Véronique Forin

Respiratory muscle decline in duchenne muscular dystrophy

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.

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

BACKGROUNDnSpinal 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.nnnMETHODSnThirty-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.nnnRESULTSnAt 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.nnnCONCLUSIONnOur 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

ObjectiveTo document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children.Study designCorrespondents 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.Results21 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.ConclusionAggressive 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.

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.

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

OBJECTIVESnOsteogenesis 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.nnnMETHODSnA 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 -xa0scoliosis, kyphosis, vertebral arthrodesis, chest wall deformities, basilar impression, autonomyxa0- as well as data already known to be associated with obstructive sleep apnea such as body mass index and upper-airway impairment.nnnRESULTSnWe 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.nnnCONCLUSIONnFor 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.

Results of the prophylactic surgery of lumbosacral lipomas: the pendulum of management?

Dear Editor: We read with interest the article by Perez da Rosa et al. published in CNS November 2016 [1]: BResults of the prophylactic surgery of lumbosacral lipomas 20 years of experience in the Paediatric Neurosurgery Department La Timone Enfants Hospital, Marseille, France.^ Lipoma of the conus medullaris is the most frequent forms of occult spinal dysraphism and represents a considerable challenge in clinical decision-making [2]. There is an ongoing unresolved debate in the neurosurgical community about its optimal management: Should children diagnosed with this condition be offered prophylactic surgery? Recent papers by Pang et al. [3–5] are in favor of an aggressive attitude towards conus lipoma. Aiming a total resection, the overall PFS for total resection was 82.8% at 16 years, comparing much more favorably with 34.6% for partial resection at 10.5 years (P < .0001). These papers have moved the lines concerning the debate between conservative and prophylactic surgical attitude. Talamonti et al. recently published a clinical cohort study of children with asymptomatic conus lipomas [6] where they compare the outcome of surgical and conservative management of patients with an asymptomatic conus lipoma and report better clinical outcome in the surgery group vs. the conservative group. TheMarseille group reports therefore their 20 year’s attitude of surgical resection in asymptomatic lipoma of the conus. This paper is in the line of recent publications in favor of a prophylactic surgical attitude. They report in 66 asymptomatic children retrospectively reviewed and they were operated with a prophylactic purpose. According to the material and method, one should notice that these 66 patients were retrieved among 321 patients operated. Though the authors did not describe it, we could hypothesize that asymptomatic lipomas accounted for only 20% of the Marseille population of lipomas. The authors should give information about these figures they do not discuss, as it appears low compared to the Paris group where 41% of referred lipomas were asymptomatic at first clinical evaluation both in a recent thesis by Lallement-Dudek and a previous report by Pierre-Kahn where among 93 patients operated and followed more than 5 years, 39 were asymptomatic [7, 8]. In order to make a possible comparison, one should be informed of the epidemiology of such population on the one hand and of the way clinical assessment was performed on the other hand. No information was given on the scale used to make this evaluation and clinical assessment in order to assess asymptomatic children. There is no clear indication as to why asymptomatic patients were brought to medical attention, leaving the reader to assume that it was because of suspicious cutaneous stigmata as all 66 patients had it. All patients were asymptomatic and had preoperative MR, postoperative MR, and urodynamic evaluation, in order to ascertain, as we may understand, that they were asymptomatic. The mean age of the population was 13 months with 86% operated under 1 year old. * Thomas Roujeau t-roujeau@chu-montpellier.fr