Incidence Of Amyotrophic Lateral Sclerosis Research Articles

Incidence of amyotrophic lateral sclerosis in Rhineland-Palatinate, Germany

There is a lack of prospective and population based epidemiological data on amyotrophic lateral sclerosis in Germany to date. The ALS registry Rhineland-Palatinate was established to investigate the incidence, course and phenotypic variety of ALS in this south-west German state of about 4 million inhabitants. During the period 2010–2011, consecutive incident patients with amyotrophic lateral sclerosis according to the revised El Escorial criteria were included and followed up using multiple overlapping sources of case ascertainment. One hundred and forty-six patients were enrolled. The annual crude incidence for amyotrophic lateral sclerosis in Rhineland-Palatinate was 1.8/100,000 person-years (95% CI 1.6–2.2). Male to female ratio was 1.1:1. Incidence increased with age reaching a peak in the 70–74 years age group and declined thereafter. Late-onset ALS (≥ 75 years) was found in 14.4% of patients. About 32% of patients presented with bulbar onset. In conclusion, incidence rate of amyotrophic lateral sclerosis in Rhineland-Palatinate is within the range of other prospective population based registers in Europe and North America. Gender ratio is nearly balanced.

Prevalence and Incidence of Amyotrophic Lateral Sclerosis in Japan

BackgroundPrevious studies have reported a high incidence of amyotrophic lateral sclerosis (ALS) in endemic foci in the Kii Peninsula, Japan. However, little is known about the ALS frequency in the whole country. Furthermore, the presence of ethnic variation in the incidence of ALS remains unknown.MethodsWe conducted a nationwide survey of ALS frequency in 2013 to estimate its annual prevalence and incidence. ALS was diagnosed based on the El Escorial Criteria. The study period was the 2009 fiscal year, from April 2009 to March 2010. To compare the incidence of ALS among prefectures, standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated under the assumption of Poisson distribution.ResultsThe annual crude prevalence and incidence rates per 100 000 people per year were 9.9 (95% CI 9.7–10.1) and 2.2 (95% CI 2.1–2.3), respectively. The age group with the highest prevalence as well as incidence was 70–79 years, and the male-female ratio was approximately 1.5. The annual incidence rate adjusted for age and sex using the 2000 U.S. standard population was 2.3 (95% CI 2.2–2.4) per 100 000 people. Some prefectures had significantly high SIRs: Okinawa, Nara and Wakayama in the Kii Peninsula, and Niigata for males; Kumamoto for females.ConclusionsThis is the first report on the annual prevalence and incidence of ALS in the representative population of Japan. We identified some prefectures with a high incidence of ALS. However, the incidence of ALS in the Japanese population was much lower than in the Caucasian populations of Europe and North America.

Feedback interaction of research, advocacy, and clinical care applied to ALS research in South America

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing motor neuron loss and weakness. Worldwide prevalence is 4-6/100,000. Incidence is 1.5-2.7/100,000 per year and may be increasing. Studies suggest race and ethnicity affect the prevalence and incidence of ALS.(1) Understanding the impact of these variables on disease incidence could provide important insight into ALS determinants. A major roadblock for comparison across populations is the lack of epidemiologic data about ALS from many underdeveloped regions. In these regions, ALS is often undertreated due to health care disparities. This article discusses challenges for ALS research in South America (SA) and examines the ALS scientific record to explore the interactions and synergies of research, clinical care, and patient advocacy in underdeveloped regions.

Amyotrophic lateral sclerosis: Analysis of ALS cases in a predominantly admixed population of Ecuador

Recent studies suggest amyotrophic lateral sclerosis (ALS) prevalence, incidence, and age of onset are heterogeneous across populations. These include studies from South America (SA) where lower prevalence, earlier onset, and reduced survival time of ALS are reported. However, the scarcity of epidemiological and clinical data confounds effective comparison. To investigate ALS incidence in the predominantly admixed population of Ecuador, we analyzed patient data. We analyzed case data from two major hospitals. To confirm diagnosis, we evaluated clinical and EMG examinations in a cohort of patients. For 2000–2012, we found 116 patients with ALS diagnosis in the two hospitals. Crude incidence was 0.2–0.6 per 100,000. Median age of onset was 54.3 (+ 15.06 SD). Clinical re-evaluation found misdiagnosis in three cases in the cohort. In conclusion, ALS incidence in the Ecuadorian hospital population is in accord with rates reported in recent studies for other admixed populations, and lower than that in the United States and Europe. Our study found that appropriate EMG administration and interpretation for the purposes of supporting a diagnosis of ALS with current consensus guidelines prevent adequate use of this test as an essential tool in the evaluation and diagnosis of ALS. Training for required standardization in Ecuador is recommended.

Climatic factors associated with amyotrophic lateral sclerosis: a spatial analysis from Taiwan

Few studies have assessed the spatial association of amyotrophic lateral sclerosis (ALS) incidence in the world. The aim of this study was to identify the association of climatic factors and ALS incidence in Taiwan. A total of 1,434 subjects with the primary diagnosis of ALS between years 1997 and 2008 were identified in the national health insurance research database. The diagnosis was also verified by the national health insurance programme, which had issued and providing them with "serious disabling disease (SDD) certificates". Local indicators of spatial association were employed to investigate spatial clustering of age-standardised incidence ratios in the townships of the study area. Spatial regression was utilised to reveal any association of annual average climatic factors and ALS incidence for the 12-year study period. The climatic factors included the annual average time of sunlight exposure, average temperature, maximum temperature, minimum temperature, atmospheric pressure, rainfall, relative humidity and wind speed with spatial autocorrelation controlled. Significant correlations were only found for exposure to sunlight and rainfall and it was similar in both genders. The annual average of the former was found to be negatively correlated with ALS, while the latter was positively correlated with ALS incidence. While accepting that ALS is most probably multifactorial, it was concluded that sunlight deprivation and/or rainfall are associated to some degree with ALS incidence in Taiwan.

The Non-Protein Amino Acid BMAA Is Misincorporated into Human Proteins in Place of l-Serine Causing Protein Misfolding and Aggregation

Mechanisms of protein misfolding are of increasing interest in the aetiology of neurodegenerative diseases characterized by protein aggregation and tangles including Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), Lewy Body Dementia (LBD), and Progressive Supranuclear Palsy (PSP). Some forms of neurodegenerative illness are associated with mutations in genes which control assembly of disease related proteins. For example, the mouse sticky mutation sti, which results in undetected mischarging of tRNAAla with serine resulting in the substitution of serine for alanine in proteins causes cerebellar Purkinje cell loss and ataxia in laboratory animals. Replacement of serine 422 with glutamic acid in tau increases the propensity of tau aggregation associated with neurodegeneration. However, the possibility that environmental factors can trigger abnormal folding in proteins remains relatively unexplored. We here report that a non-protein amino acid, β-N-methylamino-L-alanine (BMAA), can be misincorporated in place of l-serine into human proteins. We also report that this misincorporation can be inhibited by l-serine. Misincorporation of BMAA into human neuroproteins may shed light on putative associations between human exposure to BMAA produced by cyanobacteria and an increased incidence of ALS.

Age-Period-Cohort Analysis of Trends in Amyotrophic Lateral Sclerosis in Denmark, 1970–2009

Amyotrophic lateral sclerosis (ALS) is a disease of the motor neuron with poorly understood etiology. Recent studies have suggested that the incidence rate of ALS and the rate of death from ALS are increasing, but it is unclear whether this is due to changing exposures or improvements in diagnosis. We used age-period-cohort models to investigate trends in ALS incidence (hospitalization) from 1982 to 2009 and ALS mortality from 1970 to 2009 in Denmark. Among those 45 years of age or older, 4,265 deaths (incidence rate = 5.35 per 100,000 person-years) and 3,228 incident diagnoses (incidence rate = 5.55 per 100,000 person-years) were recorded. Age-adjusted mortality rates increased by an average of 3.0% annually between 1970 and 2009 and by an average of 2.1% annually after 1982. Age-period-cohort analyses suggested that the full age-period-cohort model provided the best fit to the mortality data (P < 0.001), although restriction to the post-1982 period suggested that the age-cohort model provided the best fit. Age-adjusted incidence rates increased by 1.6% annually after 1982 (P < 0.001), which was best explained by the age-period model, with borderline significant cohort effects (P = 0.08). A consistent finding regardless of parameterization or data subset appeared to be an increase in ALS incidence and mortality rate with later birth cohorts, up to a birth year of at least 1910.

Epidemiological Surveillance of Amyotrophic Lateral Sclerosis in Saguenay Region

The Neuromuscular Registry of Saguenay-Lac-Saint-Jean (SLSJ), Québec, Canada was established for epidemiological surveillance of neuromuscular disorders including amyotrophic lateral sclerosis (ALS). The objectives of this study are to analyze the ALS clinical characteristics of the SLSJ population and to determine the incidence rate over time by five year periods since 1985. The Registry was validated by a review of the medical records maintained at the CSSS de Chicoutimi, the regional university hospital and, by the estimation of the number of hospitalizations for ALS patients using the Quebec Hospital inpatient database (MED-ECHO). A total of 109 patients were included. Overall, the clinical features of ALS observed in SLSJ population are similar to those described in the literature. We observed a significant increase in the incidence rate of ALS during the 2005-2009 period compared with the previous periods. This is due to a significant increase in the incidence rate among the ≥65 years old group, from 4.68 per 100,000 persons/year (CI 95% 2.88-6.48) during 1985-2004 period to 12.22 (CI 95% 7.43-17.02) during 2005-2009 period. Given the small size of the SLSJ population, a longer observation period will be needed to confirm a new steady state incidence of ALS in this region.

Autoimmune disease preceding amyotrophic lateral sclerosis

To study whether the risk of amyotrophic lateral sclerosis (ALS) is increased in people with prior autoimmune disease. An all-England hospital record-linkage dataset spanning 1999-2011 was used. Cohorts were constructed of people with each of a range of autoimmune diseases; the incidence of ALS in each disease cohort was compared with the incidence of ALS in a cohort of individuals without prior admission for the autoimmune disease. There were significantly more cases than expected of ALS associated with a prior diagnosis of asthma, celiac disease, younger-onset diabetes (younger than 30 years), multiple sclerosis, myasthenia gravis, myxedema, polymyositis, Sjögren syndrome, systemic lupus erythematosus, and ulcerative colitis. Autoimmune disease associations with ALS raise the possibility of shared genetic or environmental risk factors.

Spatial analysis of amyotrophic lateral sclerosis in Northern New England, USA, 1997-2009

An environmental trigger of sporadic amyotrophic lateral sclerosis (ALS) is supported by geographic disparities in ALS incidence and development of the disease in conjugal couples. This study aims to investigate the incidence of ALS in the Northern New England states of New Hampshire (NH), Vermont (VT), and Maine (ME). We reviewed medical records and community databases to identify dwelling addresses of 688 patients diagnosed with ALS in 1997-2009 in NH, VT, and ME. We used spatial analysis to identify clusters of census block groups with statistically significant high incidence. We identified 11 clusters of statistically significant high incidence, each containing 6 or more cases of ALS. These 11 clusters are grouped in 4 distinct regions. There appear to be areas of significant spatial clustering within Northern New England. Further analysis will be needed to confirm whether there is any correlation between these areas and potential environmental risk factors.

Incidence and prevalence of amyotrophic lateral sclerosis in an HMO of Buenos Aires, Argentina

The incidence of amyotrophic lateral sclerosis (ALS) ranges from 1.7 to 2.3 per 100,000 persons worldwide. Few epidemiological studies have been published in Latin America. The aim of this study was to estimate the incidence and prevalence of ALS in an HMO (Health Maintenance Organization) of Buenos Aires, capital city of Argentina. The population studied was affiliates of the Italian Hospital Medical Care Program, whose distribution across age and gender strata is similar to the population of Buenos Aires. Cases were detected from 1 January 2003 to 31 December 2010. Incidence density (ID) and prevalence for ALS were estimated for the whole period and at 31 December 2010, respectively. During the seven-year study period, the crude ID estimated was 3.17 per 100,000 person-years (95% CI 2.24–4.48) and the age-adjusted ID for the Buenos Aires population was 2.23 per 100,000 person-years (95% CI 1.45–3.01). Point prevalence at 31 December 2010 was 8.86 per 100,000 persons (95% CI 4.05–13.68). Mean age at diagnosis was 72.29 years (SD 8.5). In conclusion, estimated age-adjusted ID and prevalence of ALS were similar to the incidence and prevalence rates found in other geographical areas.

The Incidence of Amyotrophic Lateral Sclerosis in Friuli Venezia Giulia, Italy, from 2002 to 2009: A Retrospective Population-Based Study

Background: We conducted a retrospective population-based study to estimate the incidence of amyotrophic lateral sclerosis (ALS) in Friuli Venezia Giulia, Italy, from 2001 to 2009. Methods: Multiple sources were used for case ascertainment: Health databases, archives of the neurology departments and of the regional chapter of the Italian ALS Association. The diagnosis was validated through clinical documentation review. Crude and standardized incidence rates (IRs) per 100,000 person-years were calculated. Results: We identified 262 incident ALS cases, 50.4% men, 4.2% familial. Half of the patients had spinal onset (56.8% in men) and 25.2% bulbar (29% in women). Bulbar onset had a similar frequency in women (31.7%) and men (31.5%) aged 67 or above at diagnosis. The crude IR was 2.72 (95% confidence interval, 95% CI, 2.39-3.05) and the male:female ratio 1.08. The IR peaked in the 65-74 age group, with a second increase in men 85 years and older. The IR standardized to the 2001 Italian population was 2.38 (95% CI 2.13-2.63) and to the 2000 European population 2.58 (95% CI 2.34-2.81). Conclusions: This retrospective study found IRs of ALS in the range of Italian and European prospective population-based registries, suggesting an almost complete case ascertainment.

Current pathways for epidemiological research in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. The current status of the epidemiology, challenges to its study, and novel study design options are discussed in this paper. We focus on recent results from large-scale population based prospective studies, case-control studies and population based registries, risk factors, and neuropathologic findings in chronic traumatic encephalomyelopathy. We identify areas of interest for future research, including time-trends in the incidence and prevalence of ALS; the meaning of lifetime risk; the phenotypic description of ALS; the definition of familial versus sporadic ALS, syndromic aspects of ALS; specific risk factors such as military service, life style factors such as smoking, the use of statins, and the presence of β-N-methylamino-L-alanine (BMAA), an excitotoxic amino acid derivative possibly produced by cyanobacteria found in almost every terrestrial and aquatic habitat; the emergence and disappearance of an endemic ALS in areas of the Pacific; and gene-environment interactions in the etiology of ALS. To move the epidemiology forward, we suggest using well-characterized cohorts of newly diagnosed ALS patients to identify risk and prognostic factors; storing biological material for future studies; building on the National ALS Registry as a resource of future studies; working in multidisciplinary consortia; and addressing the possible early life etiology of ALS.

Amyotrophic lateral sclerosis/motor neuron disease deaths in the United States, 1999–2009

Our objective was to examine trends and epidemiology of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) associated deaths in the United States. ALS/MND associated death rates and trends in the United States for 1999–2009 were examined using the multiple cause-of-death mortality data. Age-specific and age-adjusted death rates were calculated. For 1999–2009, the average annual age-adjusted death rate was 2.17/100,000 persons. The age-specific rate increased with age until 75–79 years. Males experienced a higher death rate than females. There was no definitive trend in the annual ALS/MND associated death rate, although analyses suggested a possible decrease (p = 0.05); however, the rate increased for persons 20–49 years of age and declined for persons ≥ 65 years of age. The annual rate for males decreased whereas the rate for females showed no change. In conclusion, the suggested decreasing annual ALS/MND associated death rate for 1999–2009 contrasts with earlier reports indicating that the incidence and death rate of ALS were increasing. While the ALS/MND associated death rate slightly increased among adults 20–49 years of age, rates declined among two subpopulations at higher risk for ALS/MND – males and persons ≥ 65 years of age. Continued monitoring of ALS/MND mortality data and additional epidemiological studies will be important to further elucidate these epidemiological trends.

Motor neuron dysfunction in a mouse model of ALS: Gender-dependent effect of P2X7 antagonism

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative progressive currently untreatable disease, characterized by selective motor neuron degeneration; the incidence and prevalence of ALS are greater in men than in women. Although some important mechanisms that might contribute to the death of motor neurons have been identified, the mechanisms underlying disease pathophysiology are still uncertain. In particular, the mechanisms underlying the role of gender in ALS and whether treatments should take into account sexual dimorphism remain only partially understood. Recently, the P2X7 receptor for ATP was reported to display neurotoxic potential in motor neuron disorders, and antagonism of the receptor has been suggested to be helpful in these disorders. Studying transgenic mice with superoxide dismutase 1 gene mutations, widely used as model for ALS, may provide a better understanding of pathogenic mechanisms and of toxicity towards motor neurons, also possibly helping to understand whether treatments for ALS should take into account sexual dimorphism.The aim of the work was (1) investigating on gender-dependence of disease progression in the standard model for ALS – the transgenic mouse bearing superoxide dismutase 1 gene mutations – and (2) assessing if a P2X7 receptor antagonist treatment should take into account sexual dimorphism.We evaluated if gender affect the disease course, the motor performance, the weight loss and the lifespan in mice overexpressing mutant superoxide dismutase 1. We measured motor impairment, motor strength and coordination by rotarod and grip strength testing. Further, we assessed if a treatment with the P2X7 receptor antagonist Brilliant Blue G – a dye that can cross the blood–brain barrier, has low toxicity, and has exhibited therapeutic effects in animal models of neurodegenerative diseases – impact on the disease progression, in male and female ALS mice.We found that (1) the onset and the disease progression, and the survival were dependent on gender: male performed worst than female, lost body weight and died before; (2) treatment with the P2X7 receptor antagonist Brilliant Blue G ameliorated the disease progression. The treatment effect was gender-dependent: amelioration was greater in male than in female.In conclusions, we suggest that not only pathogenetic mechanism of motor neuron toxicity but also the drug treatment effectiveness may depend on gender; sexual dimorphism should be considered when investigating on ALS treatment efficacy in the ALS animal model. Our findings also point on the potential relevance of P2X7 receptor antagonism for ALS treatment, and highlight the importance of adopting a sex-specific approach to searching for treatment of ALS.

Incidence of Amyotrophic Lateral Sclerosis Among American Indians and Alaska Natives

More thorough evaluation of amyotrophic lateral sclerosis (ALS) and motor neuron disease in unique populations could provide clues to etiologies for these idiopathic conditions, and educational programs for American Indian and Alaska Native (AI/AN) people and health care professionals on reservations could improve awareness, understanding, diagnosis, and treatment. In the ongoing search for susceptibility genes, studying particular racial groups, such as AI/ANs,might facilitate the identification of new mutations. To provide better understanding of ALS and secondarily of motor neuron disease among AI/AN people by estimating the incidence and prevalence among AI/ANs served by the Indian Health Service health care system. Analysis of electronic records for AI/ANs with ALS and with motor neuron disease separately for the calendar years 2002-2009 using inpatient and outpatient visit data from the Indian Health Service, which provides health care to eligible AI/ANs nationwide. Cases were defined by at least 2 inpatient or outpatient visits with the diagnosis. Crude and age-adjusted incidence and prevalence rates were calculated. Seventy-one AI/ANs were diagnosed with ALS, yielding an average annual crude incidence rate of 0.63 cases per 100 000 and an age-adjusted incidence of 0.92. The median age at onset was 56.0 years and was higher among women than men (62.0 vs 55.0 years; P=.06). Age-specific incidence increased to 70 to 74 years. The crude and age-adjusted point prevalence rates were 2.00 and 4.12, respectively. The crude and age-adjusted incidence rates for motor neuron disease were 1.08 and 1.50, respectively. The annual rates were unchanged across the study period. The incidence of ALS among AI/ANs appears to be lower than that reported for white populations, a finding congruent with reports of other minority populations. Community-based studies are important to confirm these findings and to examine reasons for the low rate of ALS among AI/ANs.

Incidence, prevalence, and medical expenditures of classical amyotrophic lateral sclerosis in Taiwan, 1999-2008.

Amyotrophic lateral sclerosis (ALS) is a rare disease, which makes the estimation of incidence and prevalence difficult in Taiwan. This study was conducted to investigate the incidence, prevalence, and medical expenditure of ALS in Taiwan. Patients who had at least one service claim either as an outpatient or inpatient between the years 2004 and 2007 and were over 15 years of age with a primary diagnosis of ALS were identified from the National Health Insurance Research Database. Additionally, ALS patients with serious disability database certificates over 15 years of age were included for the calculation of incidence and prevalence between the years 1999 and 2008. Lastly, the total medical expenditure, including ventilator use and riluzole, were reported. In 2006 and 2008, the average annual incidence and prevalence of ALS was 0.51 and 1.97 (per 10(5)), respectively, in Taiwan. The male-to-female ratio of incidence for ALS was 1.67. The average medical expenditure for ALS patients stayed steady at 16-fold greater than the general population of Taiwan in 2008. The percentage of ventilator and riluzole expenditure as a proportion of total medical expense decreased from 55% in 2000 to 33% in 2008. The incidence and average medical expenditure of ALS patients remained stable over the years in Taiwan, however, as a proportion of total medical expenses, expenditure on ventilator and riluzole decreased over the study period.

Assessing the Safety of a Replacement Chemical: Nongenomic Activity of Bisphenol S

Suspected links between bisphenol A (BPA) and adverse human health effects have spurred a search for replacement chemicals for use in common applications such as polycarbonate plastics, food can linings, and thermal papers. Bisphenol S (BPS) has been adopted for some uses. A new study now shows that low doses of BPS can disrupt nongenomic signaling pathways in cultured pituitary cells [EHP 121(3):352–358; Vinas and Watson]. Nearly 93% of U.S. residents over age 6 carry measurable amounts of BPA in their bodies. The compound is suspected to contribute to the development of diseases such as diabetes, asthma, and cancer, and animal studies have shown it adversely affects reproduction. In contrast to genomic regulation, which involves receptors in the cell nucleus, nongenomic regulation involves receptors in the cell membrane. Since BPA can interact with cell-membrane estrogen receptors, researchers explored whether structurally similar BPS might likewise influence nongenomic pathways. Treatments included various low doses of BPS alone and paired with estradiol, an endogenous estrogen. Measured responses included activation of ERK and JNK, mitogen-activated protein kinases involved in cell growth, proliferation, and apoptosis (programmed cell death); activation of caspases 8 and 9, enzymes that also are involved in apoptosis; and release of prolactin, a hormone that helps regulate hundreds of biological functions, including metabolism, reproduction, and lactation. BPS has been adopted as a replacement for BPA in applications such as thermal receipt paper. BPS appeared to interact predominantly with the cell-membrane estrogen receptor ER〈. Estradiol and BPS each increased cell proliferation, but following exposure to both compounds there were fewer cells than in control cultures. This can result from decreased proliferation or increased cell death, which is why the investigators also looked at caspase 8 and caspase 9. The former was activated by BPS alone and when combined with estradiol, but caspase 9 was less affected, consistent with an increase in apoptosis. The lowest concentrations of BPS triggered the strongest ERK response; however, ERK activation was not as strong in the presence of both compounds. BPS alone did not activate JNK, but in combination with estradiol it increased JNK activation more than the estrogen alone. The quality and timing of ERK and JNK responses to activation by estradiol were often altered by BPS. By itself, BPS did not affect prolactin secretion, but it significantly suppressed estradiol-induced secretion at most concentrations. Based on these results, low concentrations of BPS appear to affect nongenomic signaling in estrogen-responsive cells, with potential consequences for cell function. The results emphasize the need to screen compounds for estrogenic activity prior to their use in manufacturing.

Validation of the analytical procedure for the determination of the neurotoxin β-N-methylamino-l-alanine in complex environmental samples

The neurotoxic l-2-amino-3-methylaminopropionic acid (BMAA) was hypothesized to be involved in sporadic cases of amyotrophic lateral sclerosis (ALS). Studies highlighting a possible implication of environmental factors in the incidence of sporadic ALS have become more numerous over recent years. Over the past years, the most widely used method for quantifying BMAA was based on the derivatization of this polar and basic molecule with a fluorescent compound (6-aminoquinolonyl-N-hydroxysuccinimidyl, 6-AQC). This derivatization allows the retention of the conjugate by reversed-phase liquid chromatography and its detection by fluorescence. Nevertheless, recent findings have shown that this method applied to complex samples may cause false positive responses. We therefore developed an analytical procedure for the determination of underivatized BMAA at trace level in complex environmental matrices (river water, cyanobacteria and biofilm) using solid-phase extraction (SPE) based on mixed mode sorbent to concentrate and clean up real samples. Analyzes were performed by hydrophilic interaction chromatography (HILIC) coupled to electrospray ionization and tandem mass spectrometry used in multiple reaction monitoring scan mode. Analytical procedures were validated for the different natural samples using the total error approach. BMAA can be quantified by these reliable and highly selective analytical methods in a range of only a few ngmL−1 in river water and a few ngmg−1 dry weight in cyanobacteria and biofilm matrices.

Environmental Characteristics and Oxidative Stress of Inhabitants and Patients with Amyotrophic Lateral Sclerosis in a High-incidence Area on the Kii Peninsula, Japan

Although Oshima, in the Kii Peninsula of Japan, is located within a high incidence area of amyotrophic lateral sclerosis (ALS) (Koza/Kozagawa/Kushimoto area, K area), no patients with ALS were detected between 1960 and 1999. However, the incidence recently increased between 2000 and 2009. On Oshima, the source of drinking water was changed from a regional river/wells to the Kozagawa River in the K area in 1975. We speculate that this change in water source may have played a role in the recent increase in the incidence of ALS. The aim of this study is to find contributing factors that may have triggered the locally high incidence of ALS. We investigated a possible association between the mineral content of drinking water and serum and oxidative stress markers among patients with ALS in the K area (K-ALS), residents of Oshima and controls. We found that the levels of Ca and Zn in the recent drinking water in Oshima are low and that the serum levels of Ca and Zn in the Oshima residents and patients with K-ALS were significantly lower, while the oxidative stress markers were significantly higher, than those of the controls. The serum Zn and urinary 8-OHdG/creatinine levels explained 60% and 58% of the variations among the three groups, respectively. The serum Zn levels were negatively correlated with the serum Cu levels in the patients with K-ALS, and the serum Cu levels exhibited a tendency to be positively correlated with the 8-OHdG/creatinine levels in both the patients with K-ALS (r: 0.64) and the residents free from K-ALS (r: 0.32, p<0.01). Taken together, we suggest that the low levels of Ca and Zn in the drinking water are possibly associated with an imbalance of metal metabolism in Oshima residents and an increase in oxidative stress markers in patients with K-ALS, although the causative relationship is not clear. This is a cross-sectional study, and a prospective study is needed in the future.