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Objective: Epilepsy is a chronic condition that can affect patients of all ages. Women with epilepsy (WWE) require access to specific counseling and information regarding issues related to contraception, pregnancy, and hormonal effects on seizure control and bone mineral density. This study investigated the knowledge among WWE regarding their condition, and whether epilepsy-specific knowledge has improved over the last 15 years., Methods: A total of 280 WWE aged 18 to 82 years participated in this multicenter, questionnaire-based study. The study was conducted at four epilepsy centers in Germany, between October 2020 and December 2020. Sociodemographic and epilepsy-specific data for participating women were analyzed and compared with the results of a similar survey performed in 2003-2005 among 365 WWE in Germany., Results: The questionnaire-based survey revealed considerable knowledge deficits without significant improvements over the last 15 years, particularly among those with less education and with regards to information on the more pronounced effects of epilepsy in older WWE (>50 years), including interactions with menopause and osteoporosis. In WWE ≤29 years, a significant increase in the knowledge score was observed in 2020 compared with this age group in 2005 (mean 7.42 vs. 6.5, p = .036). Mothers frequently reported epilepsy-related concerns regarding childrearing, particularly of seizures scaring their child and the need to rely on other people., Conclusion: WWE continue to demonstrate inadequate epilepsy-related knowledge. Despite increasing information availability and the aspiration toward better awareness among medical professionals, overall knowledge has not increased sufficiently compared with the levels observed in recent studies., (Copyright © 2022. Published by Elsevier Ltd.)

In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate. The analysis provides a decision whether for a specific patient a particular anti-epileptic drug is increasing or reducing the seizure rate. Through a simulation study the proposed algorithm is validated. Additionally, for clinical data results obtained by the proposed algorithm are compared with the results from a Cox-Stuart trend test as well as with the visual assessment of experienced pediatric epileptologists.

Objectives: Due to demographic change and high incidence of epilepsy in elderly, the number of elderly with epilepsies is increasing. However, only few studies investigated the impact of epilepsy on quality of life (QoL). We investigated how epilepsy affects different aspects of QoL dependent on the age of the patients and the age of onset of epilepsy., Materials and Methods: In a multicenter, cross-sectional study, three patient groups were recruited from five centers: Group A1: 45 elderly (≥65 years.) with late onset of epilepsy (≥65 years), group A2: 51 elderly (≥65 years.) with early-onset, long-lasting epilepsy (≤50 years), group B: 41 young adults (≤50 years) with epilepsy. Statistical analysis of differences between groups was performed using generalized linear models., Results: Elderly with late-onset epilepsy (group A1) had a significantly lower seizure frequency, were treated with less anti-epileptic drugs (AEDs), and reported a better tolerability of AED treatment, but had more comorbidities compared with groups A2 and B. After adjusting for seizure frequency, tolerability of AEDs and comorbidity, young adults (group B) reported the highest overall QoL, whereas patients of group A1 and A2 did not differ significantly. Epilepsy-related fears, especially fears of stigmatization, were significantly higher in elderly with long-lasting epilepsy compared with groups A1 and B., Conclusion: Seizure-related variables, tolerability of AEDs and comorbidity have a stronger impact on QoL and on restrictions due to epilepsy than age, age at onset of epilepsy or duration of epilepsy. However, some results indicate group-specific patterns of impairment and epilepsy-related fears., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The prevalence of psychiatric disorders in people with epilepsy is high. Depression and anxiety disorders are especially frequent. These comorbid disorders are, however, easily overlooked. The neurological disorders depression inventory for epilepsy (NDDI-E) was developed and validated as a screening instrument with six questions. The aim of the present study was to validate a German version of the NDDI-E. After translation into German and back translation into English, the NDDI-E was presented to 144 patients at the Bethel Epilepsy Center. The Beck depression inventory II (BDI-II), the revised symptom check list by Derogatis (SCL-90-R) and the state-trait anxiety inventory (STAI) were also used. The patients were examined using the mini international neuropsychiatric interview plus (MINI Plus). The German version of the NDDI-E proved to be valid, internally consistent and easy to use.

The prevalence and incidence of epilepsies in elderly is high. Due to demographic development, the portion of elderly patients with epilepsy will continue to rise over the next decades. In this study, we aimed to investigate seizure semiology, etiology, comorbidity, and therapy in elderly patients dependent on onset of epilepsy and in comparison with younger patients. In a prospective multicentre study, 202 epilepsy patients were included in a consecutive manner and subdivided into three groups (group A1: >65 years, onset of epilepsy after the age of 65 years; group A2: >65 years with early onset epilepsy, seizure onset before the age of 50 years; and group B: <50 years with epilepsy). Clinical data with respect to epilepsy, seizures, comorbidity, etiology, and anti-epileptic drug (AED) therapy were assessed using a questionnaire developed especially for these patient groups and filled out by the physicians. The clinical profile with regard to etiology, postictal conditions, and comorbidities clearly depends on the age of the patients and age of onset of epilepsy. Patients with an epilepsy onset after 65 years need lower doses of AEDs, gain better seizure control and have more concomitant diseases than younger patients or elderly epilepsy patients with early-onset epilepsy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Feasibility of the educational program FAMOSES (modular service package epilepsy for families) was evaluated in a controlled pilot study. Parents of children with epilepsy from epilepsy centers in Germany were allocated to either educational group (treatment group, n=55) or waiting-list group (control group, n=48). Questionnaires included epilepsy-specific scales (knowledge, coping, adaptation, anxiety, rules and limitations, seizure management, impact of epilepsy). Multivariate analysis of variance with repeated measurements indicated significant improvements in the treatment group compared to the control group (time×group interaction: p<0.01). Univariate analyses (ANOVA) confirmed improvements in knowledge (p<0.001), adaptation (p<0.01), epilepsy-related anxiety (p<0.05), and seizure management (p<0.05). Surveillance as well as seizure frequency (p<0.05) of children whose parents participated in the treatment group was reduced (p<0.05). Furthermore, parents' satisfaction with the content and interactive didactic format of the program was assessed in a survey with 852 parents over a five-year period. This survey showed an improvement over the course of time (p<0.05). Feasibility and need for the educational program were confirmed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To present long-term outcome and predictors of the health related quality of life (HRQOL) in a large group of patients operated for refractory extratemporal epilepsy., Methods: A German QOLIE-31 questionnaire and additional questions has been mailed for all adult patients operated for extratemporal epilepsy in the Bethel Epilepsy Centre, between 1992 and 2003, 87 patients were eligible for this study., Results: Seizure freedom, intake of antiepileptic drugs (AEDs), presence of AEDs side effect medical comorbidities and driving a car were significantly correlated to HRQOL in all subscales of QOLIE-31. Gender, age at epilepsy onset, the presence of a partner, psychiatric disease, the presence of auras and tumour pathology have a correlation to QOL in some subscales. Stepwise regression for all patients revealed that seizure freedom and medical comorbidities were highly predictive for most of the subscales of QOLIE-31. Intake of anti-epileptic drugs and AED side effects had a modest effect on QOL. The need for psychiatric treatment predicted poor cognitive function scores. Epilepsy onset at an older age predicted a minimal increase in the overall health scores. An aura at the last follow-up predicted poor medication scores. Regarding the importance of the predictors, seizure freedom and medical comorbidities were the most important predictors of QOL after surgery. AED intake and side effects had an intermediate effect on QOL; however, the gender of the patient and age at epilepsy onset had a minimal effect on QOL., Conclusions: HRQOL after extratemporal epilepsy surgery has multiple determinants. Medical comorbidities should be considered a negative risk factor for QOL during preoperative and postoperative evaluation process.

Phenobarbital and primidone frequently have adverse effects on mental functions. Therefore, an attempt was made to taper barbiturates in 85 patients out of a resident population with epilepsy and intellectual disability who were selected according to clinical criteria. The objectives were to reduce the use of barbiturates, to improve the patients' cognitive and psychological state, and to reduce polypharmacy while avoiding seizure exacerbation. Four months after complete withdrawal changes in seizure frequency were assessed as well as changes in cognitive abilities, psychological state and behaviour (using the clinical global impression scale). In 13 patients the tapering failed due to complications (seizure increase in 11 patients). In 72 patients the barbiturate was completely withdrawn (mean duration of tapering: 393 days). Cognitive improvement was achieved in 17 patients (23.6%), 5 patients (6.9%) deteriorated. Seizure frequency remained unchanged in 33 patients (45.8%), in another 15 patients (20.8%) the seizure frequency decreased. Reduction in polypharmacy was obtained in 61 patients (84.7%). In an overall judgement (clinical global impression scale) of cognitive abilities AND seizure control, 25 patients (34.7%) were improved. 31 patients (43.1%) remained unchanged while 12 patients deteriorated (4 patients: impossible to judge). For statistical analysis three outcome groups were defined: the improved group (N=25), the unchanged group (N=31), and the deteriorated/failed group (N=25) consisting of the 12 deteriorated patients plus the 13 patients in whom tapering failed. Stepwise logistic regression revealed a history of an attempt to withdraw phenobarbital/primidone (p=0.017; OR 3.8), age (p=0.012) and seizure frequency (marginally significant: p=0.097) as outcome predictors. Older age was associated with better outcome. A high seizure frequency before tapering was related to good outcome, while seizure freedom and a history of failed withdrawal were associated with deterioration/failure. Outcome did not depend on duration of barbiturate therapy, dosage or serum concentration, co-medication, reduction rate, degree of intellectual disability, or epilepsy syndrome. In summary, the number of barbiturate medications has been considerably reduced, but the principal aim of the project, to relieve patients from assumed barbiturate side effects, has been achieved only in one out of four patients.

Background: Women with epilepsy are particularly affected by their condition and need therefore specific counseling and comprehensive information about issues related to contraception, pregnancy, hormone effects on seizure control, bone mineral density, etc. The primary aim of this study was to investigate the knowledge of women with epilepsy about their condition and their need for information and counseling., Methods: A total of 365 women with epilepsy aged from 16 to 75 years of age took part in this prospective, cross-sectional study. All were treated by neurologists in private practice or outpatient clinics. The physicians distributed anonymous questionnaires to the women, who mailed them unsigned to the Society for Epilepsy Research. Sociodemographic and epilepsy-specific data of the women, their experiences and fears regarding partnership, family planning, pregnancy, care of children, and their self-rated and actual knowledge were assessed., Results: Most women (80.9%) lived together with partners, and about half of the women (44.9%) had children. The majority of those with children were greatly worried during pregnancy about risks to their newborn child. They were afraid of potential handicaps (57.9%) and potential epileptic seizures of the child (52.5%) because of their own epilepsy or antiepileptic drugs. Another 39.0% had had great reservations about becoming pregnant. About every fifth woman (18.2%) stopped or reduced antiepileptic medication during pregnancy without consulting her doctor. Women who consciously abstained from having own children (n=87, 23.8%) often reported epilepsy-related reasons (e.g. risk of malformation caused by antiepileptic drugs, 40.8%). Epilepsy also affects the mother-child relationship. For example 40.8% of the women were worried that the child could be harmed during a mother's seizure and 36% reported that their seizures would frighten their children. About 56-66% of the epileptic women stated that they were well to very well informed about topics on contraception, pregnancy, prophylaxis of malformations, and heredity of epilepsies. The knowledge questionnaires revealed however considerable knowledge deficits. These were especially widespread concerning older women and epilepsy, e.g. antiepileptic drugs and osteoporosis, and more pronounced in older women (>50 years) and those with low school education. In all, self-rated and actual knowledge correlated only slightly (r=0.25). Of the women, 60% preferred personal counseling by their physicians. However, especially younger women wanted further information, primarily easy-to-understand brochures (32%) and educational courses (31%)., Conclusion: Our results are in accordance with other studies from Great Britain and the U.S. They confirm that women with epilepsy have considerable deficits in epilepsy-specific knowledge and a great need of counselling and information.

In a retrospective evaluation of 32 inpatients with therapy-resistant epilepsy and intellectual disability, the efficacy of pregabalin (PGB) treatment was assessed after 6 and 12 months. The combined efficacy measure included the percentage reduction in seizure frequency, as well as the Clinical Global Impression (CGI) scale. Tolerability was assessed using a list of the 10 adverse effects most frequently observed in the regulatory studies and also by the CGI scale. After 6 months, the retention rate was 75%. Six patients (18.75%) were responders (50% seizure reduction and/or "good" or "very good" effect on CGI). No patient was seizure free. Seven patients had adverse effects that were not impairing. Eight patients had side effects that were essentially impairing. Weight gain, somnolence, asthenia, and ataxia were the most frequent adverse effects. Rare adverse events were severe mental slowing and loss of daily life capacities on a low dose of PGB in one patient and increase in auto-aggression in another patient. After 12 months, the retention rate was 40.6%, the responder rate was 25%, and one patient was seizure free. Statistical analysis did not identify any predictor of outcome (seizure type, epilepsy syndrome, co-medication, degree of intellectual disability). In this highly selected population, the efficacy of PGB was only moderate.

Experts from epileptology and psychiatry reviewed the current significance of therapeutic drug monitoring (TDM) of antiepileptic drugs and psychiatric drugs in a workshop at Bethel Epilepsy Centre in December 2005. TDM has been essential in epileptology for about 30 years, and it is also increasingly important in psychiatry, in which consensus recommendations were published recently. With regard to cost-cutting in the health system, there are discussions about the financial effect of TDM and outsourcing it to bigger laboratories. In psychiatry it has however been shown that sensibly used TDM may lead to reduced costs. Many issues in TDM require the knowledge and experience of specialised laboratories. The use of TDM data for scientific purposes was discussed at the workshop as well.

Objective: To examine the predictive value of demographic data for the seizure outcome after extratemporal epilepsy surgery., Methods: Eightyone patients who underwent resective extratemporal epilepsy surgery were retrospectively studied concerning (a) age at surgery, (b) onset of epilepsy, (c) duration of epilepsy, (d) number of seizures at the time of presurgical evaluation, (d) number of presurgically tested antiepileptic substances and (f) number of seizure types. The data were correlated to the postoperative seizure outcome after two years., Results: 33 patients (40.7%) were seizure free two years after surgery. Univariate and multivariate analysis revealed that both tumor etiology and low presurgical seizure frequency were independently associated with seizure freedom after epilepsy surgery. The recurrence rate in patients with one or more seizures per day was more than two-fold if compared with patients with fewer seizures. The remaining demographic factors did not show a significant association with seizure outcome in our 81 patients., Conclusions: Fewer than daily seizures prior to surgery and a tumoral etiology independently increase the likelihood of remaining seizure free two years after extratemporal epilepsy surgery.

Unlabelled: This study was designed to describe the course of epilepsy (in terms of seizure frequency) and to assess the variables (antiepileptic therapy regimens and others) correlated to improvement. Seizure frequency (categories: seizure free, more than one seizure/year, monthly seizures, weekly seizures and daily seizures) and antiepileptic medication were retrospectively compared between 1992 and 2002 in a large cohort of 550 inpatients with chronic epilepsy and different degrees of intellectual disability or multiple handicaps., Results: Seizure frequency decreased significantly (p<0.001). 218 of the 394 patients (55.3%) not seizure free in 1992 improved (changed into a better frequency category). The improvement rate was marginally higher in patients who had undergone a medication change (p=0.08). A high seizure frequency in 1992 (p=0.016) and older age (p=0.006), but not epilepsy syndrome or degree of intellectual disability, were predictors for improvement (stepwise logistic regression analysis). 56.4% of the improved patients were on combinations of two AEDs (17.4%, monotherapy; 20.2%, triple therapy). The most frequent therapy regimens in the improved patients were lamotrigine/valproate (48 patients), carbamazepine/phenobarbital (21) and carbamazepine only (19). Lamotrigine/valproate was effective in all kinds of epileptic syndromes. Most patients on lamotrigine had serum concentrations above 10microg/ml, approximately one half had dosages above 200mg/day. The rate of seizure freedom increased from 28.4 to 37.6%. The 84% of the patients seizure free in 1992 remained seizure free. Predictors for seizure freedom in 2002 were higher age (stepwise logistic regression, p<0.0005) and seizure freedom in 1992 (p<0.0005)., Conclusions: Substantial improvement can be achieved even in intellectually disabled patients with chronic epilepsy. Although the rate of seizure freedom is reduced in comparison with a non-ID population, once seizure freedom has been achieved it is most likely to continue. For a majority of this patient population, monotherapy may not be sufficient. Lamotrigine/valproate appears to be a major therapeutic innovation.

Purpose: The aim of the study was to evaluate the efficacy of the modular educational program for children with epilepsy and their parents (FAMOSES). This program was developed by an interdisciplinary project group to improve knowledge, coping, treatment outcome, emotional and practical adaptation to the condition., Methods: A prospective, controlled, multi-center, pre-post study design was used to examine the efficacy of the program in the treatment group compared to the waiting group (control group). Questionnaires included epilepsy specific scales regarding knowledge, attitudes, restrictions in daily living, epilepsy related fears, coping with the chronic disease and generic instruments (quality of life, KINDL). 55 parents of the treatment group completed the questionnaires three months before the course and three months later; the corresponding waiting group included 48 parents. Respectively, 31 children, who participated in the program, completed the questionnaires immediately before the course and three months later; the corresponding waiting group included 19 children., Results: Children, who attended the program, showed improvements in the domains perceived restrictions (significant, medium effect size), absence from school and seizure frequency. Not significantly greater compared to the control group were the improvements of knowledge, attitudes and fears regarding to the epilepsy. Parents of the treatment group showed significant enhancements in epilepsy specific knowledge (large effect size), attitudes toward the epilepsy, management of epileptic seizures and significant reductions of fears and restrictions of their child with epilepsy (small to medium effect sizes).

Purpose: The regulation of extracellular ion concentrations plays an important role in neuronal function and epileptogenesis. Despite the many studies into the mechanisms of epileptogenesis in human experimental models, no data are available regarding the fluctuations of extracellular potassium ([K(+)](o)) and chloride ([Cl(-)](o)) concentrations, which could underlie seizure susceptibility in human chronically epileptic tissues in vivo., Methods: By using cerebral microdialysis during surgical resection of epileptic foci, the basic [K(+)](o) and [Cl(-)](o) as well as their changes after epicortical electric stimulation were studied in samples of dialysates obtained from 11 patients by ion-selective microelectrodes., Results: The mean basal values of [K(+)](o) and [Cl(-)](o) in all patients were 3.83 +/- 0.08 mM and 122.9 +/- 2.6 mM, respectively. However, significant differences were observed in the basal levels of both [K(+)](o) and [Cl(-)](o) between different patients. Statistically, no correlation was found between basal [K(+)](o) or [Cl(-)](o) and electrocorticogram (ECoG) spike activity, but in one patient, dramatically lowered baseline [Cl(-)](o) was accompanied by enhanced ECoG spike activity. Application of epicortical electrical stimulation increased [K(+)](o) but not [Cl(-)](o) in all cases. According to the velocity as well as spatial distribution of [K(+)](o) reduction to the prestimulation levels, three different types of responses were observed: slow decline, fast decline, and slow and fast declines at adjacent sites., Conclusions: These data may represent abnormalities in ion homeostasis of the epileptic brain.

Purpose: To evaluate the efficacy and tolerability of Levetiracetam (LEV) in a large pediatric cohort with drug-resistant epilepsy from a prospective multicenter observational study., Methods: We report the results of a multicenter observational survey of a cohort of 285 pediatric patients (mean: 9.9 years, range: 0; 6-17; 11) with refractory generalized and focal epilepsy who received Levetiracetam as an add-on open label treatment trial. The average duration of epilepsy was 6.0 years and the patients were treated with a mean of 7.0 antiepileptic drugs (AED) before LEV was introduced., Results: No serious persistent adverse events were reported. Reversible colitis and an apnoea syndrome in a child with phosphorylase-A-kinase-deficiency were noted. Mild to moderate side effects were reported in 128 patients (44.9%), consisting most frequently of somnolence (23.9%), general behavioral changes (15.4%), aggression (10.5%) and sleep disturbances (3.2%). In 209 patients, efficacy was analyzed over a treatment period of at least 12 weeks compared to a baseline of 2 weeks. Thirteen patients (6.2%) became seizure free, 39 (18.7%) responded with a seizure reduction of more than 50% following introduction of LEV. No response to LEV was reported in 65.1% (n=136). A decrease of initial treatment effect was seen in 37 patients (17.8%) while in 6.7% the seizure frequency doubled to the baseline (n=14). In seven patients (3.3%), the effect of LEV on seizure frequency could not be evaluated. A positive psychotropic effect was observed in 18 patients (8.6%). Mental retardation was associated with poor response and associated with more side effects and earlier discontinuation of LEV therapy., Conclusion: LEV is a well-tolerated new AED that may effectively improve seizure control as an add-on drug in resistant epilepsy in childhood with good tolerability. However, neurologically handicapped children appear at increased risk for reversible neurocognitive side effects and have a poorer treatment response.

We investigated the correlation of interictal epileptiform discharges (IED) in routine EEG 6 and 24 months after epilepsy surgery with regard to long-term seizure outcome. In 148 patients (74% temporal lobe epilepsy (TLE), 26% extratemporal epilepsy) EEG results (IED present or absent) were correlated with the postoperative outcome using the Engel classification 6 and 24 months after resection (PO6m and PO2y, respectively). Self-evaluation was conducted 3 and 5 years after resection (PO3y and PO5y, respectively). Ninety-one patients (62%) were seizure-free 5 years after resection; 88% of them showed no IED in PO6m. Twenty-eight patients (19%) displayed IED in routine EEG 6 months after resection; 61% of them had recurrent seizures at PO5y, whereas of 120 patients without IED only 33% had recurrent seizures at PO5y; p=0.01. Absence of IED in PO6m and PO2y correlated with good outcome: 71% without IED remained seizure-free, whereas only 25% with IED at PO6m and PO2y remained seizure-free; p=0.001. Seizure-free patients (Engel 1) and patients with less favourable outcome (Engel 3-4) at PO6m and PO2y rarely changed categories of outcome during the following years (p<0.001). Half of the patients with favourable seizure reduction (Engel 2) changed to seizure-free (Engel 1) or to a worse outcome category (Engel 3-4). Postoperative routine EEG is a good prognostic instrument for the prediction of long-term seizure outcome, especially for TLE. It predicts the running up and down of fits in patients with rare seizures (Engel 2).

Introduction: The purpose was to evaluate the effects of levetiracetam (LEV) in routine therapy in learning disabled patients with therapy-resistant epilepsy., Methods: In an open observational add-on study design, 46 patients (residents of the Bethel Epilepsy Centre) with severe therapy-resistant epilepsy and different degrees of learning disabilities, who were treated with LEV between its introduction in Autumn 2000 and February 2002, were evaluated retrospectively. Information on monthly seizure frequencies, seizure severity and psychiatric status was extracted from the current patient case records. A 3 months baseline and a 3 months LEV treatment period (after 3 months of titration) were compared. Responders were defined as having a 50% reduction in seizure frequency and being evaluated as good or very good in an ad hoc global clinical efficacy scale. When only one criterion was positive, a careful individual decision was made based on the impact on the patients' daily activities., Results: The responder rate was 41.3% (34.8 for 50% seizure reduction). It was higher in focal and multifocal epilepsy as compared to symptomatic generalised epilepsy/Lennox Gastaut Syndrome (P<0.05). Antiepileptic response occurred in doses between 500 and 4000 mg/day. Changes in seizure severity were rare. Nine patients experienced positive psychotropic effects (mostly improved vigilance and mood); six of these patients had antiepileptic effects as well. Twelve patients had adverse effects, mostly mild; in three cases, however, more severe effects led to discontinuation., Conclusions: LEV is an effective and generally well-tolerated drug for this patient group, especially in focal and multifocal epilepsy.

The symptoms of epileptic seizures in old patients differ from those in younger patients. Therefore, these seizures may be misinterpreted as symptoms of other "typical" diseases in old people. In an old people's home, we assessed whether a standardized questionnaire is able to reveal undiagnosed epilepsy in the elderly. Reported sudden falls, loss of consciousness, and cramps were the criteria for further diagnostic procedures. We found epilepsy in 11 of 389 study participants. In four of them (1% of the total sample), the epilepsy was newly diagnosed; five more cases remained unclear. Therefore, the total number of epileptic patients might have been even higher. Most of the reported sudden falls and unconsciousness (89%) were due to internal medical or other neurological or orthopaedic causes. Once these have been excluded, the diagnosis of epilepsy should be considered. The results of our pilot study suggest that epilepsy in old people's homes is often unrecognised. Early diagnosis and treatment of epilepsy in the elderly is important to improve prognosis and social consequences for affected persons.

Compared with temporal or frontal resections, epilepsy surgery in the posterior cortex is rarely performed, and the literature concerning clinical predictors for the postoperative seizure outcome in this particular subgroup is sparse. The data of 42 patients with lesional focal epilepsies of the parieto-occipital lobe and the occipital border of the temporal lobe were evaluated retrospectively and related to the seizure outcome 2 years after epilepsy surgery. The investigated parameters included ictal semiology, pre- and postoperative EEG and neuroimaging, histological findings and demographic data. Postoperatively, seizure-free outcome was seen in: (i) 69% of patients with lateralizing auras, but only in 28% of patients without lateralizing auras (P = 0.01); and (ii) 57% of the patients with lateralizing seizures, but only in 17% of patients without lateralizing ictal semiology (P = 0.02). None of the patients with neither lateralizing auras nor lateralizing seizures achieved freedom from seizures (P < 0.01). The proportion of lateralizing seizures (P < 0.01) and auras (P = 0.02) in the total number of recorded seizures and auras was significantly related to the probability of a favourable surgical outcome. No patient with clinical lateralizing signs to the non-lesional hemisphere but 58% without such "false" lateralization achieved freedom from seizures (P = 0.02). The following parameters also proved to be predictive for a favourable seizure outcome: (i) tumoural aetiology; and (ii) absence of epileptiform discharges in the postoperative EEG. The presence and frequency of ictal semiology lateralizing to the lesional hemisphere and the absence of lateralizing signs to the non-lesional hemisphere are highly predictive of a favourable outcome after surgical treatment of epilepsy in the posterior cortex.

Purpose: To estimate the incidence rate of epilepsies and epileptic syndromes in German children and adolescents aged 1 month to <15 years, and to provide data on their classification., Methods: A population-based prospective study was performed between July 1, 1999, and June 30, 2000. All children aged 1 month to <15 years with a newly diagnosed epilepsy or epileptic syndrome were recorded by private pediatricians, EEG laboratories, and the two University Children's Hospitals in the neighboring cities of Heidelberg and Mannheim. The diagnoses were classified according to the International Classification of Epilepsies and Epileptic Syndromes of the International League Against Epilepsy (ILAE)., Results: The total age-adjusted annual incidence rate was 60/100,000 (95% confidence interval, 42-84), with the highest incidence in the first year of life (146/100,000). Focal epilepsies or epileptic syndromes (58%; incidence rate, 35/100,000) were more common than were generalized ones (39%; incidence rate, 24/100,000), and 3% (incidence rate, 2/100,000) of the epilepsies or epileptic syndromes were undetermined. The rate of idiopathic (47%; incidence rate, 29/100,000) and symptomatic or cryptogenic epilepsies (50%; incidence rate, 30/100,000) was equal. No significant difference in incidence between boys and girls was found., Conclusions: Incidence rates for epilepsy in German children aged 1 month to <15 years are about equal to those of other countries in Europe and North America. In accordance with studies from the United States and from many European countries, incidence was highest in the first year of life, and no difference in the incidence between girls and boys was found. In Germany as throughout Europe, idiopathic generalized epileptic syndromes are more often diagnosed than in the United States.

Objective: To test the hypothesis that sudden unexplained death (SUD) in epilepsy is related to geomagnetic activity., Background: Prior studies presume that geomagnetic activity (with average amplitudes above 50 nanotesla [nT]) is associated with SUD in epileptic human patients and in epileptic laboratory rats., Methods: In a retrospective study, 46 epileptic patients with definite SUD were compared with 108 epileptic patients with known cause of death (KCD) who died between 1981 and 1992. A complete postmortem examination was performed in all cases. The time of the day and date of death, as well as two international geomagnetic indices concerning Bartels' planetary 3-hour signs (Kp) and the mean planetary daily amplitudes (Ap) at time of death, were assessed., Results: Among 45 SUD individuals, the local time (37.8%) and the universal time of death (35.6%) peaked within the critical period between 3 to 9 AM. However, the SUD and KCD group did not substantially differ in regard to the distribution of local or universal time of death (p > 0.2, Fisher test). Neither the Kp signs at death and 2 hours before death nor the Ap values showed considerable differences between the SUD and KCD series (p > 0.2, Mann-Whitney test). Merely 4.3% of SUD patients and 3.7% of KCD patients were associated with Ap indices above 50 nT (p > 0.2, Fisher test)., Conclusion: The results do not support the hypothesis that geomagnetic activity is related to occurrence of sudden unexplained death in epileptic patients.

The last premortem serum concentrations of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ) and its CBZ-10,11-epoxide metabolite (CE) were compared with the corresponding postmortem serum concentrations in 16 adult patients of an epilepsy centre. Based on complete postmortem examinations, 12 individuals showed a known cause of death (KCD) and four patients succumbed from sudden unexplained death (SUD). The last premortem and the postmortem serum levels of PB (r = 0.991), PHT (r = 0.986), CBZ (r = 0.985) and CE (r = 0.936) were highly correlated. However, the regression analysis indicated that, except for CE, the premortem concentrations were significantly higher than the postmortem concentrations, i.e. 65% for PB, 34% for PHT, and 16% for CBZ. Varying time lapses (4-62 h) between death and serum sampling during autopsy did not significantly influence the ratio of premortem to postmortem serum levels for PB, PHT, CBZ, and CE (p > 0.1). Furthermore we found no significant differences between the premortem and the postmortem serum concentration ratios CE/CBZ. Considering the above variables, the data of SUD and KCD patients were comparable. Postmortem decrease in anticonvulsant serum concentrations, especially for PB and PHT, should be considered in order to avoid misinterpretation in respect to so-called 'subtherapeutic' serum levels and noncompliance in context with SUD or fatal intoxication.

Post-mortem concentrations of phenytoin (PHT) and phenobarbital (PB) were determined by high-performance liquid chromatography in the cortical matter of specified brain regions and in the serum (total and free) from 3 epileptic males in vegetative state and compared to the data of 45 deceased epileptic control patients. The duration of the vegetative state was 12 days, 15 days or about 4 months until death and was associated with corresponding stages of generalized ischemic brain damage. The histological examination was completed by immunohistochemical and morphometric methods. According to other investigators nerve cells are the major binding sites for PHT and PB in the cerebral cortex of rodents. But, in the 3 comatose patients the PHT and PB concentrations of the isocortex and neocerebellum were not significantly decreased in comparison with the control patients despite necrosis and loss of neurons as well as other distinct tissue alterations. The results strongly favor the non-specific binding of PHT and PB to cells and subcellular structures of the brain-mainly based on simple physico-chemical principles.

Lamotrigine (LTG) is a new antiepileptic drug (AED), chemically unrelated to the drugs in current use. Previous studies have shown that LTG has only a limited effect on other AEDs, but its own metabolism can be strongly induced or inhibited by the comedication. We investigated the influences of carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), valproic acid (VPA), and combinations of these drugs on the serum concentration of LTG. A total of 588 blood samples from 302 patients were analyzed. The mean duration of LTG therapy was 141 +/- 137 days (mean +/- SD). A patient was only considered twice in this study if his or her comedication had been changed. The LTG serum concentration in relation to LTG dose/body weight (level-to-dose ratio, LDR, microgram/ml/mg/kg) was calculated and compared for different drug combinations. The results showed that comedication had a highly significant (p < 0.001) influence on the LTG serum concentrations. The mean LDR for LTG was 0.32 (LTG + PHT) < 0.52 (LTG + PB) approximately equal to 0.57 (LTG + CBZ) < 0.98 (LTG mono) approximately equal to 0.99 (LTG + VPA + PHT) < 1.67 (LTG + VPA + CBZ) approximately equal to 1.80 (LTG + VPA + PB) < 3.57 (LTG + VPA (<, p < 0.05; approximately equal to, p > 0.05, multiple comparisons). The mean LTG concentrations in patients on comedication with VPA were about two times higher than on patients on LTG monotherapy or on comedication without VPA (5.0 vs. 2.6 micrograms/ml), despite the LTG doses being half as high (3.0 vs. 5.9 mg/kg). The correlations of the serum concentrations and doses of CBZ, PB, PHT, and VPA with the LDR of LTG were only weak or not significant. Furthermore, the distribution of LTG serum concentrations and dosages was compared with the tentative therapeutic range for the LTG concentration (1-4 micrograms/ml), proposed by some investigators, and the recommendations for the LTG dosage. Remarkable discrepancies were observed. The comedication has an important influence on the LTG concentration and should be considered in LTG dosage.

Post-mortem concentrations of carbamazepine (CBZ) and its anticonvulsive metabolite carbamazepine-10,11-epoxide (CE) were determined in different lesions of the cerebral cortex and in the serum (total and free) from 13 epileptic patients. Twenty cortical specimens were obtained from the superior frontal gyrus, the temporopolar region and the neocerebellum. The cortical samples showed various pathological changes characterized by augmented glial cells, fibre gliosis or ulegyria as well as abundant corpora amylacea or encephalitic signs of viral type besides neuronal depletion. The CBZ and CE concentrations in the 20 cortical lesions were not significantly decreased when compared to the control specimens of 32 epileptic patients without essential histopathological alterations of the specified cortical areas (p < 0.05). A comparable result had been found in our former study on phenytoin (PHT) and phenobarbital (PB). Six patients with cortical lesions of the present series had already been included in this PHT/PB study. Five of these patients revealed unchanged CBZ and CE as well as PHT and PB concentrations. Only in one neocerebellar specimen the CE concentration was just above the upper 95% confidence limit of the control group. But, most probably this finding has no further relevance. The results greatly favour the nonspecific binding of CBZ and CE to cerebral tissue constituents.

Oxcarbazepine (OCBZ) is a new antiepileptic drug with a chemical structure similar to carbamazepine. We investigated the daily fluctuations of 10-OH-carbazepine (monohydroxy derivative, MHD), the clinically relevant metabolite of OCBZ, in patients with or without comedication. Twenty-two profiles of (total) serum concentrations of MHD from 18 epileptic patients on a b.i.d. OCBZ regimen were determined at 8.00, 11.00, 14.00, 17.00, 20.00 h (and 22.00 h/23.00 h). A patient was only considered twice if his comedication or OCBZ dosage had been changed. The maximal MHD concentrations were about 33% +/- 14% higher than the minimal MHD concentrations during the day. The free MHD concentrations were determined in 17 profiles. The mean free fraction of MHD was 56.7% +/- 5.5%. In combination with valproic acid the free fraction (64.0% +/- 1.4%) was slightly, but significantly higher (p < 0.05) than in monotherapy (52.3% +/- 0.9%) or in combination (58.0% +/- 2.6%) with other antiepileptic drugs (2 x phenobarbital, 2 x methsuximide, 1 x sulthiame). Further studies are necessary to clarify if the observed fluctuations of MHD are of clinical importance.

Postmortem concentrations of phenytoin (PHT) and phenobarbital (PB) were determined in 24 specimens of the frontal, temporal, occipital or neocerebellar cortex with different pathological changes and in the serum (total and free) from 11 epileptic patients. The cortical lesions were characterized by various degrees of neuronal loss or necrosis associated with other changes such as proliferated gliocytes, fibre gliosis, Rosenthal fibres or numerous corpora amylacea. According to other investigators neurons are the main binding sites of PHT and PB in rodent brains. The PHT and PB concentrations in 20 cortical lesions from nine patients were not significantly reduced as compared to the data of 46 deceased epileptic control patients. A significantly decreased PB value could only be demonstrated in the temporal specimen of an old scarred infarction with complete demyelination. On the other hand a slight but significant increase of PB was observed in three neocortical samples from a child exhibiting severe brain oedema and thrombosis of the sinuses. The results favour the unspecific binding of PHT and PB to cerebral tissue constituents and do not support the hypothesis of major binding to specific receptors.

Trends in treatment of epilepsy in an institution for handicapped patients with epilepsy were investigated in a retrospective longitudinal study. Medications and seizure frequencies in the period 1971 to 1986 were compared in 663 patients living in the institution at least since 1971. The results show that the majority of patients were on polytherapy, being treated on average with 2.95 (1971) to 2.60 (1986) anticonvulsants. The use of phenytoin, primidone and the succinimides clearly declined; the use of phenobarbitol declined slightly. The use of carbamazepine and valproic acid and their mean doses increased. The mean serum concentration of most of the anticonvulsants studied tended to move into the "therapeutic" range. The primidone and phenytoin concentrations remained rather low. The frequency of seizures, in particular of grand mal seizures, decreased between 1971 and 1981; from 1981 to 1986, no clear trend could be established. The results are compared with those of studies carried out in various other countries. It is discussed whether special antiepileptic therapy is required for the treatment of handicapped patients.

Sulthiame is an antiepileptic drug that was introduced approximately 30 years ago for the treatment of epilepsy. Currently it is rarely used, but recent studies show its efficacy, especially in the treatment of focal epilepsies in children. Because there are hardly any pharmacokinetic studies of sulthiame in humans, we studied the dose-level relationship, the elimination half-life, and the daily fluctuations in the concentration of sulthiame among children and adults with epilepsy. The evaluation of the sulthiame serum concentrations of 86 patients gave, considering age and comedication, a relatively high correlation (r = 0.82) between the sulthiame dose/body weight and the sulthiame serum concentration. Children on a comparable sulthiame dose per body weight have lower sulthiame concentrations than adults. In our study sulthiame was, with few exceptions, administered in combination with other antiepileptic drugs. The sulthiame serum concentrations were lower in comedication with carbamazepine than with valproic acid. The evaluation of the individual sulthiame dose-level relationship of 8 patients showed in most cases a close and linear relationship. After withdrawal of sulthiame in 11 patients, short elimination half-lives (8.65 +/- 3.10 h) were estimated. This was in accordance with the large daily fluctuations in the sulthiame concentrations (swing: 103.9 +/- 59.3%) of the nine patients examined. The shorter half-lives and higher daily fluctuations in children indicate a higher clearance of sulthiame among children.

Concentrations of carbamazepine (CBZ) and its metabolite carbamazepine-10, 11-epoxide (CE) were determined in serum (free and total), brain tumors and paratumorous cortex from 37 epileptic patients. Tumor biopsies were available from 25 different gliomas, 5 hamartomas and 1 angioma. The free serum concentrations of CBZ and CE were highly correlated with the corresponding paratumorous concentrations (r = 0.94 and r = 0.93) and to a lower extent with the tumorous concentrations (r = 0.78 and r = 0.75). For CBZ the concentration ratios paratumorous cortex/serum free and tumor/serum free showed no significant differences between CBZ-resistant and -nonresistant patients. Apart from histological grade a significant influence of type and site of the tumors on their CBZ and CE concentration was not recognizable. The results indicate that resistance to CBZ therapy cannot be sufficiently explained by decreased paratumorous or tumorous levels of CBZ and CE.

Postmortem concentrations of phenobarbital (PB), carbamazepine (CBZ), and its metabolite carbamazepine-10,11-epoxide (CE) were determined by high-performance liquid chromatography in the serum (total and free) and in specified areas of the brain (frontal, temporal, occipital cortex, and white matter, as well as cerebellum) of 51 deceased epileptic patients. The concentrations of PB and CBZ in the frontal cortex were approximately 1.4 times higher, and of CE were 1.1 times higher than the total concentrations in the serum. Furthermore, the concentrations of PB in the frontal cortex were approximately 2.1 times, of CBZ were 4.5 times, and of CE were 2.1 times higher than the free concentrations in the serum. The distribution of the three substances in the brain is rather homogeneous and seems to follow basic physicochemical principles. This means that the concentrations of the substances in the white matter are, depending on their lipophilicity, modestly but significantly higher than in the cortex. Small and in part statistically significant concentration differences between different regions of the cortex and also of the white matter may be explained by differences in the lipid content of the respective regions and by the lipophilicity of the respective substance. The concentrations in the cerebellar hemisphere (neocerebellum) were nearly identical to those in the frontal cortex. Remarkably increased or decreased concentrations were not observed in any region of the brain.

The effects of the withdrawal of phenytoin (PT) on cognitive and psychomotor functions of long-term patients in an epilepsy centre were studied. The patients had been treated for many years (31.1 +/- 10.8 yrs.) with PT in combination with other antiepileptic drugs. The serum concentration of PT was in the lower to middle therapeutic range (6.8 +/- 3.1 mg/l). Only patients in which the efficacy of PT was questionable were included in the study. PT was withdrawn in 17 patients. The PT dose was not changed in 12 patients (control group). Psychological tests were carried out immediately before the withdrawal of PT and about 10 weeks later. Tests were also carried out with the control group at the same time. A significantly improved performance (using a composite score) was noted after the withdrawal of PT. The statistical evaluation of the different tests showed an significant improvement in one test of concentration and two tests of psychomotor function (tapping and pursuit rotor with the dominant hand). There was no significant change in the frequency of seizures.

Postmortem concentrations of phenytoin (PHT) were determined by high-performance liquid chromatography in the serum (total and free) and in specified areas of the brain (frontal, temporal, occipital cortex and white matter, as well as cerebellum) of 18 epileptic patients who died following chronic diseases (group A) and of six otherwise healthy epileptic patients who died suddenly and unexpectedly (group B). The free concentrations in the serum correlated considerably better (r = 0.987) than the total concentrations in the serum (r = 0.871) with the concentrations in the frontal cortex. The concentrations in the frontal cortex were about nine times that of the free serum concentrations. The data show that the PHT concentrations in the frontal, temporal and occipital cortex largely agree. The concentrations in the white matter were significantly higher (frontal region 54%, temporal region 30%, occipital region 36%) than in the cortex. The concentrations in the cerebellar hemisphere (neocerebellum) were nearly identical with those in the frontal cortex. Regression analysis showed that on comparable total serum concentration the patients of group A had significantly higher free serum concentrations and significantly higher concentrations in the frontal cortex than the patients of group B. In respect of the concentration ratios cortex to serum free and in regard of the local distribution of PHT in the brain no difference, however, was found between those patients who died from chronic diseases and those who died suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

The free fraction of antiepileptic drugs can, in certain diseases, be greatly increased in the serum. In order to study the significance of this increase for the concentration in the brain, the postmortem concentrations of phenytoin (PT), phenobarbital (PB), carbamazepine (CBZ), and its metabolite carbamazepine-10,11-epoxide (CE) in the serum (total and free), as well as in specimens of the frontal cortex of 45 epileptic patients who died from various causes, were determined. The postmortem free fractions were higher than reported in the literature and varied considerably from subject to subject. For PT the free fraction was 21.7% (median), for PB 68.0%, for CBZ 33.4%, and for its metabolite CE 53.6%. The values for a control group of 236 otherwise healthy epileptic patients were in agreement with those given in the literature, namely 10.4% for PT, 55.6% for PB, 20.9% for CBZ, and 42.5% for CE. Using a nonparametric correlation coefficient (Kendall T), the concentrations in the frontal cortex of the autopsied patients correlated with the postmortem free serum concentrations, especially for the substances with high protein binding (PT and CBZ), better (PT r = 0.88, PB r = 0.86, CBZ r = 0.87, CE r = 0.79) than with the total concentrations (PT r = 0.69, PB r = 0.80, CBZ r = 0.77, CE r = 0.77). The study indicates that in critically ill patients the determination of the free concentration in serum is indispensable. If treatment is orientated solely on the total concentration, unexpectedly high concentrations in the brain and hence possible intoxication of the patient in the critical or final state can result.

The influence of daily fluctuations in the concentration of valproic acid (VPA) on the unbound and total concentration of phenytoin (PT) was examined in a prospective study. The serum concentrations of 28 patients with epilepsy (group PT + VPA) who were treated with PT and concurrently with VPA and 15 patients (group PT) who were treated with PT but without VPA comedication were determined at 8.00, 11.00, 14.00, 17.00, and in part at 20.00 h. The results show that there are significantly greater fluctuations in the total PT concentration among patients on VPA than those not on VPA. The fluctuations in the total PT concentration during the day correlated with the fluctuations in the VPA concentration. On the other hand, the fluctuations in the concentrations of unbound PT of patients on VPA were comparable with those not on VPA. In the absence of VPA, the diurnal fluctuations of the total PT concentration correlated highly significantly with the fluctuations of the unbound PT concentration. This is not the case in patients on VPA. Our data are a further indication of the smaller significance of the total PT concentration as compared with the unbound PT concentration in the combined treatment of PT and VPA.

The study of 14 children and adolescents shows that the addition of carbamazepine (CBZ) to a basic valproic acid (VPA) therapy can result in unexpectedly high concentrations of carbamazepine-10,11-epoxide (CE) in the serum (up to 13 micrograms/ml). These concentrations were associated with marked side effects, especially vomiting and tiredness. The concentrations of CBZ were within the therapeutic range. Very high CE concentrations can largely be avoided at the commencement of the CBZ treatment if the CBZ dose is slowly increased. But high CE concentrations (4-8 micrograms/ml) associated with side effects can also be reached in later stages during the build up of CBZ treatment and under steady state conditions. The determination of the CE concentration is important when VPA and CBZ are administered together, especially when side effects occur.

The influence of carbamazepine (CBZ) dose, CBZ preparation used, comedication (phenobarbital, phenytoin, primidone, valproate), and factors such as age, weight, and sex on the concentration of CBZ and its metabolites carbamazepine-10,11-epoxide (CBZ-epoxide) and 10,11-dihydro-10,11-dihydroxy-carbamazepine (CBZ-diol) in serum was investigated. A non-linear regression analysis using the data of 609 patients shows that other anti-epileptic drugs can influence the metabolism of CBZ in various ways. The mean serum concentration of CBZ is lower when the drug is given in combination with phenytoin (59.4%), primidone (58.2%), phenobarbital (65.7%), and valproate (83.0%) than when CBZ is given alone (100%), whereas the mean concentration of CBZ-epoxide is increased by valproate (144.8%), by primidone (118.5%), and by a combination of the latter (167.4%). The CBZ-diol concentrations are also increased during concomitant treatment with the other antiepileptic drugs. Our results indicate a nonlinear relationship between the CBZ dose and the CBZ concentration, but a linear relationship between the CBZ dose and the CBZ-diol concentration.

The ratio of the concentration of the phenytoin metabolite hydroxyphenyl phenylhydantoin (HPPH) to the creatinine concentration in morning urine samples was used as an index of compliance in adult epileptic patients on phenytoin therapy. For this purpose, the phenytoin dose was estimated from the urinary HPPH/creatinine ratio with the help of a regression equation that took into consideration body weight, height, age, and sex. A high correlation (r = 0.927 for men and r = 0.954 for women) between the prescribed and estimated dose was found for a reference group (127 hospitalized patients on supervised drug regimen). Compliance was judged from the discrepancy between the prescribed and the estimated dose for 45 patients immediately after their admittance to an epilepsy clinic, as well as for 98 outpatients, who had been treated by neurologists. Noncompliance was suspected in 6.7% of patients admitted to the clinic, as well as in 28.6% of the outpatients.

Background and purpose In the epilepsy community, there is talk that the number of classical patients with early onset temporal lobe epilepsy ( TLE) and Ammon's horn sclerosis ( AHS) is decreasing. This is counterintuitive, considering the success story of epilepsy surgery, improved diagnostic methods and the current recommendation of early admission to surgery. In order to recognize trends, the development of temporal lobe surgery over 20 years in three major German epilepsy centers was reviewed. Methods Age at surgery and duration of epilepsy, which was differentiated according to histopathology ( AHS, developmental, tumor, vascular), year of surgery and center, were evaluated in a cohort of 2812 patients from three German epilepsy centers who underwent temporal lobe surgery between 1988 and 2008. The analysis was carried out for the pooled cohort as well as for each center separately. Results Of all patients, 52% showed AHS. Compared with other pathologies, the AHS group had the earliest epilepsy onset and the longest duration of epilepsy. Across five time epochs, the diagnosis of AHS increased in the first epoch, remaining constant thereafter. Contrary to the trends in other pathologies, in the AHS group the mean age of patients at surgery increased by 7 years and the duration of epilepsy until surgery increased by 5 years. This trend could be replicated in all three centers. As initially hypothesized for all groups, age and duration of epilepsy in other pathology groups remained constant or indicated earlier submission to surgery. Conclusions During the first few years studied, most probably due to progress in brain imaging, the proportion of patients with AHS increased. However, despite stable numbers over time, and contrary to the trends in other pathology groups, age and duration of epilepsy in mesial TLE with AHS ( mTLE + AHS) increased over time. This supports the hypothesis of a decreasing incidence of AHS. This trend is discussed with respect to disease-modifying factors which have changed the incidence of classical mTLE + AHS or, alternatively, to recent developments in antiepileptic drug treatment, the appraisal of surgery and economic incentives for treatment options other than surgery. [ABSTRACT FROM AUTHOR]

Objective: To assess the predictive diagnostic added value of positron emission tomography (PET) in preoperative epilepsy surgery evaluation for patients with temporal lobe epilepsy (TLE). Methods: A meta-analysis of publications from 1992 to 2006 was performed. Forty-six studies were identified that met inclusion criteria presenting detailed diagnostic test results and a classified postoperative outcome. Studies exclusively reporting on patients with brain tumors or on children were excluded. Results: The analyses were complicated by significant differences in study design and often by lack of precise patient data. Ipsilateral PET hypometabolism showed a predictive value of 86% for good outcome. The predictive value was 80% in patients with normal MRI and 72% in patients with non-localized ictal scalp EEG. In a selected population of 153 TLE patients with a follow-up of >12 months PET correlated well with other non-invasive diagnostic tests, but none of the odds ratios of any test combination was significant. Conclusion: Our data confirm that ipsilateral PET hypometabolism may be an indicator for good postoperative outcome in presurgical evaluation of drug-resistant TLE, although the actual diagnostic added value remained questionable and unclear. PET does not appear to add value in patients localized by ictal scalp EEG and MRI. Prospective studies limited to non-localized ictal scalp EEG or MRI-negative patients are required for validation. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: We aimed to assess the additional pre-operative value of 1H MRS in identifying the epileptogenic zone (EZ) for epilepsy surgery by performing a meta-analysis considering publications from 1992 to 2003. Methods: From an extensive computer and hand search 22 studies were included. For inclusion, studies had to report post-operative outcome and detailed diagnostic test results for each individual patient. Studies exclusively reporting on patients with brain tumors or on children were excluded. Results: Great heterogeneity among studies regarding methodological and technical aspects and concerning evaluation and interpretation of data was observed. Only patients with intractable temporal lobe epilepsy were presented. Sixty-four percent of all patients and 72% of patients with good outcome had an ipsilateral MRS abnormality concordant with the EZ. The positive predictive value of all patients with ipsilateral MRS abnormality for good outcome was 82%. An odds ratio weighted by inverse variance showed a 4.891 better chance of seizure free outcome [CI=1.965–12.172; Q =2.748; d.f.=5; critical χ 2-value=11.07] in patients with an ipsilateral MRS abnormality when compared to patients with bilateral MRS abnormalities. Data for MRI-negative patients were conflicting. One study stressed a role for MRS in patients with bilateral hippocampal atrophy at MRI. Conclusions: MRS still remains a research tool with clinical potential. Our findings indicate the connection of ipsilateral MRS abnormality to good outcome. The ability for prediction of post-operative outcome may depend on the assessed population. Prospective studies limited to non-localized ictal scalp EEG or MRI-negative patients are required for validation of these data. [Copyright &y& Elsevier]