Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes

Coadministration of entacapone with levodopa attenuates motor complications in experimental models of Parkinson's disease. The mechanisms underlying entacapone effects are unknown. We investigated the effect of entacapone, on: long-duration response (LDR) to levodopa, levodopa-induced postsynaptic pharmacodynamic mechanisms and molecular changes in hemiparkinsonian rats. 6-Hydroxydopamine-unilaterally lesioned rats were treated with levodopa (25 mg/kg) + vehicle; levodopa + entacapone (30 mg/kg) or saline, twice daily for 22 days. The LDR and the apomorphine-induced rotations were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin and dopamine D-3 receptor mRNAs, subthalamic cytochrome oxidase mRNA and nigral glutamic acid decarboxylase mRNA. Entacapone potentiated the LDR but did not modify either the apomorphine-induced rotational behavior or the molecular changes. Our results suggest that the effects of entacapone on levodopa-induced motor response are not mediated by postsynaptic mechanisms and that administration of entacapone is not able to normalize the molecular alterations induced by levodopa in the basal ganglia.     

Parenting stress in parents of children with epilepsy and asthma

The purposes of this study were to identify differences in parenting stress between 2 samples and examine the factors associated with parenting stress. An asthma sample was selected to contrast with the epilepsy sample because both medical conditions are chronic episodic conditions that require daily medication. Data from 49 parents of epileptic children and 54 parents of asthmatic children were examined in this study. Samples were conducted in a hospital pediatric clinic. Parental stress was measured using Abidin's Parenting Stress Index-long form. There were 2 major domains in the Parenting Stress Index: parent domain and child domain. The parent domain included 7 subscales, and the child domain included 6 subscales. Overall, results showed that parental stress was higher in the epilepsy group. Significant differences were found in 7 subscales: adaptability, demanding, hyperactivity/distractibility, role restrictions, depression, relationship to spouse, and parental health. Possible explanations for a higher level of parenting stress in the epilepsy group were discrimination, poor child adaptation, the threat of unpredictability of the seizures, and neurological dysfunction. The causes of higher levels of parenting stress in the asthma group were limitation of activities and parental health condition. These differences should be considered when psychosocial care is offered. Results also showed that demographic variables (gender, age, and family social economic status), age at onset, and condition severity were not effective predictors for parenting stress.     

Temporal lobe epilepsy does not impair visual perception

Temporal lobe epilepsy (TLE) can impair interictal cognitive function. In the perceptual domain, previous psychophysical studies demonstrated specific deficits in auditory and tactile perception in patients with TLE. This study compared performance of 25 TLE subjects and 27 controls on two low-level, visual tasks: luminance discrimination and frequency discrimination. Both tasks were performed under a relatively easy and a relatively difficult condition, by adjusting the stimulus duration. TLE subjects performed as well as controls on both tasks at both stimulus durations. These results imply that interictal occipital lobe function, as reflected in performance on low-level visual tasks, is not impaired in TLE, consistent with functional imaging data. Furthermore, since TLE subjects performed normally while taking therapeutic doses of multiple AEDs, the data suggest that these AEDs do not impair visual perception.     

Seizures after epilepsy surgery

This article reviews types and prognostic significance of seizures that occur after epilepsy surgery, so-called postsurgical seizures.     

Obsessive-compulsive disorder after epilepsy surgery

It is a well-known fact that after epilepsy surgery (ES) preexisting psychopathology may deteriorate or de novo psychopathological syndromes, mainly of a depressive and psychotic nature, may appear. Previously, recovery of obsessive-compulsive disorder (OCD) after ES has been reported in patients who had comorbid OCD preoperatively; however, there have been no reports on the appearance of de novo OCD interfering with daily living activities post-ES. This is the first report of OCD after ES in patients with mesial temporal lobe epilepsy (MTLE). Five patients with MTLE were identified with obsessive personality traits before surgery. Within the first 2 months after ES, two of these MTLE patients fulfilled OCD diagnostic criteria. These OCD patients were not any different from the other three patients with respect to age, age of onset of epilepsy, seizure types, and seizure frequency. All patients stopped having seizures postoperatively, but the OCD patients had worse quality of life postoperatively than preoperatively. Our findings show that those patients with obsessive traits preoperatively should be carefully monitored after ES.     

Marital status after epilepsy surgery

PURPOSE: To characterize features influencing marital status in a group of patients with refractory epilepsy before and after epilepsy surgery and to assess the effect of seizure control on marital status after epilepsy surgery. METHODS: We analyzed marital status in 430 epilepsy surgery patients and in a subset with temporal lobe epilepsy. Marital status was assessed in relation to gender and age of epilepsy onset and compared with marital rates for the U.S. population. Patients who had > or =4 years of postsurgical follow-up were examined for change in marital status after surgery. Those patients who changed marital status were then evaluated for change in employment. RESULTS: Marital rates were lower than expected in men. Men with onset of epilepsy by age 11 years were less likely to be married than men whose seizures began after age 11 or women whose seizures began at any age. Men and women with temporal lobe epilepsy had higher marriage rates than those with extratemporal lobe epilepsy. More than 4 years after epilepsy surgery (n = 190), patients who had no recurrent seizures were more likely to change marital status (28 of 124, 23%), than those who had recurrent seizures (five of 66, 8%). Seizure-free women were more likely to divorce (n = 9) than were seizure-free men (n = 1). Most men who married were employed (77%), whereas women who divorced were usually unemployed (67%). CONCLUSIONS: The age at which seizures begin influences later marital status in men, who have reduced marriage rates. The abolition of seizures by epilepsy surgery creates new opportunities for changing social relationships. Location of the epileptic focus may influence psychosocial function.     

Excessive masturbation after epilepsy surgery

Sexual behavior changes as well as depression, anxiety, and organic mood/personality disorders have been reported in temporal lobe epilepsy (TLE) patients before and after epilepsy surgery. The authors describe a 14-year-old girl with symptoms of excessive masturbation in inappropriate places, social withdrawal, irritability, aggressive behavior, and crying spells after selective amygdalohippocampectomy for medically intractable TLE with hippocampal sclerosis. Since the family members felt extremely embarrassed, they were upset and angry with the patient which, in turn, increased her depressive symptoms. Both her excessive masturbation behavior and depressive symptoms remitted within 2 months of psychoeducative intervention and treatment with citalopram 20mg/day. Excessive masturbation is proposed to be related to the psychosocial changes due to seizure-free status after surgery as well as other possible mechanisms such as Kluver-Bucy syndrome features and neurophysiologic changes associated with the cessation of epileptic discharges. This case demonstrates that psychiatric problems and sexual changes encountered after epilepsy surgery are possibly multifactorial and in adolescence hypersexuality may be manifested as excessive masturbation behavior.     

Maternal adaptation to a child's epilepsy

Mothers of children with epilepsy are at risk for problems in adapting to their child's condition; however, factors associated with maternal adaptation to a child's epilepsy have not been well articulated. The purpose of this study was to investigate the associations among maternal and child characteristics, maternal beliefs, and maternal adaptation outcomes. A conceptual model was formulated based on the literature. Maternal beliefs were proposed to mediate the relationships between maternal and child characteristics and maternal adaptation outcomes. A sample of 156 maternal-child dyads provided data via structured telephone interviews. Multiple regression analysis was used to test for additive and mediated relationships. Mediation was not supported statistically. Child behavior problems, maternal satisfaction with family, and maternal learned helplessness had the strongest associations with maternal outcomes, suggesting that maternal adaptation to a child's epilepsy is complex and includes multiple factors in addition to the child's seizure condition.     

Speech arrest with stimulation may not reliably predict language deficit after epilepsy surgery

The authors present a patient in whom electrical cortical stimulation of the posterior temporal cortex induced speech arrest, comprehension deficits, and other language-related impairments. This area was ultimately resected because of persistence of a severe seizure disorder. No postoperative aphasia was observed despite the cortical stimulation results, and the patient is since seizure free. These findings question the well-established principle that corticography directly reflects local cortical functions in all patients.     

Postnatal handling does not normalize hypothalamic corticotropin-releasing factor mRNA levels in animals prenatally exposed to ethanol

Postnatal handling has been shown to attenuate some of the deficits in developmental outcome observed following prenatal ethanol exposure (E) although it appears to be ineffective at ameliorating the hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors that has been observed in adult E animals. However, the effects of postnatal handling on central regulation of HPA activity in E animals, particularly with regard to alterations in steady-state hypothalamic corticotropin-releasing factor (CRF) activity, have not been examined. In the present study, offspring from E, pair-fed (PF), and ad-libitum-fed control (C) groups were exposed to daily handling during the first 2 weeks of life (H) or were left entirely undisturbed until weaning (NH). Basal CRF and arginine vasopressin (AVP) mRNA in the parvocellular portion of the paraventricular nucleus (pPVN) of the hypothalamus were assessed at 90-110 days of age. Prenatal ethanol exposure resulted in elevated basal pPVN CRF mRNA levels compared to those in ad-libitum-fed controls. Handling altered CRF mRNA levels in a sex-specific and prenatal treatment-specific manner. Females showed no significant effects of handling. In contrast, handling decreased CRF mRNA levels in PF and C but not E males compared to their NH counterparts. There were no effects of prenatal ethanol or postnatal handling on AVP mRNA levels. These findings indicate that prenatal ethanol exposure results in elevated basal CRF mRNA levels in adulthood and that handling appears to be ineffective in normalizing those elevations, supporting the suggestion that altered basal HPA regulation in E animals may, at least in part, underlie their HPA hyperresponsiveness to stressors.     

Tissue plasminogen activator does not alter development of acquired epilepsy

Purpose: Tissue plasminogen activator (t‐PA), a proven therapy for acute ischemic stroke, is an endogenous serine protease associated with neuronal activity and synaptic plasticity in the brain. Its expression is enhanced after seizures, and is involved in seizure propagation throughout the brain. Therefore, the increased use of t‐PA to treat stroke may have important implications for the development of poststroke epilepsy. Using experimental and clinical approaches, we investigated the role of t‐PA in the development of epilepsy. Methods: Mice deficient in t‐PA (t‐PA^?/?) or mice transgenically modified to overexpress neuronal t‐PA (T4) underwent amygdala kindling, and seizure threshold and rates of kindling were compared to those in wild‐type mice. For the clinical study, we recruited acute ischemic stroke patients who either received intravenous t‐PA treatment on admission to hospital (n = 177; cases) or did not (n = 158; controls). We then assessed the incidence of early and late onset seizures and epilepsy in these patients. Key Findings: T4 mice were more seizure‐prone than wild‐type mice, exhibiting lower seizure thresholds (p = 0.002), but there were no significant differences observed in the rate of kindling development when comparing either T4 mice, or t‐PA^?/? mice, to their wild‐type controls. Furthermore, we found no significant differences between the proportion of poststroke patients experiencing early or late seizures, or developing epilepsy, between those who received t‐PA and those who did not. Significance: Overexpression of endogenous t‐PA lowers seizure threshold but does not influence kindling epileptogenesis. Moreover, the therapeutic administration of t‐PA in humans does not influence the development of acquired poststroke epilepsy.     

Suicide outcomes after resective epilepsy surgery

People with epilepsy have a higher risk for suicide than people without epilepsy. The relationship between seizure control and suicide is controversial. A standardized protocol to record history, diagnostic testing, and neuropsychiatric assessments was administered. The Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were administered presurgically and yearly for up to 5 years. Among the 396 enrolled, 4 of 27 deaths were attributed to suicide. The standardized mortality ratio, compared with suicides in the U.S. population and adjusted for age and gender, was 13.3 (95% CI=3.6-34.0). Only one patient had a BDI score suggestive of severe depression (BDI=33), one had depressive symptoms that did not the meet the depressive range (BDI=7), and the other two reported no depressive symptoms. Two of the patients reported moderate to severe anxiety symptoms (BAI=17 and 21, respectively). Suicide may occur after epilepsy surgery, even when patients report excellent seizure control.     

Nonepileptic seizures after resective epilepsy surgery

PURPOSE: To identify factors that are associated with the emergence of nonepileptic seizures (NES) after resective epilepsy surgery. METHODS: Twenty-two patients with medically refractory epilepsy in whom NESs were documented by EEG after resective surgery were compared with a larger series of epilepsy surgery patients on demographic, neurologic, and psychiatric variables. RESULTS: NES tended to become apparent in the first few months after surgery. Patients who developed NESs did not differ from other epilepsy surgery patients in terms of age, IQ, or preoperative psychiatric diagnoses. However, surgical NES patients' neurologic problems and seizures began later in life, the NES group included a larger proportion of female subjects and patients with right hemisphere surgery, and NES patients were more likely to develop non-NES psychiatric problems after surgery. CONCLUSIONS: The heterogeneous collection of behaviors subsumed under the label NESs are determined by multiple factors. Several variables were found to be specifically associated with the development of NES after resective epilepsy surgery: A disproportionate number of postsurgical NES patients are female, they have primary neurologic dysfunction in the right hemisphere, and their epileptic seizures often began after adolescence. We propose that at least one group of patients with somatoform tendencies develop NESs as part of the psychiatric instability that occurs often in the few months after resective surgery.     

Reoperation after failed resective epilepsy surgery

PurposeResection of the seizure focus leads to sustained seizure-freedom in intractable focal epilepsy in up to 80% of selected populations. However, surgery fails to help in a considerable proportion of patients. Reevaluation and reoperation may be considered in a selected group of patients with an unfavorable postsurgical outcome. Here, we reviewed 15 case series on reoperation after failed resective epilepsy surgery in adults in order to identify factors associated with a good chance of benefitting from a second operation.MethodsLiterature review of case series describing the outcome of epilepsy surgical re-operations.ResultsOverall, 3.8–14% of all patients who had resective epilepsy surgery underwent a second operation. A total of 402 reoperated patients were included. Reoperation was performed in average between 2 and 5.5 years after the first surgery. 36.6% of all patients were seizure-free with a minimal follow-up of 6 months to 4 years after the second operation. Postsurgical complications were observed in 13.5% and mainly consisted of visual field defects and, less frequently, of hemiparesis. The causes of failed first epilepsy surgery were heterogeneous and included incorrect localization or incomplete resection of the seizure focus, presence of additional seizure foci or progression of the underlying disease. Some features appear to indicate successful reoperation, such as concordance of postsurgical imaging and electroclinical findings as well as absence of brain trauma and cerebral infection prior to epilepsy onset.ConclusionReoperation after thorough assessment of all available clinical, imaging and EEG findings can be an efficacious and reasonably safe treatment option which can achieve sustained seizure control after failed resective epilepsy surgery.     

Mortality after temporal lobe epilepsy surgery

Purpose: To report mortality, after a longer interval, in a cohort of patients with drug‐resistant epilepsy treated by temporal lobe surgery between 1975 and 1995. A previous audit of these patients ending December 1, 1997 observed a standardized mortality ratio (SMR) of 4.5. Methods: We analyzed mortality in a cohort of 306 patients with temporal lobe epilepsy (TLE) who underwent temporal lobe resections between December 1, 1975 and December 1, 1995. Deaths occurring after December 1,1997 and until December 1, 2009 were evaluated. Medical records, death certificates, postmortem examination reports, coroner officer’s reports, and coroner’s inquest reports were sought, and causes of death were ascertained. Sudden unexpected death in epilepsy (SUDEP) cases were identified. Key Findings: In 3,569 person‐years of follow‐up 19 deaths occurred, [SMR 2.00, 95% confidence interval (CI) 1.27–3.13], 14 men (SMR 2.01, 95% CI 1.19–3.39) and 5 women (SMR 1.68, 95% CI 0.70–4.03). On analysis of subgroups, SMRs were significantly elevated in patients with mesial temporal sclerosis (MTS) (SMR 2.50, 95% CI 1.38–4.51), men with MTS (SMR 3.12, 95% CI 1.56–6.25), men with nonspecific lesions (SMR 2.68, 95% CI 1.00–7.09), and right‐sided resections in MTS (SMR 3.33, 95% CI 1.39–8.00). During follow‐up, six SUDEP cases were observed with a rate of 1/595 person‐years. Significance: In this cohort, the risk for premature death in patients undergoing TLE surgery decreased over time but remained above the standard population. Men had a slightly higher risk than women, as did right‐sided resections in MTS, confirming this observation in the original cohort. Although lower, the risk of SUDEP remained. Without up‐to‐date information on seizure outcome, we were unable to directly relate this to mortality.     

Quality of life after epilepsy surgery

OBJECTIVE—To assess the relation between seizurestatus and quality of life after surgery for drug resistant epilepsy,using a previously validated quality of life model developed for use in epilepsy.
METHODS—A retrospective postal survey was made on94 patients who underwent surgery for epilepsy between 1986 and 1994, and 36 patients who after investigation during the same period werefound to be unsuitable for surgery. A health related quality of lifemodel was used containing validated measures of anxiety, depression, self esteem, mastery, impact of epilepsy, affect balance, stigma, overall health status, and overall quality of life, to examine therelation between postoperative seizure status and quality of life.
RESULTS—Overall 47.9% of patients were seizurefree after surgery. On all measures seizure free patients scoredsignificantly better than either patients deemed unsuitable for surgeryor those having more than 10 seizures per year after surgery. Patientshaving less than 10 seizures per year obtained intermediate scores.There was no difference between the groups unsuitable for surgery or having more than 10 seizures per year postoperatively. Employment rateswere significantly different between groups, 80% of seizure free and53% of patients having less than 10 seizures per year in gainfulemployment postoperatively, compared with 28% and 27% of patientshaving greater than 10 seizures per year or those who were unsuitablefor surgery.
CONCLUSIONS—Within broad categories,postoperative quality of life is clearly related to seizure outcome,but the study emphasises the importance of long term follow up indefining the tangible psychosocial effects of freedom from seizures.