Étude de la corrélation génotype–phénotype dans l’amyotrophie spinale infantile (ASI) dans une famille marocaine

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a highly variable clinical course and prognosis. We report on the cases of three siblings with SMA. The weakness muscular observes at three siblings but more earlier and severe to the index case with a fast evolution towards respiratory distress syndrome resulting in its death at 5 years. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene were found in all three siblings. No child showed deletion of NAIP gene. Muscular weakness and respiratory distress severity however were different among the siblings. The index patient died at the age of 5 because of respiratory insufficiency. Several molecular mechanisms may be involved in such phenotypic variability. The PCR-RFLP method allows to confirm clinical diagnosis of SMA in children, while avoiding more invasive methods such as EMG and muscular biopsy. However, this diagnostic tool does not allow yet the distinction between different clinical forms of SMA.     

What’s new in surfactant?

Surfactant therapy has significantly changed clinical practice in neonatology over the last 25 years. Recent trials in infants with respiratory distress syndrome (RDS) have not shown superiority of any natural surfactant over another. Advancements in the development of synthetic surfactants are promising, yet to date none has been shown to be superior to natural preparations. Ideally, surfactant would be administered without requiring mechanical ventilation. An increasing number of studies investigate the roles of alternative modes of administration and the use of nasal continuous positive airway pressure to minimise the need for mechanical ventilation. Whether children with other lung diseases benefit from surfactant therapy is less clear. Evidence suggests that infants with meconium aspiration syndrome and children with acute lung injury/acute respiratory distress syndrome may benefit, while no positive effect of surfactant is seen in infants with congenital diaphragmatic hernia. However, more research is needed to establish potential beneficial effects of surfactant administration in children with lung diseases other than RDS. Furthermore, genetic disorders of surfactant metabolism have recently been linked to respiratory diseases of formerly unknown origin. It is important to consider these disorders in the differential diagnosis of unexplained respiratory distress although no established treatment is yet available besides lung transplantation for the most severe cases. Conclusion: Research around surfactant is evolving and recent developments include further evolution of synthetic surfactants, evaluation of surfactant as a therapeutic option in lung diseases other than RDS and the discovery of genetic disorders of surfactant metabolism. Ongoing research is essential to continue to improve therapeutic prospects for children with serious respiratory disease involving disturbances in surfactant. Funding: Jasper Been is supported by a Profileringsfonds grant from the Maastricht University Hospital.     

The use of invasive ventilation is appropriate in children with genetically proven spinal muscular atrophy type 1: the motion against

Spinal muscular atrophy (SMA) is a relatively common, profoundly disabling and incurable disease that presents in early childhood with hypotonia, weakness and decreased movement. Without ventilatory support, premature death from respiratory insufficiency is universal in children with spinal muscular atrophy type 1 (SMA1). With mechanical ventilation, however, long-term survival in SMA1 has been reported from numerous international centres. Children kept alive by this means experience progressive paralysis and eventually become effectively 'locked in' on the ventilator, with no useful movements of the extremities, progressive facial and bulbar weakness, and complete inability to communicate. Prolongation of life by invasive ventilation in such cases is futile given the absence of curative treatments for infants with SMA1, and overly burdensome given the unacceptable quality of life of such children.     

Myocarditis in a pediatric case of pandemic 2009H1N1 influenza

We report a 6‐year‐old boy with no major disease history or allergic conditions initially presented with pneumonia, progressed to acute respiratory distress syndrome and acute myocarditis caused by pandemic 2009H1N1 influenza diagnosed with RT‐PCR testing, successfully managed with mechanical ventilation and percutaneous cardiopulmonary support system. Marked transient elevation of IgE in acute phase of the disease and the subsequent diagnosis of atopic asthma in our patient suggested a possible role of an underlying allergic condition in the clinicopathological process. Critically ill 2009H1N1‐infected patient with acute respiratory failure should carefully be physiologically monitored together with serial assessment of biomarkers aiming at a favorable cardiac outcome by giving the timely diagnosis and intervention.     

Physician attitudes towards ventilatory support for spinal muscular atrophy type 1 in Australasia

BACKGROUND: Without ventilatory support, premature death from respiratory insufficiency is virtually universal in infants with spinal muscular atrophy type 1 (SMA1). With mechanical ventilation, however, long-term survival has been reported from numerous international centres. We aimed to characterize physician attitudes to the various forms of ventilatory support for children with SMA1. METHODS: We surveyed neurologists, respiratory physicians, clinical geneticists and intensivists from all major paediatric hospitals in Australia and New Zealand regarding their views on ventilatory management of SMA1. RESULTS: Ninety-two of the 157 (59%) physicians surveyed replied. Respondents included 16 clinical geneticists, 19 intensive care physicians, 28 neurologists and 29 respiratory physicians. Almost half (47%) opposed invasive ventilation of children with SMA1 and respiratory failure precipitated by intercurrent illness. The majority (76%) opposed invasive ventilatory support for chronic respiratory failure in SMA1. In contrast, non-invasive ventilation was felt by 85% to be appropriate for acute respiratory deteriorations, with 49% supporting long-term non-invasive ventilatory support. Most physicians felt that decisions regarding ventilation should be made jointly by parents and doctors, and that hospital Clinical Ethics Committees should be involved in the event of discordant opinion regarding further management. A majority felt that a defined hospital policy would be valuable in guiding management of SMA1. CONCLUSIONS: Respiratory support in SMA1 is an important issue with significant ethical, financial and resource management implications. Most physicians in Australian and New Zealand oppose invasive ventilatory support for chronic respiratory failure in SMA1. Non-invasive ventilation is an accepted intervention for acute respiratory decompensation and may have a role in the long-term management of SMA1. Clinical Ethics Committees and institutional policies have a place in guiding physicians and parents in the management of children with SMA1.     

Noninvasive treatment of bronchomalacia, successful ventilation of a severely ill infant

Noninvasive treatment of bronchomalacia.Successful ventilation of a severely ill infant. AIM: To describe an effective treatment of a boy with bronchomalacia by noninvasive mechanical ventilation support. METHODS: We describe a case of a severely ill patient with bronchomalacia from the time he was born and until the age of five. Bi-level positive airway pressure given through a specially adapted full face mask was used to treat his respiratory condition. RESULT: Our patient responded well to the noninvasive treatment of bronchomalacia. CONCLUSION: We found that noninvasive mechanical ventilation support is a low risk and highly effective treatment of infants and children with respiratory distress caused by bronchomalacia.     

Early Surgical Intervention for Diaphragmatic Paralysis in a Neonate; Report of a Case and Literature Review

Background

Diaphragmatic paralysis in newborns is related to brachial plexus palsy. It can cause respiratory failure necessitating prolonged mechanical ventilation and subsequent extubation failure.

Case Presentation

We present a two-hour-old male newborn with a birth weight of 4500 grams who had a right-sided brachial plexus palsy and right diaphragmatic paralysis due to shoulder dystocia. He developed respiratory distress due to isolated paralysis of the right hemi diaphragm. The clinical course was progressive, his condition worsening despite oxygen application. Physical examination, chest X-rays and M-mode ultrasonography of the diaphragm confirmed the diagnosis diaphragmatic paralysis. Surgical plication of diaphragm was done earlier than the usual time because of recurrent extubation failure. Diaphragmatic plication led to rapid improvement of pulmonary function and allowed discontinuation of mechanical ventilation in less than 3 days.

Conclusion

Early diaphragmatic plication enhances weaning process and may prevent or minimize the morbidity associated with long-term mechanical ventilation in a neonate with diaphragmatic paralysis.     

小儿进行性脊髓性肌萎缩83例临床分析

目的总结小儿进行性脊髓性肌萎缩(SMA)各类型的临床表现、神经电生理及肌肉病理特点,提高对本病的认识水平并探讨基因诊断及产前诊断的临床意义。方法83例各型SMA患儿,男55例,女28例,年龄1d∽14岁,平均23．7个月,对本组病例进行临床特点、神经电生理、肌肉病理及基因分析。结果83例SMA临床分为3型,其中SMA-1型60例,SMA-2型19例,SMA-3型4例,3型SMA各有特点,但临床均表现为近端肌肉无力,肌张力低下。本病为单纯运动神经元受累,故患儿电生理表现均为神经源性损害而无感觉神经受累及明显的运动神经传导速度减慢;2例行肌活检显示大组萎缩肌纤维;13例行运动神经元生存基因(SMN)检测,11例外显子7和8联合缺失,1例仅第7外显子缺失,1例仅第8外显子缺失。结论根据临床特点,电生理,肌肉病理及基因诊断可与其他松软婴综合征鉴别,而能确诊SMA。基因诊断可为产前诊断提供依据,达到预防本病发生的目的。     

脊髓性肌萎缩症合并脊柱侧凸的临床诊治

脊髓性肌萎缩症(SMA)是一种以脊髓前角α运动神经元退行性病变、进行性近端肌无力为特征的严重神经肌肉疾病,随着疾病的进展,还会引发包括骨骼系统、呼吸系统、消化系统等其他多系统疾病,其中脊柱侧凸是最常见的骨骼系统并发症.文章介绍SMA合并脊柱侧凸的自然史,以及不同程度脊柱侧凸的临床保守治疗和手术治疗方法,重点阐述了多学科...     

精准医学时代中国脊髓性肌萎缩症诊治发展之路

脊髓性肌萎缩症(SMA)是一种常染色体隐性遗传神经肌肉疾病,因运动神经元存活基因(SMN)1缺失/变异导致SMN蛋白缺乏致病,临床表现为进行性肌萎缩与肌无力,并常伴呼吸、消化、营养、骨骼等多系统器官损害,属严重致死致残性遗传病,2018年被纳入国家《第一批罕见病目录》.近年来随着精准医学的发展,SMA的药物治疗获得前所...     

Powder aspiration in children. Report of two cases.

Two cases of powder aspiration are reported. A 7 1/2-month-old girl showed a classical course with an asymptomatic period of 3-4 hours, then severe respiratory distress developed. Acute respiratory insufficiency made tracheal intubation and mechanical ventilation necessary for 10 days. Complications included insufficient alveolar ventilation, atelectasis, pneumothorax, and superinfection. But the baby recovered with some residual radiological changes in the lungs. A 13-month-old boy was treated immediately after massive powder aspiration by tracheal intubation and bronchial wash-out. The postoperative course was unevetful and no respiratory distress developed. Powder aspiration leads to severe bronchiolar obstruction with a delay of several hours and has a high mortality rate. The best results in treatment are obtained by immediate intubation and bronchial wash-out, even in the absence of respiratory symptoms. Artifical ventilation may be necessary with the special problem of overcoming very high airway resistance. Corticosteroids and bronchodilators may be helpful.     

Powder aspiration in children. Report of two cases

Two cases of powder aspiration are reported. A 7 1/2-month-old girl showed a classical course with an asymptomatic period of 3-4 hours, then severe respiratory distress developed. Acute respiratory insufficiency made tracheal intubation and mechanical ventilation necessary for 10 days. Complications included insufficient alveolar ventilation, atelectasis, pneumothorax, and superinfection. But the baby recovered with some residual radiological changes in the lungs. A 13-month-old boy was treated immediately after massive powder aspiration by tracheal intubation and bronchial wash-out. The postoperative course was unevetful and no respiratory distress developed. Powder aspiration leads to severe bronchiolar obstruction with a delay of several hours and has a high mortality rate. The best results in treatment are obtained by immediate intubation and bronchial wash-out, even in the absence of respiratory symptoms. Artifical ventilation may be necessary with the special problem of overcoming very high airway resistance. Corticosteroids and bronchodilators may be helpful.     

Neonatal respiratory insufficiency due to centronuclear myopathy

Two neonates showing generalized hypotonia, weakness of limbs, trunk, and oral musculature died because of muscular respiratory distress. The diagnosis of centronuclear (or myotubular) myopathy was established by histological and histochemical techniques. The genetic situation and routine laboratory data including electromyography were compared with similar cases in the literature; findings were inconclusive with respect to this diagnosis. These results indicate the need for a muscle biopsy and the use of histochemical stainings and/or electronmicroscopical investigation for a proper diagnosis in hypotonic newborns under respiratory distress after exclusion of etiologies other than neuromuscular diseases. Still the diagnosis of centronuclear myopathy in a neonate does not allow a precise prognosis. Increased awareness of this disorder and adequate diagnostic workup is needed in order to extend our understanding and to clarify the prognosis.     

Continuous positive airway pressure - a gentler approach to ventilation

Continuous positive airway pressure (CPAP) has become a useful modality in management of respiratory distress, especially in preterm babies. Main indications for use of CPAP are respiratory distress syndrome (RDS) and apnea of prematurity. It decreases the need of invasive and costly mechanical ventilation. This review details the physiological effects of CPAP, its methods of delivery, and its need in a country like India. It also describes the guidelines for initiating and weaning CPAP. The review concludes that use of CPAP in respiratory distress syndrome is associated with lower rates of failed treatment, decreased incidence of chronic lung disease and lower overall mortality, specially in infants with birth weight above 1500 grams. Early use of CPAP is more beneficial, Surfactant and CPAP act in conjunction for babies with RDS. CPAP is a low-cost, simple and noninvasive option for a country like India, where most places lack facilities of mechanical ventilation. Systematic reviews, randomized and quasi-randomized trials by searching MEDLINE and the Cochrane Library formed the basis of this update.     

早产儿呼吸窘迫综合征高频振荡通气后两种撤机方式的安全性研究：前瞻性随机对照试验

目的 探讨高频振荡通气（HFOV）治疗早产儿呼吸窘迫综合征（RDS）后两种撤机方式的安全性。方法 前瞻性纳入2019年1月1日至2020年6月30日厦门市妇幼保健院新生儿科重症监护病房（NICU）收治的胎龄≤ 32⁺⁶周或体重≤ 1 500 g、首选HFOV治疗的RDS早产儿101例,随机分为HFOV直接撤机组（观察组）50例,HFOV转为常频机械通气撤机组（对照组）51例。比较两组患儿撤机后72 h内的撤机失败率,撤机前2 h、撤机后2 h、撤机后24 h的血气分析各指标,比较两组呼吸支持治疗情况、并发症的发生率及出院时的转归情况。结果 观察组和对照组撤机失败率差异无统计学意义（8% vs 14%,P > 0.05）。观察组有创机械通气时间较对照组缩短[（64±39）h vs（88±69）h,P < 0.05]。两组患儿总机械通气时间、总用氧时间、撤机前后的血气分析各指标、并发症发生率、出院时转归情况差异均无统计学意义（均P > 0.05）。结论 对于RDS早产儿,使用HFOV后采取直接撤机策略是安全可靠的,且可减少有创呼吸机使用时间,值得临床推广应用。     

Guillain-Barré syndrome as a rare cause of acute respiratory insufficiency

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating disease of peripheral nerves. Antibodies acting against antigens on the myelin or the axons seem to play a causative role. In up to 80 % the onset of GBS follows an antecedent respiratory or gastrointestinal infection. CASE REPORT: An 20 month old boy was referred to our hospital because of meningism and aspiration pneumonia. 10 days earlier the patient had experienced a period of fever. Because of respiratory insufficiency the patient was intubated, sedated and received mechanical ventilation. That's why a major neurological examination was not possible. The patient demonstrated a flaccid tetraplegic paralysis and autonomic dysfunction with elevated blood pressure, tachycardia, elevated ADH level and hyperglycaemia. Decreased motor nerve conduction and an increased CSF protein with normal CSF cell count confirmed diagnosis of GBS. Active CMV infection was diagnosed by PCR as the possible trigger factor. Intravenous immunoglobulins were given and the patient reached a complete remission except a slight disturbance of peroneal nerve. CONCLUSIONS: IVIG and PP therapy are equally effective in GBS. In contrast corticosteroids are not of benefit. Prognosis of childhood GBS is good. Only 4 % of affected children demonstrate persistent muscular weakness. The long interval between admission and diagnosis in the reported case emphasized the importance of neurological examination especially in sedated patients.     

Successful surfactant therapy of ARDS in an immunodepressed child

The acute respiratory distress syndrome in childhood is a rare disease, but as in the past still plagued with a high mortality rate. It is caused by severe pneumoniaes or infectious diseases with multiorgan failure, aspiration, trauma or immunodepression. There are no therapeutic guidelines based on controlled studies. Therefore different therapies i. e. high frequency oscillatory ventilation, nitric oxide application, surfactant therapy, extracorporal membrane oxygenation or a combination of these methods are used. We present the case of a 4 (3)/ 12 year old boy, who suffered from an acute lymphatic leukaemia. Caused by immunosuppressive therapy he got a severe broncho-pneumonia. During ventilation therapy an acute respiratory distress syndrome occurred. Due to a surfactant application over 7 days with a doses of 360 mg/kg body weight this RDS could be dominated. The extubation was possible after 17 days of ventilatory support. 3 weeks later the lung function was normalized and the chemotherapy resumed.     

A 7-year-old boy with mycoplasmal infection requiring extracorporeal membrane oxygenation

A 7-year-old boy with Down syndrome developed severe acute respiratory distress syndrome after a respiratory infection with Mycoplasma pneumoniae with an unusually high agglutination titre (1:10240). Initially, mechanical ventilation and nitric oxide inhalation were used, but these did not improve the alveolar-arterial oxygen gradient. Extracorporeal membrane oxygenation for 152 h improved the lung condition. CONCLUSION: our case suggests that Mycoplasma pneumoniae should be considered as an aetiological agent in acute respiratory distress syndrome. Extracorporeal membrane oxygenation might have a valuable role in the management.     

Prenatal onset spinal muscular atrophy.

Five patients with severe spinal muscular atrophy (SMA) type I, all of whom presented with reduced fetal movements in utero, severe weakness at birth, and short survival time were assessed to attempt to determine whether their phenotype could be explained by their genotype. The diagnosis was confirmed by clinical, electrophysiological and histopathological features. Polymerase chain reaction assays were used to define the molecular diagnosis. A gene-dosage assay was used to assess the quantity of centromeric survival motor neuron gene (SMNc) present. In all cases the telomeric survival motor neuron gene (SMNt) was absent. The SMNc gene was present but in reduced copy number compared with a control group of children with less severe type I SMA, so may be important in determining severity. In the differential diagnosis of reduced fetal movements, SMA should be considered. The clinical classification may in future be clarified by molecular genetic findings.     

Stable microbubble test on tracheal aspirate for the diagnosis of respiratory distress syndrome

BACKGROUND: Exogenous surfactant should be used as early as possible in the presence of respiratory distress syndrome (RDS), but diagnosis may only become clear late in the course of the disease. The stable microbubble test (SMT) in the tracheal aspirates could help in the decision to give early surfactant to preterm babies with respiratory distress. OBJECTIVES: The objective of this study was to evaluate the accuracy of the SMT on tracheal aspirate for the diagnosis of RDS in newborns requiring mechanical ventilation. METHODS: The test was performed on specimens obtained from 74 infants requiring mechanical ventilation, through routine suctioning. RESULTS: Patients with RDS and meconium aspiration syndrome (MAS) had a significantly lower stable microbubble count than non-RDS and non-MAS patients. Preterm infants without RDS had a significantly higher microbubble count than preterm babies with RDS and a similar count to that of term babies. Considering a cutoff point of 120 microbubbles/mm(2) for the diagnosis of RDS, the sensitivity of the microbubble test was 96.3% (95% CI: 79.1-99.8) and the specificity 97.6% (95% CI: 85.9-99.9). CONCLUSIONS: The SMT on tracheal aspirates is accurate for RDS diagnosis and may be useful to support the decision to give surfactant to newborns on mechanical ventilation.