Angela M. Malek

Pesticide exposure as a risk factor for amyotrophic lateral sclerosis: A meta-analysis of epidemiological studies ☆: Pesticide exposure as a risk factor for ALS

BACKGROUND Exposure to pesticides and agricultural chemicals has been linked to amyotrophic lateral sclerosis (ALS) although findings have been inconsistent. A meta-analysis of studies published through May, 2011 was conducted to investigate the association of pesticide exposure and risk of ALS. METHODS Six peer-reviewed studies that met criteria were included in a meta-analysis of men involving 1,517 ALS deaths from one retrospective cohort study and 589 ALS or motor neuron disease cases from five case-control studies. A random effects model was used to calculate sex-specific pooled odds ratios (ORs). RESULTS Evidence was found for an association of exposure to pesticides and risk of ALS in male cases compared to controls (OR=1.88, 95% CI: 1.36-2.61), although the chemical or class of pesticide was not specified by the majority of studies. CONCLUSION This meta-analysis supports the relationship of exposure to pesticides and development of ALS among male cases compared to controls. The weight of evidence links pesticide exposure to ALS; however, additional prospective studies with a target exposure group are necessary to better elucidate the relationship. Future research should focus on more accurate exposure assessment and the use of job exposure matrices.

Exposure to hazardous air pollutants and the risk of amyotrophic lateral sclerosis

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a serious and rapidly fatal neurodegenerative disorder with an annual incidence of 1-2.6/100,000 persons. Few known risk factors exist although gene-environment interaction is suspected. We investigated the relationship between suspected neurotoxicant hazardous air pollutants (HAPs) exposure and ALS. METHODS A case-control study involving sporadic ALS cases (n = 51) and matched controls (n = 51) was conducted from 2008 to 2011. Geocoded residential addresses were linked to U.S. EPA NATA data (1999, 2002, and 2005) by census tract. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. RESULTS Residential exposure to aromatic solvents significantly elevated the risk of ALS among cases compared to controls in 2002 (OR = 5.03, 95% CI: 1.29, 19.53) and 1999 (OR = 4.27, 95% CI: 1.09, 16.79) following adjustment for education, smoking, and other exposure groups. Metals, pesticides, and other HAPs were not associated with ALS. CONCLUSIONS A potential relationship is suggested between residential ambient air aromatic solvent exposure and risk of ALS in this study.

Neurodevelopmental and mental health comorbidities in children and adolescents with epilepsy and migraine: a response to identified research gaps

To determine the distribution and risk characteristics of comorbid neurodevelopmental and mental health comorbidities among children and adolescents (6–18y) with epilepsy or migraine (i.e. a neurological condition with shared features and potential etiology) compared with lower extremity fracture (LEF).

The epidemiology of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults and is characterized by neurodegeneration of motor neurons in the brain and spinal cord. The incidence of ALS is approximately 1-2.6 cases per 100 000 persons annually, whereas the prevalence is approximately 6 cases per 100 000. The average age of onset of ALS is currently 58-60 years and the average survival from onset to death is 3-4 years. Between October 19, 2010 and December 31, 2011, there were an estimated 12 187 prevalent cases diagnosed with definite ALS in the USA alone. Sporadic ALS (90-95%) constitutes the large majority of cases, while the remaining 5-10% are hereditary and termed familial ALS. Sporadic ALS is suspected to involve genetic susceptibility to environmental risk factors. The purpose of this review is to present a clinical overview of ALS and provide an epidemiologic summary of personal and environmental risk factors shown to be related to the risk of disease. A discussion of the most recent research initiatives is also included.

Stroke after adult-onset epilepsy: A population-based retrospective cohort study

BACKGROUND Earlier studies indicate a higher risk of subsequent stroke in PWE aged ≥60. However, little is known of the incidence of subsequent stroke in people with epilepsy (PWE) aged 35 through 60. We determined the risk factors that increase the incidence of stroke following adult-onset epilepsy in a large statewide population over a 10-year period. METHODS South Carolina hospital discharge and emergency department (ED) data from 2000 to 2011 were used. The study was limited to persons aged ≥35years without prior stroke. Cases included patients diagnosed with epilepsy who were hospitalized or visited the ED. Controls were people with an isolated fracture of the lower extremity without any history of epilepsy or seizure disorders, presumed to approximate the health status of the general population. Epilepsy, fracture, stroke, and comorbid conditions were ascertained by diagnostic codes from health-care encounters. Only persons having stroke occurring ≥6months after the onset of epilepsy or after the first clinical encounter for controls were included. Cox proportional hazards modeling was performed to determine the risk of stroke. RESULTS There were 21,035 cases with epilepsy and 16,638 controls who met the inclusion criteria. Stroke incidence was 2.5 times higher following adult-onset epilepsy (6.3%) compared with controls (2.5%). After adjusting for comorbidities and other factors, cases with epilepsy showed a 60% higher risk of stroke (HR=1.6; 95% CI: 1.42-1.80) compared with controls. Nearly half of the strokes in cases with epilepsy occurred in those with first diagnosis between ages 35 and 55. Somatic comorbidities associated with increased risk of stroke were more prevalent in cases with epilepsy than controls yet similar in both groups with stroke. Risk of stroke increased with increasing age in both groups. However, the risk of stroke in cases with epilepsy increased faster and was similar to that in controls who were ≥10years older. CONCLUSION Adult-onset epilepsy at age 35 and older warrants consideration for occult cerebrovascular disease as an etiology of the epilepsy, which may also increase the risk of subsequent stroke. Somatic comorbidities frequently associated with epilepsy include comorbid conditions that share the same underlying pathology with stroke (i.e., hypertension, hyperlipidemia, myocardial infarction, diabetes, and arteriosclerosis). This increased risk of stroke in patients with adult-onset epilepsy should dictate the evaluation and management of stroke risk factors to prevent stroke.

Secondhand Smoke Exposure and Stroke The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

INTRODUCTION Stroke is a major public health concern worldwide given the associated morbidity and mortality. Smoking is a risk factor for stroke, but the relationship between secondhand smoke (SHS) exposure and stroke has been inconsistent to date. The aim of the current study was to examine the association of SHS exposure and risk of stroke and its subtypes (ischemic and hemorrhagic stroke) among nonsmokers. METHODS Demographic and clinical characteristics were compared by SHS exposure status for African American and white nonsmokers aged ≥45 years in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study in 2014. Hazard ratios (HRs) and corresponding 95% CIs were calculated by Cox proportional hazards models to assess the relationship between SHS exposure and stroke risk. RESULTS Of the 21,743 participants (38% African American, 45% male), SHS exposure in the past year was reported by 23%. Compared with those without SHS exposure, exposed participants were more likely to be female, white, younger, and reside with a smoker (all p<0.001). A total of 428 incident strokes were observed from April 2003 to March 2012 during a mean follow-up of 5.6 years. The risk of overall stroke was increased 30% among those with SHS exposure after adjustment for other stroke risk factors (95% CI=2%, 67%). This relationship appeared to be driven by ischemic strokes. CONCLUSIONS SHS exposure is independently associated with an increased risk of stroke. Future studies are needed to confirm these findings and examine the role of long-term effects of SHS exposure on stroke outcomes.

The National ALS Registry: A recruitment tool for research

Introduction: Subject recruitment is critical for understanding fatal diseases like ALS, however linking patients with researchers can be challenging. The U.S. population‐based National ALS Registry allows recruitment of persons with ALS (PALS) for research opportunities. Methods: The Registrys Research Notification Mechanism was used to recruit PALS aged ≥21 years; participants completed a Web‐based epidemiologic survey. PALS (n = 2,232) were sent an email describing the study, and 268 surveys were completed. Results: The mean age (± SD) of eligible participants was 57.7 ± 9.3 years for men and 61.5 ± 8.9 for women. Most were men (63%) and Caucasian (92%). Of 256 potentially eligible participants, 37.5% (n = 96) returned an authorization to disclose protected health information. ALS was confirmed for 94% (83/88) from physician responses. Conclusions: This analysis demonstrates the National ALS Registrys usefulness in recruiting PALS for research. This recruitment source can potentially foster the discovery of better treatment options and therapies, and of prevention strategies. Muscle Nerve 50: 830–834, 2014

Patient Awareness and Perception of Stroke Symptoms and the Use of 911

BACKGROUND Response to stroke symptoms and the use of 911 can vary by race/ethnicity. The quickness with which a patient responds to such symptoms has implications for the outcome and treatment. We sought to examine a sample of patients receiving a Remote Evaluation of Acute isCHemic stroke (REACH) telestroke consult in South Carolina regarding their awareness and perception of stroke symptoms related to the use of 911 and to assess possible racial/ethnic disparities. METHODS As of September 2013, 2325 REACH telestroke consults were conducted in 13 centers throughout South Carolina. Telephone surveys assessing use of 911 were administered from March 2012-January 2013 among 197 patients receiving REACH consults. Univariate and multivariate logistic regression was performed to assess factors associated with use of 911. RESULTS Most participants (73%) were Caucasian (27% were African-American) and male (54%). The mean age was 66 ± 14.3 years. Factors associated with use of 911 included National Institutes of Health Stroke Scale scores >4 (odds ratio [OR], 5.4; 95% confidence interval [CI], 2.63-11.25), unknown insurance which includes self-pay or not charged (OR, 2.90; 95% CI, 1.15-7.28), and perception of stroke-like symptoms as an emergency (OR, 4.58; 95% CI, 1.65-12.67). African-Americans were significantly more likely than Caucasians to call 911 (62% vs. 43%, P = .02). CONCLUSIONS African-Americans used 911 at a significantly higher rate. Use of 911 may be related to access to transportation, lack of insurance, or proximity to the hospital although this information was not available. Interventions are needed to improve patient arrival times to telemedicine equipped emergency departments after stroke.

Mortality following status epilepticus in persons with and without epilepsy

PURPOSE Incidence of status epilepticus (SE) ranges from 6.8 to 41.0 per 100,000 population. Although SE is associated with significant morbidity and mortality, the temporal relationship between SE, epilepsy, and mortality is less clear. The risk of all-cause mortality following SE with and without prior epilepsy was investigated. METHOD This study identified hospitalizations and emergency department visits for persons with SE and persons with epilepsy between 2000 and 2013. Excluded were those with epilepsy subsequent to SE, epilepsia partialis continua, less than 90days follow-up, and less than 2 years of data prior to first diagnosis. The cohort was grouped into: 1) SE only, 2) post-epilepsy SE (PES), and 3) epilepsy only. The risk of mortality was estimated using Cox proportional hazard models adjusting for potential confounders. RESULTS The cohort (N=82,331) consisted of 1296 SE only cases (1.6%); 2136 PES cases (2.6%); and 78,899 epilepsy only controls (95.8%) with 24.9%, 29.2% and 20.0% mortality, respectively. Compared with controls, the hazard of mortality was increased for those with SE only (hazard ratio [HR]=1.61, 95% CI=1.41-1.82) and PES (HR=1.16, 95% CI=1.07-1.25) after adjustment for demographic and clinical factors. Prior stroke, central nervous system infection, and brain tumor increased the mortality hazard. CONCLUSION There is a statistically significant increased risk of all-cause mortality with SE. The risk is stronger in those with no prior epilepsy. Specific etiologies increase mortality risk in those with SE warranting further investigation of the complex associations between these etiologies and SE.

Risk of venous thromboembolism in people with epilepsy

Risk of venous thromboembolism (VTE) among people with epilepsy (PWEs) has not been previously reported. Standard VTE prevention methods may increase the risk of complications in this population. This statewide study assessed the risk of VTE in PWEs.