Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy.

Diabetic sensorimotor peripheral neuropathy (DSPN) is a serious complication of diabetes mellitus and is associated with increased mortality, lower-limb amputations and distressing painful neuropathic symptoms (painful DSPN). Our understanding of the pathophysiology of the disease has largely been derived from animal models, which have identified key potential mechanisms. However, effective therapies in preclinical models have not translated into clinical trials and we have no universally accepted disease-modifying treatments. Moreover, the condition is generally diagnosed late when irreversible nerve damage has already taken place. Innovative point-of-care devices have great potential to enable the early diagnosis of DSPN when the condition might be more amenable to treatment. The management of painful DSPN remains less than optimal; however, studies suggest that a mechanism-based approach might offer an enhanced benefit in certain pain phenotypes. The management of patients with DSPN involves the control of individualized cardiometabolic targets, a multidisciplinary approach aimed at the prevention and management of foot complications, and the timely diagnosis and management of neuropathic pain. Here, we discuss the latest advances in the mechanisms of DSPN and painful DSPN, originating both from the periphery and the central nervous system, as well as the emerging diagnostics and treatments.

Long-term survival following initiation of home non-invasive ventilation: a European study.

INTRODUCTION: Although home non-invasive ventilation (NIV) is increasingly used to manage patients with chronic ventilatory failure, there are limited data on the long-term outcome of these patients. Our aim was to report on home NIV populations and the long-term outcome from two European centres. METHODS: Cohort analysis including all patients established on home NIV from two European centres between 2008 and 2014. RESULTS: Home NIV was initiated in 1746 patients to treat chronic ventilatory failure caused by (1) obesity hypoventilation syndrome±obstructive sleep apnoea (OHS±OSA) (29.5%); (2) neuromuscular disease (NMD) (22.7%); and (3) obstructive airway diseases (OAD) (19.1%). Overall cohort median survival following NIV initiation was 6.6 years. Median survival varied by underlying aetiology of respiratory failure: rapidly progressive NMD 1.1 years, OAD 2.7 years, OHS±OSA >7 years and slowly progressive NMD >7 years. Multivariate analysis demonstrated higher mortality in patients with rapidly progressive NMD (HR 4.78, 95% CI 3.38 to 6.75), COPD (HR 2.25, 95% CI 1.64 to 3.10), age >60 years at initiation of home NIV (HR 2.41, 95% CI 1.92 to 3.02) and NIV initiation following an acute admission (HR 1.38, 95% CI 1.13 to 1.68). Factors associated with lower mortality were NIV adherence >4 hours per day (HR 0.64, 95% CI 0.51 to 0.79), OSA (HR 0.51, 95% CI 0.31 to 0.84) and female gender (HR 0.79, 95% CI 0.65 to 0.96). CONCLUSION: The mortality rate following initiation of home NIV is high but varies significantly according to underlying aetiology of respiratory failure. In patients with chronic respiratory failure, initiation of home NIV following an acute admission and low levels of NIV adherence are poor prognostic features and may be amenable to intervention.

Persistent critical illness: baseline characteristics, intensive care course, and cause of death.

OBJECTIVES: Persistent critical illness (PerCI) is associated with high mortality and discharge to institutional care. Little is known about factors involved in its progression, complications and cause of death. We aimed to identify such factors and the time when the original illness was no longer the reason for intensive care unit (ICU) stay. DESIGN: Retrospective matched case-control study using an accepted PerCI definition (> 10 days in ICU). SETTING: Single-centre tertiary metropolitan ICU. PARTICIPANTS: All adult patients admitted during a 2-year period were eligible, matched on diagnostic code, gender, age and risk of death. MAIN RESULTS: Seventy-two patients staying > 10 days (PerCI cases) were matched to 72 control patients. The original illness was no longer a cause for continued ICU stay after a median of 10 days (interquartile range [IQR], 7-16) versus 2 days (IQR, 0-3); P < 0.001. Patients with PerCI were more likely to develop new sepsis (52.8% v 23.6%; P < 0.001), delirium (37.5% v 9.7%; P < 0.001), ICU-acquired weakness (15.3% v 0%, P = 0.001), and to be discharged to chronic care or rehabilitation (37.5% v 16.7%; P < 0.005). Death resulting from sepsis with multi-organ failure occurred in 16.7% v 8.3% of control patients (P = 0.13), and one-third of patients with PerCI were not mechanically ventilated on Day 10. CONCLUSION: PerCI likely results from complications acquired after ICU admission and mostly unrelated to the original illness; by Day 10, the original illness does not appear to be its cause, and new sepsis appears an important association.

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.

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)

Neuromuscular scoliosis complication rates from 2004 to 2015: a report from the Scoliosis Research Society Morbidity and Mortality database.

OBJECTIVE Postoperative complications are one of the most significant concerns in surgeries of the spine, especially in higher-risk cases such as neuromuscular scoliosis. Neuromuscular scoliosis is a classification of multiple diseases affecting the neuromotor system or musculature of patients leading to severe degrees of spinal deformation, disability, and comorbidity, all likely contributing to higher rates of postoperative complications. The objective of this study was to evaluate deformity correction of patients with neuromuscular scoliosis over a 12-year period (2004-2015) by looking at changes in postsurgical complications and management. METHODS The authors queried the Scoliosis Research Society (SRS) Morbidity and Mortality (M&M) database for neuromuscular scoliosis cases from 2004 to 2015. The SRS M&M database is an international database with thousands of self-reported cases by fellowship-trained surgeons. The database has previously been validated, but reorganization in 2008 created less-robust data sets from 2008 to 2011. Consequently, the majority of analysis in this report was performed using cohorts that bookend the 12-year period (2004-2007 and 2012-2015). Of the 312 individual fields recorded per patient, demographic analysis was completed for age, sex, diagnosis, and preoperative curvature. Analysis of complications included infection, bleeding, mortality, respiratory, neurological deficit, and management practices. RESULTS From 2004 to 2015, a total of 29,019 cases of neuromuscular scoliosis were reported with 1385 complications, equating to a 6.3% complication rate when excluding the less-robust data from 2008 to 2011. This study shows a 3.5-fold decrease in overall complication rates from 2004 to 2015. A closer look at complications shows a significant decrease in wound infections (superficial and deep), respiratory complications, and implant-associated complications. The overall complication rate decreased by approximately 10% from 2004-2007 to 2012-2015. CONCLUSIONS This study demonstrates a substantial decrease in complication rates from 2004 to 2015 for patients with neuromuscular scoliosis undergoing spine surgery. Decreases in specific complications, such as surgical site infection, allow us to gauge our progress while observing how trends in management affect outcomes. Further study is needed to validate this report, but these results are encouraging, helping to reinforce efforts toward continual improvement in patient care.

The new neuromuscular disease related with defects in the ASC-1 complex: report of a second case confirms ASCC1 involvement.

Next-generation sequencing technology aided the identification of the underlying genetic cause in a female newborn with a severe neuromuscular disorder. The patient presented generalized hypotonia, congenital bone fractures, lack of spontaneous movements and poor respiratory effort. She died within the first days of life. Karyotyping and screening for several genes related with neuromuscular diseases all tested negative. A male sibling was subsequently born with the same clinical presentation. Whole-exome sequencing was performed with variant filtering assuming a recessive disease model. Analysis focused on genes known to be related firstly with congenital myopathies, extended to muscle diseases and finally to other neuromuscular disorders. No disease-causing variants were identified. A similar disorder was described in patients with recessive variants in two genes: TRIP4 (three families) and ASCC1 (one family), both encoding subunits of the nuclear activating signal cointegrator 1 (ASC-1) complex. Our patient was also found to have a homozygous frameshift variant (c.157dupG, p.Glu53Glyfs*19) in ASCC1 , thereby representing the second known case. This confirms ASCC1 involvement in a severe neuromuscular disease lying within the spinal muscular atrophy or primary muscle disease spectra.

Home Mechanical Ventilation: An Overview.

Prevalence studies have shown heterogeneous use of home mechanical ventilation in different conditions, with a marked increase in uptake especially in users of noninvasive ventilation. Although randomized controlled trials have examined noninvasive ventilation in acute exacerbations of chronic obstructive pulmonary disease, for weaning from invasive ventilation and for postextubation respiratory failure, the evidence base for long-term noninvasive ventilation and comparisons with invasive ventilation are less well developed. The combination of noninvasive ventilation and cough-assist devices has reduced the indications for tracheotomy ventilation in some situations (e.g., Duchenne muscular dystrophy, spinal muscular atrophy, myopathies, and amyotrophic lateral sclerosis) and has also prolonged survival. Several excellent overviews have been written on the history of home mechanical ventilation and its evolution from negative pressure to positive pressure techniques, including a systematic review of outcomes. This review, instead, will cover recent trials, trends in the field, outcomes, and safety. Because the greatest growth has been in home noninvasive ventilation, this will be the main focus of this article.

Target resequencing of neuromuscular disease-related genes using next-generation sequencing for patients with undiagnosed early-onset neuromuscular disorders.

Neuromuscular disorders are clinically and genetically heterogeneous diseases with broadly overlapping clinical features. Progress in molecular genetics has led to the identification of numerous causative genes for neuromuscular disorders, but Sanger sequencing-based diagnosis remains labor-intensive and expensive because the genes are large, the genotypes and phenotypes of neuromuscular disorders overlap and multiple genes related to a single phenotype exist. Recently, the advent of next-generation sequencing (NGS) has enabled efficient, concurrent examination of several related genes. Thus, we used NGS for target resequencing of neuromuscular disease-related genes from 42 patients in whom undiagnosed early-onset neuromuscular disorders. Causative genes were identified in 19/42 (45.2%) patients (six, congenital muscular dystrophy; two, Becker muscular dystrophy (BMD); three, limb-girdle muscular dystrophy; one, concurrent BMD and Fukuyama congenital muscular dystrophy; three, nemaline myopathy; one, centronuclear myopathy; one, congenital fiber-type disproportion; one, myosin storage myopathy; and one, congenital myasthenic syndrome). We detected variants of uncertain significance in two patients. In 6/19 patients who received a definitive diagnosis, the diagnosis did not require muscle biopsy. Thus, for patients with suspected neuromuscular disorders not identified using conventional genetic testing alone, NGS-based target resequencing has the potential to serve as a powerful tool that allows definitive diagnosis.

[Clinical Importance of Central Nervous System Dysfunction in Myopathy].

Multidisciplinary treatments including mechanical ventilation and cardioprotective therapy have improved life expectancy in many neuromuscular disorders such as Duchenne muscular dystrophy. For these patients, central nervous system disturbances such as intellectual and/or developmental disability can hinder social activities and communications. In myotonic dystrophy, the personality and/or cognitive dysfunction affects medical consultation behavior and decreases the efficacy of medical treatments. Understanding central nervous system disturbances in myopathies and providing care keeping in mind the patient burden are critical for improving prognosis and quality of life.

A comparison of invasive and noninvasive ventilation in children less than 1 year of age: A long-term follow-up study.

BACKGROUND: We report on the long-term survival of children initiated on invasive and noninvasive positive pressure ventilation (NiPPV) before the age of 1 to assess the safety and efficacy of long-term ventilation at home. METHODS: A chart review was performed of children initiated on long-term home mechanical ventilation (LTHV) before the age of 1 year, at The Hospital for Sick Children (SickKids), Canada, between January 1991 and April 2014. RESULTS: We report on 51 children. Twenty-five children (49%) received NiPPV and 26 (51%) received invasive mechanical ventilation via tracheostomy (IMV). There was one NiPPV initiation between 1991 and 2001, the rest were in subsequent years. Most children had a "musculoskeletal disorder" in the NiPPV cohort, n = 14 (56%) and a "central nervous system" disorder in the IMV cohort, n = 13 (50%). The pCO2 improved with the initiation of NiPPV, P = < 0.0001. Of the 25 subjects initiated on NiPPV, eight (32%) are currently being followed as compared to 22 (84%) in the IMV cohort. Seven (28%) of the NiPPV group were weaned off ventilation as compared to three (11.5%) in the IMV cohort. There were two NiPPV treatment failures. There were more deaths in the NiPPV cohort: eight (32%) versus two (7.6%) in the IMV cohort. Four of the deaths in the NiPPV cohort were in children in whom a palliative approach was taken. None were due to NiPPV technical failure. CONCLUSIONS: Based on this long-term follow-up study, NiPPV use in infants appears to be a viable long-term ventilation strategy.

Persistent critical illness characterised by Australian and New Zealand ICU clinicians.

OBJECTIVE: To identify the characteristics of patients with "persistent critical illness" (PerCI), as perceived by Australian and New Zealand intensive care unit clinicians. Patients with PerCI were defined as those whose reason for being in the ICU was now more related to their ongoing critical illness than their original reason for admission to the ICU. DESIGN AND PARTICIPANTS: Using a web-based survey, we recruited clinicians affiliated with the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group (CTG) who cared for adults. Clinicians included doctors, nurses, physiotherapists, dietitians, research managers and others. We used the ANZICS-CTG mailing list to email a single request for anonymous participation. RESULTS: A total of 101 eligible clinicians responded to our survey. PerCI was believed to develop after a median of 10 days (IQR, 7-14 days), and to be somewhat uncommon (occurring in 10% of all ICU patients [IQR, 5%-15%], and in 50% of all patients with a prolonged ICU length of stay [IQR, 20%-60%]). Ninety per cent of respondents thought that patients with PerCI required ongoing invasive mechanical ventilation, and the most common problems were thought to be respiratory insufficiency (68%), delirium (59%) and acquired neuromuscular disease (54%). Ten per cent of patients with PerCI were expected to be alive and well and at home 6 months after ICU discharge, with another 15% alive and at home but requiring significant help. The remainder were expected to die within 6 months or to need institutional care. CONCLUSION: Patients with PerCI appear to be an identifiable group of ICU patients, with definable characteristics, substantial stress associated with their care, and poor perceived long-term outcomes.

Neuromuscular comorbidity, heart failure, and atrial fibrillation as prognostic factors in left ventricular hypertrabeculation/noncompaction.

BACKGROUND: There is some controversy concerning the prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT). LVHT is frequently associated with neuromuscular disorders (NMDs). The aim of this study was to assess cardiac and neurological findings as predictors of mortality in patients with LVHT. PATIENTS AND METHODS: The study included patients with LVHT diagnosed between June 1995 and January 2014 in one echocardiographic laboratory. They underwent a baseline cardiologic examination and were invited for a neurological examination. Between January and February 2014, their survival status was assessed. RESULTS: LVHT was diagnosed in 220 patients (68 female, aged 52 ± 17 years) with a prevalence of 0.35 %/year. During a follow-up of 72 ± 61 months, 65 patients died. The mortality was 5 %/year. A neurological investigation was performed on 173 patients (79 %) and revealed specific NMDs in 31 (14 %), NMD of unknown etiology in 103 (47 %), and normal findings in 39 (18 %) patients. In multivariate analysis, the predictors of mortality were increased age (p = 0.0001), presence of a specific NMD (p = 0.0062) or NMD of unknown etiology (p = 0.0062), heart failure NYHA III (p = 0.0396), atrial fibrillation (p = 0.0022), and sinus tachycardia (p = 0.0395). CONCLUSIONS: LVHT patients should undergo systematic neurological examinations. Whether an optimal therapy of heart failure and atrial fibrillation will improve the prognosis of LVHT patients needs to be addressed in further studies.

Home mechanical ventilation in childhood-onset hereditary neuromuscular diseases: 13 years' experience at a single center in Korea.

INTRODUCTION: Children with hereditary neuromuscular diseases (NMDs) are at a high risk of morbidity and mortality related to respiratory failure. The use of home mechanical ventilation (HMV) has saved the lives of many children with NMD but, due to a lack of studies, dependable guidelines are not available. We drew upon our experience to compare the various underlying NMDs and to evaluate HMV with regard to respiratory morbidity, the proper indications and timing for its use, and to develop a policy to improve the quality of home noninvasive ventilation (NIV). METHODS: We retrospectively analyzed the medical records of 57 children with childhood-onset hereditary NMDs in whom HMV was initiated between January 2000 and May 2013 at Seoul National University Children's Hospital. The degree of respiratory morbidity was estimated by the frequency and duration of hospitalizations caused by respiratory distress. RESULTS: The most common NMD was spinal muscular atrophy (SMA, n = 33). Emergent mechanical ventilation was initiated in 44% of the patients before the confirmed diagnosis, and the indicators of pre-HMV respiratory morbidity (e.g., extubation trials, hypoxia, hospitalizations, and intensive care unit stay) were greater in these patients than in others. The proportion of post-HMV hospitalizations (range, 0.00-0.52; median, 0.01) was lower than that of pre-HMV hospitalizations (0.02-1.00; 0.99) (P < 0.001). Eight patients were able to maintain home NIV. The main causes of NIV failure were air leakage and a large amount of airway secretions. CONCLUSIONS: The application of HMV helped reduce respiratory morbidity in children with childhood-onset hereditary NMD. Patients with SMA type I can benefit from an early diagnosis and the timely application of HMV. The choice between invasive and noninvasive HMV should be based on the patient's age and NIV trial tolerance. Systematic follow-up guidelines provided by a multidisciplinary team are needed.

Deletion of RIC8A in neural precursor cells leads to altered neurogenesis and neonatal lethality of mouse.

RIC8A is a noncanonical guanine nucleotide exchange factor for a subset of Gα subunits. RIC8A has been reported in different model organisms to participate in the control of mitotic cell division, cell signalling, development and cell migration. Still, the function of RIC8A in the mammalian nervous system has not been sufficiently analysed yet. Adult mice express RIC8A in the brain regions involved in the regulation of memory and emotional behaviour. To elucidate the role of RIC8A in mammalian neurogenesis we have inactivated Ric8a in neural precursor cells using Cre/Lox system. As a result, the conditional knockout mice were born at expected Mendelian ratio, but died or were cannibalized by their mother within 12 h after birth. The cerebral cortex of the newborn Nes;Ric8a(CKO) mice was thinner compared to littermates and the basement membrane was discontinuous, enabling migrating neurons to invade to the marginal zone. In addition, the balance between the planar and oblique cell divisions was altered, influencing the neuron production. Taken together, RIC8A has an essential role in the development of mammalian nervous system by maintaining the integrity of pial basement membrane and modulating cell division.

Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14).

In this study, we identified and characterized an N-ethyl-N-nitrosourea (ENU) induced mutation in Usp14 (nmf375) that leads to adult-onset neurological disease. The nmf375 mutation causes aberrant splicing of Usp14 mRNA, resulting in a 95% reduction in USP14. We previously showed that loss of USP14 in ataxia (ax (J)) mice results in reduced ubiquitin levels, motor endplate disease, Purkinje cell axonal dystrophy and decreased hippocampal paired pulse facilitation (PPF) during the first 4-6 weeks of life, and early postnatal lethality by two months of age. Although the loss of USP14 is comparable between the nmf375 and ax (J) mice, the nmf375 mice did not exhibit these ax (J) developmental abnormalities. However, by 12 weeks of age the nmf375 mutants present with ubiquitin depletion and motor endplate disease, indicating a continual role for USP14-mediated regulation of ubiquitin pools and neuromuscular junction (NMJ) structure in adult mice. The observation that motor endplate disease was only seen after ubiquitin depletion suggests that the preservation of NMJ structure requires the stable maintenance of synaptic ubiquitin pools. Differences in genetic background were shown to affect ubiquitin expression and dramatically alter the phenotypes caused by USP14 deficiency.

Quantitative electrocardiographic measures, neuromuscular disorders, and survival in left ventricular hypertrabeculation/noncompaction.

BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVHT) is frequently associated with neuromuscular disorders (NMDs) and electrocardiographic (ECG) abnormalities. Quantitative ECG-measures (QEMs) are risk markers for mortality in cardiomyopathies. We measured QEMs in the ECGs in LVHT patients with and without NMDs. METHODS: Included were patients in whom (a) LVHT was diagnosed between 1995 and 2011 and (b) baseline ECG recordings were available. All underwent a clinical examination and were invited for a neurological investigation. QRS duration, QT, QTc and PR intervals were analyzed. Survival status was assessed in June 2011. RESULTS: In 141 patients (mean age 54 years, 49 females) QRS duration ranged from 40 to 200 ms, a QRS duration >120 ms was found in 19% and was associated with increased age, heart failure, left ventricular dilatation and systolic dysfunction (P < 0.001). QT intervals ranged from 240 to 600 ms. The QTc intervals ranged from 302 to 612 ms, a QTc interval >440 ms was found in 38% and was associated with left ventricular dilatation and systolic dysfunction (P < 0.001). PR intervals ranged from 90 to 360 ms, a PR interval >200 ms was found in 16% and associated with left ventricular dilatation (P < 0.01). No QEM differences were found in 86 patients with and 13 without NMD. During 59 months follow-up 45 patients died. QEMs were no mortality predictors, whereas multivariate analysis identified heart failure (P < 0.01), atrial fibrillation (P < 0.01) and diabetes mellitus (P < 0.05) as mortality predictors. CONCLUSIONS: Prolonged QRS complexes, PR and QTc intervals in LVHT are associated with heart failure and left ventricular dilatation, but not with NMD. The prognostic role of QEMs in LVHT needs further investigations in larger series.

A review of pediatric palliative care service utilization in children with a progressive neuromuscular disease who died on a palliative care program.

Recent studies and consensus statements have expressed the need to involve palliative care services in the care of children with progressive neuromuscular diseases (PMD), yet there have been no reviews of the utilization of palliative care services by children who died on a palliative care program. We conducted a retrospective chart review of all children who had a PMD who died on a single-center palliative care program. Twenty cases were identified. Services utilized by these patients included respite care, transition services, pain and symptom management, and end-of-life care. Prominent symptoms in the last 24 hours of life included respiratory distress, pain, nausea/vomiting, and anxiety; however, symptom management was very good. Utilization of services differed depending on the disease trajectory, with respite playing a critical role in the care of children with PMD. Good symptom management can be achieved.

A cohort study of children and young people with progressive neuromuscular disorders: clinical and demographic profiles and changing patterns of referral for palliative care.

BACKGROUND: Progressive neuromuscular disease in children is life limiting and these children and young people would benefit from palliative care services, but data are limited on the number and demography of these children. AIM: To describe the clinical and demographic profile of children referred to a Children's hospice in the UK with progressive neuromuscular disease. SETTING/PARTICIPANTS: All children and young people with progressive neuromuscular disorders referred to Martin House Children's Hospice between 1987 and 2010. DESIGN: Retrospective cohort study. RESULTS: 300 children with progressive neuromuscular disease were referred to the hospice. Seventy percent (210) of these children had Duchenne Muscular Dystrophy, 22% (67) had Spinal Muscular Atrophy (34 with Type I) and 8% had other neuromuscular diseases. Numbers of referrals have not significantly increased over the last 15 years, although an increasing number come from a South Asian background (from 4% to 32%) and a higher number of children have conditions other than Duchenne Muscular Dystrophy. A total of 55.3% (166) of all referrals came from areas of the highest deprivation. Survival patterns varied by diagnostic group, but ethnicity and deprivation were not associated with survival in these children. CONCLUSIONS: The profile of children with progressive neuromuscular conditions who were referred for palliative care has changed over the last 20 years, with a different spectrum of underlying diagnoses and a greater number from a South Asian background. The higher than expected proportion of children living in areas of high deprivation has been consistent over time.

Management and long-term outcome of patients with chronic neuromuscular disease admitted to the intensive care unit for acute respiratory failure: a single-center retrospective study.

BACKGROUND: Patients with chronic neuromuscular disease represent less than 10% of those receiving mechanical ventilation in the intensive care unit (ICU). Little has been reported regarding either ICU management of acute respiratory failure (ARF) in the era of noninvasive mechanical ventilation (NIV) or long-term outcomes. OBJECTIVE: To describe the respiratory management of patients with chronic neuromuscular diseases admitted to our university hospital ICU for ARF, and the long-term outcomes. METHODS: We retrospectively analyzed patients with chronic neuromuscular diseases admitted to our ICU for a first episode of ARF between January 1, 1996, and February 27, 2007. We assessed severity of illness on ICU admission, respiratory management during ICU stay, and outcomes on June 15, 2008. RESULTS: During the study period, 87 patients (44 with hereditary and 43 with acquired neuromuscular diseases) had their first ARF episode that required ICU admission. In the hereditary-diseases group and the acquired-diseases group, respectively, the rates of NIV use during the ICU stay were 82% and 63% (P = .040), the intubation rates were 30% and 56% (P = .02), and the tracheotomy rates were 9% and 12% (difference not significant). At the final assessment (median 3 years) the mortality rate was 58%, and mortality was not significantly related to the type of neuromuscular disease. At final assessment, 46% of the patients were on NIV and 29% had tracheotomy. CONCLUSIONS: In our ICU, chronic neuromuscular disease is an uncommon cause of ARF, for which we often use NIV. These patients had a low probability of death in the ICU. Long-term outcome was independent of the type of neuromuscular disease.