Physical fitness in children with Marfan and Loeys-Dietz syndrome: associations between cardiovascular parameters, systemic manifestations, fatigue, and pain.

Children with Marfan (MFS) and Loeys-Dietz syndrome (LDS) report limitations in physical activities, sports, school, leisure, and work participation in daily life. This observational, cross-sectional, multicenter study explores associations between physical fitness and cardiovascular parameters, systemic manifestations, fatigue, and pain in children with MFS and LDS. Forty-two participants, aged 6-18 years (mean (SD) 11.5(3.7)), diagnosed with MFS (n = 36) or LDS (n = 6), were enrolled. Physical fitness was evaluated using the Fitkids Treadmill Test's time to exhaustion (TTE) outcome measure. Cardiovascular parameters (e.g., echocardiographic parameters, aortic surgery, cardiovascular medication) and systemic manifestations (systemic score of the revised Ghent criteria) were collected. Pain was obtained by visual analog scale. Fatigue was evaluated by PROMIS® Fatigue-10a-Pediatric-v2.0-short-form and PROMIS® Fatigue-10a-Parent-Proxy-v2.0-short-form. Multivariate linear regression analyses explored associations between physical fitness (dependent variable) and independent variables that emerged from the univariate linear regression analyses (criterion p < .05). The total group (MFS and LDS) and the MFS subgroup scored below norms on physical fitness TTE Z-score (mean (SD) -3.1 (2.9); -3.0 (3.0), respectively). Univariate analyses showed associations between TTE Z-score aortic surgery, fatigue, and pain (criterion p < .05). Multivariate analyses showed an association between physical fitness and pediatric self-reported fatigue that explained 48%; 49%, respectively, of TTE Z-score variance (F (1,18) = 18.6, p ≤ .001, r2 = .48; F (1,15) = 16,3, p = .01, r2 = .49, respectively).    Conclusions: Physical fitness is low in children with MFS or LDS and associated with self-reported fatigue. Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with MFS and LDS. What is Known: • Marfan and Loeys-Dietz syndrome are heritable connective tissue disorders and share cardiovascular and systemic manifestations. • Children with Marfan and Loeys-Dietz syndrome report increased levels of disability, fatigue and pain, as well as reduced levels of physical activity, overall health and health-related quality of life. What is New: • Physical fitness is low in children with Marfan and Loeys-Dietz syndrome and associated with self-reported fatigue. • Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with Marfan and Loeys-Dietz syndrome.

Surgical treatment options for spasticity in children and adolescents with hereditary spastic paraplegia.

PURPOSE: To provide an overview of outcome and complications of selective dorsal rhizotomy (SDR) and intrathecal baclofen pump implantation (ITB) for spasticity treatment in children with hereditary spastic paraplegia (HSP). METHODS: Retrospective study including children with HSP and SDR or ITB. Gross motor function measure (GMFM-66) scores and level of spasticity were assessed. RESULTS: Ten patients were included (most had mutations in ATL1 (n = 4) or SPAST (n = 3) genes). Four walked without and two with walking aids, four were non-walking children. Six patients underwent SDR, three patients ITB, and one both. Mean age at surgery was 8.9 ± 4.5 years with a mean follow-up of 3.4 ± 2.2 years. Five of the SDR patients were walking. Postoperatively spasticity in the legs was reduced in all patients. The change in GMFM-66 score was + 8.0 (0-19.7 min-max). The three ITB patients treated (SPAST (n = 2) and PNPLA6 (n = 1) gene mutation) were children with a progressive disease course. No complications of surgery occurred. CONCLUSIONS: SDR is a feasible treatment option in carefully selected children with HSP, especially in walking patients. The majority of patients benefit with respect to gross motor function, complication risk is low. ITB was used in children with severe and progressive disease.

Surgical complications of intrathecal baclofen in children: A single centre, 20-year retrospective cohort study.

INTRODUCTION: Complications of intrathecal baclofen treatment (ITB) with an implanted pump can be severe and require surgery. Surgical implantation techniques and catheter materials for continuous ITB treatment have improved over the past years with the aim to reduce complications. OBJECTIVE: To assess: 1) the type and rate of complications of ITB that require surgical intervention, 2) which risk factors influence the occurrence of complications, and, specifically, 3) whether complication rate is influenced by type of catheter used. METHODS: A retrospective cohort study was conducted including all children (<18 years old) in one university medical center with pump implantation between 2001 and 2017. All complications requiring surgery were recorded. Risk factors for surgical intervention were determined using multiple logistic regression analysis. Catheter related complications between two types of catheters (silicone vs coated) were compared. RESULTS: In total, 88 complications of ITB treatment requiring surgery were found in 47 (36.2%) out of 130 children. These included catheter-related complications (55.7% of all complications), infections (21.6%), cerebrospinal fluid leakage (14.8%), and pump-related complications (7.9%). The silicone catheter type, used until 2012, was found to be a significant risk factor for complications (Odds Ratio 3.75; 95% CI: 1.30-10.83). Since the introduction of the coated catheter type, in 2012, the rate of catheter-related complications decreased, from 0.15 to 0.10 complications per pump year. CONCLUSION: The rate of surgical complications of intrathecal baclofen in children is high, and most frequently catheter-related. The number of complications decreased since the introduction of a new, coated, catheter in 2012. This study helps to inform children and their caregivers about the risk of possible complications of ITB, and to identify directions for future improvement of ITB care.

Evolution of gait in adolescents and young adults with spastic diplegia after selective dorsal rhizotomy in childhood: A 10 year follow-up study.

BACKGROUND: Short-term benefit on gait of selective dorsal rhizotomy (SDR) surgery, which relieves spasticity of the lower extremities has been demonstrated in children with cerebral palsy (CP). However very little is known of the evolution of gait when patients become adolescents and young adults. RESEARCH QUESTION: How does the gait pattern evolve in adolescents and young adults who underwent SDR during childhood? METHODS: A longitudinal study was performed including 19 ambulant patients with spastic diplegia due to CP or other causes (mean age at SDR: 6.6 ±â€¯1.6 years) who were assessed four times: pre-SDR, 2 years post- SDR, 5 years post-SDR and at least 10 years post-SDR. From 2D video recordings, Edinburgh Visual Gait Score and lower limb joint kinematic parameters were calculated. RESULTS: Our data show that the improvement in the gait pattern obtained short-term after SDR continues during into adolescence and adulthood. Ten years after SDR all patients improved compared to baseline. Considering the lower limb joint kinematics, most notable improvements were found at knee and ankle joints. Compared to the evaluation before SDR, the range of motion of the knee increased: the knee was more extended at initial contact and knee flexion in midswing improved. Excessive ankle plantar flexion was reduced during the entire gait cycle. Only minor changes were found at hip and pelvis. Eight patients underwent additional orthopaedic surgery in the years after SDR, and the present findings should be considered as a combination of SDR, development and additional treatment. SIGNIFICANCE: We demonstrate lasting improvement of gait quality in ambulant patients with spastic diplegia who underwent SDR during childhood when they become adolescents and young adults.

Outcome of medial hamstring lengthening in children with spastic paresis: A biomechanical and morphological observational study.

To improve gait in children with spastic paresis due to cerebral palsy or hereditary spastic paresis, the semitendinosus muscle is frequently lengthened amongst other medial hamstring muscles by orthopaedic surgery. Side effects on gait due to weakening of the hamstring muscles and overcorrections have been reported. How these side effects relate to semitendinosus morphology is unknown. This study assessed the effects of bilateral medial hamstring lengthening as part of single-event multilevel surgery (SEMLS) on (1) knee joint mechanics (2) semitendinosus muscle morphology and (3) gait kinematics. All variables were assessed for the right side only. Six children with spastic paresis selected for surgery to counteract limited knee range of motion were measured before and about a year after surgery. After surgery, in most subjects popliteal angle decreased and knee moment-angle curves were shifted towards a more extended knee joint, semitendinosus muscle belly length was approximately 30% decreased, while at all assessed knee angles tendon length was increased by about 80%. In the majority of children muscle volume of the semitendinosus muscle decreased substantially suggesting a reduction of physiological cross-sectional area. Gait kinematics showed more knee extension during stance (mean change ± standard deviation: 34±13°), but also increased pelvic anterior tilt (mean change ± standard deviation: 23±5°). In most subjects, surgical lengthening of semitendinosus tendon contributed to more extended knee joint angle during static measurements as well as during gait, whereas extensibility of semitendinosus muscle belly was decreased. Post-surgical treatment to maintain muscle belly length and physiological cross-sectional area may improve treatment outcome of medial hamstring lengthening.

Analysis of gait patterns pre- and post- Single Event Multilevel Surgery in children with Cerebral Palsy by means of Offset-Wise Movement Analysis Profile and Linear Fit Method.

Gait analysis is used for the assessment of walking ability of children with cerebral palsy (CP), to inform clinical decision making and to quantify changes after treatment. To simplify gait analysis interpretation and to quantify deviations from normality, some quantitative synthetic descriptors were developed over the years, such as the Movement Analysis Profile (MAP) and the Linear Fit Method (LFM), but their interpretation is not always straightforward. The aims of this work were to: (i) study gait changes, by means of synthetic descriptors, in children with CP that underwent Single Event Multilevel Surgery; (ii) compare the MAP and the LFM on these patients; (iii) design a new index that may overcome the limitations of the previous methods, i.e. the lack of information about the direction of deviation or its source. Gait analysis exams of 10 children with CP, pre- and post-surgery, were collected and MAP and LFM were computed. A new index was designed asa modified version of the MAP by separating out changes in offset (named OC-MAP). MAP documented an improvement in the gait pattern after surgery. The highest effect was observed for the knee flexion/extension angle. However, a worsening was observed as an increase in anterior pelvic tilt. An important source of gait deviation was recognized in the offset between observed tracks and reference. OC-MAP allowed the assessment of the offset component versus the shape component of deviation. LFM provided results similar to OC-MAP offset analysis but could not be considered reliable due to intrinsic limitations. As offset in gait features played an important role in gait deviation, OC-MAP synthetic analysis was proposed as a novel approach to a meaningful parameterisation of global deviations in gait patterns of subjects with CP and gait changes after treatment.

Knee Moment-Angle Characteristics and Semitendinosus Muscle Morphology in Children with Spastic Paresis Selected for Medial Hamstring Lengthening.

To increase knee range of motion and improve gait in children with spastic paresis (SP), the semitendinosus muscle (ST) amongst other hamstring muscles is frequently lengthened by surgery, but with variable success. Little is known about how the pre-surgical mechanical and morphological characteristics of ST muscle differ between children with SP and typically developing children (TD). The aims of this study were to assess (1) how knee moment-angle characteristics and ST morphology in children with SP selected for medial hamstring lengthening differ from TD children, as well as (2) how knee moment-angle characteristics and ST morphology are related. In nine SP and nine TD children, passive knee moment-angle characteristics and morphology of ST (i.e. fascicle length, muscle belly length, tendon length, physiological cross-sectional area, and volume) were assessed by hand-held dynamometry and freehand 3D ultrasound, respectively. At net knee flexion moments above 0.5 Nm, more flexed knee angles were found for SP compared to TD children. The measured knee angle range between 0 and 4 Nm was 30% smaller in children with SP. Muscle volume, physiological cross-sectional area, and fascicle length normalized to femur length were smaller in SP compared to TD children (62%, 48%, and 18%, respectively). Sixty percent of the variation in knee angles at 4 Nm net knee moment was explained by ST fascicle length. Altered knee moment-angle characteristics indicate an increased ST stiffness in SP children. Morphological observations indicate that in SP children planned for medial hamstring lengthening, the longitudinal and cross-sectional growth of ST muscle fibers is reduced. The reduced fascicle length can partly explain the increased ST stiffness and, hence, a more flexed knee joint in these SP children.

Sudden falls as a persistent complication of selective dorsal rhizotomy surgery in children with bilateral spasticity: report of 3 cases.

Selective dorsal rhizotomy (SDR) surgery is a well-established treatment for ambulatory children with bilateral spastic paresis and is performed to eliminate spasticity and improve walking. The objective of this case report is to describe sudden falls as a persistent complication of SDR. The authors report on 3 patients with bilateral spastic paresis, aged 12, 6, and 7 years at the time of surgery. The percentage of transected dorsal rootlets was around 40% at the L2-S1 levels. Sudden falls were reported with a frequency of several a day, continuing for years after SDR. The falls were often triggered by performing dual tasks as well as occurring in the transition from sitting to standing, during running, after strenuous exercise, or following a fright. Patients also had residual hyperesthesia and dysesthesia of the foot sole. The authors hypothesize that the sudden falls are caused by a muscle inhibition reflex of the muscles in the legs, as an abnormal reaction to a sensory stimulus that is perceived with increased intensity by a patient with hyperesthesia. A favorable effect of gabapentin medication supports this hypothesis.

Satisfaction and pain levels after proximal femoral valgus osteotomy according to Schanz in patients with cerebral palsy and hip dislocation.

Outcome after Schanz osteotomy in the treatment of chronic hip dislocation in children with cerebral palsy was evaluated. Medical charts and questionnaires were used to assess pain, functional outcome and satisfaction. A total of 24 children, with a mean age of 13.8 years (± 8.9), were included in the study, out of which 11 were classified with Gross Motor Function Classification System (GMFCS) level IV and 13 with GMFCS level V. Current pain was comparable to patients without chronic hip dislocation, and satisfaction was intermediate. Functional outcome improved in several domains. Longer postoperative time was associated with improved pain and satisfaction. The Schanz osteotomy allowed improvement in pain levels; however, it did not completely meet caregiver's expectation and has high reoperation rates.

Effects of chemotherapy on neurocognitive function in children with acute lymphoblastic leukemia: a critical review of the literature.

Chemotherapy-only treatment has increasingly become the standard of treatment for childhood acute lymphoblastic leukemia (ALL). The objective of this review is to assess the present state of knowledge of the neurocognitive effects of central nervous system (CNS)-directed chemotherapy in children with ALL, and to formulate directions for future research. We performed a review of studies published since 1997, that included an ALL group treated with chemotherapy only and a control group. Twenty-one studies met our inclusion criteria. There is evidence of subtle long-term neurocognitive deficits survivors of childhood ALL after treatment with chemotherapy only. These involve mainly processes of attention and of executive functioning, while global intellectual function is relatively preserved. Young age at diagnosis and female sex emerged as risk factors.

Behavioral and educational limitations after chemotherapy for childhood acute lymphoblastic leukemia or Wilms tumor.

BACKGROUND: The improved prognosis of childhood cancer makes monitoring of functional outcome important. The purpose of this study was to evaluate behavioral and educational functioning in survivors of childhood acute lymphoblastic leukemia (ALL) or a Wilms tumor. In this study, children with ALL received central nervous system directed chemotherapy without cranial irradiation. METHODS: In a multicenter study, behavioral functioning and school performance was examined in 199 children age 4 to 18. Sixty-four children were at least 1 year from finishing treatment with chemotherapy for ALL (n = 28) or a Wilms tumor (n = 36). They were compared with siblings (n = 37) and with a control group of healthy schoolchildren (n = 98). RESULTS: A moderately increased risk of behavioral and educational problems was found in children with ALL but not in children with Wilms tumor. School performance was poorer in children with ALL attending primary school compared with same-age peers; however, the rate of utilization of special education services was low. Teacher-rated behavior and mathematics performance was correlated with attention function in children with ALL. An excess of problem behavior and underperformance at school was found in the ALL high-risk group compared with the standard-risk group. No differences were found between siblings and controls. CONCLUSION: Evidence is provided of subtle but significant behavioral and educational problems in survivors of childhood ALL, but no dysfunctions in survivors of a Wilms tumor. Careful follow-up of children with ALL treated with chemotherapy only is warranted.

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only.

Treatment for childhood acute lymphoblastic leukemia (ALL), which includes CNS prophylaxis, is associated with central and peripheral neurotoxicity. The purpose of the present study was to analyze the effects of chemotherapy on various levels of visuomotor control in survivors of childhood ALL treated without cranial irradiation, and to identify risk factors for possible deficits. Visuomotor function was compared between children after treatment for ALL (n = 34), children after treatment for Wilms tumor, which consists of non-CNS directed chemotherapy (n = 38), and healthy controls (n = 151). Three tasks were administered: a simple visual reaction time task and two tasks measuring visuomotor control with one requiring a higher level of cognitive control than the other. Visuomotor deficits were detected only in the ALL group, with poorer performance restricted to the condition requiring the highest level of control. Significant risk factors for poorer performance were female gender and a short time since end of treatment, and a trend was found for a young age at diagnosis. A high cumulative methotrexate dose was an adverse predictive factor in girls. The results indicate that chemotherapy-induced central neurotoxicity in childhood ALL treatment is associated with higher order visuomotor control deficits. Girls appear to be particularly vulnerable.

Chemotherapy and attentional dysfunction in survivors of childhood acute lymphoblastic leukemia: effect of treatment intensity.

BACKGROUND: Central nervous system (CNS) directed chemotherapy is replacing prophylactic cranial irradiation in treatment protocols for childhood acute lymphoblastic leukemia (ALL), mainly to reduce long-term neuropsychological sequelae. We evaluated the effects of chemotherapy on attentional function in survivors of ALL and examined whether possible deficits are related to treatment intensity. METHODS: In a multi-center study, we compared attentional function in 36 children at least 1 year after finishing treatment with chemotherapy only for ALL, with a cancer control group consisting of 39 Wilms tumor patients and with 110 healthy children. We differentiated between standard- and intensified ALL treatment. The role of previously reported risk factors for neuropsychological deficits was also assessed. RESULTS: After chemotherapy, attentional deficits were detected in patients with ALL, but not in Wilms tumor patients. Children treated according to standard ALL protocols performed worse than healthy controls on only 1 of 10 outcome measures (P = 0.004), while those who had received intensified treatment performed worse on four outcome measures (0.0001 < P < 0.004). Higher treatment intensity, young age at diagnosis, and female gender were associated with worse performance. CONCLUSIONS: CNS-directed chemotherapy, even in the absence of cranial irradiation, is associated with attentional dysfunction in survivors of childhood ALL, particularly in case of intensified treatment protocols. These sequelae stress the importance of reducing doses of neurotoxic chemotherapy as much as possible in the design of future treatment protocols for ALL.