Prognostic factors for surgery of neocortical temporal lobe epilepsy.

OBJECTIVES: In the current classification of epilepsies two forms of temporal lobe epilepsy (TLE) were included: mesial and lateral (neocortical) TLE. We aimed at identifying prognostic factors for the surgical outcome of lesional neocortical TLE. METHODS: We included consecutive patients who had undergone presurgical evaluation including ictal video-EEG and high-resolution MRI, who had TLE due to neocortical lateral epileptogenic lesions, who had a lesionectomy and who had >2-year follow-up. RESULTS: There were 29 patients who met the inclusion criteria. Twenty of them became postoperatively seizure-free. Patients' mean age was 34.8+/-9 years (range 18-52). The age at epilepsy onset was 20.1+/-8 years. We found that left-sided surgery (p=0.048) and focal cortical dysplasia (FCD) on MRI (p=0.005) were associated with non-seizure-free outcome, while lateralized/localized EEG seizure pattern (p=0.032), tumors on the MRI (p=0.013), and a favorable seizure situation at the 6-month postoperative evaluation were associated with 2-year postoperative seizure-freedom (p<0.001). Multivariate analysis indicated that the side of surgery was not an independent predictor. CONCLUSION: More than two-thirds of the patients with neocortical TLE became seizure-free postoperatively. Lateralized/localized EEG seizure pattern and tumors on the MRI were associated with postoperative seizure-freedom, while FCD were associated with a poor outcome. The 6-month postoperative outcome is a reliable predictor for the long-term outcome.

Failed surgery for temporal lobe epilepsy: predictors of long-term seizure-free course.

OBJECTIVES: To identify prognostic factors which predict the outcome 2 years after TLE surgery in those patients who were not seizure-free at the 6-month postoperative examination. METHODS: We included 86 postoperative TLE patients who had undergone presurgical evaluation, including video-EEG and high-resolution MRI, and who had seizures between the second and sixth postoperative months. RESULTS: 32% of patients were seizure-free in the second postoperative year. We found that normal MRI findings and secondarily generalized seizures (SGTCS) preoperatively were associated with a non-seizure-free outcome, while rare postoperative seizures and ipsilateral temporal IED with seizure-free outcome. Newly administered levetiracetam showed a significant positive effect on the postoperative outcome independent of other prognostic factors. Five of seven patients who received levetiracetam became seizure-free (p = 0.006). CONCLUSION: One-third of patients who did not become seizure-free immediately after surgery, eventually achieved long-term seizure freedom. We suggest watching for long-term seizure freedom after failed epilepsy surgery especially in patients who had rare postoperative seizures, focal MRI abnormality, ipsilateral temporal spikes, or no SGTCS preoperatively. Levetiracetam may have a positive effect on postsurgical seizures.

Vagus nerve stimulation: predictors of seizure freedom.

OBJECTIVES: To identify predictive factors for the seizure-free outcome of vagus nerve stimulation (VNS). METHODS: All 47 patients who had undergone VNS implantation at one centre and had at least one year of follow up were studied. They underwent complete presurgical evaluation including detailed clinical history, magnetic resonance imaging, and long term video-EEG with ictal and interictal recordings. After implantation, adjustment of stimulation parameters and concomitant antiepileptic drugs were at the discretion of the treating physician. RESULTS: Mean (SD) age of the patients was 22.7 (11.6) years (range 7 to 53). Six patients (13%) became seizure-free after the VNS implantation. Only two variables showed a significant association with the seizure-free outcome: absence of bilateral interictal epileptiform discharges (IED) and presence of malformation of cortical development (MCD). Epilepsy duration showed a non-significant trend towards a negative association with outcome. By logistic regression analysis, only absence of bilateral IED correlated independently with successful VNS treatment (p<0.01, odds ratio = 29.2 (95% confidence interval, 2.4 to 353)). Bilateral IED (independent or bilateral synchronous) was found in one of six seizure-free patients and in 33 of 41 non-seizure-free patients. When bilateral IED were absent, the sensitivity for seizure-free outcome was 0.83 (0.44 to 0.97), and the specificity was 0.80 (0.66 to 0.90). CONCLUSIONS: Bilateral IED was independently associated with the outcome of VNS. These results are preliminary because they were based on a small patient population. They may facilitate prospective VNS studies enrolling larger numbers of patients to confirm the results.

Temporal lobe epilepsy with hippocampal sclerosis: predictors for long-term surgical outcome.

Temporal lobe epilepsy (TLE) accompanied by hippocampal sclerosis (HS) is the type of epilepsy most frequently operated on. The predictors for long-term seizure freedom after surgery of TLE-HS are unknown. In this study, we aimed to identify prognostic factors which predict the outcome 6 months and 2, 3 and 5 years after epilepsy surgery of TLE-HS. Our working hypothesis was that the prognostic value of potential predictors depended on the post-operative time interval for which the assessment was made. We included 171 patients (100 females and 71 males, aged 16-59 years) who had undergone presurgical evaluation, including video-EEG, who had had MRI-defined HS, and who had undergone temporal lobectomy. We found that secondarily generalized seizures (SGTCS) and ictal dystonia were associated with a worse 2-year outcome. Both these variables together with older age and longer epilepsy duration were also related to a worse 3-year outcome. Ictal limb dystonia, older age and longer epilepsy duration were associated with long-term surgical failure evaluated 5 years post-operatively. In order to determine the independent predictors of outcomes, we calculated multivariate analyses. The presence of SGTCS and ictal dystonia independently predicted the 2-year outcome. Longer epilepsy duration and ictal dystonia predicted the 3-year outcome. Longer epilepsy duration (P = 0.003) predicted a poor 5-year outcome. Conclusively, predictors for the long-term surgical results of TLE with HS are different from those variables that predict the short-term outcome. Epilepsy duration is the most important predictor for long-term surgical outcome. Our results strongly suggest that surgery for TLE-HS should be performed as early as possible.

Effect of levetiracetam on epileptiform discharges in human neocortical slices.

PURPOSE: The anticonvulsant effects of the novel antiepileptic drug (AED) levetiracetam (LEV) were tested in neocortical slice preparations from 23 patients who underwent surgery for the treatment of refractory epilepsy. METHODS: Slices were used to evaluate the effects of LEV on two different models of epilepsy: low-Mg2+-induced untriggered and bicuculline-evoked stimulus-triggered epileptiform burst discharges and spontaneously appearing rhythmic sharp waves. RESULTS: LEV (0.1-1 mM) did not influence spontaneously appearing rhythmic sharp waves or Mg2+-free aCSF-induced epileptiform field potentials. LEV affected neither the amplitudes or duration nor the repetition rates of burst discharges in these epilepsy models. However, LEV (100-500 microM) significantly suppressed the ictal-like discharges elicited by the gamma-aminobutyric acid subtype A (GABAA)-receptor antagonist bicuculline. A marked reduction of the amplitude and duration of bicuculline-evoked field response in the presence of LEV was observed. CONCLUSIONS: The results indicate the potential for LEV to inhibit epileptiform burst discharges in human neocortical tissue, which is consistent with its effects in animal models of epilepsy. These results also support the seizure reduction observed in clinical trials and support that this may, in part, be related to the ability of LEV to inhibit epileptiform discharges.

Hyperammonemia-induced depletion of glutamate and branched-chain amino acids in muscle and plasma.

BACKGROUND/AIMS: Exogenous hyperammonemia is known to decrease the plasma levels of branched-chain amino acids (BCAA). To investigate whether changes in intracellular amino acid concentrations of muscle are associated with and may, at least in part, mediate this effect, experiments were carried out on a total of 60 male Wistar rats. METHODS: Five groups were formed in a randomized manner. Group A: no treatment; groups B1 and B2: 2-hour and 6-hour continuous central-venous infusions, respectively, of sodium salts; groups C1 and C2: 2-hour and 6-hour infusions of ammonium salts. We obtained venous blood samples and muscle biopsies. Plasma ammonia, whole blood glucose, serum insulin, blood pH, and amino acids in plasma as well as in the intracellular water of muscle were measured. RESULTS: As compared with control group A, groups C1 and C2 displayed a 3.3- and a 4-fold increase, respectively, in the plasma ammonium concentration. Regarding insulin, the ammonium-infused rats were similar to group A but not to the sodium-infused B groups, which had significantly lower insulin concentrations. Administering ammonium brought about a decline in BCAA concentrations in plasma after 2 hours and in muscle after 6 hours. The ammonium-induced fall in intracellular BCAA values was preceded by an increase of glutamine as well as by a decrease of glutamate and alanine in both plasma and muscle. CONCLUSIONS: It is pointed out that the inter-group differences in serum insulin, although possibly accounting for some of the findings, can by no means explain the entire pattern of amino acid concentrations seen after the ammonium infusions. Instead, our results agree with the hypothesis that hyperammonemia indirectly lowers the plasma levels of BCAA by stimulating glutamine synthesis, thus reducing the intracellular glutamate pool, which is likely to be restored, at least in part, by an intensified BCAA transamination. Clarification is needed as to whether carbon skeletons derived from valine and isoleucine additionally contribute to replenishing the glutamate pool.

[The action profile of D,L-kavain. Cerebral sites and sleep-wakefulness-rhythm in animals]. / Untersuchungen zum Wirkungsprofil von D,L-Kavain. Zerebrale Angriffsorte und Schlaf-Wach-Rhythmus im Tierexperiment.

To investigate neurophysiological effects of D,L-kavain, two studies were conducted on unrestrained cats with chronically implanted electrodes. In group A animals (n = 26) we recorded the blood pressure, the EEG of cortical and subcortical areas, the electromyogram, EEG arousal reactions, and subcortical evoked potentials elicited by central stimulation. This was done before and after injection of D,L-kavain (10-50 mg/kg i.p.) or--for comparison--of a kava extract in Ol. arachidis (50-100 mg pyrones/kg i.p.). Group B cats (n = 9) served for polygraphic, 10-h analyses of the sleep-wakefulness rhythm; they received--in a random sequence--0.9% NaCl (3 ml i.p.), D,L-kavain (28 mg/kg p.o.), pentobarbital (1 mg/kg i.m.), or the combination D,L-kavain plus pentobarbital. With both D,L-kavain and the extract, muscle tone was seen to be diminished in about 50% of the experiments. It was only the extract which exerted marked effects on the EEG; it induced high amplitude delta waves, spindle-like formations, and a continuous alpha- or beta-synchronization in the amygdalar recordings (p less than 0.001). Neither D,L-kavain nor the kava extract changed the threshold of the EEG arousal reaction. As to the evoked potentials, the hippocampal response following stimulation of the amygdalar nucleus showed an increase in amplitude in the animals given D,L-kavain (50 mg/kg; p less than 0.05) and in those given the extract (100 mg pyrones/kg; p less than 0.01). In addition, after injection of the extract, further projections arising from the amygdala as well as the connection from the caudate nucleus to the amygdala proved to be activated. The percentage duration of active wakefulness was significantly shortened by both D,L-kavain and pentobarbital, as compared to placebo. There was a likewise significant prolongation of synchronized sleep with D,L-kavain, pentobarbital, and the combination of both these agents. However, a potentiation of drug effects failed to occur. It is concluded from the findings that limbic structures and, in particular, the amygdalar complex represent the preferential site of action for both D,L-kavain and the kava extract. The participation of these structures in modulating emotional processes may explain the promotion of sleep, even in the absence of sedation. There is no congruity of D,L-kavain with either the tricyclic thymoleptics or the benzodiazepines regarding the profile of neurophysiological effects.