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Background: Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. Methods: We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. Results: In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P Conclusions: Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug.

In young children presenting drug-resistant epilepsy, the number of approved antiepileptic drugs is limited. Levetiracetam (LEV) is one of the most recent antiepileptic drugs (AED) introduced on the market and data on its effectiveness and tolerance in children are scarce.The objective of this retrospective study was to report our experience with the use of levetiracetam as an adjuvant therapy in a population of 42 children presenting a drug-resistant epilepsy. The study was conducted over a 5-year-period (from 1 January 2004 to 30 June 2007).The patients' mean age was 10.8 years (range, 2.1-19 years). The mean duration of epilepsy was 6.6 years (range, 1.5-19 years). After the administration of LEV, 10 patients (23.8%) became seizure-free and 16 (38.1%) had more than 50% seizure reduction. A reduction of less than 50% was observed in 13 patients (31%). Three patients (7.1%) presented an increase in seizure frequency. The effectiveness of LEV was similar in partial and generalized epilepsy. LEV was well tolerated by these patients. The main adverse effects were anorexia, asthenia, and behavioral disorders, and drowsiness was encountered in 17% of the patients. All persistent adverse events were noted. In children under 4 years of age, LEV was particularly well tolerated.This study confirms the effectiveness and tolerance of LEV used as an adjuvant therapy in children presenting drug-resistant epilepsy, particularly in the very young ones.

Among the epileptic syndromes occurring during infancy, which are mostly non-idiopathic and associated with a poor prognosis, benign infantile convulsions are characterized by a favourable evolution. This work aims to analyse and compare the clinical, EEG and outcome characteristics of familial benign infantile convulsions (FBIC) and non-familial benign infantile convulsions (NFBIC). This is a retrospective study, conducted between 1988 and 2008, in 40 infants who presented benign infantile seizures during the two first years of life. All of them had no personal history, normal psychomotor development, normal neurological examinations, no abnormalities on biological and radiological investigations and a favourable outcome. In 14 cases, there was a familial history of familial benign infantile convulsions. However, among the 26 cases with non-familial benign infantile convulsions, 11 children had a familial history of other epileptic syndrome. That may suggest a genetic familial susceptibility. In the two groups, the clinical features and the electroencephalography were similar. The seizures had short duration and occurred most often in clusters. Twenty-nine children had secondarily generalized partial seizures and 11 infants had generalized seizures but a focal onset cannot be excluded. The antiepileptic drugs allowed rapid resolution of seizures. One child necessitated a prolonged antiepileptic treatment. In the other cases, seizures cured in the first year without recurrence of seizures after treatment discontinuation. The evolution was characterised in five children by a later occurrence of dystonia. This subgroup was described as infantile convulsion and choreoathetosis syndrome (ICCA). Benign infantile convulsions are probably an underestimated epileptic syndrome. The diagnosis is relatively easy in the familial forms with dominant autosomal transmission. In contrast, in sporadic forms, the diagnosis can be confirmed only by the evolution. The good prognosis must be tempered by the subsequent onset of dystonia consisted in the ICCA syndrome and justifies a prolonged follow-up.

Ischemic stroke is rare in children, most of which occur in the supratentorial brain, and infratentorial infarcts are very rare. Some clinical manifestations may be similar but others such as ataxia and cranial nerve palsy are more specific. Vertebral artery dissection is the most frequent cause of stroke in the vertebrobasilar territory, but the cause most often remains unknown in children. We report three cases of infratentorial stroke in children. The first observation concerns a 4-year-old boy brought to medical attention because left hemicorporal motor deficit associated with ataxia following a minor cranial traumatism. While computed tomography (CT) of the brain was normal, magnetic resonance imaging (MRI) revealed an area of signal alteration on the diffusion-weighted image within the right protuberance. The second observation is a 15-year-old girl who developed sudden-onset ataxia. The CT scan and MRI of the brain revealed an acute bilateral cerebellar stroke. MRI angiography showed an anatomical variant of the left vertebral artery that did not participate in the Willis polygon. In these two observations, no other abnormalities were detected except they were homozygotous for MTHFR mutation in the first observation and minor alpha-thalassemia for the second one. The outcome in these two children was good without sequelae after a 6-month follow-up. The third observation is a 6-year-old girl who suddenly exhibited cephalalgia, ataxia, and left visual impairment. The brain MRI revealed left occipital and cerebellar strokes due to vertebral artery dissection. The authors recommend the systematic search for vertebral artery dissection in cases of infratentorial stroke.

Rotavirus is a major cause of acute gastroenteritis in infants worldwide and there is need for an effective vaccine. Rotavirus Wistar calf 3 (WC3) is a strain of bovine origin attenuated by 12 passages in cell culture. A lyophilized candidate vaccine containing 1 x 10(7) PFU of WC3 has been developed. An oral dose was given to 25 French infants 5-12-months old (mean age 8.6 months). No diarrhoea was observed within 2 weeks after vaccination. Unexplained vomiting was reported once and isolated fever greater than 37.8 degrees C was reported 3 times during the first week. One month later, a neutralizing antibody response to serotypes tested was shown in 88% of cases, with heterotypic responses to human serotype 3 (SA11 strain) in 72% and to type 1 (WA strain) in 48%. The percentage of immune response was similar whether the infant had antibody prior to immunization or not, but a booster effect was observed in children who had pre-immunization rotavirus antibodies. Considering these promising results, efficacy trials are in the planning in different parts of the world.

Gastro-esophageal reflux (G.E.R.) in children has been implicated in various recurring respiratory diseases. Several techniques including oesophageal pH testing and scintigraphy have been devised to detect and quantify G.E.R. Limitations have been found for each test: short duration with gamma-camera and restricted acceptability of the pH probe by children. A single isotopic probe was designed for a non-invasive screening test of G.E.R. in infants. This device was checked by comparison with oesophageal scintigraphy using a gamma camera. Only 1 discrepancy was detected in 19 reflux episodes. This method, using a relatively inexpensive detector and data acquisition module, seems to be well accepted by children, and may be associated with a pH probe for GER diagnosis.

The authors discuss the etiological features of interstitial pneumopathies, with particular emphasis on their characteristics in the newborn and in immunodeficient children, and review the diagnostic findings : clinical and radiological signs, functional disturbances, and results of pulmonary biopsy. The results of 154 needle biopsies in 124 children aged 1 month to 16 years are described. In 103 cases a diffuse pneumopathy was present and 80 % of the biopsies were successful. Precise diagnosis could be made from the histology specimen in 22 cases out of the 82 examined, while in 60 of these cases the specimen could be identified.

100 cases of bronchial foreign body seen over a period of 4 years represent 1.2% of the admissions of a paediatric pneumology unit; 73% of the children were aged between 6 months and 3 years. The foreign body was vegetable in 61% of cases (a peanut in 44% of cases). The time between the inhalation and the endoscopic diagnosis was greater than 7 days in 70% of cases and greater than 30 days in 37% of cases. Removal of the foreign body was possible in all but one case. In particular, the authors studied the pneumological implications of a foreign body: the value of a quantitative bacteriological study of the bronchial secretions, which was significant in 43% of cases, and detection of the sequelae by prospective clinical and functional surveillance with a follow-up of 3 to 24 months. After 6 months, persistent radiological abnormalities were found in 40% of cases, perfusion disorders were found in 35% and ventilation disorders were found in 64%. A surgical operation was performed in 7 cases: one case of bronchotomy for extraction of the foreign body and 6 cases of parenchymal excision, including 2 total pneumonectomy for a destroyed lung. These were no death. The pathophysiology of the complications of functional disorders and of dilatation of the bronchi is discussed in the context of the experience gained from this series.

127 cases of tracheal dyskinesia were seen in infants and children out of which 87 were 1 to 12 months of age. The diagnosis was based on the existence of a collapse reducing the tracheal diameter of more than 50% on endoscopy. Endoscopic examination was performed without general anesthesia. This material represents 5,8% of the patients submitted to this procedure. 85 patients had "primitive" dyskinesia and 42 had major associated abnormalities. Uni or bilateral bronchial dyskinesia was associated in 43% of the cases. The four commonest presenting symptoms were a stridulous or wheezing respiration, recurrent bronchitis, chronic cough, cyanosis. The frequency of associated digestive troubles: gastroesophageal reflux aspiration was noteworthy. Several functional consequences were encountered: hypoxemia, hypercapnia, abnormalities of FRC, increased RL, lowering of dynamic compliance, alterations of perfusion and ventilation on scintiscans. The prognosis was good in primitive cases. Two deaths occurred, in the group with associated abnormalities. The pattern of the patient with primitive dyskinesia and that of the patient with dyskinesia and associated abnormalities are outlined. Some features remarkable in this series of patients are pointed out in a discussion of the pathophysiology of the syndrome. Increased transmural pressure is not a common cause of tracheal dyskinesia and infection as well. The possibility of a temporary intrinsic anomaly of the tracheal wall is suggested. Even if its exact mechanism remains unknown, tracheal dyskinesia is a distinct entity observed in infants and children. It appears as a common cause of recurrent bronchopulmonary disease in the young.

Four children aged between 7 and 19 months with severe bronchopneumonia due to adenovirus type 7, proved by virology and/or serology developed severe hyponatraemia. One of them is reported in detail: it was possible to estimate plasma ADH levels and thereby prove the existence of reversible hypersecretion of the hormone. Whilst the syndrome of hyponatraemia with inappropriate secretion of ADH has not yet been reported in association with severe pneumonia in the child, it is known in adults. The limits of the syndrome and its physiopathology are discussed. It may be due either to vagal stimulation as a result of a fall in left aressure, or to central involvement. Therapeutic implications of the problem are emphasized.

The early onset of the disease (between the 13th and 15th days of life) and its long duration in 2 out of 3 cases, the absence of infectious symptoms and the efficacy of erythromycin treatment were characteristic features. The diagnosis was confirmed by positive (greater than 1/32th) serological tests in both infants and parents. Chlamydia trachomatis lung infection should be suspected in infants presenting, during the first weeks of life, with cough and dyspnoea unaccompanied by fever, radiological evidence of interstitial pneumonia, blood eosinophilia and raised immunoglobulin levels. The disease results from intranatal contamination and might represent, in France as in the U.S.A., an important percentage of respiratory infections occurring during the early months of life.

Five cases of hypersensitivity pneumonitis in children are reported. Four had the pattern of bird breeder's disease and one of aspergillus lung hypersensitivity. All were clearly defined by clinical, radiological, functional and immunologic features. The possible difficulties in diagnosis are emphasized. The disease might be frequently overlooked and its frequency underestimated in children. The diagnostic value of precipitating antibodies is discussed. Although some immunologic studies suggest immune complex mechanisms, recent experimental and clinical data are in favor of a role for cell-mediated immunity. In addition whether or not immunological damage is to occur and result into disease depends not merely upon the characteristics of the antigen exposure. Genetic and/or acquired individual differences in immune reactivity can play a definite role as well. The risk of secondary pulmonary fibrosis and chronic respiratory failure in untreated patients is emphasized. Immunologic and functional tests for identification of the provoking antigen and ceasing of contamination exposure are urgent : they are also useful for monitoring steroid therapy.