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.

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.

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.

Hospice provision and usage amongst young people with neuromuscular disease in the United Kingdom.

AIM: To identify the nature of services for children and young people with progressive neuromuscular disorders (NMD) provided by Children's Hospices in the UK. METHODS: A questionnaire requesting aggregate data on the number of patients with a neuromuscular condition was sent to all children's hospices in the UK, in addition, specific data was collected on services for young people with DMD presenting to a single local hospice. RESULTS: 87% of eligible hospices responded (27/31). 756 young people with an NM condition were being cared for by the hospices. These patients accounted for a mean of 17% of the total hospice population (range 5-35%). The age at which young people were required to leave the children's hospices varied from 18 up to 35 years. 73% of 'visits' were described as 'planned stays'. Although 'end of life care' is provided, few young people with NMD died in a hospice. CONCLUSIONS: Children and young people with NMD form a large proportion of the Children's Hospice's caseload. Many valued services provided by children's hospices are not available through NHS funding. The lack of similar adult based services is a concern as increasing numbers of young people are surviving into adulthood.

Neuromuscular and cardiac comorbidity determines survival in 140 patients with left ventricular hypertrabeculation/noncompaction.

BACKGROUND: The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) is controversial. We assessed cardiologic and neurologic predictors for mortality in LVHT patients and how many received implantable cardioverters/defibrillators(ICD) or cardiac resynchronization devices (CRT). METHODS AND RESULTS: Included were patients with LVHT diagnosed echocardiographically between June 1995 and May 2009. All patients underwent a baseline cardiologic examination, and were invited for a neurological investigation. During June 2009, the patients were contacted by telephone and their records were screened if they had received ICD or CRT. In 140 patients (29% females, mean age 53 ± 16, range 14-94 years) LVHT was diagnosed. The neurologic investigation, carried out in 76%, disclosed a neuromuscular disorder of definite (n = 22) or unknown (n = 68) etiology or was normal (n = 16). During a follow-up of 4.5 years the mortality was 5.7%/year. Causes of death were heart failure(n = 11), pneumonia (n = 6), sudden cardiac death (n = 3), malignancy (n = 3), pulmonary embolism(n = 2), sepsis (n = 2), stroke (n = 2), hepatic failure (n = 1) or unknown (n = 6). Sixteen patients received devices (ICD n = 4, CRT n = 3, ICD plus CRT n = 9). Predictors for mortality were increased age (p = 0.0307), neuromuscular disorder of definite or unknown etiology (p = 0.0063), exertional dyspnea (p =0.0018), edema (p = 0.0000), heart failure (p = 0.0002), ventricular ectopic beats (p = 0.0119), atrial fibrillation (p = 0.0000), low voltage (p = 0.0139), presence of one or more ECG abnormalities (p = 0.0420), left ventricular fractional shortening <25% (p = 0.0046), extension of LVHT (p = 0.0063) and LVHT affecting the lateral wall (p = 0.0110). CONCLUSION: Mortality in LVHT is high and due to cardiac and neuromuscular comorbidity, why monitoring and therapy, including device therapy, should be improved.

Recent advances in respiratory care for neuromuscular disease.

The impact of ventilatory support on the natural history of neuromuscular disease (NMD) has become clearer over the last 2 decades as techniques have been more widely applied. Noninvasive ventilation (NIV) allows some patients with nonprogressive pathology to live to nearly normal life expectancy, extends survival by many years in patients with other conditions (eg, Duchenne muscular dystrophy), and in those patients with rapidly deteriorating disease (eg, amyotrophic lateral sclerosis) survival may be increased, but symptoms can be palliated even if mortality is not reduced. A growing number of children with NMD are surviving to adulthood with the aid of ventilatory support. The combination of NIV with cough-assist techniques decreases pulmonary morbidity and hospital admissions. Trials have confirmed that NIV works in part by enhancing chemosensitivity, and in patients with many different neuromuscular conditions the most effective time to introduce NIV is when symptomatic sleep-disordered breathing develops.

Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease.

OBJECTIVES: The aim of this study was to elucidate the frequency of major clinical manifestations in children with mitochondrial disease and establish their clinical course, prognosis, and rates of survival depending on their clinical features. METHODS: We performed a retrospective review of the medical records of 400 patients who were referred for evaluation of mitochondrial disease. By use of the modified Walker criteria, only patients who were assigned a definite diagnosis were included in the study. RESULTS: A total of 113 pediatric patients with mitochondrial disease were identified. A total of 102 (90%) patients underwent a muscle biopsy as part of the diagnostic workup. A significant respiratory chain (RC) defect, according to the diagnostic criteria, was found in 71% of the patients who were evaluated. In this cohort, complex I deficiency (32%) and combined complex I, III, and IV deficiencies (26%) were the most common causes of RC defects, followed by complex IV (19%), complex III (16%), and complex II deficiencies (7%). Pathogenic mitochondrial DNA abnormalities were found in 11.5% of the patients. A substantial fraction (40%) of patients with mitochondrial disorders exhibited cardiac disease, diagnosed by Doppler echocardiography; however, the majority (60%) of patients had predominant neuromuscular manifestations. No correlation between the type of RC defect and the clinical presentation was observed. Overall, the mean age at presentation was 40 months. However, the mean age at presentation was 33 months in the cardiac group and 44 months in the noncardiac group. Twenty-six (58%) patients in the cardiac group exhibited hypertrophic cardiomyopathy, 29% had dilated cardiomyopathy, and the remainder (13%) had left ventricular noncompaction. Patients with cardiomyopathy had an 18% survival rate at 16 years of age. Patients with neuromuscular features but no cardiomyopathy had a 95% survival at the same age. CONCLUSIONS: This study gives strong support to the view that in patients with RC defects, cardiomyopathy is more common than previously thought and tends to follow a different and more severe clinical course. Although with a greater frequency than previously reported, mitochondrial DNA mutations were found in a minority of patients, emphasizing that most mitochondrial disorders of childhood follow a Mendelian pattern of inheritance.

Percutaneous endoscopic gastrostomy: results of 115 cases.

BACKGROUND/AIMS: Percutaneous endoscopic gastrostomy is one of the gastrostomy methods used for patients who are unable to take food orally. We aimed to present our results for percutaneous endoscopic gastrostomy. METHODOLOGY: One hundred and fifteen patients undergoing percutaneous endoscopic gastrostomy by pull technique were retrospectively evaluated in terms of indications, complications, durability of tube, and mortality. RESULTS: Of the 115 cases, 60 were males and 55 females with the median age of 67 (2-93) years. Indications for percutaneous endoscopic gastrostomy placement were cerebrovascular accident in 39, brain tumors in 24, subarachnoidal hemorrhage in 21, several neurologic disorders in 17, miscellaneous extracerebral tumors in 6, head injury in 5, hypoxic encephalopathy in 2, and iatrogenic in 1. The durability of the tube was a median of 242 (9-1988) days. The tube was removed in 16 patients and was changed in 11 patients with a median interval of 142.5 (35-427) and 133 (24-1251) days, respectively. Four wound infections, two buried bumper syndromes, and two aspiration pneumonias developed. Total follow-up was 114.1 patient-years with procedure-related mortality, 30-day mortality, and overall mortality of 0%, 3.5% (4/115), and 17.4% (20/115), respectively. The mortality rate was 45% for patients who had brain tumor and 11.6% for the remainder. CONCLUSIONS: Percutaneous endoscopic gastrostomy is a minimally invasive gastrostomy method with low morbidity and mortality rates, easy to follow-up, and easy to replace when clogged.

Posterior leukoencephalopathy in association with the tumour lysis syndrome in acute lymphoblastic leukaemia--a case with clinicopathological correlation.

We report a case and autopsy findings of posterior leukoencephalopathy (PL) developing during induction chemotherapy for B-cell acute lymphoblastic leukaemia (B-ALL) complicated by tumour lysis syndrome. PL may present with seizures, headache, altered mental status and occipital blindness, associated with transient parieto-occipital abnormalities on neuro-imaging studies. Precipitants include immunosuppressive agents, renal insufficiency, hypertension and fluid retention. It has also been reported in association with pre-eclamptic and eclamptic states, nephrotic syndrome and following liver and bone marrow transplantation. Only rare cases of PL developing during treatment for haematological malignancy have been reported and to our knowledge it has not been previously reported in association with tumour lysis syndrome. Since the condition is generally regarded as being fully reversible few autopsy findings have been reported.

Threats to "informed" advance directives for the severely physically challenged?

The neuromuscular diseases, such as infantile spinal muscular atrophy, Duchenne's muscular dystrophy, and amyotrophic lateral sclerosis, are widely considered to be terminal illnesses. However, as with many neuromuscular and neurologic diseases, morbidity and mortality are caused by dysfunction of inspiratory, expiratory, and bulbar musculature. This article will discuss how inspiratory and expiratory musculature can be supported by simple, noninvasive means that are rarely considered when, as with the general population, individuals with disabilities are counseled about advance directives. Failure to use noninvasive aids almost invariably results in respiratory failure, intubation, and tracheostomy or death. When noninvasive aids are available, invasive measures referred to in advance directives (eg, intubation) are often needed only temporarily. Yet, ill-informed patients are often advised to refuse intubation and die or to be intubated and left to decide whether to undergo tracheostomy for long-term ventilatory support. Further, despite severe disability, ventilator users with neuromuscular disease report normal life satisfaction. Health care professionals, on the other hand, tend to ignore the patient's life satisfaction and consider quality of life measures not designed for the disabled to justify withholding life-saving interventions. Advance directives, although sometimes appropriate for patients with irretractable pain and advanced cancer, are inappropriate for patients with severe disability because of muscle weakness, and virtually no patients are appropriately counseled about all therapeutic options.

Clinical features for prediction of survival in neonatal muscle disease.

Review of 17 newborns with muscle disease demonstrated that clinical features associated with survival beyond 1 year of age included gestational age of at least 35 weeks and requirement of mechanical ventilation for less than 21 days. In contrast, poor outcome was associated with Apgar scores below 5 at 5 min, pulmonary complications, arthrogryposis, or other congenital anomalies. The incidence of decreased fetal movements, polyhydramnios, hypotonia, and assisted delivery was not statistically different between infants who died early and those who survived beyond 1 year of age. Clinical features of newborns with muscle disease may be useful for prediction of outcome, especially when muscle biopsy abnormalities are nonspecific.

Motor neuron disease in the United States, 1971 and 1973-1978: patterns of mortality and associated conditions at the time of death.

Mortality rates for deaths "due to" and "with" motor neuron disease are presented for the first time. Age-specific mortality rates increase with age until 70 to 74 years and then decline. There appear to be no major differences by race in the age-adjusted mortality rates, but these rates are higher for males both white and nonwhite. A case-control study of all deaths with amyotrophic lateral sclerosis (ALS) was conducted for deaths due to ALS in the year 1971. Conditions associated with ALS at the time of death include pneumonia and bronchopneumonia, symptoms referable to respiratory system, superficial injury to shoulder and upper arm, essential benign hypertension, chronic skin ulcer, and malnutrition. No association was found between ALS and malignancies, Parkinson's disease, or dementia.

Motor neurone disease in the Lothian Region of Scotland 1961-81.

One hundred and sixty one patients with motor neurone disease (MND), from the Lothian Region of Scotland, were studied in an attempt to identify factors important in disease aetiology. Onset of the disease was between 1961 and 1981 and the incidence was highest between 1968 and 1975. The probability of developing MND was greatest between the ages of 65 and 69, and a greater proportion of female patients than of males had onset in the bulbar muscles. Some 5% of patients had a positive family history of MND. There was no evidence that infective agents were important in the aetiology of the disease. There was a suggestion that the patient group contained a greater number of electrical workers, food, drink and tobacco workers, and rubber workers than would have been expected. However, a larger series of patients would be needed to confirm an increased susceptibility to MND in individuals engaged in these occupations.

Geographic distribution of motor neuron disease and correlation with possible etiologic factors.

Average annual age-adjusted motor neuron disease (MND) mortality rates were mapped for the first time at the county level in the continental United States. Although the great majority of the rates did not differ significantly from the US average, the highest mortality rates were generally found west of the Mississippi and the lowest rates east of the Mississippi. MND mortality was associated with rural farming and socioeconomic status but not with urbanization, physician-population ratios, lead or mercury exposure, or mortality rates of five kinds of cancer.