Self-rated executive dysfunction in adults with epilepsy and effects of a cognitive-behavioral intervention (HOBSCOTCH).

RATIONALE: Cognitive problems are common in adults with epilepsy and significantly affect their quality of life. HOBSCOTCH (HOme Based Self-management and COgnitive Training CHanges lives) was developed to teach problem-solving and compensatory memory strategies to these individuals. This study examined whether HOBSCOTCH is associated with improvement in specific aspects of subjective executive functions. METHODS: Fifty-one adults, age 18-65, with epilepsy and subjective cognitive concerns were randomized to receive HOBSCOTCH (n = 31) or a care-as-usual control sample (n = 20). Participants completed the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A), as well as the Patient Health Questionnaire-9 (PHQ-9) to assess depression. Rates of elevated (i.e., T ≥ 65, impaired) BRIEF-A scores at baseline, as well as pre-post score changes for the BRIEF-A clinical scales were evaluated. Significance was set at α = 0.05, one-tailed, given our directional hypothesis. RESULTS: At baseline, a considerable percentage of patients in the overall sample endorsed executive dysfunction on BRIEF-A scales: Inhibit = 28%, Shift = 51%, Emotional Control = 45%, Self-Monitor = 33%, Initiate = 35%, Working Memory = 88%, Plan/Organize = 45%, Task Monitor = 47%, Organization of Materials = 28%. Significant improvement was seen in mean T-scores for Inhibit, Shift, Initiate, and Working Memory in the treatment group, but only Working Memory improved in the control group. The control group endorsed worse task monitoring and organization of materials at baseline and follow-up. Change in depression was not observed for either group, and there was no association between changes in depression and BRIEF-A scores. CONCLUSIONS: A sizeable subset of adults with epilepsy reported experiencing executive dysfunction in their everyday lives, especially for working memory. HOBSCOTCH resulted in amelioration of subjective executive functioning independent of changes in mood.

Toenail mercury Levels are associated with amyotrophic lateral sclerosis risk.

INTRODUCTION: Mercury is a neurotoxic metal that is potentially a risk factor for amyotrophic lateral sclerosis (ALS). Consumption of methylmercury contaminated fish is the primary source of US population exposure to mercury. METHODS: We used inductively coupled plasma mass spectrometry to measure levels of mercury in toenail samples from patients with ALS (n = 46) and from controls (n = 66) as a biomarker of mercury exposure. RESULTS: Patients with ALS had higher toenail mercury levels (odds ratio 2.49, 95% confidence interval 1.18-5.80, P = 0.024) compared with controls, adjusted for age and sex. We also estimated the amount of mercury consumed from finfish and shellfish and found toenail mercury levels elevated overall among patients with ALS and controls in the top quartile for consumption (P = 0.018). DISCUSSION: Biomarker data show that ALS is associated with increased with mercury levels, which were related to estimated methylmercury intake via fish. Replication of these associations in additional populations is warranted. Muscle Nerve, 2018.

Medical history of chemotherapy or immunosuppressive drug treatment and risk of amyotrophic lateral sclerosis (ALS).

A recent population-based analysis demonstrated lower risk of the lethal degenerative neuromuscular disease, amyotrophic lateral sclerosis (ALS) associated with history of the use of 'antineoplastic agents' and 'immunosuppressants'. To see if this finding was generalizable to other ALS cohorts, we examined associations between use of these agents and ALS risk in an independent case-control study of n = 414 ALS patients and n = 361 controls in an Eastern US population. Controls were sampled from the general population and among non-neurodegenerative disease patients. A history of chemotherapy treatment was significantly associated with a decreased ALS risk (OR 0.46, 95% CI 0.22-0.89, P = 0.026). We did not observe an association between risk of ALS and immunosuppressant therapy use (OR 0.78, 95% CI 0.50-1.02, P = 0.23). Analyses were adjusted for age, gender, and smoking. Our results support the prior report for chemotherapy treatment and lead to further discussion of the underlying mechanism.

Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England.

BACKGROUND: Recent data provide support for the concept that potentially modifiable exposures are responsible for sporadic amyotrophic lateral sclerosis (ALS). OBJECTIVE: To evaluate environmental and occupational exposures as risk factors for sporadic ALS. METHODS: We performed a case-control study of ALS among residents of New England, USA. The analysis compared questionnaire responses from 295 patients with a confirmed ALS diagnosis to those of 225 controls without neurodegenerative illness. RESULTS: Self-reported job- or hobby-related exposure to one or more chemicals, such as pesticides, solvents, or heavy metals, increased the risk of ALS (adjusted OR 2.51; 95% CI 1.64-3.89). Industries with a higher toxicant exposure potential (construction, manufacturing, mechanical, military, or painting) were associated with an elevated occupational risk (adjusted OR 3.95; 95% CI 2.04-8.30). We also identified increases in the risk of ALS associated with frequent participation in water sports, particularly waterskiing (adjusted OR 3.89; 95% CI 1.97-8.44). Occupation and waterskiing both retained independent statistical significance in a composite model containing age, gender, and smoking status. CONCLUSIONS: Our study contributes to a growing body of literature implicating occupational- and hobby-related toxicant exposures in ALS etiology. These epidemiologic study results also provide motivation for future evaluation of water-body-related risk factors.

A cognitive behavioral intervention (HOBSCOTCH) improves quality of life and attention in epilepsy.

OBJECTIVE: Cognitive difficulties in epilepsy are common and add to disability beyond seizures alone. A self-management intervention targeting cognitive dysfunction was developed and assessed for whether it improves quality of life, objective memory, and mood in adults with epilepsy. METHODS: The HOme Based Self-management and COgnitive Training CHanges lives (HOBSCOTCH) program was developed to incorporate (1) psychoeducation, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem solving therapy. Adults aged 18-65 years with epilepsy (n=66) were randomized into 3 groups, to receive 8 weeks of HOBSCOTCH, with (H+) or without (H) additional working memory training on a commercial gaming device, or to a waitlisted control group. The primary outcome was quality of life (Quality of Life in Epilepsy scale, QOLIE-31) with secondary outcomes of objective cognition measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and depression (as measured by PHQ9 and NDDIE). RESULTS: Both intervention arms showed a significant improvement in quality of life, as compared with controls who demonstrated a decline in QOLIE-31 scores. There was significant improvement in objective cognitive performance among the intervention groups, most notably in attention, compared with the waitlisted controls. There was no significant change in depression scores. SIGNIFICANCE: The HOBSCOTCH program significantly improved quality of life and appeared to be an effective intervention to address cognitive dysfunction in adults with epilepsy. Further studies are needed to assess the generalizability and cost-effectiveness of this intervention.

Discharge Delays for Patients Requiring In-Hospital Guardianship: A Cohort Analysis.

OBJECTIVE: To assess nonclinical factors delaying hospital discharge of guardianship patients. DATA: Utilization review data over 3 years. DESIGN: Retrospective cohort study. ANALYSIS: Mann-Whitney test was used to compare patients' medically unnecessary days (MUD) of hospitalization with additional subcategories of delays-defined as beyond clinicians' control. FINDINGS: Overall median number of MUD was 19.5; 14 of 48 patients were additionally delayed while awaiting long-term care Medicaid approval (N = 7, 50%), pending insurance (N = 3, 21%), social or transportation difficulties (N = 3, 21%), or preadmission review (N = 1, 7%). The median number of MUD for the 14 delayed patients was 63, a difference of 53 days compared with the routine guardianship cohort (P < .0001) and $5.5M in net revenue opportunity. CONCLUSIONS: Nonclinical discharge delays for guardianship patients are costly and potentially unavoidable. Further exploration into policy change is therefore recommended.

The Epidemiology of Amyotrophic Lateral Sclerosis in New Hampshire, USA, 2004-2007.

BACKGROUND/AIMS: Trends in disease incidence and mortality can provide clues to disease etiology. Previously, we described a town in New Hampshire (N.H.), USA, with 25 times the expected incidence rate of amyotrophic lateral sclerosis (ALS). This study aimed to describe the incidence and mortality of ALS across the state to assess rates relative to other states and industrialized nations. METHOD: A retrospective review of records from regional ALS centers, clinics and ALS organizations was conducted to obtain demographics and diagnostic details for patients diagnosed with ALS or primary lateral sclerosis in N.H. from January 2004 to December 2007. Data on mortality from review of death certificates were obtained for a similar time frame. RESULTS: We identified 113 N.H. residents diagnosed with ALS in 2004-2007, yielding an age-standardized incidence rate ranging from 1.3 to 2.2 per 100,000 of the population per year. During the same period, the standardized mortality rate per 100,000 varied from 2.6 to 3.5. ALS was more common among men (ratio 1.6:1), who were more likely than women to have an earlier age at onset (59 ± 14.2 vs. 65 ± 11.8 years, p = 0.01). CONCLUSION: While localized areas in N.H. with high ALS incidence rates have been reported previously, the overall incidence and mortality rates of ALS in N.H. are similar to those in other industrialized nations.

Design and feasibility of a memory intervention with focus on self-management for cognitive impairment in epilepsy.

The aim of this study was to assess the feasibility of a self-management intervention targeting cognitive dysfunction to improve quality of life and reduce memory-related disability in adults with epilepsy. The intervention incorporates (1) education on cognitive function in epilepsy, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem-solving therapy. In addition to the behavioral modification, formal working memory training was conducted by utilizing a commercially available program in a subgroup of patients. Our findings suggest that a self-management intervention targeting cognitive dysfunction was feasible for delivery to a rural population with epilepsy, with 13 of 16 enrolled participants completing the 8-session program. Qualitative data indicate high satisfaction and subjective improvement in cognitive functioning in day-to-day life. These findings provide support for further evaluation of the efficacy of this intervention through a randomized controlled trial.

Reducing severity of comorbid psychiatric symptoms in an epilepsy clinic using a colocation model: results of a pilot intervention.

RATIONALE: Patients with epilepsy (PWEs) and patients with nonepileptic seizures (PWNESs) constitute particularly vulnerable patient populations and have high rates of psychiatric comorbidities. This potentially decreases quality of life and increases health-care utilization and expenditures. However, lack of access to care or concern of stigma may preclude referral to outpatient psychiatric clinics. Furthermore, the optimal treatment for NESs includes longitudinal psychiatric management. No published literature has assessed the impact of colocated psychiatric services within outpatient epilepsy clinics. We, therefore, evaluated the colocation of psychiatric services within a level 4 epilepsy center. METHODS: From July 2013 to June 2014, we piloted an intervention to colocate a psychiatrist in the Dartmouth-Hitchcock Epilepsy Center outpatient clinic one afternoon a week (0.1 FTE) to provide medication management and time-limited structural psychotherapeutic interventions to all patients who scored greater than 15 on the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and who agreed to referral. Psychiatric symptom severity was assessed at baseline and follow-up visits using validated scales including NDDI-E, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and cognitive subscale items from Quality of Life in Epilepsy-31 (QOLIE-31) scores. RESULTS: Forty-three patients (18 males; 25 females) were referred to the clinic over a one-year interval; 27 (64.3%) were seen in follow-up with a median of 3 follow-up visits (range: 1 to 7). Thirty-seven percent of the patients had NESs exclusive of epilepsy, and 11% of the patients had dual diagnosis of epilepsy and NESs. Psychiatric symptom severity decreased in 84% of the patients, with PHQ-9 and GAD-7 scores improving significantly from baseline (4.6±0.4 SD improvement in PHQ-9 and 4.0±0.4 SD improvement in GAD-7, p-values<0.001). Cognitive subitem scores for NDDI-E and QOLIE-31 at their most recent visit were significantly improved compared with nadir scores (3.3±0.6 SD improvement in NDDI-E and 1.5±0.2 SD improvement in QOLIE-31, p-values<0.001). These results are, moreover, clinically significant-defined as improvement by 4-5 points on PHQ-9 and GAD-7 instruments-and are correlated with overall improvement as measured by NDDI-E and cognitive subscale QOLIE-31 items. CONCLUSION: A colocated psychiatrist demonstrated reduction in psychiatric symptoms of PWEs and PWNESs, improving psychiatric access and streamlining their care. Epileptologists were able to dedicate more time to managing epilepsy as opposed to psychiatric comorbidities. As integrated models of collaborative and colocated care are becoming more widespread, mental health-care providers located in outpatient neurology clinics may benefit both patients and providers.

Predictors for readmissions after video-EEG monitoring.

OBJECTIVE: Identification of variables prognosticating 30-day readmission among adult patients admitted for video-EEG (VEEG) monitoring at a major epilepsy center. METHODS: A retrospective cohort study was conducted, examining 865 consecutive admissions to the epilepsy monitoring unit (EMU) from January 2010 to June 2013. Data extracted from chart review included demographics, length of stay (LOS), seizure type(s), number of 30-day readmissions or emergency department (ED) visits and reasons for these, and patient and system/provider factors potentially contributing to the readmission. RESULTS: Of 865 elective admissions for VEEG monitoring, 49 patients accounted for 33 readmissions and 40 ED visits within 30 days of discharge for an overall 30-day encounter rate of 7.0% after excluding those lost to follow-up; 9 patients had more than one ED visit or readmission. Statistically significant risk factors for urgent 30-day encounters included a history of nonepileptic seizures (NES) (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.4), a dual diagnosis of both epilepsy and NES (OR 5.9, 95% CI 3.0-11.8), an urgent index admission to the EMU (OR 2.5, 95%CI 1.4-4.8), and a shorter LOS of index hospitalization (median 4.0 days vs 5.0 days, p < 0.01). The most common contributing patient factors included active psychiatric symptoms, medically refractory epilepsy, and living alone; the most common hospitalization-related factors included antiepileptic drug (AED) treatment adverse events or AED adjustment. CONCLUSIONS: In addition to the presence of intractable epilepsy and shorter LOS, mental health comorbidities and the presence of NES were important risk factors for 30-day readmissions and ED visits in the epilepsy population. Therefore, proactively addressing mental health comorbidities may decrease urgent health care utilization after VEEG monitoring.

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

INTRODUCTION: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Linking ß-methylamino-L-alanine exposure to sporadic amyotrophic lateral sclerosis in Annapolis, MD.

Most amyotrophic lateral sclerosis (ALS) cases occur sporadically. Some environmental triggers have been implicated, including beta-methylamino-L-alanine (BMAA), a cyanobacteria produced neurotoxin. This study aimed to identify environmental risk factors common to three sporadic ALS patients who lived in Annapolis, Maryland, USA and developed the disease within a relatively short time and within close proximity to each other. A questionnaire was used to identify potential risk factors for ALS among the cohort of patients. One common factor among the ALS patients was the frequent consumption of blue crab. Samples of blue crab from the patients' local fish market were tested for BMAA using LC-MS/MS. BMAA was identified in these Chesapeake Bay blue crabs. We conclude that the presence of BMAA in the Chesapeake Bay food web and the lifetime consumption of blue crab contaminated with BMAA may be a common risk factor for sporadic ALS in all three patients.

Aerosolization of cyanobacteria as a risk factor for amyotrophic lateral sclerosis.

Sporadic amyotrophic lateral sclerosis (sALS) is a fatal neurodegenerative disease with no known cause. There are many clues to suggest an environmental trigger for the disease, including reports of conjugal couples and co-localized employees that developed sALS. On the island of Guam,a very high incidence of sALS occurred among the Chamorro natives back in the 1940s and 1950s and has been linked to the neurotoxin beta-N-methylamino-L-alanine (BMAA) that is produced by cyanobacteria that live symbiotically in the roots of the cycad plant, the seeds from which were a staple of the Chamorro diet. It has been shown that BMAA was biomagnified up the food chain from the cycad seeds to the now largely extinct, indigenous flying foxes, a former delicacy of the Chamorro natives. Recent evidence suggests that long term, chronic exposure to low levels of BMAA might cause ALS in genetically predisposed individuals. Many exposure routes to BMAA have been implicated thus far, including consumption of contaminated food and exposure to water harboring cyanobacterial blooms which have the capability of producing BMAA. Aerosolization is a well documented means for bacterial or toxin exposure causing subsequent illness, as in the case of brevetoxins and pulmonary disease and Legionnaire's disease. We hypothesize that some cases of ALS may be related to chronic exposure to the aerosolization of cyanobacteria derived BMAA from cooling towers and might explain the observation of conjugal ALS couples.

Spatial clustering of amyotrophic lateral sclerosis and the potential role of BMAA.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative syndrome which has no known cause, except for a small proportion of cases which are genetically inherited. The development of ALS likely involves both genetic and environmental risk factors. Environmental risk factors implicated in ALS have included heavy metals, trauma, pesticides, electrical injuries, electromagnetic radiation and the cyanobacterial-derived neurotoxin beta-N-methylamino-L-alanine (BMAA). To investigate possible environmental risks, a number of epidemiological studies of ALS have been conducted. Some of these studies employ spatial analysis techniques that examine for spatial clusters of ALS and can help guide further research into identifying environmental exposures. Despite identifying geographical disparities in the distribution of ALS cases, these studies have not provided any clear associations with environmental factors. We review the literature on important studies of spatial clustering of ALS and explore the hypothesized link between the neurotoxin BMAA and ALS.

An explanation for the changes in collagen in sporadic amyotrophic lateral sclerosis.

There is evidence showing abnormalities in collagen from the skin of patients with sporadic Amyotrophic Lateral Sclerosis (sALS) both from Guam and elsewhere. The non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam, and has been implicated as a potential environmental factor in ALS and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-proteinogenic amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. We hypothesize that the abnormalities seen in sALS collagen may result from the misincorporation of BMAA and subsequent misfolding of the collagen protein.

The cyanobacteria derived toxin Beta-N-methylamino-L-alanine and amyotrophic lateral sclerosis.

There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis). The non-protein amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer's disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin.

A cluster of amyotrophic lateral sclerosis in New Hampshire: a possible role for toxic cyanobacteria blooms.

Cyanobacteria produce many neurotoxins including beta-methylamino-L-alanine (BMAA) that has been liked to amyotrophic lateral sclerosis (ALS) and neurodegenerative disease. A number of ALS cases have been diagnosed among residents of Enfield, NH, a town encompassing a lake with a history of cyanobacteria algal blooms. To investigate an association between toxic cyanobacterial blooms in New Hampshire and development of ALS, we reviewed records from our institution and other community databases to obtain demographic information on patients diagnosed with ALS within New England. We identified nine ALS patients who lived near Lake Mascoma in Enfield, NH, an incidence of sporadic ALS that is 10 to 25 times the expected incidence of 2/100,000/year. We suggest that the high incidence of ALS in this potential cluster could be directly related to chronic exposure to cyanobacterial neurotoxins such as BMAA. Possible routes of toxin exposure include inhalation of aerosolized toxins, consuming fish, or ingestion of lake water. Further investigation, including analysis of brain tissue for cyanobacterial toxins, will be helpful to test for an association between BMAA and ALS.