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Purpose: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE)., Methods: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years., Results: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts., Conclusions: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.

Purpose: The goal of the study was to evaluate the safety and efficacy of a broad oxcarbazepine (OXC) dosage range (600, 1200, and 2400 mg/d) as adjunctive therapy for uncontrolled partial seizures and to determine the relationship between trough plasma 10-monohydroxy derivative concentrations and OXC safety and efficacy., Methods: This multinational, multicenter, randomized, 28-week, double-blind, placebo-controlled, four-arm, parallel-group trial enrolled 694 patients aged 15-65 years with uncontrolled partial seizures with or without secondarily generalized seizures. The primary efficacy variable was percentage change in seizure frequency per 28 days relative to baseline., Results: The median reduction in seizure frequency was 26%, 40%, 50%, or 8% for patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively (all p < or = 0.0001). Of patients in the 600, 1200, or 2400 mg/d OXC groups, 27%, 42%, and 50% respectively, had more than 50% reduction in seizure frequency compared with 13% for placebo (all p < 0.001). Higher plasma 10-monohydroxy derivative concentrations were associated with larger decreases in seizure frequency (p = 0.0001). During the double-blind treatment phase, 84%, 90%, 98%, and 76% of patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively, reported one or more adverse events. The most common adverse events were related to the nervous and digestive systems., Conclusions: OXC is safe and effective as adjunctive therapy in patients with uncontrolled partial seizures. OXC 600 mg/d was the minimum effective dosage; effectiveness of OXC increased with dose. The rapid and fixed titration to high doses was associated with an increased risk of adverse events, which could potentially be reduced by adjusting concomitant antiepileptic medication and by using a slower, flexible OXC titration schedule.

Telemedicine is a rapidly expanding discipline. Looking back on a long tradition of telemetric measurement and transmission of brain electrical data, one might ask how relevant telecommunication techniques have become for clinical work in epileptology. In principle, communication can be either between patient and doctor or between doctor and doctor. The former includes telephone reports on frequency and severity of seizures and on mental and physical state. Because of the special problems of patients with epilepsy, the need for traveling should be minimized. To maintain close contact, telemetric transmission of electroencephalograms (EEG), seizure video-registration, and monitoring of anti-epileptic drug (AED) blood levels from home are desirable, but the technical tools now available are not of sufficiently high performance for these applications. However, physicians and medical units can communicate using high-rate data transfer. There are major problems with this technology. Transfer rates using the internet are not fixed. Moreover, using six digital telephone lines simultaneously, good-quality transmission of a 3-min video may take more than 1 h, restricting interactivity. In contrast to imaging (e.g., magnetic resonance imaging), there is no generally accepted protocol for handling EEG/electrocorticography data. There are also legal problems relating to the responsibility for failures and safety of personal or medical data. Nevertheless, the expenses of installation and use of such equipment appear justified by the expected benefits, for the patients (avoiding travel and multiple investigations, checking diagnosis and therapy, amending quality of life), for the physician (sparing equipment and manpower, accelerating and improving diagnosis), for the epilepsy center (increased database for expert systems, improved logistic and data storage) and, finally, for insurance providers (reduced overall costs). When the neurosurgical procedure is remote from the place of presurgical evaluation, telecommunication should be obligatory.

Purpose: To evaluate the neuropsychological performance of children before and after temporal lobe resection (TLR)., Methods: Memory, attention, language, and visuoconstructive abilities were examined in 20 children (age 10-16 years) before, and 3 and 12 months after TLR (right, n = 10; left, n = 10; two-thirds anterior resection, n = 16; amygdalohippocampectomy, n = 4). Preoperative performance was compared with data of 30 age-matched healthy children; changes in performance after surgery were determined by repeated-measurement multivariate analysis of variance (MANOVA) and by use of reliable change indices (RCI)., Results: Preoperatively, no differences were observed between patients and controls in verbal and figural memory performance. Children with temporal lobe epilepsy (TLE), however, and particularly those with a left temporal focus, showed significantly reduced language performance. Repeated-measurement statistics indicated that memory performance did not change after surgery, whereas language performance and attention significantly improved 3 months and 1 year after surgery, respectively. Individual evaluations of memory showed gains in five children and deterioration in four children. Poor seizure control appeared the decisive variable characterizing children with losses in memory., Conclusions: Compared with adults, pre- and postoperative memory data suggest less pronounced hemispheric differences in school-age children with TLE. The results raise the possibility that children have a lower risk of memory deterioration after TLR, which may be due to their larger potential for cerebral plasticity.

Purpose: Because a low IQ score indicates global brain damage, several authors consider it a contraindication for resective epilepsy surgery. This study reports the postoperative results of a small group of subaverage-intelligence patients with epilepsy who underwent focal resections., Methods: We report on 16 patients who underwent focal resections (no callosotomy or hemispherectomy). All had IQ's <85 and were >13 years of age at the time of surgery. Low IQ was psychometrically assessed (mean IQ = 70) and confirmed by the patients' educational/occupational status. Clinical characteristics, findings from the preoperative workup, and the surgical treatment are described in detail. Postoperative outcome was evaluated with respect to seizure relief and cognitive/ socioeconomic development., Results: Three months after surgery, 14 (87%) of 16 patients were completely seizure free, and nine (64%) of 14 were seizure free at the 1-year follow-up. Patients' cognitive abilities and socioeconomic status were mostly unchanged and in some cases improved. Seizure outcome was not related to IQ level, and there was no evidence of multiple epileptic foci in the patients with continued seizures., Conclusions: A low IQ level does not entail the presence of extended epileptogenic regions or multiple epileptic foci. Seizure-relief rates in our group concurred with the rates in patients of average intelligence, and the cognitive/socioeconomic outcome was favorable. We conclude that focal surgery in intellectually impaired patients can be recommended if the preoperative diagnostics confirm a circumscribed seizure onset.

Purpose: In spite of unequivocal results of the presurgical evaluation, between 10 and 30% of patients with medial temporal lobe epilepsy (MTLE) do not become seizure free by temporal lobe surgery. Because event-related potentials (ERPs) recorded within the hippocampal formation have been shown to be sensitive to the epileptogenic process, we examined whether ERPs can help to improve the prediction of postoperative seizure control., Methods: We recorded ERPs to words from bilateral intrahippocaampal electrodes by using a visual word-recognition paradigm in 70 patients with unilateral hippocampal pathology and related these measurements to seizure outcome after temporal lobe surgery., Results: Words elicited N400 potentials, which were reduced in amplitude on repetition on the side contralateral to hippocampal sclerosis. This contralateral repetition effect, however, was significantly diminished in the group of patients who experienced seizure recurrence after the operation. Contralateral repetition effects thus permitted correct prediction of postoperative seizure control in 94% of all patients., Conclusions: Recording ERPs to words within the medial temporal lobes can improve the prediction of postoperative seizure control. Reduced repetition effects contralateral to the side of hippocampal sclerosis may indicate bilateral epileptogenicity.

Long-term antiepileptic drug (AED) treatment is the standard therapy for epilepsies. In about 60% of patients, the first AED tried usually leads to seizure control. After failure of the first AED, it is important to achieve seizure control rapidly and without side effects. Combining the first drug with an add-on drug appears to be more effective than a second monotherapy. However, no scientifically based data are available that favor any particular drug combination. Along with pharmacokinetic considerations, clinical experience is an important determinant in choosing a second AED for use as an add-on. The time needed to introduce a particular AED is a further consideration. The simultaneous introduction of two add-on drugs, one requiring slow titration and one permitting rapid introduction, may be a useful strategy. If the quickly introduced drug is effective as an add-on, introduction of a slowly titrated second add-on can be obviated. If the quickly introduced drug reduces seizure frequency, the patient's quality of life is improved during titration of the second add-on. If the second, slowly titrated drug is more effective than the quickly introduced one, the less-effective drug can be withdrawn. This strategy also allows a direct comparison between two add-on drugs at the same time.

Purpose: The anticonvulsants phenytoin (PHT), carbamazepine (CBZ), and gabapentin (GBP) are commonly used in the treatment of temporal lobe epilepsy. Ca2+ current modulation has been proposed to contribute to the antiepileptic activity of these drugs. The purpose of this study was to determine the effects of these anticonvulsants on voltage-dependent calcium channels in pathologically altered neurons from patients with chronic temporal lobe epilepsy., Methods: Acutely isolated human hippocampal granule cells were examined by using the whole-cell configuration of the patch-clamp technique., Results: PHT and CBZ produced a reversible, concentration-dependent inhibition of high-voltage-activated (HVA) Ca2+ currents without affecting voltage-dependent activation. The concentration-response curves of PHT and CBZ indicated maximal inhibition of 35 and 65%, respectively, with half-maximal inhibition being obtained at 89 and 244 microM, respectively. At therapeutic cerebrospinal fluid (CSF) concentrations, HVA currents were not significantly altered by PHT and CBZ. However, PHT but not CBZ showed a reduction of HVA currents of 16% at a therapeutic whole-brain concentration of 80 microM. In contrast to CBZ, PHT produced a small hyperpolarizing shift in the voltage dependence of steady-state inactivation. PHT, 80 microM, shifted the potential of half-maximal inactivation by -3.1 +/- 0.5 mV (p < 0.05). GBP, which was recently found to bind to the alpha2delta subunit of a neuronal Ca2+ channel, showed no modulation of Ca2+ conductances., Conclusions: These results suggest that, in contrast to GBP and CBZ, modulation of postsynaptic Ca2+ channels can contribute to the anticonvulsant action of PHT in human hippocampal granule cells.

Aggravation of focal epileptic seizures in adults is common after the antiepileptic drug (AED) therapy is initiated. Sometimes aggravation is mimicked by clustering of the seizures. Therefore, it is always necessary to analyze the patient's history and therapy carefully before drawing any conclusions. It is likely that a paradoxical aggravation of epileptic seizures can be attributed to the given AED and is sometimes, but only rarely, due to drug interactions.

Purpose: We evaluated retrospectively the socioeconomic development of epilepsy patients after temporal or extratemporal epilepsy surgery and analyzed the relationship to clinical and neuropsychological data., Methods: 151 patients (from ages 11-65 years; mean postoperative followup: 3 years) replied to a structured questionnaire, which referred to objective data of the patient's educational and vocational development. Neuropsychological data were obtained from pre- and postoperative (1-year follow-up) examinations., Results: The preoperative development data indicated that patients exposed to epilepsy at any developmental stage had a higher prevalence of educational/vocational difficulties as compared with patients with a later onset of epilepsy. Postoperatively, the integration of the formerly unemployed improved and the unemployment rate decreased from 33 to 16%. Out of those patients who had been schooled or who were employed, 79%-91% made progress in development, or were at least able to keep their status. Only 2 of 14 patients, who had been retired early because of their epilepsy, returned to employment. In general, a deterioration of the socioeconomic status was significantly related to insufficient seizure control. A reemployment of patients who were formerly unemployed depended mainly on age and neuropsychological outcome., Conclusions: Our results suggest that early and successful surgical intervention improves or at least maintains the socioeconomic situation, especially the employment status.

Purpose: Intracerebral depth electrodes are used in preoperative evaluation of selected patients with intractable epilepsies. In spite of their usefulness, safety of depth electrodes is disputed, and the number of insertions is decreasing. This study examined retrospectively possible deleterious effects such as perioperative complications, induction of epileptogenesis, and neuropsychologic deficits., Methods: Clinical course and neuroradiologic findings of 115 patients with bilaterally inserted longitudinal intrahippocampal depth electrodes (IDEs) were analyzed. Hippocampal resection specimens were examined histopathologically. To detect newly developed epileptogenic areas, EEG recordings, seizure control, and semiology after standardized resection procedures were compared between patients who received IDEs and those who did not. To demonstrate functional deficits caused by IDE insertion into an unaffected hippocampus of the speech-dominant hemisphere, changes of verbal learning and memory performances before and after right amygdalohippocampectomy were compared between patients evaluated with and without IDEs., Results: Five significant complications without any permanent neurologic deficit were noted, and only one was specifically linked to IDE insertion. The tissue damage associated with the insertion was minimal and sharply circumscribed. No differences of seizure outcome after standardized resections were identified between patients with and without IDEs. In postoperative EEG recordings, there was no evidence of new epileptogenic areas. No verbal memory deficit caused by IDE implantation into the hippocampus of the speech-dominant hemisphere was detectable., Conclusions: Results indicate that it is safe to implant these IDEs in selected patients.

Purpose: To assess the efficacy and safety of multiple subpial transection (MST), a new technique in epilepsy surgery, alone and in combination with resection., Methods: MST was performed in 22 patients with intractable epilepsy, 10 of whom were treated with a combination of a resection and MST in functionally important cortex, 6 of whom were treated with a combination of a resection and MST performed outside functionally important cortex, and 6 of whom were treated with MST alone., Results: Of the 6 patients who received MST alone, none became seizure free and 4 showed > 50% reduction of all seizure types. In 2 patients, including 1 with Rasmussen's encephalitis, no change in seizure frequency or intensity occurred. Of the 16 patients in whom MST was combined with a resection, 9 (56%) became seizure free. Six of the remaining 7 patients showed > 95% reduction of all seizure types. Disappearance of epileptiform potentials in the postoperative EEG correlated significantly with complete relief from seizures. Subtle, permanent neurological deficits remained in 5 of 14 patients who received MST in functionally important brain areas., Conclusions: Reduction of the seizure frequency was substantial in 4 of 6 patients who received MST alone, but complete seizure control was not observed. MST surrounding a lesionectomy may be a new surgical approach which would minimize the excised volume and improve seizure control.

Purpose and Methods: The aim of this study was to analyze clinical, radiologic, and histopathologic findings in 60 consecutive patients with medically intractable extratemporal epilepsy who were operated on between November 1987 and May 1993., Results: Histologically, there were distinct structural abnormalities in 50 (83%) of the surgical specimens. Signal abnormalities on magnetic resonance imaging (MRI) were present in all patients with neoplastic lesions (n = 17) and in 94% of patients with nonneoplastic focal lesions (n = 32). Overall, structural abnormalities were detected by MRI in 47 (96%) of 49 patients with focal lesions. During a mean follow-up of 4 years, 30 (54%) patients remained completely seizure free, 11 (20%) had < or = 2 seizures per year, seven (12%) showed a seizure reduction of > or = 75%, and eight (14%) had < 75% reduction in seizure frequency. The fraction of seizure-free patients was 12 (80%) of 15 in patients with neoplastic lesions, 16 (52%) of 31 in patients with nonneoplastic focal lesions, and two (20%) of 10 for those without histopathologic abnormalities. The differences in seizure outcome between patients with and without focal lesions were statistically significant (p < 0.05), if seizure-free outcome was compared with persistent seizures., Conclusions: Focal lesions and particularly neoplasms are associated with improved postoperative seizure control compared with patients without histopathologic abnormalities. We advise caution in considering surgery to treat extratemporal epilepsy in patients who have normal MRI scans, because the outcome with the approach described in this study is poor in such cases.

The semiology of complex partial seizures (CPS) of temporal lobe origin in adults is well known and is important in establishing seizure localization in patients considered for epilepsy surgery. In contrast, the behavioral features of temporal lobe seizures (TLS) in children described in the literature have not been consistent. In the present study, we investigated children with TLS to compare their attacks to TLS occurring in adults. The study was based on video recordings of 29 children with TLS aged 18 months to 16 years. Children were included, if they became seizure-free after temporal lobectomy (except 4 children with a marked reduction in seizure frequency and 1 with isolated auras), and if clear unitemporal seizure onset in ictal EEG-recordings, unilateral radiological lesions, and corresponding histopathological findings were detected. Children aged > 6 years had TLS with features similar to those of adults. In younger children, typical semiology included symmetric motor phenomena of the limbs, postures similar to frontal lobe seizures in adults, and head nodding as in infantile spasms. We concluded that the clinical features of TLS in younger children can be misleading and should therefore be considered with caution in selecting patients for surgical procedures on the temporal lobe.

Long-term electrocorticograms (ECoG), recorded by chronically implanted subdural electrodes during preoperative evaluation of 59 patients with temporal lobe epilepsy (TLE) were analyzed retrospectively to assess the prognostic relevance of distribution of interictal epileptiform potentials (IEP) and seizure origin (SO) and to investigate factors affecting their lateralization. Subsequent to preoperative evaluation, a standardized two thirds anterotemporal lobectomy including subtotal hippocampectomy had been performed in all patients. The following results were obtained: (a) Only patients with 100% lateralization of SO and IEP had excellent seizure outcome (= 89% seizure-free); (b) patients with bitemporal SO were unlikely to benefit from surgical treatment (= 12.5% seizure-free); (c) 40-56% patients with unilateral temporal SO and bitemporal IEP, became seizure-free irrespective of the degree of lateralization of IEP; and (d) multidimensional analysis of variance showed that lateralization of SO, presence of a magnetic resonance imaging (MRI)-detectable lesion, presence of hippocampal sclerosis, presence of febrile seizures and seizures at age < or = 6 years are the five most important variables indicating abolition of seizures. Combined analysis of ECoG-recorded SO and IEP allows prediction of postoperative seizure control within close boundaries.

A short anesthesia was provided by methohexital for painless percutaneous removal of subdural electrodes in 27 patients with medically intractable, complex partial seizures who had undergone invasive preoperative evaluation. Electrocorticographic(ECoG) recordings performed before and during the narcosis were submitted to visual (n = 27) and computerized (n = 3) analysis to obtain additional information about the location of the epileptic focus (or foci). The following observations were made: focal epileptiform potentials were induced in 24 of 27 patients (89%); (b) in 20 of these 24, the induced spikes appeared amid or were followed by isoelectric or subdelta activity. These spikes were characterized by high amplitude as well as rhythmic and synchronized appearance over a circumscribed focal area (or areas) known to be spontaneously epileptogenic. This phenomenon, termed spike-burst-suppression (SBS) pattern, allowed identification of the primary epileptic focus in many patients with temporal lobe epilepsy. Furthermore, it indicated a good outcome of epilepsy surgery. Computerized analysis of the induced synchronized spikes (n = 3) allowed further delineation of the primary site of epileptogenicity and quantitative comparison of multiple epileptic generators. ECoG recording during deep methohexital-induced narcosis is a valuable tool for lateralization and delineation of the primary epileptogenic focus.