Individual, seizure-related, and psychosocial predictors of depressive symptoms among people with epilepsy over six months.

Depression is the most frequently diagnosed psychiatric disorder among people with epilepsy. A variety of risk factors for depression among people with epilepsy have been identified; however, few studies have examined these risk factors over time. The primary purpose of this study was to explore the relationship between demographic characteristics, seizure-related factors, and psychosocial factors and depressive symptoms over 6 months. Three hundred and nineteen adults with epilepsy completed three surveys at 3-month intervals. Multiple linear regression was used with the baseline variables to predict depressive symptoms at baseline, 3 months, and 6 months. Employment status, social support, and stigma emerged as predictors of depressive symptoms at all three time points. Other factors that predicted depression symptoms in one or two time points were self-management, financial strain, and activity restriction due to seizures. The results indicate that multiple factors influence depressive symptoms among people with epilepsy.

A telephone-based self-management program for people with epilepsy.

The study was conducted to test the feasibility of a telephone-based self-management program for adults with epilepsy. The program was based on social cognitive theory and principles of motivational interviewing (MI). Twenty-two adults with epilepsy were recruited from hospital-based epilepsy clinics. The mean age of participants was 43 years, and 68% were men. Participants were randomly assigned to the intervention or control group. Those in the intervention group received a five-session intervention with a nurse trained in MI counseling. Following an in-person introductory session, the remaining four sessions were conducted by phone. Ninety-five percent of the 55 planned MI sessions and the 44 planned courtesy calls for those in the control group were completed, demonstrating high acceptance of the program. Participants were very satisfied with the program and noted the benefits of the telephone delivery method. Analysis of outcomes provided support for continued development and testing of the program.

Evaluation of WebEase: an epilepsy self-management Web site.

People with epilepsy have various education needs and must adopt many self-management behaviors in order to control their condition. This study evaluates WebEase, an Internet-based, theory-driven, self-management program for adults with epilepsy. Thirty-five participants took part in a 6-week pilot implementation of WebEase. The main components of WebEase are My Log, a behavioral journal, and the Medication, Stress and Sleep Modules, which provide tailored information and feedback designed to prompt participants to assess their status with self-management behaviors, think about their behaviors and make a goal. In this article, we discuss the results of the feasibility, acceptability and usability assessments and the behavioral outcomes. The process results indicate that theoretical components that served as the program framework were successfully integrated into the program and that participants viewed WebEase as relevant, acceptable and easy to use. Additionally, participants showed some improvement in epilepsy self-management, adherence, sleep quality, self-efficacy and social support following the program. The initial results are encouraging and continued development of WebEase has the potential to facilitate education and self-management strategies among people with epilepsy.

WebEase: development of a Web-based epilepsy self-management intervention.

People with epilepsy must adopt many self-management behaviors, especially regarding medication adherence, stress management, and sleep quality. In response to the need for theory-based self-management programs that people with epilepsy can easily access, the WebEase Web site was created and tested for feasibility, acceptability, and usability. This article discusses the theoretical background and developmental phases of WebEase and lessons learned throughout the development process. The WebEase research team developed content for the Web site on the basis of social cognitive theory, the transtheoretical model of behavior change, and motivational interviewing. Formative research and development of the WebEase program included a literature search, computer use survey, a focus group, and review by content experts and consumers. The program has 2 main components: 1) the modules, which provide a tailored opportunity for learning, reflection, and goal setting, and 2) MyLog, a place to enter daily information.

A descriptive analysis of seizure events among adults who participated in a computer-based assessment.

The purpose of this study was to document seizure events associated with the use of a computer-based assessment and to describe the contextual factors surrounding these seizure episodes. Study participants were adults with epilepsy who were enrolled at research sites in Atlanta and Boston. Subjects were asked to complete a computer-based assessment at 3 time points. Fourteen seizure events were documented; they occurred during 1.6% of all completed assessments (896) and affected 4.4% of the participants (320). The mean age of participants who experienced seizure events was 41.4 years; about 70% were female, and 70% were white. A variety of possible precipitating factors for seizure events included hunger, fatigue, stress, and medication changes. Participants indicated computer use could have triggered their seizures in 2 instances. These findings suggest use of computer-based assessments may pose minimal risks for adults with epilepsy, particularly those without a history of photosensitivity epilepsy.

Use of computers and the Internet for health information by patients with epilepsy.

The purpose of this study was to describe computer and Internet use among an online group and a clinic-based group of people with epilepsy. Greater than 95% of the online group and 60% of the clinic group have access to computers and the Internet. More than 99% of the online group and 57% of the clinic group used the Internet to find health information. A majority of people reported being likely to employ an Internet-based self-management program to control their epilepsy. About 43% reported searching for general information on epilepsy, 30% for medication, 23% for specific types of epilepsy, and 20% for treatment. This study found that people with epilepsy have access to computers and the Internet, desire epilepsy-specific information, and are receptive to online health information on how to manage their epilepsy.

Human immunodeficiency virus-encoded Tat activates glycogen synthase kinase-3beta to antagonize nuclear factor-kappaB survival pathway in neurons.

The pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated dementia is mediated by neuronal dysfunction and death, brought about by the action of soluble neurotoxic factors that are released by virally infected macrophages and microglia. Paradoxically, many candidate HIV-1 neurotoxins also possess the ability to activate nuclear factor-kappa B (NF-kappaB), which has a potent pro-survival effect in primary neurons. The present study explored this conundrum and investigated why NF-kappaB might fail to protect neurons that are exposed to candidate HIV-1 neurotoxins. Here, we evaluated the ability of virus-depleted conditioned medium produced by HIV-1-infected human macrophages (HIV-MCMs) to modulate NF-kappaB activity in neurons. We demonstrated that HIV-MCMs inhibit the normal signaling pathways that lead to NF-kappaB activation in neurons. This inhibitory effect of HIV-MCM is dependent upon the presence of HIV-1 Tat, which activates glycogen synthase kinase (GSK)-3beta in neurons. Activation of GSK-3beta, in turn, results in modification of the NF-kappaB subunit RelA at serine 468, thereby regulating the physical interaction of RelA with histone deacetylase-3 corepressor molecules. Furthermore, neutralization of Tat or inhibition of GSK-3beta activity prevents neuronal apoptosis induced by HIV-MCM. We conclude that HIV-1 Tat may compromise neuronal function and fate by interfering with normal survival pathways subserved by NF-kappaB. These findings may have important therapeutic implications for the management of HIV-1-associated dementia.

Inhibition of mixed lineage kinase 3 prevents HIV-1 Tat-mediated neurotoxicity and monocyte activation.

The HIV-1 gene products Tat and gp120 are toxic to neurons and can activate cells of myeloid origin, properties that are thought to contribute to the clinical manifestations of HIV-1-associated dementia (HAD). To investigate the intracellular signaling mechanisms involved in these events, the effect of Tat and gp120 on mixed lineage kinase (MLK) 3 activation was examined. Tat and gp120 were shown to induce autophosphorylation of MLK3 in primary rat neurons; this was abolished by the addition of an inhibitor of MLK3 (CEP1347). CEP1347 also enhanced survival of both rat and human neurons and inhibited the activation of human monocytes after exposure to Tat and gp120. Furthermore, overexpression of wild-type MLK3 led to the induction of neuronal death, whereas expression of a dominant negative MLK3 mutant protected neurons from the toxic effects of Tat. MLK3-dependent downstream signaling events were implicated in the neuroprotective and monocyte-deactivating pathways triggered by CEP1347. Thus, the inhibition of p38 MAPK and JNK protected neurons from Tat-induced apoptosis, whereas the inhibition of p38 MAPK, but not of JNK, was sufficient to prevent Tat- and gp120-mediated activation of monocytes. These results suggest that the normal function of MLK3 is compromised by HIV-1 neurotoxins (Tat, gp120), resulting in the activation of downstream signaling events that result in neuronal death and monocyte activation (with release of inflammatory cytokines). In aggregate, our data define MLK3 as a promising therapeutic target for intervention in HAD.