Uwe Mellies

117th ENMC workshop: ventilatory support in congenital neuromuscular disorders -- congenital myopathies, congenital muscular dystrophies, congenital myotonic dystrophy and SMA (II) 4-6 April 2003, Naarden, The Netherlands.

Eighteen participants from Australia, Austria, Denmark, Finland, France, Germany, The Netherlands, the UK, and the USA met in Naarden, representing a variety of disciplines with experience in the respiratory management of patients with neuromuscular disorders (NMD). The aims of the workshop were to agree upon and report minimum recommendations for the investigation and treatment of respiratory involvement in congenital muscular disorders, and to identify areas where further research is needed. The workshop specifically excluded patients with Duchenne muscular dystrophy where evidence for the need for and efficacy of the treatment of respiratory failure is better established. All participants contributed to the review and assessment of published evidence in the field, and current practice amongst the group was also compared. Despite the individual rarity of the conditions under consideration in this workshop, the accumulated experience of the group represented the care of more than 545 patients with these disorders, of whom around one-third were receiving mechanical ventilation.

Sleep disordered breathing in spinal muscular atrophy

Sleep disordered breathing is a common but under-diagnosed complication causing sleep disturbance and daytime symptoms in children with spinal muscular atrophy. Non-invasive (positive pressure) ventilation is an established treatment of respiratory failure; its role in treatment of sleep disordered breathing though remains controversial. Aim of this study was to verify the hypothesis that nocturnal non-invasive ventilation has beneficial impact on breathing during sleep, sleep quality and daytime complaints in children with spinal muscular atrophy. Twelve children with spinal muscular atrophy type I or II (7.8+/-1.9 years) underwent polysomnography and were asked to fill out a symptom questionnaire. Seven patients (six with spinal muscular atrophy I and one with spinal muscular atrophy II) had sleep disordered breathing and received non-invasive ventilation during sleep. Five less severely affected patients (one with spinal muscular atrophy I and four with spinal muscular atrophy II) had no sleep disordered breathing and served as reference group. Patients were restudied after 6-12 months. In patients with sleep disordered breathing both sleep architecture and disease related symptoms were significantly worse than in the reference-group. Non-invasive ventilation during sleep completely eliminated disordered breathing, normalized sleep architecture and improved symptoms (P<0.05 for all). In children with spinal muscular atrophy sleep disordered breathing may cause relevant impairment of sleep and well-being. Both can be highly improved by nocturnal non-invasive ventilation.

Predictors of severe chest infections in pediatric neuromuscular disorders.

Chest infections are serious complications in neuromuscular disorders. The predictive values of lung and respiratory muscle function including peak cough flow still remain unclear. We performed retrospective analysis of 46 children and adolescents (12.7+/-3.7 years) in whom lung function, respiratory muscle function and peak cough flows had been obtained. Data were related to: (1). number of chest infections and days of antibiotic treatment the year prior to the study and (2). history of severe chest infection requiring hospital admission. The number of chest infections and the number of days treated with antibiotics correlated with Inspiratory Vital Capacity IVC, peak cough flow PCF and Peak Expiratory Pressure PEP. Twenty-two patients were hospitalized at least once due to severe chest infection. IVC (0.65 vs. 1.44 l; P<0.0001) and PCF (116 vs. 211 l/min; P<0.0005) in these patients were significantly lower than in the non-hospitalized group. IVC<1.1l and PCF<160 l/min were specific and sensitive thresholds to discriminate between patients who had already suffered severe chest infections and those who had not. Therefore, spirometry and peak cough flow are reliable tests to identify patients at high risk for severe chest infections. Patients with IVC below 1.1l and/or PCF below 160 l/min should be well monitored and introduced to assisted coughing techniques.

Pompe disease: A neuromuscular disease with respiratory muscle involvement

Pompe disease is a single disease continuum that includes variable neuromuscular symptoms and rates of progression. However, specific clinical features, such as an early onset of respiratory problems preceding limb muscular weakness, distinguish Pompe disease from other neuromuscular diseases in which respiratory insufficiency occurs after loss of ambulation. The management of Pompe disease also differs from other neuromuscular diseases in that specific treatment is now available, making early recognition of the disease a priority. The results from clinical trials with recombinant human acid alpha-glucosidase have been published, and they show promising results with regards to the improvement of respiratory function in patients with Pompe disease. This review aims to give an overview of Pompe disease and to describe the current concepts of the disease. A focus is placed on the pathophysiology and clinical presentation of respiratory muscle involvement in adults. Additionally, new approaches and therapies available for the management of respiratory complications observed in Pompe disease are discussed in detail.

Airway clearance techniques in neuromuscular disorders: A state of the art review

This is a unique state of the art review written by a group of 21 international recognized experts in the field that gathered during a meeting organized by the European Neuromuscular Centre (ENMC) in Naarden, March 2017. It systematically reports the entire evidence base for airway clearance techniques (ACTs) in both adults and children with neuromuscular disorders (NMD). We not only report randomised controlled trials, which in other systematic reviews conclude that there is a lack of evidence base to give an opinion, but also include case series and retrospective reviews of practice. For this review, we have classified ACTs as either proximal (cough augmentation) or peripheral (secretion mobilization). The review presents descriptions; standard definitions; the supporting evidence for and limitations of proximal and peripheral ACTs that are used in patients with NMD; as well as providing recommendations for objective measurements of efficacy, specifically for proximal ACTs. This state of the art review also highlights how ACTs may be adapted or modified for specific contexts (e.g. in people with bulbar insufficiency; children and infants) and recommends when and how each technique should be applied.

Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease

Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Additionally, respiratory muscle weakness leads to decreased cough and impaired airway clearance, increasing the risk of acute respiratory illness. Progressive respiratory muscle weakness is a major cause of morbidity and mortality in late-onset Pompe disease even if enzyme replacement therapy has been established. Practical knowledge of how to detect, monitor and manage respiratory muscle involvement is crucial for optimal patient care. A multidisciplinary approach combining the expertise of neurologists, pulmonologists, and intensive care specialists is needed. Based on the authors’ own experience in over 200 patients, this article conveys expert recommendations for the diagnosis and management of respiratory muscle weakness and its sequelae in late-onset Pompe disease.

Bacteraemia and fungaemia in cystic fibrosis patients with febrile pulmonary exacerbation: a prospective observational study

BackgroundBloodstream pathogens can be identified by multiplex PCR (SeptiFast (SF)) or blood culture (BC); whether these pathogens are present in cystic fibrosis (CF) patients during febrile pulmonary exacerbations (FPE) has not been sufficiently studied.MethodsIn this prospective observational study, blood from CF patients experiencing FPE was tested with SF and BC before the initiation of antibiotic treatment.ResultsAfter contaminants had been excluded, 9 of 72 blood samples tested positive by BC or SF. SF exclusively detected four pathogens; BC, one. Pulmonary pathogen transmission was likely in all cases except for 2 cases of candidaemia, which were believed to be caused by catheter-related infections. For three cases, test results caused us to change the antibiotic regimen. Sensitivity (85.7% vs. 42.9%) and negative predictive value (98.4% vs. 87.0%) tended to be higher for SF than for BC.ConclusionsThe results of SF and BC show that bacteraemia and fungaemia are present in CF patients during FPE and may affect antibiotic therapy. SF can help rule out catheter-related bloodstream infections.