Enfermedad neuromuscular en pediatría: estudio descriptivo de los pacientes asistidos en la policlínica de Neumología Pediátrica del Centro Hospitalario Pereira Rossell en el período 1/6/2006-31/12/2019 / Pediatric neuromuscular disease: study of patients assisted at the Pediatric Pneumology department of the Pereira Rossell Pediatric Hospital during 1/6/2006-31/12/2019 / Doença neuromuscular em pediatria: estudo descritivo de pacientes atendidos no policlínio de Pneumologia Pediátrica do Hospital Pereira Rossell no período 1/6/2006-31/12/2019

Las enfermedades neuromusculares (ENM) afectan los distintos componentes de la unidad motora. Desde el diagnóstico deben ser seguidos por un equipo interdisciplinario, donde el neumólogo pediátrico desempeña un papel importante en la valoración de la pérdida de fuerza muscular cuando afecta a la musculatura respiratoria o de la vía aérea superior. Objetivos: conocer las diferentes enfermedades neuromusculares atendidas en el Centro Hospitalario Pereira Rossell, analizar las características de la población y describir los resultados de los principales estudios solicitados por la policlínica de neumológica pediátrica. Metodología: estudio descriptivo, analítico y retrospectivo de los pacientes con enfermedad neuromuscular atendidos en el Centro Hospitalario Pereira Rossell entre el 1/6/2006 y el 31/12/2019. Resultados: las patologías neuromusculares más frecuentemente encontradas fueron distrofias musculares, miopatías, distrofia miotónica de Steinert y atrofia muscular espinal. No tienen diagnóstico definitivo 21/73 pacientes. La espirometría mostró una alteración restrictiva en la mayoría de los pacientes. Para descartar trastornos respiratorios del sueño se realizó oximetría nocturna con gasometría al despertar. La hipoventilación nocturna y las apneas obstructivas fueron las alteraciones encontradas. En 12/73 se inició ventilación no invasiva. Conclusiones: los pacientes con ENM experimentan un deterioro progresivo de la función respiratoria que contribuye a una elevada tasa de morbimortalidad. La evaluación y seguimiento regular de la función respiratoria junto con estudios de sueño, son fundamentales para el inicio oportuno de ventilación no invasiva.

Neuromuscular diseases (NMD) affect the different components of the motor system. As of diagnosis, they should be followed by an interdisciplinary team, in which pediatric pulmonologists play an important role in assessing the loss of muscle strength when NMD affects the respiratory or upper airway muscles. Objectives: to learn about the different neuromuscular diseases treated at the Pereira Rossell Hospital Center, to analyze the characteristics of this population and to describe the results of the main studies requested by the pediatric pulmonology clinic. Methodology: descriptive, analytical and retrospective study of patients with neuromuscular disease treated at the Pereira Rossell Hospital Center between 6/1/2006 and 12/31/2019. Results: the most frequent neuromuscular pathologies were muscular dystrophies, myopathies, Steinert's myotonic dystrophy and spinal muscular atrophy. 21/73 patients did not have a definitive diagnosis. Spirometry showed a restrictive alteration in most of the patients. To rule out respiratory sleep disorders, nocturnal oximetry with blood gas was performed upon awakening, with nocturnal hypoventilation and obstructive apneas being the alterations found. In 12/73 non-invasive ventilation was applied. Conclusions: patients with NMD experience a progressive deterioration of respiratory function that contributes to a high rate of morbidity and mortality. Regular evaluation and monitoring of respiratory function, along with sleep studies, are essential for the timely initiation of non-invasive ventilation.

As doenças neuromusculares (DNM) afetam os diferentes componentes da unidade motora. Desde o diagnóstico, os pacientes devem ser acompanhados por uma equipe interdisciplinar, onde o pneumologista pediátrico desempenha um papel importante na avaliação da perda de força muscular quando atinge a musculatura respiratória ou das vias aéreas superiores. Objetivos: conhecer as diferentes doenças neuromusculares tratadas no Centro Hospitalar Pereira Rossell, analisar as características desta população e descrever os resultados dos principais estudos solicitados à policlínica de pneumologia pediátrica. Metodologia: estudo descritivo, analítico e retrospectivo de pacientes com doenças neuromusculares atendidos no Centro Hospitalar Pereira Rossell entre 01/06/2006 e 31/12/2019. Resultados: as patologias neuromusculares mais encontradas foram distrofias musculares, miopatias, distrofia miotônica de Steinert e atrofia muscular espinhal. 21/73 pacientes não tiveram um diagnóstico definitivo. A espirometria mostrou alteração restritiva na maioria dos pacientes. Para afastar distúrbios respiratórios do sono, foi realizada oximetria noturna com gasometria ao despertar, sendo a hipoventilação noturna e as apneias obstrutivas as alterações encontradas. Em 12/73 foi iniciada ventilação não invasiva. Conclusões: os pacientes com DNM experimentam uma deterioração progressiva da função respiratória que contribui para uma alta taxa de morbidade e mortalidade. A avaliação regular e o monitoramento da função respiratória, juntamente com os estudos do sono, são essenciais para o início oportuno da ventilação não invasiva.

Is it accurate to classify ALS as a neuromuscular disorder?

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the progressive loss of upper and lower motor neurons. ALS has traditionally been classified within the domain of neuromuscular diseases, which are a unique spectrum of disorders that predominantly affect the peripheral nervous system. However, over the past decades compounding evidence has emerged that there is extensive involvement of the central nervous system. Therefore, one can question whether it remains accurate to classify ALS as a neuromuscular disorder. AREAS COVERED: In this review, the authors sought to discuss current approaches toward disease classification and how we should classify ALS based on novel insights from clinical, imaging, pathophysiological, neuropathological and genetic studies. EXPERT OPINION: ALS exhibits the cardinal features of a neurodegenerative disease. Therefore, classifying ALS as a neuromuscular disease in the strict sense has become untenable. Diagnosing ALS however does require significant neuromuscular expertise and therefore neuromuscular specialists remain best equipped to evaluate this category of patients. Designating motor neuron diseases as a separate category in the ICD-11 is justified and adequately deals with this issue. However, to drive effective therapy development the fields of motor neuron disease and neurodegenerative disorders must come together.

Implantación emergente de un servicio de Teleneurología en la Unidadde Neuromuscular del Hospital Regional de Málaga durante la pandemia por SARS-CoV-2 / Emergency implementation of a teleneurology service at the neuromuscular diseases unit of Hospital Regional de Málaga during the COVID-19 pandemic

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AANEM - IFCN Glossary of Terms in Neuromuscular Electrodiagnostic Medicine and Ultrasound.

Modern neuromuscular electrodiagnosis (EDX) and neuromuscular ultrasound (NMUS) require a universal language for effective communication in clinical practice and research and, in particular, for teaching young colleagues. Therefore, the AANEM and the IFCN have decided to publish a joint glossary as they feel the need for an updated terminology to support educational activities in neuromuscular EDX and NMUS in all parts of the world. In addition NMUS has been rapidly progressing over the last years and is now widely used in the diagnosis of disorders of nerve and muscle in conjunction with EDX. This glossary has been developed by experts in the field of neuromuscular EDX and NMUS on behalf of the AANEM and the IFCN and has been agreed upon by electronic communication between January and November 2019. It is based on the glossaries of the AANEM from 2015 and of the IFCN from 1999. The EDX and NMUS terms and the explanatory illustrations have been updated and supplemented where necessary. The result is a comprehensive glossary of terms covering all fields of neuromuscular EDX and NMUS. It serves as a standard reference for clinical practice, education and research worldwide. HIGHLIGHTS: Optimal terminology in neuromuscular electrodiagnosis and ultrasound has been revisited. A team of international experts have revised and expanded a standardized glossary. This list of terms serves as standard reference for clinical practice, education and research.

Facing the challenges of electrodiagnostic studies in the very elderly (>80 years) population.

OBJECTIVE: Studies on electrodiagnostic (EDX) methods usually exclude the very elderly. This also holds true for studies of normal EDX values. We analyzed the outcome and diagnostic value of EDX and collected reference data in a large cohort of patients ≥80 years of age. METHODS: Referral information, ICD-10 diagnoses and EDX data were retrieved from all patients ≥80 years of age referred for EDX studies at our department in 1995-2015. Normative data, including reference ranges, were obtained using the extrapolated norms (e-norms) method. RESULTS: 1966 unique patients (2335 examinations) were included. Only 11% were considered to have normal findings. 66% had pathological EDX findings in accordance with the indication for referral. Carpal tunnel syndrome was by far the most common diagnosis. Normative data retrieved using e-norms were similar to those of reference values from healthy subjects regarding EMG multiMUP data, but typically provided a wider normality window when applied to nerve conduction parameters. CONCLUSIONS: EDX studies are valuable in the diagnostic work-up of very elderly patients. Using the e-norms method may be a useful alternative when obtaining reference values in this age group. SIGNIFICANCE: Our findings provide additional insights to the challenges of evaluating very elderly patients with neuromuscular disease and underline the importance of including this growing part of the patient population in EDX research.

Trends in incidence, prevalence, and mortality of neuromuscular disease in Ontario, Canada: A population-based retrospective cohort study (2003-2014).

BACKGROUND: Population trends of disease prevalence and incidence over time measure burden of disease and inform healthcare planning. Neuromuscular disorders (NMD) affect muscle and nerve function with varying degrees of severity and disease progression. OBJECTIVE: Using health administrative databases we described trends in incidence, prevalence, and mortality of adults and children with NMD. We also explored place of death and use of palliative care. METHODS: Population-based (Ontario, Canada) cohort study (2003 to 2014) of adults and children with NMD identified using International Classification of Disease and health insurance billing codes within administrative health databases. RESULTS: Adult disease prevalence increased on average per year by 8% (95% confidence interval (CI) 6% to 10%, P <.001), with the largest increase in adults18-39 years. Childhood disease prevalence increased by 10% (95% CI 8% to 11%, P <.0001) per year, with the largest increase in children 0 to 5 years. Prevalence increased across all diagnoses except amyotrophic lateral sclerosis and spinal muscular atrophy for adults and all diagnoses for children. Adult incidence decreased by 3% (95% CI -4% to -2%, P <.0001) but incidence remained stable in children. Death occurred in 34,336 (18.5%) adults; 21,236 (61.8%) of whom received palliative care. Death occurred in 1,009 (5.6%) children; 507 (50.2%) of whom received palliative care. Mortality decreased over time in adults (odds ratio (OR) 0.86, 95% CI 0.86-0.87, P <.0001) and children (OR 0.79, 95% CI 0.76-0.82, P <.0001). Use of palliative care over time increased for adults (OR 1.18, 95% CI 1.09 to 1.28, P <.0001) and children (OR 1.22, 95% CI 1.20 to 1.23, P <.0001). CONCLUSIONS: In both adults and children, NMD prevalence is rising and mortality rates are declining. In adults incidence is decreasing while in children it remains stable. This confirms on a population-based level the increased survival of children and adults with NMD.

A nomenclature and classification for the congenital myasthenic syndromes: preparing for FAIR data in the genomic era.

BACKGROUND: Congenital myasthenic syndromes (CMS) are a heterogeneous group of inherited neuromuscular disorders sharing the common feature of fatigable weakness due to defective neuromuscular transmission. Despite rapidly increasing knowledge about the genetic origins, specific features and potential treatments for the known CMS entities, the lack of standardized classification at the most granular level has hindered the implementation of computer-based systems for knowledge capture and reuse. Where individual clinical or genetic entities do not exist in disease coding systems, they are often invisible in clinical records and inadequately annotated in information systems, and features that apply to one disease but not another cannot be adequately differentiated. RESULTS: We created a detailed classification of all CMS disease entities suitable for use in clinical and genetic databases and decision support systems. To avoid conflict with existing coding systems as well as with expert-defined group-level classifications, we developed a collaboration with the Orphanet nomenclature for rare diseases, creating a clinically understandable name for each entity and placing it within a logical hierarchy that paves the way towards computer-aided clinical systems and improved knowledge bases for CMS that can adequately differentiate between types and ascribe relevant expert knowledge to each. CONCLUSIONS: We suggest that data science approaches can be used effectively in the clinical domain in a way that does not disrupt preexisting expert classification and that enhances the utility of existing coding systems. Our classification provides a comprehensive view of the individual CMS entities in a manner that supports differential diagnosis and understanding of the range and heterogeneity of the disease but that also enables robust computational coding and hierarchy for machine-readability. It can be extended as required in the light of future scientific advances, but already provides the starting point for the creation of FAIR (Findable, Accessible, Interoperable and Reusable) knowledge bases of data on the congenital myasthenic syndromes.

Informe de la Fundación Del Cerebro sobre el impacto social de la esclerosis lateral amiotrófica y las enfermedades neuromusculares / Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders

Introducción: El conocimiento del alcance socioeconómico de la patología neuromuscular es esencial para la planificación de recursos y la concienciación social. Desarrollo: Se ha realizado una revisión de los datos publicados hasta el momento sobre epidemiología, mortalidad, dependencia e impacto sociosanitario de la esclerosis lateral amiotrófica y las enfermedades neuromusculares en España. Además, se ha recogido cómo está organizada la atención neurológica en estos pacientes. Conclusiones: La patología neuromuscular constituye un grupo muy heterogéneo de enfermedades, algunas de las cuales se consideran raras por su baja frecuencia. Esta patología supone entre el 2,8 y el 18% de los motivos de consulta en un Servicio de Neurología. En España, las cifras de prevalencia e incidencia de esclerosis lateral amiotrófica son similares a otros países; sin embargo, se desconoce el número de pacientes con otras enfermedades neuromusculares. Son enfermedades crónicas, progresivas y debilitantes, lo que condiciona una importante discapacidad y dependencia. Esto repercute directamente en los costes sanitarios y sociales asociados a la enfermedad. Se ha calculado que el coste de un paciente con esclerosis lateral amiotrófica o enfermedad de Duchenne se acerca a los 50.000 euros anuales. La patología neuromuscular tiene una gran complejidad etiológica, diagnóstica y pronóstica, y requiere un manejo multidisciplinar. Las Unidades especializadas deben ser las encargadas del seguimiento de estos pacientes (AU)

Introduction: A thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. Development: Our group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. Conclusions: Neuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50 000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units (AU)

A Historical and Current Review of Newborn Screening for Neuromuscular Disorders From Around the World: Lessons for the United States.

BACKGROUND: We aimed to review the history of newborn screening for three neuromuscular disorders (Duchenne muscular dystrophy, Pompe disease, and spinal muscular atrophy [SMA]) to determine best practices. METHODS: The history of newborn screening for Duchenne muscular dystrophy began in 1975 with the measurement of creatinine kinase on newborn male blood spots from two Midwestern hospitals in the United States. Over the next 40 years, ten programs were implemented around the globe although none currently remain. The first experimental pilot program for Pompe disease began in 2005 in Taiwan. In 2013, Missouri was the first US state to implement Pompe newborn screening before its inclusion in the Recommended Uniform Screening Panel (RUSP) in 2015 by the Advisory Committee on Heritable Disorders in Newborns and Children (United States). In 2008, SMA was reviewed and rejected for inclusion in the RUSP because no treatment existed. With the approval of nusinersen in late 2016, spinal muscular atrophy is being reconsidered for the RUSP. RESULTS: A condition should meet public health screening criteria to be included in the RUSP. Duchenne muscular dystrophy, Pompe, and SMA challenge traditional screening criteria: Duchenne muscular dystrophy does not present in infancy and lacks effective treatment; Pompe and SMA may not present until adulthood; and safety and efficacy of long-term intrathecal treatment for SMA is unknown. Potential reproductive benefit and improved research recruitment do not justify a public health screening program. CONCLUSIONS: This review provides lessons that could benefit US public health departments as they consider expanding screening to include neuromuscular disorders like Duchenne muscular dystrophy, Pompe, and SMA.

A population-based epidemiologic study of adult neuromuscular disease in the Republic of Ireland.

OBJECTIVE: To estimate the prevalence rates (PRs) of acquired and inherited neuromuscular diseases (NMD) in the adult Irish population, reflecting the burden of these conditions in a single country. METHODS: This population-based study was performed in the Republic of Ireland (RoI), with a PR estimated for December 2013. Multiple case ascertainment sources were utilized. Demographic and clinical information and relevant diagnostic results were registered. RESULTS: A total of 2,641 adults were identified, giving a PR of 62.6/100,000 (95% confidence interval [CI] 59.95-65.24) for all NMD in RoI. Disease-specific PR include chronic inflammatory demyelinating polyradiculoneuropathy 5.87/100,000 (95% CI 5.06-6.68), Charcot-Marie-Tooth 10.52/100,000 (95% CI 9.44-11.61), hereditary neuropathy with liability to pressure palsies 0.84/100,000 (95% CI 0.54-1.15), myotonic dystrophy type I 6.75/100,000 (95% CI 5.88-7.61), Duchenne muscular dystrophy 3.0/100,000 (95% CI 2.33-3.70), Becker muscular dystrophy 2.2/100,000 (95% CI 1.64-2.88), facioscapulohumeral dystrophy 2.59/100,000 (95% CI 2.05-3.13), limb-girdle muscular dystrophy 2.88/100,000 (95% CI 2.31-3.45), periodic paralysis 1.72/100,000 (95% CI 1.28-2.15), myotonia congenita 0.32/100,000 (95% CI 0.18-0.56), paramyotonia congenita 0.15/100,000 (95% CI 0.06-0.34), Kennedy disease 0.83/100,000 (95% CI 0.40-1.27), Lambert-Eaton myasthenic syndrome 0.29/100,000 (95% CI 0.11-0.47), myasthenia gravis 15.12/100,000 (95% CI 13.82-16.42), and sporadic inclusion body myositis 11.7/100,000 (95% CI 9.82-13.58). PR for amyotrophic lateral sclerosis was established from an existing Register as 7.20/100,000 (95% CI 6.34-8.15). CONCLUSIONS: The PR of all adult NMD in RoI is relatively high when compared with other chronic neurologic disorders, although some figures may be an underestimate of the true prevalence. The data provide a framework for international comparison and service planning.

The Epidemiology of Neuromuscular Diseases.

Neuromuscular disorders as a group are linked by anatomy with significant differences in pathogenetic mechanisms, clinical expression, and time course of disease. Each neuromuscular disease is relatively uncommon, yet causes a significant burden of disease socioeconomically. Epidemiologic studies in different global regions have demonstrated certain neuromuscular diseases have increased incidence and prevalence rates over time. Understanding differences in global epidemiologic trends will aid clinical research and policies focused on prevention of disease. There is a critical need to understand the global impact of neuromuscular diseases using metrics currently established for communicable and noncommunicable diseases.

What's New in the Management of Neuromuscular Scoliosis.

BACKGROUND: Patients with neuromuscular scoliosis (NMS) can pose treatment challenges related to medical comorbidities and altered spinopelvic anatomy. We reviewed the recent literature regarding evaluation and management of NMS patients and explored areas where further research is needed. METHODS: We searched the PubMed database for all papers related to the treatment of NMS published from January 1, 2011 through July 31, 2014, yielding 70 papers. RESULTS: A total of 39 papers contributed compelling new findings. Steroid treatment has been most promising in patients with Duchenne muscular dystrophy, leading to a significantly lower death rate, better pulmonary function, and longer independent ambulation. Growing rods in early-onset NMS were shown to result in significant improvements in major Cobb angles and pelvic obliquity, with low complication rates in patients with spinal muscular atrophy but high infection rates in those with cerebral palsy. Early reports of magnetic growing rods in NMS patients are favorable. Intraoperative neural monitoring is variable in this patient population; however, use of transcranial motor-evoked potentials in NMS patients seems to be safe. Blood loss is the highest in NMS patients when compared with all other diagnostic categories. However, tranexamic acid seems to significantly lower intraoperative blood loss. In a multicenter study, patients diagnosed with NMS had the highest surgical-site infection rate at 13.1%. Best-practice guidelines have been created regarding prevention of infection in NMS patients. Preoperative nutritional optimization and postoperative nutritional supplementation seem to help with lowering the infection rate in these patients. CONCLUSIONS: There have been major advances in the management of NMS patients, but many challenges remain. Further multicenter studies and randomized clinical trials are needed, particularly in the areas of infection prophylaxis, nutritional optimization, improvement in intraoperative neural monitoring, and prevention of proximal junctional kyphosis. LEVEL OF EVIDENCE: Level 4-literature review.

What does end stage in neuromuscular diseases mean? Key approach-based transitions.

PURPOSE OF REVIEW: To revise the definition of end stage in the setting of neuromuscular disease (NMD), to understand the implications for the patient, family and healthcare team, and to address the obstacles involved in the lack of definition. RECENT FINDINGS: Unlike several conditions such as cancer, kidney or liver disease, the literature reveals no clear definition or categorization for NMD. Many articles mention end stage without defining it. Many years ago an expert consensus panel defined it based on functional criteria (forced vital capacity values and hypercapnic events). Only for amyotrophic lateral sclerosis/motoneurone disease has a wider criteria been proposed. As a consequence, the management of this heterogeneous group of disorders is often fragmented compared with the well organized palliative care program for cancer patients. SUMMARY: Better end-stage NMD definitions should help to identify the goals of care, but a broad range in time and intensity of deterioration make a valid definition difficult for end-stage NMD. Respiratory care, life-prolonging therapies, and structured care planning should be seen as complementary rather than dichotomous. This article emphasized the relevance of an integrated approach through the whole trajectories of NMD patients considering key transitions.

Early stages of building a rare disease registry, methods and 2010 data from the Belgian Neuromuscular Disease Registry (BNMDR).

The Belgian Neuromuscular Disease Registry, commissioned in 2008, aims to collect data to improve knowledge on neuromuscular diseases and enhance quality health services for neuromuscular disease patients. This paper presents a clear outline of the strategy to launch a global national registry. All patients diagnosed with one of the predefined 62 neuromuscular disease groups and living in Belgium may be included in the yearly updated Registry. Basic core data is harvested through a newly designed web application by the six accredited neuromuscular reference centres. In 2010, 3,424 patients with a neuromuscular disorder were registered. The most prevalent disease group in the Registry is Hereditary Motor and Sensory Neuropathy, as similarly stated by other studies, albeit the prevalence in Belgium is five times lower: 6.5 per 100,000 in the north of Belgium, versus 17.0-41.0 per 100,000 in other areas of Europe. Very few patients were captured in the south of the country. With the aim to collect valuable epidemiological data, the registry targets to gather high quality data, that the sample to be representative of the population and that it be complete. The past 5 years of building the registry have improved its quality, albeit the consistent gap in data from the south of the country prevails, influencing the estimated prevalence of these diseases. To this day, the true burden of neuromuscular diseases in Belgium is not known but actions have been undertaken to address these issues.

Decreased variability of the 6-minute walk test by heart rate correction in patients with neuromuscular disease.

OBJECTIVE: The 6-minute walk test is widely used to assess functional status in neurological disorders. However, the test is subject to great inter-test variability due to fluctuating motivation, fatigue and learning effects. We investigated whether inter-test variability of the 6MWT can be reduced by heart rate correction. METHODS: Sixteen patients with neuromuscular diseases, including Facioscapulohumeral muscular dystrophy, Limb-girdle muscular dystrophy, Charcot-Marie-Tooths, Dystrophia Myotonica and Congenital Myopathy and 12 healthy subjects were studied. Patients were excluded if they had cardiac arrhythmias, if they received drug treatment for hypertension or any other medical conditions that could interfere with the interpretation of the heart rate and walking capability. All completed three 6-minute walk tests on three different test-days. Heart rate was measured continuously. RESULTS: Successive standard 6-minute walk tests showed considerable learning effects between Tests 1 and 2 (4.9%; P = 0.026), and Tests 2 and 3 (4.5%; P = 0.020) in patients. The same was seen in controls between Tests 1 and 2 (8.1%; P = 0.039)). Heart rate correction abolished this learning effect. CONCLUSION: A modified 6-minute walk test, by correcting walking distance with average heart rate during walking, decreases the variability among repeated 6-minute walk tests, and should be considered as an alternative outcome measure to the standard 6-minute walk test in future clinical follow-up and treatment trials.

[Neuromuscular disease: respiratory clinical assessment and follow-up]. / Enfermedad neuromuscular: evaluación clínica y seguimiento desde el punto de vista neumológico.

Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper.

Clustering gene expression regulators: new approach to disease subtyping.

One of the main challenges in modern medicine is to stratify different patient groups in terms of underlying disease molecular mechanisms as to develop more personalized approach to therapy. Here we propose novel method for disease subtyping based on analysis of activated expression regulators on a sample-by-sample basis. Our approach relies on Sub-Network Enrichment Analysis algorithm (SNEA) which identifies gene subnetworks with significant concordant changes in expression between two conditions. Subnetwork consists of central regulator and downstream genes connected by relations extracted from global literature-extracted regulation database. Regulators found in each patient separately are clustered together and assigned activity scores which are used for final patients grouping. We show that our approach performs well compared to other related methods and at the same time provides researchers with complementary level of understanding of pathway-level biology behind a disease by identification of significant expression regulators. We have observed the reasonable grouping of neuromuscular disorders (triggered by structural damage vs triggered by unknown mechanisms), that was not revealed using standard expression profile clustering. For another experiment we were able to suggest the clusters of regulators, responsible for colorectal carcinoma vs adenoma discrimination and identify frequently genetically changed regulators that could be of specific importance for the individual characteristics of cancer development. Proposed approach can be regarded as biologically meaningful feature selection, reducing tens of thousands of genes down to dozens of clusters of regulators. Obtained clusters of regulators make possible to generate valuable biological hypotheses about molecular mechanisms related to a clinical outcome for individual patient.