Motor Neuron Disease Mortality Research Articles

Effects of COVID-19 on motor neuron disease mortality in the United States: a population-based cross-sectional study

Background In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) to be a pandemic, stating that those with underlying health conditions are most susceptible, including motor neuron disease (MND). Objective To examine the effect the COVID-19 pandemic had on deaths from MND in the United States. Methods Death certificate data for all MND deaths aged 20 years and older were analyzed from 2017 to 2019 (pre-COVID), then expanded to include 2020 and 2021 (COVID) deaths to evaluate if COVID-19 impacted MND deaths. Results The average number of MND deaths documented during the COVID-19 years was 8009, up from 7485 MND deaths pre-COVID. The age-adjusted mortality rate among the non-Hispanic population increased during COVID to 2.78 per 100,000 persons (95% CI = 2.73–2.82) from 1.81 (95% CI = 1.78–1.84). The Hispanic population also saw an increase in mortality rate during COVID (1.61, 95% CI = 1.51–1.71) compared with pre-COVID (1.10, 95% CI = 1.03–1.17). Decedent’s home as a place of death also saw a mortality rate increase during COVID (1.51, 95% CI = 1.48–1.54) compared with pre-COVID (1.30, 95% CI = 1.27–1.32). For the Hispanic population, the rate peaked at 80–84 years pre-COVID, but for the COVID years, the rate peaked earlier, at 75–79 years. Conclusion The total number of MND deaths was greater during COVID than in the preceding years. The analysis suggests there might have been a consequence of circumstances surrounding the global pandemic and the associated restrictions.

Place of Death Surrounding Motor Neuron Disease Mortality in the United States Before and During the COVID-19 Pandemic, 2018–2021 (P5-6.007)

Place of Death Surrounding Motor Neuron Disease Mortality in the United States Before and During the COVID-19 Pandemic, 2018–2021 (P5-6.007)

O029 Clinical features and outcomes of patients referred to a Respiratory Failure service

Abstract Non-invasive ventilation (NIV) improves quality of life and mortality in patients with hypercapnic respiratory failure. We reviewed the last decade of long-term home NIV provision in a single centre via an observational retrospective study. Data were prospectively collected in a database. Anthropometric and demographic data were expressed as mean±SD. Indications for chronic home NIV were categorised into: neuromuscular diseases (NMD) [including motor neuron disease (MND)]; obstructive sleep apnoea/obesity hypoventilation (OSA/OHS); pulmonary disease; and others. Linear regression analysis was performed for the annual incidence by indication, and multivariate Cox regression performed compares MND mortality with other causes. 541 new patients (Age 60.8 ±17.1 years; 273 Female; BMI 33.4±13.9 kg/m2 (n=380)) were commenced on NIV between 2012-2022. Patient numbers increased by 2.3 (0.4-4.1) per year (slope, (95% confidence intervals); p<0.02). Indications for treatment included: 52% NMD (29% MND); 19% OSA/OHS; 19% pulmonary disease; and 10 % other causes. Average referral age, BMI and gender composition were stable over the time period. There was an increase in patients with pulmonary disease commenced on NIV of 0.6 (0.7-3.5)% per year (p<0.008), other indications for treatment were unchanged. 31.4% patients died (16.8% MND). Multivariate Cox regression analysis showed that a diagnosis of MND was associated with an increased likelihood of death (HR 11.42, p<0.0001). In the last decade, there’s been a gradual increase in patient numbers treated with chronic home NIV, with an increasing percentage of patients with pulmonary disease commenced on treatment. Mortality in MND patients on NIV is higher compared with other indications.

Incidence, Prevalence, and Geographical Clustering of Motor Neuron Disease in the Netherlands.

ObjectiveTo assess time trends in motor neuron disease (MND) incidence, prevalence, and mortality and to investigate geographic clustering of MND cases in the Netherlands from 1998 to 2017, we analyzed data from the Netherlands Personal Records database, the Netherlands MND Center, and the Netherlands Patient Association of Neuromuscular Diseases.MethodsIn this prospective cohort study, Poisson regression was used to assess time trends in MND risk. We calculated age- and sex-standardized, observed, and expected cases for 1,694 areas. Bayesian smoothed risk mapping was used to investigate geographic MND risk.ResultsWe identified 7,992 MND cases, reflecting an incidence of 2.64 (95% confidence interval [CI] 2.62–2.67) per 100,000 person-years and a prevalence of 9.5 (95% CI 9.1–10.0) per 100,000 persons. Highest age-standardized prevalence and mortality rates occurred at a later age in men than in women (p < 0.001). Unadjusted mortality rates increased by 53.2% from 2.57 per 100,000 person-years in 1998 to 3.86 per 100,000 person-years in 2017. After adjustment for age and sex, an increase in MND mortality rate of 14.1% (95% CI 5.7%–23.2%, p < 0.001) remained. MND relative risk ranged from 0.78 to 1.43 between geographic areas; multiple urban and rural high-risk areas were identified.ConclusionsWe found a significant national increase in MND mortality from 1998 through 2017, explained only partly by an aging Dutch population, and a geographic variability in MND risk, suggesting a role for environmental or demographic risk factors.

Geographic Analysis of Motor Neuron Disease Mortality and Heavy Metals Released to Rivers in Spain.

The etiology of motor neuron disease (MND) is still unknown. The aims of this study were to: (1) analyze MND mortality at a fine-grained level; and (2) explore associations of MND and heavy metals released into Spanish river basins. MND deaths were extracted from the Spanish nationwide mortality registry (2007–2016). Standardized mortality ratios (SMRs) for MND were estimated at a municipal level. Sites that emitted quantities of heavy metals above the regulatory thresholds were obtained from the European Pollutant Release and Transfer Register database (2007–2015). The relative risks for non-exposed and exposed municipalities (considering a downstream 20 km river section) by type of heavy metal were analyzed using a log-linear model. SMRs were significantly higher in central and northern municipalities. SMRs were 1.14 (1.10–1.17) higher in areas exposed to heavy metals than in non-exposed areas: 0.95 (0.92–0.96). Considering the different metals, we found the following increased MND death risks in exposed areas: 20.9% higher risk for lead, 20.0% for zinc, 16.7% for arsenic, 15.7% for chromium, 15.4% for cadmium, 12.7% for copper, and 12.4% for mercury. This study provides associations between MND death risk and heavy metals in exposed municipalities. Further studies investigating heavy metal exposure are needed to progress in MND understanding.

Motor neuron disease mortality rates in New Zealand 1992–2013

Background: We determined the mortality rates of motor neuron disease (MND) in New Zealand over 22 years from 1992 to 2013. Previous studies have found an unusually high and/or increasing incidence of MND in certain regions of New Zealand; however, no studies have examined MND rates nationwide to corroborate this. Methods: Death certificate data coded G12.2 by International Classification of Diseases (ICD)-10 coding, or 335.2 by ICD-9 coding were obtained. These codes specify amyotrophic lateral sclerosis, progressive bulbar palsy, or other motor neuron diseases as the underlying cause of death. Mortality rates for MND deaths in New Zealand were age-standardized to the European Standard Population and compared with rates from international studies that also examined death certificate data and were age-standardized to the same standard population. Results and Conclusion: The age-standardized mortality from MND in New Zealand was 2.3 per 100,000 per year from 1992–2007 and 2.8 per 100,000 per year from 2008–2013. These rates were 3.3 and 4.0 per 100,000 per year, respectively, for the population 20 years and older. The increase in rate between these two time periods was likely due to changes in MND death coding from 2008. Contrary to a previous regional study of MND incidence, nationwide mortality rates did not increase steadily over this time period once aging was accounted for. However, New Zealand MND mortality rate was higher than comparable studies we examined internationally (mean 1.67 per 100,000 per year), suggesting that further analysis of MND burden in New Zealand is warranted.

Symptomatic treatments for amyotrophic lateral sclerosis/motor neuron disease.

Symptomatic treatments for amyotrophic lateral sclerosis/motor neuron disease.

Geographic distributions of motor neuron disease mortality and well water use in U.S. counties

Objective: We recently reported that U.S. mortality rates for motor neuron disease (MND) at the level of the state are associated with well water use. However, data at the state level may not accurately reflect data at the individual level. We therefore examined the association between MND mortality and well water use utilizing data from smaller geographic units that may better reflect exposure and disease at the individual level. Methods: We used data on age-adjusted MND mortality rates at the level of the county, obtained from the CDC, and corresponding data on the prevalence of well water use, obtained from the U.S. Geological Survey. Data were analyzed by multivariate linear regression and by Getis-Ord Gi*, a measure of spatial clustering. Results: Age-adjusted mortality rates for MND in 923 U.S. counties were significantly correlated with the prevalence of well water (p < 0.0001). ‘Hot spots’ of MND mortality were significantly associated with ‘hot spots’ of well water use (p < 0.0005). Conclusions: These findings support the hypothesis that an agent present in well water plays an etiologic role in ALS. Further study of water use among individuals with ALS is warranted.

Motor neuron disease mortality and lifetime petrol lead exposure: Evidence from national age-specific and state-level age-standardized death rates in Australia

BackgroundThe age standardized death rate from motor neuron disease (MND) for persons 40–84 years of age in the Australian States of New South Wales, Victoria, and Queensland increased dramatically from 1958 to 2013. Nationally, age-specific MND death rates also increased over this time period, but the rate of the rise varied considerably by age-group. The historic use of lead (Pb) additives in Australian petrol is a candidate explanation for these trends in MND mortality (International Classification of Disease (ICD)-10 G12.2). MethodsLeveraging temporal and spatial variation in petrol lead exposure risk resulting from the slow rise and rapid phase-out of lead as a constituent in gasoline in Australia, we analyze relationships between (1) national age-specific MND death rates in Australia and age-specific lifetime petrol lead exposure, (2) annual between-age dispersions in age-specific MND death rates and age-specific lifetime petrol lead exposure; and (3) state-level age-standardized MND death rates as a function of age-weighted lifetime petrol lead exposure. ResultsOther things held equal, we find that a one percent increase in lifetime petrol lead exposure increases the MND death rate by about one-third of one percent in both national age-specific and state-level age-standardized models of MND mortality. Lending support to the supposition that lead exposure is a driver of MND mortality risk, we find that the annual between-age group standard deviation in age-specific MND death rates is strongly correlated with the between-age standard deviation in age-specific lifetime petrol lead exposure. ConclusionLegacy petrol lead emissions are associated with age-specific MND death rates as well as state-level age-standardized MND death rates in Australia. Results indicate that we are approaching peak lead exposure-attributable MND mortality.

Motor neuron disease mortality rates in U.S. states are associated with well water use

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an unknown cause and invariably fatal outcome. We sought to evaluate a correlation between motor neuron disease (MND) mortality rates and residential radon levels that was previously reported for counties in the United Kingdom. We examined the relationships between age-adjusted MND mortality rates in U.S. states with residential radon levels, well water use, and other variables using structural equation modeling. We observed a significant correlation between MND mortality rates and radon levels. However, in structural equation models, radon did not have a significant, direct effect on MND mortality rates. Conversely, MND mortality rates were significantly and directly predicted by race and by the percentage of the population of each state using well water (p < 0.001 and p = 0.022). We observed similar, significant effects for well water use and MND mortality for males and females separately (p < 0.05). In conclusion, we hypothesize that the association of MND mortality rates with well water use reflects contamination of wells with Legionella, a bacterium common in well water that is known to cause neurologic disease. A Legionella hypothesis is a biologically plausible cause of ALS and suggests new avenues for etiologic research.

Evaluation of Occupational Exposure to Magnetic Fields and Motor Neuron Disease Mortality in a Population-Based Cohort

Epidemiologic evidence for the association between electromagnetic fields and amyotrophic lateral sclerosis, the most common form of motor neuron disease (MND), has been inconclusive. We evaluated the association between electromagnetic fields and MND among workers in occupations potentially exposed to magnetic fields MND mortality (ICD-9 335.2) was examined in the National Longitudinal Mortality Study using multivariable proportional hazards models. Occupational exposure to magnetic fields was determined on the basis of a population-based job-exposure matrix. Age at entry, education, race, sex, and income were considered for inclusion as covariates After adjusting for age, sex, and education, there were no increased risks of MND mortality in relation to potential magnetic field exposure, with hazard ratios around the null in all magnetic field exposure quartiles Our study does not provide evidence for an association between magnetic field exposure and MND mortality.

Changing mortality for motor neuron disease in France (1968–2007): an age-period-cohort analysis

The incidence and mortality of motor neuron disease (MND) increase with age and appear to have increased with time. The examination of period and cohort effects using age-period-cohort (APC) models can help characterize temporal trends. Our objective was to describe mortality from MND in France (1968-2007), and to examine the role of age, period of death, and birth-cohort on changes in mortality. The number of people who died from MND and population statistics (1968-2007) were extracted from French national records. Annual standardized (age/sex) mortality ratios (SMRs) were computed. Using Poisson regression, APC models examined the relationship between mortality rates and age, period of death, and birth-cohort in subjects aged 40-89 years. Deviance/degrees-of-freedom ratios evaluated model fit; ratios close to one indicated adequate fit. Between 1968 and 2007, 38,863 individuals died from MND (mortality rate = 1.74/100,000); 37,624 were aged 40-89 years. SMRs increased from 54 (95% CI = 49-59) in 1968 to 126 (120-132) in 2007. Male-to-female ratios declined from 1.80 in 1968 to 1.45 in 2007. Changing mortality rates were best explained by cohort effects (deviance/degrees-of-freedom = 1.09). The relative risk of dying from MND increased markedly for persons born between 1880 and 1920, and more slowly after 1920. In conclusion, mortality rates for MND increased between 1968 and 2007, and more rapidly in women than men. This increase was better explained by the birth-cohort of individuals than by period effects. Changing environmental exposures may be a possible explanation and these findings warrant the continued search for environmental risk factors for MND.

Increase in motor neuron disease mortality in Spain: Temporal and geographical analysis (1990–2005)

The aim of this study was to assess the trend of motor neuron disease mortality in Spain from 1990 to 2005, and to ascertain the existence of geographical differences in mortality rates. MND deaths are registered by the National Statistics Institute of Spain – International Classification of Diseases (ICD) codes ICD9 335.2 (1990-1998) and ICD10 G12.2 (1999-2005). Annual sex- and age-specific rates, as well as rates adjusted for the standard European population were obtained. Provincial standardized mortality ratios (SMRs) were calculated for the study period. Respective provincial SMRs were smoothed with data from adjacent provinces using a Poisson model. Results showed that MND mortality increased in Spain from 1990 to 2005. Geographical differences between provinces were evident throughout the study period. In general, risk of death due to MND was higher in regions lying to the north of Spain. In conclusion, the temporal and geographical variability observed might be explained by genetic factors, differences in environmental exposures and the possible influence of the type of medical care and treatment received. Mortality depends also on health service quality and diagnostic validity. All these factors may play a very important role in analysis of MND mortality in Spain, and the contribution of each of these will have to be examined in depth by ad hoc studies.

Geographic distribution of amyotrophic lateral sclerosis through motor neuron disease mortality data

Amyotrophic lateral sclerosis (ALS) is a rare and devastating neurological disorder of the adult age with a prognosis of about 2-3 years from the onset of the disease. No clear cause has been identified but it seems to be a multifactorial disease with genetic and environmental components involved. Increments of mortality rates were observed since 1980 both in Italy and in many other countries. The objective of the present study is to describe the distribution of ALS mortality in Italy in the period 1980-2001 detecting single municipalities or clusters with high mortality levels for motor neuron disease (MND). ALS represents the main part (85%) of the MND group which is globally identified by the IX ICD (International Classification of Diseases and Causes of Death) 335.2 code. Death numbers and standardized mortality ratios (SMR) for MND were calculated for all Italian municipalities through the ENEA mortality database system (data source: National Institute of Statistics-ISTAT), using national mortality rates as reference. Subsequently, in order to detect municipal clusters, spatial analysis was performed. Out of the 8,099 Italian municipalities, 132 where characterized by SMR values higher than expected. Moreover 16 clusters with significant high relative risk values (RR) were identified, 12 out of them including only a single municipality. Only 22 of the municipalities with high SMR were included in the clusters. In conclusion, the two different epidemiological methodologies demonstrated to be widely complementary in detecting the geographical distribution of the disease in terms of risk for populations. A first selection of the priority areas where analytical studies should be carried on, in order to identify risk factors associated to ALS, is tentatively suggested.

Motor neuron disease mortality in Great Britain continues to rise: Examination of mortality rates 1975 – 2004

Motor neuron disease (MND) mortality rates are rising in Europe and the USA. The most comprehensive UK study was conducted more than 15 years ago. This study examines trends in mortality from MND in England & Wales, and Scotland, between 1975 and 2004. Age, gender, and cause-specific mortality rates were calculated for the period 1975-2004 using national data from England & Wales, and Scotland. Rates were directly age-standardized to the European standard population. Trends in mortality rates over time were examined for men and women separately, as well as by the age groups 0-59 years, and 60 or more years. MND mortality rates rose steadily over the 30-year period 1975-2004 in both sexes in England & Wales, and Scotland. There is a clear upward trend in all four groups (p for trend <0.001). All increases were largely restricted to the age group 60 years and above, with rates showing increases of 70-80%, and no evidence of a flattening of this trajectory. Rates for the 0-59 years age group remained stable over the period. There is evidence of a narrowing of the male-female gap in mortality rates for the age group over 60 years in England and Wales.

Temporal and geographic variation in United States motor neuron disease mortality, 1969–1998

To describe temporal trends of motor neuron disease (MND) mortality in the United States. Variations in MND by demographic variables of sex, age, geography, and race/ethnicity were evaluated to assess the possible explanations for observed trends. Multiple-cause mortality files from the National Center for Health Statistics for the years 1969 through 1998 were searched for all United States death records with codes corresponding to MND. Age-adjusted mortality rates were calculated by sex, race/ethnicity, age, birth cohort, and place of death. Overall MND mortality rates increased from 1.25 per 100,000 to 1.82 per 100,000, representing a 46% increase during the 30-year period. Rates among women increased by 60% and continue to rise. Rates among men rose by 35% during this period but have leveled off in the most recent decade evaluated. Mortality rates among African Americans and Hispanics were approximately 50% lower than rates among non-Hispanic whites. A southeast to northwest gradient was observed when rates were grouped by 12 geographic areas. MND mortality rates per 100,000 (and 95% CI) ranged from 2.22 (1.89 to 2.55) in the Northwest to 1.57 (1.44 to 1.71) in the Southeast. Variations in motor neuron disease (MND) mortality by time, race/ethnicity, sex, and geography were consistent with the hypothesis that environmental exposures, combined with factors of genetic susceptibility, play a role in the development of MND.

Differential features of motor neuron disease mortality in Spain.

The objective of this study was to describe the temporal and spatial patterns of motor neuron disease (MND) in Spain. We studied data where MND was stated as the principal cause of death in official statistics from Spain. Time trends were analysed for age-, sex-specific and age-adjusted rates for the period 1951-1990. Age-adjusted mortality and relative risk, obtained by Poisson regression adjusting for age, were calculated for each province from deaths during the period 1975-1988. Maps were constructed using log transformed rates. Statistical significance of spatial aggregation was assessed using the Ohno et al. test. The 1951-1990 mortality rate, age- and sex-adjusted to the European population, for the population aged > or = 40 years was 1.49 per 100,000; 1.90 and 1.21 for males and females respectively. In general, mortality increased with age. Age-adjusted rates rose until 1960, dropped by 70% during the 1960s and declined slightly over the 1951-1990 period as a whole. From 1970 onwards MND mortality rose evenly, particularly in the 60-69 age group. A North-South gradient was suggested for both sexes with statistically significant clustering in the Northern coastal regions and--for males alone--in the Midwest provinces. Mortality from MND in Spain displayed a magnitude and recently rising temporal trend similar to that described in several other countries. Specific traits were: a decrease during the 1960s, which has been described for Japan only, as well as spatial heterogeneity and a predominant recent increase among the 60-69 age group. The determinants of these unusual MND mortality patterns are unknown.

Ecological correlates of motor neuron disease mortality: a hypothesis concerning an epidemiological association with radon gas and gamma exposure.

This study investigates variations in motor neuron disease (MND) mortality rates between the counties of England and Wales from 1981 to 1989, and their relationship with gamma-ray dose rates, indoor radon gas concentrations and enhanced general life expectancy. A strong correlation was confirmed between age-adjusted rates of MND mortality and life expectancy. Weaker, but statistically significant, associations were observed between indoor radon gas concentrations, terrestrial gamma radiation and marginal variations in MND mortality. Life expectancy and radon gas concentrations were positively associated with MND mortality rates whilst gamma radiation was negatively associated. The negative correlation of gamma radiation with MND mortality may be understood with reference to its negative effects on overall population life expectancy. Radon gas concentrations seemingly account for a small elevation in MND mortality, amounting to at most 4% of total deaths. Further research is required to investigate this association.

Mortality from motor neuron disease in Japan, 1950–1990: association with radioactive fallout from atmospheric weapons testing

Motor neuron disease (MND) is a progressive and invariably fatal disease affecting the nuclei of the pyramidal tract and anterior horn cells. Despite intensive research into environmental agents associated with the onset or course of the disease, there is no single factor that can be confidently linked over time with regional, national or international variations in mortality rates. However, unusual variations in MND mortality rate in Japan from 1950–1990 were found to correlate highly significantly with variations in radioactive fallout released by atmospheric weapons testing in the Pacific. This association could be explained by the ingestion of alpha-emitting radionuclides acting upon a pre-existing susceptible subpopulation, a hypothesis which is consistent with recent research on the epidemiology and pathology of MND. However, it is likely that radiation is only one of many factors that act singly or in combination to accelerate the condition in subpopulations susceptible to MND.

Motor neuron disease and multiple sclerosis among immigrants to England from the Indian subcontinent, the Caribbean, and east and west Africa.

The mortality from motor neuron disease (MND) and multiple sclerosis (MS) was studied among immigrants to England and Wales from the Indian subcontinent, the Caribbean, and East and West Africa during the 10 years 1979-88. The MND mortality among ethnic Asian males was only half and for females one fifth of that expected at English rates. MND mortality in Caribbean immigrants was somewhat lower than expected. White immigrants from the Indian subcontinent had the expected MND mortality. MS mortality was low among Asian, West Indian, and African immigrants. This study is evidence that MND mortality is not the same in all ethnic groups.