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Item does not contain fulltext PURPOSE: Hereditary spastic paraplegia type 4 is extremely variable in age at onset; the same variant can cause onset at birth or in the eighth decade. We recently discovered that missense variants in SPAST, which influences microtubule dynamics, are associated with earlier onset and more severe disease than truncating variants, but even within the early and late-onset groups there remained significant differences in onset. Given the rarity of the condition, we adapted an extreme phenotype approach to identify genetic modifiers of onset. METHODS: We performed a genome-wide association study on 134 patients bearing truncating pathogenic variants in SPAST, divided into early- and late-onset groups (aged ≤15 and ≥45 years, respectively). A replication cohort of 419 included patients carrying either truncating or missense variants. Finally, age at onset was analyzed in the merged cohort (N = 553). RESULTS: We found 1 signal associated with earlier age at onset (rs10775533, P = 8.73E-6) in 2 independent cohorts and in the merged cohort (N = 553, Mantel-Cox test, P < .0001). Western blotting in lymphocytes of 20 patients showed that this locus tends to upregulate SARS2 expression in earlier-onset patients. CONCLUSION: SARS2 overexpression lowers the age of onset in hereditary spastic paraplegia type 4. Lowering SARS2 or improving mitochondrial function could thus present viable approaches to therapy.

Objectives: The aim of the study was to report a subtype of dysraphism designated as myelic limited dorsal malformation (MyeLDM) and to describe its characteristics at prenatal ultrasound (US). Methods: It was a retrospective study from 2014 to 2020 based on second-line US evaluation of patients referred to our institution for myelomeningocele (MMC). Magnetic resonance imaging and acetylcholine esterase evaluation in the amniotic fluid were also offered. Major and minor criteria for open and closed dysraphism were defined and recorded for each patient. Patients were included as MyeLDM when both criteria of closed and open dysraphism were observed in the same fetus. Correlations were obtained with the postpartum data. Results: Twenty patients fulfilled the inclusion criteria, some of them being very close to MMC, others very close to limited dorsal myeloschisis (LDM), and others lying in between. There were 13 live-born neonates and 7 terminations of pregnancy. Correlations between prenatal and postpartum data were overall very good. Conclusion: Our series describe the ultrasonographic characteristics of an intermediate type of dysraphism and suggest that there is a continuum between MMC and LDM with numerous possibilities of hybrid forms (MyeLDM) sharing characteristics of both open and closed dysraphisms.

International audience; Hereditary spastic paraplegias (HSPs) are a group of rare, inherited, neurological diseases characterized by broad clinical and genetic heterogeneity. Lower-limb spasticity with first motoneuron involvement is the core symptom of all HSPs. As spasticity is a syndrome and not a disease, it develops on top of other neurological signs (ataxia, dystonia, and parkinsonism). Indeed, the definition of genes responsible for HSPs goes beyond the 79 identified SPG genes. In order to avoid making a catalog of the different genes involved in HSP in any way, we have chosen to focus on the HSP with cerebellar ataxias since this is a frequent association described for several genes. This overlap leads to an intermediary group of spastic ataxias which is actively genetically and clinically studied. The most striking example is SPG7, which is responsible for HSP or cerebellar ataxia or both. There are no specific therapies against HSPs, and there is a dearth of randomized trials in patients with HSP, especially on spasticity when it likely results from other mechanisms. Thus far, no gene-specific therapy has been developed for HSP, but emerging therapies in animal models and neurons derived from induced pluripotent stem cells are potential treatments for patients.

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.

Background Brachial plexus birth palsy remains a frequent condition and one of its treatments is to transfer the Latissimus Dorsi tendon to the infraspinatus muscle. The aim of this study was to analyse, for the first time, the three-dimensional kinematic effects of this operation on the upper limb joints during the five Mallet tasks and their correlation with clinical parameters. Methods Kinematic analysis was performed using an electromagnetic device. An Index of Improvement taking into account the angle in preop and postop, the reproducibility and the angle of a control group was developed. Three groups of patients were analysed: sixteen patients (mean: 10,5 years) for the reproducibility, thirty children (mean: 9,5 years) for the control group and ten patients (mean: 8 years 7 months) who were operated. Findings The humerothoracic and glenohumeral external rotations improved during the external rotation, the neck and the abduction tasks and worsened during the spine task. The glenohumeral external rotation worsened during the mouth task. The Humerothoracic abduction improved during the abduction and the neck tasks. The elbow flexion improved for the neck task. Differences were observed between patients and correlations were obtained between the Index of Improvement and clinical parameters. Interpretation Using kinematics allows to better analyse the evolution of joint angles after the latissimus dorsi transfer. The Index of Improvement allows to quickly analyse the effect of the operation for each angle and each patient. This effect depends on clinical parameters.

Methods to reconstruct anatomical structures in 3D are gaining interest in medicine because they give access to quantitative information on the patient’s geometry. However, these methods are user-dependent and require a trained operator, which is time consuming and a source of error and unreliability. The aim of this work was to validate a novel method of landmark selection to perform the 3D reconstruction of the rib cage from biplanar calibrated radiographies. The method uses digital painting for digitization of anatomical landmarks (eight ribs midlines, posterior extrema, sternum) to build a first estimate of the 3D ribcage geometry. Twenty scoliotic patients were included (Cobb angle: 43° ± 11°) and their ribcage was reconstructed twice with the proposed method by four trained operators. Measurement reproducibility was similar to previously validated methods. Uncertainty (95% CI) was 2.3° for the rib hump measurement, 9.7 mm and 3.8 mm for maximal antero-posterior and lateral diameter, 395 cm3 for ribcage volume. The method was qualitatively considered more user-friendly than previous versions, although it still requires a trained operator, and it took approximately 2 minutes of manual digitization. The new method should facilitate diffusion of 3D quantitative analysis of ribcage in clinical routine.

Background Since 2009 in France, the Peristeen® transanal irrigation (TAI) device has represented an alternative treatment of faecal incontinence (FI). Objective The primary objective of this study was to assess the mid-term adherence to TAI in paediatric patients. The secondary objective was to identify factors determining TAI continuation. Methods This observational study conducted in 5 French paediatric centres prospectively reviewed from March to May 2012 all children educated in TAI for at least 9 months. Results We included 149 children (mean [SD] age 10.6 [4.1] years) educated in TAI. Children mainly had neurogenic disorders (52.3%) or congenital malformations (30.9%). The main symptoms motivating TAI initiation were recurring faecaloma (59.7%) and daily FI (65.1%). At last follow-up (mean 14 [7.4] months), 129 (86.6%) children continued the TAI procedure, independent of pathology or age. The main motivation was resolution of FI and/or constipation (77.3%). In total, 107 (82.9%) children fulfilled the initial therapeutic contract established with their healthcare professional before TAI initiation was met. Twenty children had stopped the TAI when they answered the questionnaire, at a mean duration of 16 (8.4) months. The reasons were mainly “lack of motivation” (45%), “poor tolerance” (35%), “difficulties” performing the procedure (35%) and “inefficacy” (30%). Factors related to continuation were performing at least one TAI procedure under a nurse's supervision during the initial training and prescribing TAI at a daily frequency (P = 0.014 and P = 0.04). Continuing constipation treatment after the training session was a factor in discontinuation (P = 0.024). Conclusion This study reports a very high mid-term adherence to TAI in a paediatric cohort, provided that the training is pragmatic, personalized and repeated.

Objective Lipoma of the conus is the most frequent occult spinal dysraphism. For children with lipoma of the conus, the evolution of the symptoms remains unclear. The convention that prophylactic surgery improves outcome is discussed for the last twenty years. The aims of this work are to describe the symptoms and the natural history with or without surgery of this malformation and to highlight some prognostic factors. Material/patients and methods The children were included if they were followed by a neurosurgeon (hopital Necker–Enfants-Malades, Paris) and a rehabilitation doctor (hopital Armand-Trousseau, Paris). The study was retrospective from 1970 to 1995 then prospective to 2013. A total of 546 patients with lipomas of the conus were recruited. Results The sex-ratio is 1.24 for girls. The first symptoms appeared most commonly before the five years old. The most frequent symptoms are constipation and fecal incontinence. The bladder dysfunctions have the biggest impact on the social life of the children. Following the neurosurgery, the neurologic deterioration has continued for 12% of the patients. After 1995, 217 children without symptoms at the first consultation went to surgery only if neurological signs appeared. During the follow up, 91% of those patients remained asymptomatic. The prognostic factors we find are: the lipoma size, a very low conus medullaris position, nerve roots malformations and difficulties to obtain total or near-total resection lipoma. Discussion–conclusion After the diagnosis done, the surveillance has to be continued for asymptomatic patients. Neurosurgery is proposed only if symptoms appeared. Management of neurologic bowel and bladder is to obtain a vesicle and fecal continence adapted to the age of the child. The renal function and the integrity of bladder wall is protected with regular and complete bladder emptying with low pressure. The orthopedic problems are foot malposition, which can needed orthosis. The frequency and the severity of the urinary and bowel dysfunctions alone require a physical and rehabilitation medicine follow-up.