Temporal lobe white matter asymmetry and language laterality in epilepsy patients.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca's area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.

Familial component of epilepsy in cleft lip and palate

It is well recognized that offspring of women with epilepsy who are taking anticonvulsant medications have an increased incidence of clefting abnormalities. This increase has been attributed to the teratogenic effects of anticonvulsant medications but an alternative explanation involving a genetic association of epilepsy and clefting has also been proposed. Five family studies attempting to resolve this controversy have been inconclusive either because of study design or analytic limitations. This family study was designed to determine whether epilepsy aggregates in families ascertained by an individual with a clefting disorder. The Mayo Clinic medical linkage registry was used to identify individuals with cleft lip with or without cleft palate and cleft palate in southeast Minnesota from 1935-1986. Only those cases who were 15 years or younger during this period were included in the study. The proband's parents and descendants of their parents, including the proband's sibs, children, grandchildren, niece/nephews, grandnieces/nephews, halfsibs and spouses were also identified and all of their medical records were reviewed for seizure disorders. The standardized morbidity ratios for epilepsy of 0.9 (95% CI 0.2-2.6) observed for first degree relatives (excluding parents) and 0.0 for second degree relatives were not increased. The SMRs ranged from 0.7-2.2 for the individual relative types (parents 1.5, sibs 0.7, children 2.2, probands 1.1, spouses 2.0) and were also not increased. These results do not support the suggestions of some that clefting and epilepsy aggregate together in families. ^

GROWTH PATTERNS OF CHILDREN OF MOTHERS WITH EPILEPSY

The extent to which antiepileptic drugs (AED) in utero exposure are related to prenatal and postnatal growth is investigated in an retrospective, cohort study of children of AED treated mothers with epilepsy (N = 89) and children of women without epilepsy (N = 89). The study groups were obtained from a population based health care facility.^ Major finding was that birth head circumference of AED exposed children are significantly smaller than control children, notably male children. Other findings include birth length and weight of exposed children was slightly but not significantly smaller. Postnatal growth as measured by two velocity terms, rate of growth, and deceleration, was not significantly different between exposed and control children for height, weight, and head circumference, indicating no catch up growth. Morphologic defects, neonatal and infant mortality was more frequent in exposed children. Mothers with epilepsy reported significantly fewer spontaneous abortions. ^

Community health workers: The critical link to sustainable, healthy societies in low-resource settings---A model for the Baylor Shoulder to Shoulder Foundation

Community health workers (CHWs) can serve as a bridge between healthcare providers and communities to positively impact social determinants of health and, thus, the overall health of the population. The potential to effect lasting change is particularly significant within resource-poor settings with limited access to formally trained health care providers such as the small, rural village of Santa Ana Intibucá, Honduras and surrounding areas—located on the geographically and politically isolated border of Honduras and El Salvador. The Baylor Shoulder to Shoulder Foundation (BSTS) works in conjunction with Santa Ana's volunteer health committee to bring a health brigade that has provided health care and public health projects to the area at least twice a year since 2001. They have also hired a full-time Honduran physician, a Honduran in-country administrative director, and built a clinic; yet, no community health worker program exists. This CHW program model is the response to a clear need for a CHW program within the area served by BSTS and presents a CHW program model specific to Santa Ana Intibucá and surrounding areas to be implemented by BSTS. Methods used to develop this model include reviewing the literature for recommendations from leading authorities as well as successfully implemented CHW programs in comparable regions. This information was incorporated into existing knowledge and materials currently being used in the area. Using the CHW model proposed here, each brigade, in conjunction with the communities served, can help develop new modules to respond to the specific health priorities of the region at that time, incorporating consistent modes of contact with the local physician and the CHWs to provide refresher courses, training in new topics of interest, and to be reminded of the importance of community health workers' role as the critical link to healthy societies. With cooperation, effort, and support, the brigade can continue to help integrate a sustainable CHW system in which communities may be able to maximize the care they receive while also learning to care for their own health and the future of their communities.^

Biomedical informatics applications for epilepsy management: A systematic review

Epilepsy is a very complex disease which can have a variety of etiologies, co-morbidities, and a long list of psychosocial factors4. Clinical management of epilepsy patients typically includes serological tests, EEG's, and imaging studies to determine the single best antiepileptic drug (AED). Self-management is a vital component of achieving optimal health when living with a chronic disease. For patients with epilepsy self-management includes any necessary actions to control seizures and cope with any subsequent effects of the condition9; including aspects of treatment, seizure, and lifestyle. The use of computer-based applications can allow for more effective use of clinic visits and ultimately enhance the patient-provider relationship through focused discussion of determinants affecting self-management. ^ The purpose of this study is to conduct a systematic literature review on informatics application in epilepsy self-management in an effort to describe current evidence for informatics applications and decision support as an adjunct to successful clinical management of epilepsy. Each publication was analyzed for the type of study design utilized. ^ A total of 68 publications were included and categorized by the study design used, development stage, and clinical domain. Descriptive study designs comprised of three-fourths of the publications and indicate an underwhelming use of prospective studies. The vast majority of prospective studies also focused on clinician use to increase knowledge in treating patients with epilepsy. ^ Due to the chronic nature of epilepsy and the difficulty that both clinicians and patients can experience in managing epilepsy, more prospective studies are needed to evaluate applications that can effectively increase management activities. Within the last two decades of epilepsy research, management studies have employed the use of biomedical informatics applications. While the use of computer applications to manage epilepsy has increased, more progress is needed.^

Relationships among epilepsy self-management, health outcomes, and socioeconomic status

The purpose of this study was to investigate the association between epilepsy self-management and disease control and socio-economic status. Study participants were adult patients at two epilepsy specialty clinics in Houston, Texas that serve demographically and socioeconomically diverse populations. Self-management behaviors- medication, information, safety, seizure, and lifestyle management were tested against emergency room visits, hospitalizations, and seizure occurrence. Overall self-management score was associated with a greater likelihood of hospitalizations over a prior twelve month time frame, but not for three months, and was not associated with seizure occurrence or emergency room visits, at all. Scores on specific self-management behaviors varied in their relationships to the different disease control indicators, over time. Contrary to expectations based on the findings of previous research, higher information management scores were associated with greater likelihood of emergency room visits and hospitalizations, over the study's twelve months. Higher lifestyle management scores were associated with lower likelihood of any emergency room visits, over the preceding twelve months and emergency room visits for the last three months. The positive associations between overall self-management scores and information management behaviors and disease control are contrary to published research. These findings may indicate that those with worse disease control in a prior period employ stronger self-management efforts to better control their epilepsy. Further research is needed to investigate this hypothesis.^

Neocortical hyperexcitability defect in a mutant mouse model of spike-wave epilepsy, {\it stargazer}

Single-locus mutations in mice can express epileptic phenotypes and provide critical insights into the naturally occurring defects that alter excitability and mediate synchronization in the central nervous system (CNS). One such recessive mutation (on chromosome (Chr) 15), stargazer(stg/stg) expresses frequent bilateral 6-7 cycles per second (c/sec) spike-wave seizures associated with behavioral arrest, and provides a valuable opportunity to examine the inherited lesion associated with spike-wave synchronization.^ The existence of distinct and heterogeneous defects mediating spike-wave discharge (SWD) generation has been demonstrated by the presence of multiple genetic loci expressing generalized spike-wave activity and the differential effects of pharmacological agents on SWDs in different spike-wave epilepsy models. Attempts at understanding the different basic mechanisms underlying spike-wave synchronization have focused on $\gamma$-aminobutyric acid (GABA) receptor-, low threshold T-type Ca$\sp{2+}$ channel-, and N-methyl-D-aspartate receptor (NMDA-R)-mediated transmission. It is believed that defects in these modes of transmission can mediate the conversion of normal oscillations in a trisynaptic circuit, which includes the neocortex, reticular nucleus and thalamus, into spike-wave activity. However, the underlying lesions involved in spike-wave synchronization have not been clearly identified.^ The purpose of this research project was to locate and characterize a distinct neuronal hyperexcitability defect favoring spike-wave synchronization in the stargazer brain. One experimental approach for anatomically locating areas of synchronization and hyperexcitability involved an attempt to map patterns of hypersynchronous activity with antibodies to activity-induced proteins.^ A second approach to characterizing the neuronal defect involved examining the neuronal responses in the mutant following application of pharmacological agents with well known sites of action.^ In order to test the hypothesis that an NMDA receptor mediated hyperexcitability defect exists in stargazer neocortex, extracellular field recordings were used to examine the effects of CPP and MK-801 on coronal neocortical brain slices of stargazer and wild type perfused with 0 Mg$\sp{2+}$ artificial cerebral spinal fluid (aCSF).^ To study how NMDA receptor antagonists might promote increased excitability in stargazer neocortex, two basic hypotheses were tested: (1) NMDA receptor antagonists directly activate deep layer principal pyramidal cells in the neocortex of stargazer, presumably by opening NMDA receptor channels altered by the stg mutation; and (2) NMDA receptor antagonists disinhibit the neocortical network by blocking recurrent excitatory synaptic inputs onto inhibitory interneurons in the deep layers of stargazer neocortex.^ In order to test whether CPP might disinhibit the 0 Mg$\sp{2+}$ bursting network in the mutant by acting on inhibitory interneurons, the inhibitory inputs were pharmacologically removed by application of GABA receptor antagonists to the cortical network, and the effects of CPP under 0 Mg$\sp{2+}$aCSF perfusion in layer V of stg/stg were then compared with those found in +/+ neocortex using in vitro extracellular field recordings. (Abstract shortened by UMI.) ^

Estimates of hospital and physician costs of epilepsy in the United States for 1995 comparing the provider -based survey method and a patient -based medical charts and billing method

This investigation compares two different methodologies for calculating the national cost of epilepsy: provider-based survey method (PBSM) and the patient-based medical charts and billing method (PBMC&BM). The PBSM uses the National Hospital Discharge Survey (NHDS), the National Hospital Ambulatory Medical Care Survey (NHAMCS) and the National Ambulatory Medical Care Survey (NAMCS) as the sources of utilization. The PBMC&BM uses patient data, charts and billings, to determine utilization rates for specific components of hospital, physician and drug prescriptions. ^ The 1995 hospital and physician cost of epilepsy is estimated to be $722 million using the PBSM and $1,058 million using the PBMC&BM. The difference of $336 million results from $136 million difference in utilization and $200 million difference in unit cost. ^ Utilization. The utilization difference of $136 million is composed of an inpatient variation of $129 million, $100 million hospital and $29 million physician, and an ambulatory variation of $7 million. The $100 million hospital variance is attributed to inclusion of febrile seizures in the PBSM, $−79 million, and the exclusion of admissions attributed to epilepsy, $179 million. The former suggests that the diagnostic codes used in the NHDS may not properly match the current definition of epilepsy as used in the PBMC&BM. The latter suggests NHDS errors in the attribution of an admission to the principal diagnosis. ^ The $29 million variance in inpatient physician utilization is the result of different per-day-of-care physician visit rates, 1.3 for the PBMC&BM versus 1.0 for the PBSM. The absence of visit frequency measures in the NHDS affects the internal validity of the PBSM estimate and requires the investigator to make conservative assumptions. ^ The remaining ambulatory resource utilization variance is $7 million. Of this amount, $22 million is the result of an underestimate of ancillaries in the NHAMCS and NAMCS extrapolations using the patient visit weight. ^ Unit cost. The resource cost variation is $200 million, inpatient is $22 million and ambulatory is $178 million. The inpatient variation of $22 million is composed of $19 million in hospital per day rates, due to a higher cost per day in the PBMC&BM, and $3 million in physician visit rates, due to a higher cost per visit in the PBMC&BM. ^ The ambulatory cost variance is $178 million, composed of higher per-physician-visit costs of $97 million and higher per-ancillary costs of $81 million. Both are attributed to the PBMC&BM's precise identification of resource utilization that permits accurate valuation. ^ Conclusion. Both methods have specific limitations. The PBSM strengths are its sample designs that lead to nationally representative estimates and permit statistical point and confidence interval estimation for the nation for certain variables under investigation. However, the findings of this investigation suggest the internal validity of the estimates derived is questionable and important additional information required to precisely estimate the cost of an illness is absent. ^ The PBMC&BM is a superior method in identifying resources utilized in the physician encounter with the patient permitting more accurate valuation. However, the PBMC&BM does not have the statistical reliability of the PBSM; it relies on synthesized national prevalence estimates to extrapolate a national cost estimate. While precision is important, the ability to generalize to the nation may be limited due to the small number of patients that are followed. ^