knee motion in the sagittal plane. This study provides quantitative evidence on the beneficial effect of FDO, a surgical technique to improve internally rotated gait in cerebral palsy patients with spastic diplegia. Pre- and postoperative clinical and kinematic para- meters are compared and results are discussed. Minimum follow up was 3 years with a mean follow up of 4.65±0.83 years. The effect of age at time of surgery on recurrence and kinematic parameters were studied.

Tone Reduction and Physical Therapy: Strengthening Partners in Treatment of Children with Spastic Cerebral Palsy.

The aim of this paper is to provide a clinically applicable overview of different tone reducing modalities and how these can interact with or augment concurrent physical therapy (PT). Botulinum toxin (BoNT), oral tone-regulating medication, intrathecal baclofen (ITB), and selective dorsal rhizotomy are discussed within a physiotherapeutic context and in view of current scientific evidence. We propose clinical reasoning strategies to identify treatment goals as well as the appropriate and corresponding treatment interventions. Instrumented measurement of spasticity, standardized clinical assessment, and 3D clinical motion analysis are scientifically sound tools to help select the appropriate treatment and, when needed, to selectively target or spare individual muscles. In addition, particular attention is given to strength training as a necessary tool to tackle muscle weakness associated with specific modalities of tone reduction. More research is needed to methodologically assess the long-term effectiveness of such individualized tone treatment, optimize parameters such as medication dosage, and gain more insight into the kind of PT techniques that are essential in conjunction with tone reduction.

Medial gastrocnemius volume and echo-intensity after botulinum neurotoxin A interventions in children with spastic cerebral palsy.

AIM: This cross-sectional investigation evaluated whether recurrent botulinum neurotoxin A (BoNT-A) interventions to the medial gastrocnemius have an influence on muscle morphology, beyond Gross Motor Function Classification System (GMFCS) level. METHOD: A cohort of typically developing children (n=67; 43 males, 24 females; median age 9y 11mo [range 7y 10mo-11y 6mo]), a cohort of children with spastic cerebral palsy (CP) naive to BoNT-A interventions (No-BoNT-A; n=19; 10 males, nine females; median age 9y 3mo [range 8y 5mo-10y 10mo]) and a cohort of children with spastic CP with a minimum of three recurrent BoNT-A interventions to the medial gastrocnemius (BoNT-A; n=19; 13 males, six females; median age 9y 8mo [range 7y 3mo-10y 7mo]) were recruited. Three-dimensional freehand ultrasound was used to estimate medial gastrocnemius volume normalized to body mass and echo-intensity. RESULTS: Normalized medial gastrocnemius volume and echo-intensity significantly differed between the two spastic CP cohorts (p≤0.05), with the BoNT-A cohort having larger alterations. Associations between normalized medial gastrocnemius volume and echo-intensity were highest in the No-BoNT-A cohort, followed by the BoNT-A cohort. Multiple regression analyses revealed that both GMFCS level and BoNT-A intervention history were significantly associated with smaller normalized medial gastrocnemius volume and higher echo-intensity. INTERPRETATION: Recurrent BoNT-A interventions may induce alterations to medial gastrocnemius volume and echo-intensity beyond the natural history of the spastic CP pathology. WHAT THIS PAPER ADDS: In spastic cerebral palsy, medial gastrocnemius volumes are smaller and echo-intensities higher compared with typical development. Alterations after botulinum neurotoxin A intervention (BoNT-A) are larger than in no BoNT-A intervention. Gross Motor Function Classification System level and BoNT-A history significantly associate with medial gastrocnemius and echo-intensity alterations.

VOLUMEN DEL MÚSCULO GASTROCNEMIUS MEDIAL E INTENSIDAD DE LA ECOGRAFÍA DESPUÉS DE LA COLOCACIÓN DE NEUROTOXINA BOTULÍNICA (TIPO A), EN NIÑOS CON PARÁLISIS CEREBRAL ESPÁSTICA (PC): OBJETIVO: Esta investigación de corte transversal evaluó si la colocación recurrente de neurotoxina botulínica tipo A (BoNT-A) en el músculo gastrocnemius medial tienen una influencia en la morfología muscular, más allá del nivel del Sistema de Clasificación de la Función Motora Gruesa (GMFCS, siglas en ingles). MÉTODO: Una cohorte de niños con desarrollo tipico (n = 67; 43 varones, 24 mujeres; mediana de edad 9 años 11 meses [rango 7 años 10 meses -11 años 6 meses]), otra cohorte de niños con parálisis cerebral espástica (PC) que no habían recibido intervenciones de BoNT-A ( n = 19; 10 hombres, nueve mujeres; mediana de edad 9 años 3 meses [rango 8 años 5 meses -10 años 10 meses]) y una cohorte de niños con PC espástica con un mínimo de tres administraciones recurrentes de BoNT-A en el músculo gastrocnemius medial (BoNT-A; n = 19; 13 varones, seis mujeres; mediana de edad 9 años 8 meses [rango 7 años 3 meses - 10 años 7 meses]) fueron reclutados. Se usó ultrasonido tridimensional a mano alzada para estimar el volumen del músculo gastrocnemius medial normalizado a la masa corporal y la intensidad del eco. RESULTADOS: El volumen del músculo gastrocnemius medial normalizado y la intensidad del eco difirieron significativamente entre las dos cohortes de PC espástica (p≤0,05), la cohorte BoNT-A tuvo alteraciones mayores. Las asociaciones entre el volumen músculo gastrocnemius medial normalizado y la intensidad del eco fueron más altas en la cohorte No-BoNT-A, seguidas de la cohorte BoNT-A. Los análisis de regresión múltiple revelaron que tanto el nivel de GMFCS como el antecedente de intervención de BoNT-A se asociaron significativamente con un volumen del músculo gastrocnemius medial normalizado más pequeño y una mayor intensidad de eco. INTERPRETACIÓN: La colocación recurrentes de BoNT-A pueden inducir alteraciones en el volumen del músculo gastrocnemius medial y en la intensidad del eco más allá de la historia natural de la patología por PC espástica.

VOLUME E ECO-INTENSIDADE DO MÚSCULO GASTROCNÊMIO MEDIAL APÓS INTERVENÇÕES COM NEUROTOXINA BOTULÍNICA A EM CRIANÇAS COM PARALISIA CEREBRAL ESPÁSTICA: OBJETIVO: Esta investigação transversal avaliou se intervenções recorrentes com neurotoxina botulínica A (NTBo-A) no músculo gastrocnêmio medial têm influência na morfologia muscular, além do nível segundo o Sistema de Classificação da Função Motora Grossa (GMFCS). MÉTODO: Uma coorte de crianças com desenvolvimento típico (n=67; 43 do sexo masculino, 24 do sexo feminino; idade mediana 9a 11m [variação 7a 10m-11a 6m]), uma coorte de crianças com paralisia cerebral espástica (PC) que nunca recebeu intervenções com NTBo-A (No-NTBo-A; n=19; 10 do sexo masculino, nove do sexo feminino; idade mediana 9a 3m [variação 8a 5m-10a 10m]) e uma coorte de crianças com PC espástica com no mínimo três intervenções de NTBo-A no músculo gastrocnêmio medial (NTBo-A; n=19; 13 do sexo mascuino, seis do sexo feminino; idade mediana 9a 8m [variação 7a 3m-10a 7m]) foram recrutadas. Ultrassom tridimensional foi usado para estimar o volume do gastrocnêmio normalizado para a massa corporal e eco-intensidade. RESULTADOS: O volume normalizado e eco-intensidade do músculo gastrocnêmio medial diferiu significantemente entre as duas coortes de PC espástica (p≤0,05), com a coorte NTBo-A tendo maiores alteracões. Associações entre o volume normalizado do gastrocnêmio e eco-intensidade foram maiores na coorte No-NTBo-A, seguida pela coorte NTBo-A. Análises de regressão múltipla revelaram que tanto o nível GMFCS quanto a história de intervenção com NTBo-A foram significativamente associadas com menor volume normalizado do músculo gastrocnêmio medial e maior eco-intensidade. INTERPRETAÇÃO: Intervenções recorrentes com NTBo-A podem induzir alterações no volume e eco-intensidade do músculo gastrocnêmio medial, além da história natural da patologia da PC espástica.

Cup oversizing as a risk factor for postoperative groin pain in Total Hip Arthroplasty : a retrospective analysis of 437 hips.

The majority of patients are pain free after total hip replacement, but some experience anterior hip pain due to iliopsoas impingement. There is evidence that a prominent or malpositioned cup may cause iliopsoas tendonitis. The purpose of this study was to determine whether oversizing the cup is a risk factor for postoperative groin pain. We retrospectively investigated 437 total hip replacements in which the femoral head diameter had been measured for other research purposes. Data regarding the cup size and positioning was collected from implant identification labels and pelvis x-rays. Clinical data were recovered from the medical files. Native femoral head size, cup size, anteversion, inclination and DS (difference between native femoral head size and cup size) and type of pain (anterior hip pain or non-anterior hip pain) were analyzed and correlations were sought. There was a strong and significant correlation between native femoral head size and cup size. Mean DS was 5.5 mm in the no pain group, 6.9 mm in the anterior hip pain group and 5.9 mm in the non-anterior hip pain group. The difference in mean DS was significant (P=0.046) in patients experiencing anterior hip pain vs. those with no pain or non-anterior hip pain. As patients with anterior hip pain had a significant larger DS of 6.9 mm, it seems that a cup size of more than 6 mm above the native femoral head size should be avoided. We therefore recommend a systematic intraoperative head size measurement prior to definite cup choice.

Evolution of self-care and functional mobility after single-event multilevel surgery in children and adolescents with spastic diplegic cerebral palsy.

AIM: To explore the evolution of self-care and functional mobility after multilevel surgery in children and adolescents with spastic diplegic cerebral palsy and to identify factors affecting these outcomes. METHOD: Thirty-four participants (22 males, 12 females) were evaluated before surgery, and at 2 months, 6 months, 1 year, 18 months, and 2 years after surgery. Self-care was assessed with the Pediatric Evaluation of Disability Inventory Dutch edition. The Mobility Questionnaire47 (MobQues47) and Functional Mobility Scale (FMS) were used to measure functional mobility. RESULTS: All outcomes revealed a significant decrease 2 months after single-event multilevel surgery (SEMLS) (p-value between <0.001 and 0.02) followed by a significant increase at 6 months (p<0.001 and p=0.045). Between 6 months and 1 year, a significant increase was also revealed for Mobques47 (p<0.001), FMS (p≤0.008), and the Pediatric Evaluation of Disability Inventory Functional Skills Scale (PEDI-FSS) (p=0.001). Improvement continued until 18 months for the PEDI-FSS. Initial score, initial muscle strength, Gross Motor Function Classification System level, age, and number of surgical interventions significantly influenced time trends for self-care and/or functional mobility. INTERPRETATION: Most preoperative scores are regained at 6 months after SEMLS. Further improvement is seen until 18 months. Participants with a higher functional level before surgery will temporarily lose more than participants with lower initial functional ability, but they also fast regain their function. WHAT THIS PAPER ADDS: Self-care and functional mobility decrease significantly in the first months after single-event multilevel surgery (SEMLS). Six months after SEMLS most preoperative scores are regained. Impact of SEMLS is more pronounced for functional mobility than for self-care. Muscle strength and functionality at baseline are important influencing factors on the evolution after SEMLS.

Estimating medial gastrocnemius muscle volume in children with spastic cerebral palsy: a cross-sectional investigation.

AIM: This cross-sectional investigation evaluates the reliability of estimating medial gastrocnemius anatomical cross-sectional area (aCSA) in typically developing and spastic cerebral palsy (SCP) cohorts. It verifies whether muscle volume estimations based on aCSA improve when aCSA is multiplied by muscle-tendon unit (MTU) or muscle length, and whether the resulting errors in volume estimations are smaller than changes after intervention. METHOD: Fifteen typically developing children (mean age 8y 2mo [SD 1y 5mo], six males, nine females) and 30 children with SCP (mean age 9y 2mo [SD 2y 5mo], 22 males, eight females, Gross Motor Function Classification System [GMFCS] level I=15, II=15) participated in the investigation. The SCP cohort was divided according to GMFCS level. A three-dimensional freehand ultrasound technique was used to estimate medial gastrocnemius aCSA, muscle volume, MTU, and muscle length. Estimated muscle volume (aCSA×MTU or muscle length) was compared with the measured muscle volume. RESULTS: Anatomical cross-sectional area, muscle volume, and muscle length significantly differed between the typically developing and two SCP cohorts (p≤0.050). aCSA multiplied by either MTU or muscle length improved estimations of medial gastrocnemius volume. Leave-one-out cross-validation revealed an absolute difference with measured muscle volume of 3.77 ml (SD 2.90). INTERPRETATION: This investigation revealed that medial gastrocnemius muscle volume can be reliably estimated in a clinically feasible manner in typically developing children and those with SCP. WHAT THIS PAPER ADDS: Medial gastrocnemius anatomical cross-sectional area (aCSA) can be reliably estimated in children with spastic cerebral palsy. The location of the anatomical cross-section should be taken with respect to muscle and not bone length. Medial gastrocnemius volume can be reliably estimated by multiplying aCSA and muscle length. The errors in volume estimations are smaller than reported differences after interventions.

Combining constraint-induced movement therapy and action-observation training in children with unilateral cerebral palsy: a randomized controlled trial.

BACKGROUND: Upper limb (UL) deficits in children with unilateral cerebral palsy (uCP) have traditionally been targeted with motor execution treatment models, such as modified Constraint-Induced Movement Therapy (mCIMT). However, new approaches based on a neurophysiological model such as Action-Observation Training (AOT) may provide new opportunities for enhanced motor learning. The aim of this study is to describe a randomised controlled trial (RCT) protocol investigating the effects of an intensive treatment model, combining mCIMT and AOT compared to mCIMT alone on UL function in children with uCP. Additionally, the role of neurological factors as potential biomarkers of treatment response will be analysed. METHODS: An evaluator-blinded RCT will be conducted in 42 children aged between 6 and 12 years. Before randomization, children will be stratified according to their House Functional Classification Scale, age and type of corticospinal tract wiring. A 2-week day-camp will be set up in which children receive intensive mCIMT therapy for 6 hours a day on 9 out of 11 consecutive days (54 h) including AOT or control condition (15 h). During AOT, these children watch video sequences showing goal-directed actions and subsequently execute the observed actions with the more impaired UL. The control group performs the same actions after watching computer games without human motion. The primary outcome measure will be the Assisting Hand Assessment. Secondary outcomes comprise clinical assessments across body function, activity and participation level of the International Classification of Function, Disability and Health. Furthermore, to quantitatively evaluate UL movement patterns, a three-dimensional motion analysis will be conducted. UL function will be assessed at baseline, immediately before and after intervention and at 6 months follow up. Brain imaging comprising structural and functional connectivity measures as well as Transcranial Magnetic Stimulation (TMS) to evaluate corticospinal tract wiring will be acquired before the intervention. DISCUSSION: This paper describes the methodology of an RCT with two main objectives: (1) to evaluate the added value of AOT to mCIMT on UL outcome in children with uCP and (2) to investigate the role of neurological factors as potential biomarkers of treatment response. TRIAL REGISTRATION: NCT03256357 registered on 21st August 2017 (retrospectively registered).

Time Course of Upper Limb Function in Children with Unilateral Cerebral Palsy: A Five-Year Follow-Up Study.

Knowledge on long-term evolution of upper limb function in children with unilateral cerebral palsy (CP) is scarce. The objective was to report the five-year evolution in upper limb function and identify factors influencing time trends. Eighty-one children (mean age 9 y and 11 mo, SD 3 y and 3 mo) were assessed at baseline with follow-up after 6 months, 1, and 5 years. Passive range of motion (PROM), tone, muscle, and grip strength were assessed. Activity measurements included Melbourne Assessment, Jebsen-Taylor test, Assisting Hand Assessment (AHA), and ABILHAND-Kids. At 5-year follow-up, PROM (p < 0.001) and AHA scores (p < 0.001) decreased, whereas an improvement was seen for grip strength (p < 0.001), Melbourne Assessment (p = 0.003), Jebsen-Taylor test (p < 0.001), and ABILHAND-Kids (p < 0.001). Age influenced the evolution of AHA scores (p = 0.003), with younger children being stable over time, but from 9 years onward, children experienced a decrease in bimanual performance. Manual Ability Classification System (MACS) levels also affected the evolution of AHA scores (p = 0.02), with stable scores in MACS I and deterioration in MACS II and III. In conclusion, over 5 years, children with unilateral CP develop more limitations in PROM, and although capacity measures improve, the spontaneous use of the impaired limb in bimanual tasks becomes less effective after the age of 9 years.

Inter- and intrarater clinician agreement on joint motion patterns during gait in children with cerebral palsy.

AIM: This study aimed to quantify the inter- and intrarater clinician agreement on joint motion patterns in children with spastic cerebral palsy (CP), which were recently specified by a Delphi consensus study. It also examined whether experience with three-dimensional gait analysis (3DGA) is a prerequisite for using the patterns. METHOD: The experimental group consisted of 82 patients with CP (57 males, 25 females; uni-/bilateral CP [n=27/55]; Gross Motor Function Classification System levels I to III; mean age 9y 5mo [range 4y-18y]). Thirty-two clinicians were split into 'experienced' and 'inexperienced' rater groups. Each rater was asked to classify 3DGA reports of 27 or 28 patients twice. Inter- and intrarater agreement on 49 joint motion patterns was estimated using percentage of agreement and kappa statistics. RESULTS: Twenty-eight raters completed both classification rounds. Intrarater agreement was 'substantial' to 'almost perfect' for all joints (0.64<ĸ<0.91). Interrater agreement reached similar results (0.63<ĸ<0.86), except for the knee patterns during stance (ĸ=0.49, 'moderate agreement'). Experienced raters performed significantly better on patterns of the knee during stance and ankle during swing. INTERPRETATION: Apart from some specific knee patterns during stance and ankle patterns during swing, the results suggested that clinicians could use predefined joint motion patterns in CP with good confidence, even in case of limited experience with 3DGA.

Functional outcomes in children and young people with dyskinetic cerebral palsy.

AIM: This cross-sectional study aimed to map the functional profile of individuals with dyskinetic cerebral palsy (CP), to determine interrelationships between the functional classification systems, and to investigate the relationship of functional abilities with dystonia and choreoathetosis severity. METHODS: Fifty-five children (<15y) and young people (15-22y) (30 males, 25 females; mean age 14y 6mo, standard deviation 4y 1mo) with dyskinetic CP were assessed using the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS), Eating and Drinking Ability Classification System (EDACS), and Viking Speech Scale (VSS), as well as the Dyskinesia Impairment Scale. RESULTS: Over 50 per cent of the participants exhibited the highest limitation levels in GMFCS, MACS, and VSS. Better functional abilities were seen in EDACS and CFCS. Moderate to excellent interrelationship was found among the classification scales. All scales had significant correlation (rs =0.65 - 0.81) with dystonia severity except for CFCS in the young people group. Finally, only MACS (rs =0.40) and EDACS (rs =0.55) in the young people group demonstrated significant correlation with choreoathetosis severity. INTERPRETATION: The need for inclusion of speech, eating, and drinking in the functional assessment of dyskinetic CP is highlighted. The study further supports the strategy of managing dystonia in particular at a younger age followed by choreoathetosis in a later stage.

The Direct Anterior Approach for Complex Primary Total Hip Arthroplasty: The Extensile Acetabular Approach on a Regular Operating Room Table.

BACKGROUND: The direct anterior approach on a regular operating room table has been reported with low dislocation rates. This might be beneficial for complex primary total hip arthroplasty (THA) such as in patients with cerebral palsy or following femoral or pelvic osteotomies. Extending the approach is often required to overcome problems such as acetabular deformities or severe contractures. METHODS: We retrospectively evaluated the results and complications of 29 patients with 37 complex primary THA in which an extensile approach was used. The extensile approach is described. Functional scores were collected in case the patient was ambulatory independently (n = 17). RESULTS: The average age was 35 years (range 15-85) with a mean follow-up of 39 months (range 12-60). There were 3 (8%) intra-operative and 4 (11%) early post-operative complications (<3 months), of which 3 (8%) were anterior dislocations. Late complications (>3 months) consisted of a fibrous ingrown stem, a socket loosening following a pelvic fracture, and a late hematogenous infection (8%). Seventy-one percent of the complications occurred in the first 18 cases (49%) indicating a learning curve. The mean post-operative Harris Hip Score was 79 (range 56-97). CONCLUSION: Complex THA can be safely conducted through the extensile anterior approach on a regular operating room table with the use of conventional implants, even in cases with a high risk of dislocation.

Identification of joint patterns during gait in children with cerebral palsy: a Delphi consensus study.

AIM: This study aims to achieve an international expert consensus on joint patterns during gait for children with cerebral palsy (CP) by means of Delphi surveys. METHOD: In Stage 1, seven local experts drafted a preliminary proposal of kinematic patterns for each lower limb joint in the sagittal, coronal, and transverse plane. In Stage 2, 13 experts from eight gait laboratories (four in the USA and four in Europe), participated in a Delphi consensus study. Consensus was defined by a pre-set cut-off point of 75% agreement among participants. RESULTS: After the first stage, 44 joint patterns were presented in a first survey and 29 patterns reached consensus. Consensus improved to 47 out of 48 patterns in the third survey. Only one pattern, 'abnormal knee pattern during loading response', did not reach consensus. The expert panel agreed to define six patterns for the knee during swing, most of them representing characteristics of a stiff knee pattern. INTERPRETATION: The defined joint patterns can support clinical reasoning for children with CP as joint patterns during gait might be linked to different treatment approaches. Automating the classification process and incorporating additional trunk, foot, and electromyography features should be prioritized for the near future.

Motor endplate-targeted botulinum toxin injections of the gracilis muscle in children with cerebral palsy.

AIM: Intramuscular botulinum toxin-A (BoNT-A) injections reduce spasticity by blocking neurotransmission at the motor endplate (MEP). The goal of this study was to assess the reduction in spasticity achieved by injecting BoNT-A at different sites of the gracilis muscle. METHOD: Thirty-four gracilis muscles, in 27 children (10 females and 17 males, mean age of 8.6y [SD 2.5y]) with spastic cerebral palsy (unilateral and bilateral, Gross Motor Function Classification System [GMFCS] levels I-IV), were randomly assigned to one of two groups. In one group BoNT-A was injected proximally (at a site 25% of the distance from the pubic tubercle and the medial epicondyle) and in the other it was injected at the MEP zones (half of the dose was administered at 30% of this distance and half at 60%). Spasticity was assessed before and after BoNT-A injection using simultaneous measurements of surface electromyography (sEMG) and angular velocity during passive muscle stretch applied at different velocities. The primary outcome measure included the velocity-dependent change in average root mean square electromyography (RMS-EMG). Secondary outcome was assessed with the Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS). RESULTS: Spasticity decreased more in MEP-targeted muscles than in proximally injected muscles, as demonstrated by a larger reduction in average RMS-EMG values (p=0.04), though this difference was not found with the MAS or MTS. INTERPRETATION: The results suggest that BoNT-A injection of the gracilis at sites with a high concentration of MEPs is effective at reducing spasticity. These preliminary findings should be confirmed by larger studies. In the case of long muscles, such as the gracilis, the injection site is important.

A study of whether video scoring is a reliable option for blinded scoring of the Gross Motor Function Measure-88.

OBJECTIVE: To investigate the agreement between live and video scores of the Gross Motor Function Measure-88. DESIGN: Reliability study. SUBJECTS: Forty children with bilateral spastic cerebral palsy. INTERVENTIONS: Fifty evaluations were administered according to the test guidelines, and were videotaped. After a minimum interval of one month, the video recordings were again rated by the same assessor. Two physical therapy students also each scored the recordings twice, with a minimal interval of one month. MAIN MEASURES: Agreement between live and video scores as well as inter-rater and intra-rater agreement of the video scores were assessed using intra-class correlation coefficients (ICC), standard error of measurements (SEM), and smallest detectable changes (SDC). Weighted kappa coefficients were used to analyse individual items. RESULTS: The live and video scores from the same assessor showed good to very good agreement for the total score (ICC, 0.973; SEM, 2.28; SDC, 6.32) and dimensions B (ICC, 0.938), D (ICC, 0.965), and E (ICC, 0.992) but lower agreement for A (ICC, 0.720) and C (ICC, 0.667). Live-versus-video agreement for the total score was higher than inter-rater agreement by video (ICC, 0.949; SEM, 3.15; SDC, 8.73) but lower than intra-rater agreement by video (ICC, 0.989; SEM, 1.42; SDC, 3.96). CONCLUSION: The Gross Motor Function Measure-88 can be reliably scored using video recordings. The agreement between live and video scores is lower than the intra-rater reliability using video recordings only. Future clinical trial results should be interpreted using the appropriate SEM and SDC values.

Role of motor end plate-targeted Botulinum toxin type A injections in children with cerebral palsyitle.

Botulinum toxin type A (BTX) injections are frequently used in children with cerebral palsy (CP) to control spasticity. Injection variables still lead to variable outcomes of this treatment. Using instrumented spasticity assessment and muscle volume assessment the most effective location of the injection was demonstrated for gracilis and psoas muscles in children with CP. It was found that this treatment is most effective when injected in the motor endplate zones of the selected muscles. This review article presents all available research on the role of motor endplate-targeting of BTX injections in children with CP.

Manually controlled instrumented spasticity assessments: a systematic review of psychometric properties.

AIM: The first aim of this study was to systematically review and critically assess manually controlled instrumented spasticity assessment methods that combine multidimensional signals. The second aim was to extract a set of quantified parameters that are psychometrically sound to assess spasticity in a clinical setting. METHOD: Electronic databases were searched to identify studies that assessed spasticity by simultaneously collecting electrophysiological and biomechanical signals during manually controlled passive muscle stretches. Two independent reviewers critically assessed the methodological quality of the psychometric properties of the included studies using the COSMIN guidelines. RESULTS: Fifteen studies with instrumented spasticity assessments met all inclusion criteria. Parameters that integrated electrophysiological signals with joint movement characteristics were best able to quantify spasticity. There were conflicting results regarding biomechanical-based parameters that quantify the resistance to passive stretch. Few methods have been assessed for all psychometric properties. In particular, further information on absolute reliability and responsiveness for more muscles is needed. INTERPRETATION: Further research is required to determine the correct parameters for quantifying spasticity based on integration of signals, which especially focuses on distinguishing the neural from non-neural contributions to increased joint torque. These parameters should undergo more rigorous exploration to establish their psychometric properties for use in a clinical environment.

Is an instrumented spasticity assessment an improvement over clinical spasticity scales in assessing and predicting the response to integrated botulinum toxin type a treatment in children with cerebral palsy?

OBJECTIVE: To compare responsiveness and predictive ability of clinical and instrumented spasticity assessments after botulinum toxin type A (BTX) treatment combined with casting in the medial hamstrings (MEHs) in children with spastic cerebral palsy (CP). DESIGN: Prospective cohort study. SETTING: Hospital. PARTICIPANTS: Consecutive sample of children (N=31; 40 MEH muscles) with CP requiring BTX injections. INTERVENTION: Clinical and instrumented spasticity assessments before and on average ± SD 53±14 days after BTX. MAIN OUTCOME MEASURES: Clinical spasticity scales included the Modified Ashworth Scale and the Modified Tardieu Scale. The instrumented spasticity assessment integrated biomechanical (position and torque) and electrophysiological (surface electromyography) signals during manually performed low- and high-velocity passive stretches of the MEHs. Signals were compared between both stretch velocities and were examined pre- and post-BTX. Responsiveness of clinical and instrumented assessments was compared by percentage exact agreement. Prediction ability was assessed with a logistic regression and the area under the receiver operating characteristic (ROC) curves of the baseline parameters of responders versus nonresponders. RESULTS: Both clinical and instrumented parameters improved post-BTX (P≤.005); however, they showed a low percentage exact agreement. The baseline Modified Tardieu Scale was the only clinical scale predictive for response (area under the ROC curve=0.7). For the instrumented assessment, baseline values of root mean square (RMS) electromyography and torque were better predictors for a positive response (area under the ROC curve=.82). Baseline RMS electromyography remained an important predictor in the logistic regression. CONCLUSIONS: The instrumented spasticity assessment showed higher responsiveness than the clinical scales. The amount of RMS electromyography is considered a promising parameter to predict treatment response.