Frontal lobe tumoral epilepsy: clinical,neurophysiologic features and predictors of surgical outcome

PURPOSE: To review the clinical, neurophysiologic features and surgical outcomes in patients with frontal lobe tumors and chronic intractable seizures. METHODS: Medical records of patients with intractable epilepsy who underwent resection or stereotactic biopsy of frontal lobe tumor (confirmed by surgical pathology) seen between 1985 and 1999 at Yale University School of Medicine Epilepsy Center were reviewed for age at diagnosis, age at onset of seizures, delay between seizure onset and tumor diagnosis, types and frequencies of seizures, EEG results, use of anticonvulsants, extent of surgery, pathological diagnosis, and tumor recurrence. RESULTS: Thirty-seven patients were included. Mean age at seizure onset was 31.6 years, and at tumor diagnosis was 36.2 years. Mean duration between onset of seizures and tumor diagnosis was 6.1 years. Seventeen patients had auras. Seizure frequency averaged 7.6 seizures per week, with 58% of patients having more than one seizure type. All patients used anticonvulsants, with 90% eventually using polytherapy. All patients eventually underwent at least one surgical procedure. Only 13 (35.1%) patients were class I. Twelve (32.4%) patients were class II, seven (18.9%) class III, and five (13.5%) class IV. No statistically significant differences were seen between good and poor long-term seizure outcome in relation to specific tumor pathology, seizure types, or type of resection. CONCLUSIONS: Long-term surgical outcomes in tumoral frontal lobe epilepsy are more favorable than those in nontumoral intractable frontal lobe epilepsy (65% class I or II) and less favorable than those in other tumoral epilepsy (overall, 70% class I). Frontal location of intracranial neoplasm may predict a less favorable long-term epilepsy prognosis than tumoral epilepsy in general, an observation for which several explanations are proposed.     

Interaction of calbindin D28k and inositol monophosphatase in human postmortem cortex: possible implications for bipolar disorder

OBJECTIVES: Therapeutically relevant concentrations of lithium (Li) exert an uncompetitive inhibition on inositol monophosphatase (IMPase). It has recently been shown that calbindin D28k (calbindin) activates IMPase. Purified calbindin attaches to a specific amino acid sequence on purified IMPase enhancing its activity by several hundred fold. We studied whether calbindin activates IMPase in postmortem human brain crude homogenate, whether differences in calbindin levels between lymphocytes and brain may be responsible for our previous finding of reduced IMPase activity in lymphocytes but not brain of bipolar patients, and whether calbindin protein levels are altered in postmortem brain from bipolar patients versus control subjects and schizophrenic and major depressive patients. METHODS: IMPase activity in human postmortem brain specimens with or without 10 microM human recombinant calbindin was quantified spectrophotometrically in an enzyme-linked immunosorbent assay (ELISA) reader. Calbindin protein levels in postmortem brain were determined using Western blot analysis. RESULTS: Supplementation of human recombinant calbindin to postmortem human brain crude homogenate enhanced IMPase activity by 3.5-fold. No difference in postmortem temporal cortex calbindin protein levels was found between bipolar patients versus comparison groups. Two-fold higher calbindin protein levels were found in Li-treated bipolar patients compared with other bipolar patients. Subchronic Li treatment in mice did not affect brain calbindin protein levels significantly. Chronic Li treatment reduced calbindin protein levels in the frontal cortex but not in the hippocampus. CONCLUSIONS: Calbindin is a physiological activator of IMPase in human brain. Protein levels of calbindin are not altered in postmortem temporal cortex of bipolar patients.     

Childhood occipital epilepsy of Gastaut: a study of 33 patients

PURPOSE: To characterize the electroclinical features and evolution of childhood occipital epilepsy of Gastaut (COE-G). METHODS: Children with electroclinical criteria of COE-G were retrospectively identified and followed-up clinically, and with sleep and awake EEGs between 1990 and 2007. RESULTS: We identified 33 patients with COE-G. In the same length of time, 201 children with Panayiotopoulos syndrome and 410 children with benign childhood epilepsy with centrotemporal spikes were registered. COE-G had a peak age at onset of 8.5 years. Visual manifestations were the most common ictal event. Ictal deviation of the eyes was frequent. Approximately half of the patients had migraine-like symptoms. In all patients the seizures occurred while awake, and 11 also had seizures during sleep. The majority of the patients had occipital spike-wave discharges when the eyes were closed that disappeared or attenuated when the eyes were opened. Prognosis was excellent in 80% of the cases. CONCLUSION: This study confirms the existence of COE-G, a rare but well-defined syndrome within the group of idiopathic focal epilepsies in childhood.     

Vascularization of human glioma spheroids implanted into rat cortex is conferred by two distinct mechanisms

Aim of this study was to develop and characterize an applicable in vivo model to investigate angiogenesis of human gliomas. An established glioblastoma spheroid model was used to investigate the neovascularization of a standardized avascular solid tumor mass. Spheroids of two human glioma cell lines were labeled with an in vivo fluorescent dye. Single spheroids were implanted into the cortex of athymic rats. After 1, 3, 7, 14, and 21 days, brain sections containing the spheroid were immunostained for endothelial cells or vascular endothelial growth factor (VEGF). The dye-stained glioma spheroid and the endothelial cells were visualized by confocal microscopy. Two distinct mechanisms of tumor vascularization could be observed. (1) "Classical" angiogenesis with new vessels sprouting from existing host vessels into the spheroid was seen. (2) Individual endothelial cells were found to migrate towards and into the center of the spheroid where they coalesced to form new vessels. This process occurred as early as 24 hr after spheroid implantation. Spheroid vascularization was accompanied by an increase of VEGF expression, which peaked 7 days after implantation and returned to normal patterns by 14-21 days. Besides the "classical" angiogenesis by angiogenic blood vessels, the recruitment of individual endothelial cells seems to be an additional mechanism in early glioma vascularization. Our model proves to be a reliable, reproducible system to study in vivo angiogenesis of human gliomas.     

Comprehensive linkage and linkage heterogeneity analysis of 4344 sibling pairs affected with hypertension from the Family Blood Pressure Program

Linkage analyses of complex, multifactorial traits and diseases, such as essential hypertension, have been difficult to interpret and reconcile. Many published studies provide evidence suggesting that different genes and genomic regions influence hypertension, but knowing which of these studies reflect true positive results is challenging. The reasons for this include the diversity of analytical methods used across these studies, the different samples and sample sizes in each study, and the complicated biological underpinnings of hypertension. We have undertaken a comprehensive linkage analysis of 371 autosomal microsatellite markers genotyped on 4,334 sibling pairs affected with hypertension from five ethnic groups sampled from 13 different field centers associated with the Family Blood Pressure Program (FBPP). We used a single analytical technique known to be robust to interpretive problems associated with a lack of completely informative markers to assess evidence for linkage to hypertension both within and across the ethnic groups and field centers. We find evidence for linkage to a number of genomic regions, with the most compelling evidence from analyses that combine data across field center and ethnic groups (e.g., chromosomes 2 and 9). We also pursued linkage analyses that accommodate locus heterogeneity, which is known to plague the identification of disease susceptibility loci in linkage studies of complex diseases. We find evidence for linkage heterogeneity on chromosomes 2 and 17. Ultimately our results suggest that evidence for linkage heterogeneity can only be detected with large sample sizes, such as the FBPP, which is consistent with theoretical sample size calculations.     

Socioeconomic and racial disparities in cancer risk from air toxics in Maryland

We linked risk estimates from the U.S. Environmental Protection Agency's National Air Toxics Assessment (NATA) to racial and socioeconomic characteristics of census tracts in Maryland (2000 Census) to evaluate disparities in estimated cancer risk from exposure to air toxics by emission source category. In Maryland, the average estimated cancer risk across census tracts was highest from on-road sources (50% of total risk from nonbackground sources), followed by nonroad (25%), area (23%), and major sources (< 1%). Census tracts in the highest quartile defined by the fraction of African-American residents were three times more likely to be high risk (> 90th percentile of risk) than those in the lowest quartile (95% confidence interval, 2.0-5.0). Conversely, risk decreased as the proportion of whites increased (p < 0.001). Census tracts in the lowest quartile of socioeconomic position, as measured by various indicators, were 10-100 times more likely to be high risk than those in the highest quartile. We observed substantial risk disparities for on-road, area, and nonroad sources by socioeconomic measure and on-road and area sources by race. There was considerably less evidence of risk disparities from major source emissions. We found a statistically significant interaction between race and income, suggesting a stronger relationship between race and risk at lower incomes. This research demonstrates the utility of NATA for assessing regional environmental justice, identifies an environmental justice concern in Maryland, and suggests that on-road sources may be appropriate targets for policies intended to reduce the disproportionate environmental health burden among economically disadvantaged and minority populations.     

Urban neighborhoods, chronic stress, gender and depression

Using multilevel analysis we find that residents of "stressed" neighborhoods have higher levels of depression than residents of less "stressed" neighborhoods. Data for individuals are from two cycles of the Canadian Community Health Survey, a national probability sample of 56,428 adults living in 25 Census Metropolitan Areas in Canada, with linked information about the respondents' census tracts. Depression is measured with the Center for Epidemiologic Studies-Depression Scale Short Form and is based on a cutoff of 4+ symptoms. Factor analysis of census tract characteristics identified two measures of neighborhood chronic stress--residential mobility and material deprivation--and two measures of population structure--ethnic diversity and dependency. After adjustment for individual-level gender, age, education, marital and visible minority status and neighborhood-level ethnic diversity and dependency, a significant contextual effect of neighborhood chronic stress survives. As such, the daily stress of living in a neighborhood where residential mobility and material deprivation prevail is associated with depression. Since gender frames access to personal and social resources, we explored the possibility that women might be more reactive to chronic stressors manifested in higher risk of depression. However, we did not find random variation in depression by gender across neighborhoods.     

Imitation of cigarette smoking: an experimental study on smoking in a naturalistic setting

AIMS: Examine whether smokers imitate smoking behaviour of strangers and to what extent this is moderated by the nature of social interactions. DESIGN AND PARTICIPANTS: An experiment with a three (heavy smoking, light smoking, or no smoking condition) by two (warm versus cold social interaction condition) factorial design. Daily smoking young adults were exposed to same-gender confederates and were observed in a bar laboratory. MEASUREMENTS: Smoking and social behaviour were observed and coded during a 30-min break between two tasks, consisting of rating television advertisements. FINDINGS: Participants imitated the smoking behaviour of confederates. After controlling for young people's craving, confederate's smoking explains 35% of the variance in the number of cigarettes smoked. Participants are more likely to smoke and to continue smoking in the warm social interaction condition. Lighting up the first cigarette was affected by confederate's smoking and participant's urges to smoke. Lighting up a second was affected by the heavy smoking condition and warm social interaction condition. Lighting up a third cigarette was affected only by the heavy smoking condition. CONCLUSION: Imitation largely explains why individuals light up a cigarette and continue to smoke.