Open fetal surgery for myelomeningocele repair in France.

INTRODUCTION: Open fetal myelomeningocele (MMC) surgery is currently the standard of care option for prenatal MMC repair. We described the population referred to our center and reviewed outcome after open fetal MMC repair. MATERIAL AND METHODS: All patients referred to our center for MMC were reviewed from July 2014 to June 2020. For all the patients who underwent fetal MMC repair, surgical details, maternal characteristics and data from the neonatal to the three-years-old evaluations were collected. RESULTS: Among the 126 patients referred to our center, 49.2% were eligible and 27.4% (n = 17) of them underwent fetal MMC repair. Average gestational age at fetal surgery was 24+6 weeks. There was no case of fetal complication and the only maternal complication was one case of transfusion. We recorded 70% of premature rupture of membranes and 47% of premature labor. Average gestational age at delivery was 34+2 weeks and no patient delivered before 30 weeks. There was no case of uterine scar dehiscence or maternal complication during cesarean section. After birth, 59% of the children had a hindbrain herniation reversal. At 1-year-old, 42% were assigned a functional level of one or more better than expected according to the prenatal anatomic level and 25% required a ventriculoperitoneal shunt. At 3-year-old, all the children attended school and 75% were able to walk with orthotics or independently. CONCLUSION: Open fetal surgery enables anatomical repair of the MMC lesion, a potential benefit on cerebral anomalies and motor function, with a low rate of perinatal and maternal complications.

Ultrasound shearwave elastography to characterize muscles of healthy and cerebral palsy children.

Shear wave elastography (SWE) is an ultrasound technique to obtain soft tissue mechanical properties. The aim of this study was to establish the reliability of SWE in young children, define reference data on healthy ones and compare the shear modulus of healthy and spastic muscles from cerebral palsy (CP). The reproducibility is evaluated: at rest, on 7 children without any musculoskeletal pathology by 3 different operators, on 2 muscles: biceps brachii long head and medial gastrocnemius. The comparison study was made, on the same 2 muscles, at rest and under passive stretching, with a control group (29 healthy children), a spastic group (spastic muscles of 16 children from CP) and a non-spastic group (non-spastic muscles of 14 children from CP). The intra-operator reliability and inter-operator reliability, in terms of standard deviation, were 0.6 kPa (11.2% coefficient of variation (CV)) and 0.8 kPa (14.9% CV) for the biceps, respectively, and 0.4 kPa (11.5% CV) and 0.5 kPa (13.8% CV) for the gastrocnemius. At rest, no significant difference was found. Under passive stretching, the non-spastic CP biceps were significantly stiffer than the control ones (p = 0.033). Spastic gastrocnemius had a higher shear modulus than in the control muscles (p = 0.0003) or the non-spastic CP muscles (p = 0.017). CP stretched medial gastrocnemius presented an abnormally high shear moduli for 50% of patients.

Botulinum Toxin Type A Injection After Failure of Augmentation Enterocystoplasty Performed for Neurogenic Detrusor Overactivity: Preliminary Results of a Salvage Strategy. The ENTEROTOX Study.

OBJECTIVE: To evaluate the clinical efficacy, urodynamic effect and safety of Botulinum Toxin A (BTXA) injections after failure of augmentation enterocystoplasty (AE) performed for neurogenic detrusor overactivity. PATIENTS AND METHODS: We performed a multicenter retrospective study that included patients who had AE and at least one injection of BTXA after AE in 15 GENULF (French Speaking Neuro-Urology Study Group) centers. Clinical and urodynamic data were collected from medical files according to a standardized questionnaire and colligated in an anonymous database. RESULTS: Thirty-three patients with an injection of BTXA after AC in 9 out of 15 centers were included. Mean age at the time of AE was 24 ± 15 years. Overall efficacy (defined by clinical efficacy associated with a request by the patient for reinjection) was observed in 58% of the patients. Mean maximum cystomanometric capacity increased by 28% (333 ± 145 vs 426 ± 131 mL; P = .007) and maximum detrusor pressure (Pdet max) decreased by 43% (44 ± 37 vs 25 ± 18 cm H2O; P = .02) after BTXA. Only one side effect was recorded out of the 152 procedures (transient generalized muscle weakness without respiratory distress). CONCLUSION: In patients with failure after AE performed for neurogenic detrusor overactivity, injection of BTXA in the enlarged bladder was effective in over half of the cases with low morbidity. If this therapeutic approach were confirmed, it could be proposed as an alternative to AE surgical revision.

Intradetrusor Injections of Botulinum Toxin Type A in Children With Spina Bifida: A Multicenter Study.

OBJECTIVE: To assess the effectiveness of intradetrusor injections of botulinum toxin type A (IDBTX-A) in children with spina bifida. METHODS: All patients aged less than 16 years old who underwent IDBTX-A between 2002 and 2016 at 6 institutions were included in a retrospective study. Our primary endpoint was the success rate of IDBTX-A defined as both clinical improvement (no incontinence episodes between clean intermittent catheterizations [CICs], absence of urgency, and less than 8 CICs per day) and urodynamic improvement (resolution of detrusor overactivity and normal bladder compliance for age) lasting ≥12 weeks. Predictive factors of success were assessed through univariate analysis. RESULTS: Fifty-three patients with a mean age of 8.5 years were included. All patients were under CIC and 88.7% had received anticholinergics with either poor efficacy or bothersome adverse events. The global success rate of the first injection (clinical and urodynamic) was 30%. Patients with closed spinal dysraphism had a significantly better success rate than patients with myelomeningocele (P = .002). The clinical success rate was 66% and was significantly associated with maximum urethral closure pressure (34 cm H2O vs 54.4 cm H2O, P = .02). The urodynamic success rate was 34%. Maximum cystometric capacity (P <.0001) and compliance (P = .01) significantly improved after the first IDBTX-A and maximum detrusor pressure tended to decrease (P = .09) except in the subgroup of patients with poor compliance. After a mean follow-up of 3.7 years, 23 patients (43.4%) required augmentation cystoplasty. Excluding 6 patients who were lost to follow-up, 38.3% of patients were still undergoing botulinum toxin injections at last follow-up. CONCLUSION: In this series, despite the fact that IDBTX-A enabled clinical improvement in 66% patients, urodynamic outcomes were poor resulting in a low global success rate (30%).

Diagnosis, follow-up and management of sleep-disordered breathing in children with osteogenesis imperfecta.

OBJECTIVES: Osteogenesis imperfecta (OI) is the most common genetic skeletal disorder. Extraskeletal findings are common but an association with sleep-disordered breathing (SDB) has never been described. The aim of this study was to investigate clinical features of children with OI and suspected SDB. METHODS: A retrospective study of clinical records, signs of SDB and polysomnographic recordings of children with OI was performed. We paid particular attention to symptoms that could be associated with SDB in this population - scoliosis, kyphosis, vertebral arthrodesis, chest wall deformities, basilar impression, autonomy - as well as data already known to be associated with obstructive sleep apnea such as body mass index and upper-airway impairment. RESULTS: We reviewed the clinical charts of 188 patients referred to our genetic skeletal disorders reference center for OI. Among the 15 patients (8%) with polysomnographic recordings, 12 (6.4%) had sleep-disordered breathing. We found a negative correlation between the Brief Assessment of Motor Function score and Apnea Hypopnea Index (r=-0.68; p=0.01) and Desaturation Index (r=-0.62; p=0.02). The Apnea Hypopnea Index was higher for non-walkers than walkers (mean [SD]: 6.5 [3.6] vs. 2.4 [1.5]; p=0.02) and with type III versus IV OI. Two patients were started on continuous positive airway pressure ventilation, with clinical improvement. CONCLUSION: For OI children, symptoms suggesting obstructive sleep disorders should be searched for systematically, especially in children with compromised autonomy, high body mass index, trunk deformations, and severe OI type.

Mild clinical presentation in KLHL40-related nemaline myopathy (NEM 8).

Nemaline myopathies are clinically and genetically heterogeneous muscle diseases characterized by the presence of nemaline bodies (rods) in muscle fibers. Mutations in the KLHL40 (kelch-like family member 40) gene (NEM 8) are common cause of severe/lethal nemaline myopathy. We report an 8-year-old girl born to consanguineous Moroccan parents, who presented with hypotonia and poor sucking at birth, delayed motor development, and further mild difficulties in walking and fatigability. A muscle biopsy revealed the presence of nemaline bodies. KLHL40 gene Sanger sequencing disclosed a never before reported pathogenic homozygous mutation which resulted in absent KLHL40 protein expression in the muscle. This further expands the phenotypical spectrum of KLHL40 related nemaline myopathy.

Pro and Cons of Transurethral Self-Catheterization in Boys: A Long-Term Teaching Experience in a Pediatric Rehabilitation Centre.

PURPOSE: To describe the acceptance and efficacy of clean intermittent catheterization (CIC) in the management of lower urinary tract (LUT) dysfunction regardless of the age of the children and their degree of urethral sensation. MATERIALS AND METHODS: We retrospectively evaluated boys managed with CIC at a pediatric teaching hospital between 1992 and 2014. Age, urethral sensation, acceptance, efficacy in terms of continence and preserving upper urinary tract and genitourinary complications were reviewed in the medical records. RESULTS: Sixty boys managed with CIC for LUT dysfunction due to neurological or urological disorders were identified. The median age at CIC initiation was 8.2 years (range, 1.4-18). With regard to age, CIC was well tolerated in younger boys and without genital sensation. Failure in the CIC protocol occurred within the first six months (n = 9). More boys with genital sensation were socially continent with CIC (91% versus 83%, P = .05). Vesicoureteral reflux was resolved in 69% of boys (P = .03), and hydronephrosis in 54% (P = .07). CONCLUSION: CIC was effective in terms of continence and renal protection. The procedure was feasible even in boys with preserved urethral sensation. Therapeutic education by a dedicated urotherapy nurse is the key factor in ensuring long-term CIC compliance and acceptability.

Respiratory muscle decline in Duchenne muscular dystrophy.

OBJECTIVES: Duchenne muscular dystrophy (DMD) causes progressive respiratory muscle weakness. The aim of the study was to analyze the trend of a large number of respiratory parameters to gain further information on the course of the disease. STUDY DESIGN: Retrospective study. SUBJECT SELECTION: 48 boys with DMD, age range between 6 and 19 year old, who were followed in our multidisciplinary neuromuscular clinic between 2001 and 2011. METHODOLOGY: Lung function, blood gases, respiratory mechanics, and muscle strength were measured during routine follow-up over a 10-year period. Only data from patients with at least two measurements were retained. RESULTS: The data of 28 patients were considered for analysis. Four parameters showed an important decline with age. Gastric pressure during cough (Pgas cough) was below normal in all patients with a mean decline of 5.7 ± 3.8 cmH2 O/year. Sniff nasal inspiratory pressure (SNIP) tended to increase first followed by a rapid decline (mean decrease 4.8 ± 4.9 cmH2 O; 5.2 ± 4.4% predicted/year). Absolute forced vital capacity (FVC) values peaked around the age of 13-14 years and remained mainly over 1 L but predicted values showed a mean 4.1 ± 4.4% decline/year. Diaphragmatic tension-time index (TTdi) increased above normal values after the age of 14 years with a mean increase of 0.04 ± 0.04 point/year. CONCLUSIONS: This study confirms the previous findings that FVC and SNIP are among the most important parameters to monitor the evolution of DMD. Expiratory muscle strength, assessed by Pgas cough, and the endurance index, TTdi, which are reported for the first time in a large cohort, appeared to be informative too, even though measured through an invasive method.

Longitudinal course of lung function and respiratory muscle strength in spinal muscular atrophy type 2 and 3.

BACKGROUND: Spinal muscular atrophy (SMA) is a common genetic disorder that causes severe hypotonia and weakness, and often fatal restrictive lung disease. The aim of the study was to describe the natural history of the respiratory involvement in patients with SMA type 2 and 3 in order to assess the relevance of the clinical classification and identify the parameters associated with the earliest and most rapid decline over time. METHODS: Thirty-one patients aged 3-21 years were followed over a 10-year period. Lung function, blood gases, respiratory mechanics and muscle strength with recording of oesogastric pressures were measured during routine follow-up. RESULTS: At least two measurements were available in 16 patients (seven type 2 and nine type 3). Among all the volitional and non-volitional, invasive and non-invasive tests, forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP) were shown to be the most informative parameters, showing lower values in SMA type 2, with however a similar rate of decline in patients with SMA type 2 and 3. CONCLUSION: Our results confirm an earlier decline in lung and respiratory muscle function in patients classified as SMA type 2 as compared with patients classified as type 3. This decline can be assessed by two simple non-invasive tests, FVC and SNIP, with the last maneuver being feasible and reliable in the youngest children, underlying its interest for the monitoring of children with SMA.

Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009.

OBJECTIVE: To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children. STUDY DESIGN: Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009. RESULTS: 21 cases were identified; 62% of the patients were boys. No familial cases were observed, and the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8-16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting signs were bone fracture (n = 4) and respiratory distress (n = 7), but more indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies and pleural effusion, was the most frequent form of extraosseous involvement (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as potentially curative treatments. High-dose radiotherapy appeared to be effective on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs like alpha interferon and zoledrenate have had a limited impact on the course of pulmonary complications. The impact of bisphosphonates and alpha interferon on bone lesions was also difficult to assess, owing to insufficient follow-up in most cases, but it was occasionally positive. Six deaths were observed and the overall 10-year mortality rate was about 30%. The prognosis depended mainly on pulmonary and spinal complications. CONCLUSION: Aggressive vascular abnormalities of bone are extremely rare in childhood but are lifethreatening. The impact of anti-angiogenic drugs on pulmonary complications seems to be limited, but they may improve bone lesions.

The sagittal balance of the spine in children and adolescents with osteogenesis imperfecta.

In severe forms of osteogenesis imperfecta, multiple compression fractures of the spine, as well as vertebral height shortening could be responsible for an increased thoracic kyphosis or a diminished lumbar lordosis. Theses progressive changes in sagittal shapes of the trunk could be responsible for a global sagittal trunk imbalance. We compare the parameters of sagittal spinopelvic balance in young patients with OI to those parameters in a control group of healthy volunteers. Eighteen patients with osteogenesis imperfecta were compared to a cohort of 300 healthy volunteers. A standing lateral radiograph of the spine was obtained in a standardized fashion. The sacral slope, pelvic tilt, pelvic incidence, lumbar lordosis, thoracic kyphosis, T1 and T9 sagittal offset were measured using a computer-assisted method. The variations and reciprocal correlations of all parameters in both groups according to each other were studied. Comparison of angular parameters between OI patients and control group showed an increased T1T12 kyphosis in OI patients. T1 and T9 sagittal offset was positive in OI patients and negative in control group. This statistically significant difference among sagittal offsets in both groups indicated that OI patients had a global sagittal balance of the trunk displaced anteriorly when compared to the normal population. Reciprocal correlations between angular parameters in OI patients showed a strong correlation between lumbar lordosis (L1L5 and L1S1) and sacral slope. The T9 sagittal offset was also strongly correlated with pelvic tilt. Pelvic incidence was correlated with L1S1 lordosis, T1 sagittal offset and pelvic tilt. In OI patients, the T1T12 thoracic kyphosis was statistically higher than in control group and was not correlated with other shape (LL) or pelvic (SS, PT or PI) parameters. Because isolated T1T12 kyphosis increase without T4T12 significant modification, we suggest that vertebral deformations worsen in OI patients at the upper part of thoracic spine. Further studies are needed to precise the exact location of most frequent vertebral deformities.

[Osteogenesis imperfecta]. / Ostéogenèse imparfaite.

Osteogenesis imperfecta is a genetic disorder that causes increased bone fragility and low bone mass. Osteogenesis imperfecta is a rare disease: its estimated prevalence is between 1/10000 and 1/20000 persons. The severity of skeletal and extraskeletal manifestations varies widely. Most patients have a mutation in one of the 2 genes that encode the alpha chains of collagen type I. Treatment with bisphosphonates has produced clear improvements, especially for growing children. The appropriate regimen for bisphosphonate treatment remains to be determined: the goal is to find the lowest effective dose to minimize side effects. Treatment of osteogenesis imperfecta must be multidisciplinary, including physicians, surgeons, and physical therapists.

Respiratory muscle testing: a valuable tool for children with neuromuscular disorders.

RATIONALE: Data on respiratory muscle performance in children with neuromuscular disorders are limited. OBJECTIVES: The aim of this study was to assess respiratory muscle strength by volitional and nonvolitional tests and to compare these tests with forced vital capacity. METHODS: Inspiratory muscle strength was assessed by measuring transdiaphragmatic and esophageal pressures generated during volitional and nonvolitional maneuvers, whereas expiratory muscle strength was assessed by measuring the gastric pressure generated during a cough maneuver. Lung volumes were assessed by measuring forced vital capacity. MEASUREMENTS AND MAIN RESULTS: Forty-one patients with Duchenne muscular dystrophy (n = 20), spinal amyotrophy (n = 8), and congenital myopathy (n = 13) were included, aged 2 to 18 yr. All the patients were able to perform the sniff and the cough maneuver. Sniff transdiaphragmatic pressure decreased with age in Duchenne patients, whereas it increased with age in patients with spinal amyotrophy and congenital myopathy. Magnetic stimulation of the phrenic nerves was obtained in all patients. Twenty-five (61%) patients were able to perform forced vital capacity. In the three groups of patients, a positive correlation was observed between volitional, assessed by the sniff maneuver, and nonvolitional respiratory muscle tests, assessed by the magnetic stimulation of the phrenic nerves. Also, forced vital capacity correlated with sniff transdiaphragmatic pressure and cough gastric pressure. CONCLUSIONS: Volitional respiratory muscle tests correlated with nonvolitional tests and with forced vital capacity. Simple volitional respiratory muscle tests constitute a valuable tool for the assessment of respiratory muscle strength in young patients with neuromuscular disorders.

Benefits of pamidronate in children with osteogenesis imperfecta: an open prospective study.

OBJECTIVES: To study the efficacy of pamidronate in children with osteogenesis imperfecta (OI). PATIENTS AND METHODS: Twenty-nine patients (median age 8.7 years), were given pamidronate in cyclic infusions of 3 days. Patients received 3-13 cycles (median 6), at a dose of 0.5 mg/kg/day in infants (below 2 years of age) and 1 mg/kg/day in children (2 years and older). The interval time between cycles was 2 months in infants and 4 months in children. The median follow-up was 16 months. All patients received daily supplementation of calcium, vitamin D and physical rehabilitation. Assessments were performed at baseline and before each cycle. Fracture rate under treatment was compared to the one in the pre-treatment period. RESULTS: Pain decreased after the first infusion cycle (P < 0.0001). The median of fracture incidence decreased from 15 to 0.5 per year in infants and from 2.0 to 1 per year in children (P = 0.04). Alkaline phosphatase decreased by 31.2% and N-telopeptide collagen cross-links decreased by 61.8% (P < 0.001). Bone mineral density (BMD) of the spine increased by a median of 55.4% (P < 0.001). Z-scores increased from a median of -4.7 to -2.6 (P < 0.001). The femoral neck, BMD increased by a median of 16%. The area of the first four lumbar vertebrae increased by a median of 21.5% (P < 0.001). No adverse effect on growth or on fracture healing was observed. Side effects were symptomatic hypocalcemia in one infant, and the transient acute phase reaction. CONCLUSION: Pamidronate increases BMD, decreases bone remodeling markers, pain and fracture rate in infants and children with OI.