Summary:Purpose: The mechanisms of drug resistance in epilepsy are only incompletely understood. According to a current concept, overexpression of drug efflux transporters at the blood-brain barrier may reduce levels of antiepileptic drugs (AEDs) in epileptogenic brain tissue. Increased expression of drug efflux transporters such as P-glycoprotein has been found in brain tissue surgically resected from patients with medically intractable epilepsy, but it is not known whether this leads to decreased extracellular (interstitial) AED concentrations in affected brain regions. This prompted us to measure concentrations of AEDs in the extracellular space of human neocortical tissue by using intraoperative microdialysis (IOMD) in those parts of the brain that had to be removed for therapeutic reasons. For comparison, AED levels were determined in brain tissue, subarachnoid CSF, and serum.Methods: Concentrations of carbamazepine (CBZ), 10-hydroxy-carbazepine (10-OH-CZ, metabolite of oxcarbazepine), lamotrigine (LTG), levetiracetam (LEV), topiramate, or phenytoin were determined by using one to four catheters during IOMD in the medial temporal gyrus. Furthermore, to calculate the individual recovery of every catheter, an in vitro microdialysis was performed with ultrafiltrate of serum concurrently obtained from the respective patient. In addition, AED levels were determined in the resected brain tissue, CSF, and serum of the same patients. Altogether 22 pharmacoresistant epilepsy patients (nine male, 13 female patients; age 15-54 years) with complex partial seizures or secondarily generalized seizures were involved. In a first series, IOMD samples 40 min after beginning of the microdialysis (flow rate, 1 μl/min), and in a second series, continuous measurements 25, 30, 35, and 40 min from the beginning were evaluated (flow rate, 2 μl/min). With in vitro recovery data of the individual catheters, the concentration in the extracellular space (ECS) was estimated.Results: AED concentrations in the ECS of the cortex measured by catheters located at a distance of 0.6 cm differed markedly in some patients, whereas concentrations in the ultrafiltrate of the serum of the respective patients measured with the same catheters varied only slightly. Furthermore, ECS concentrations related to the ultrafiltrate of serum showed considerable interindividual variations. The high intra-and interindividual variation of ECS concentrations is demonstrated by the low correlation between concentrations in ECS and the ultrafiltrate of serum (CBZ, r = 0.41; 10-OH-CZ, r = 0.42; LTG, r = 0.27) in contrast to the high correlation between brain tissue concentration and the ultrafiltrate of serum (CBZ, r = 0.97; 10-OH-CZ, r = 0.88; LTG, r = 0.98) in the same group of patients. When comparing AED concentrations in the ECS with those in the CSF, ECS concentrations were significantly lower for CBZ, 10-OH-CZ, LTG, and LEV.Conclusions: The data demonstrate that AED concentrations show a considerable intraindividual and interindividual variation in the ECS of...

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. V agus nerve stimulation (VNS) has been shown to be effective treatment for drug resistant epilepsy in two randomised, double blind studies.1 2 During recent years VNS has become an accepted method of treating patients with refractory epilepsy who are not candidates for epilepsy surgery or in whom surgery resulted in no benefit. From the experience of centres using VNS, one third of patients have a reduction in seizure frequency of at least 50%, another third have a worthwhile seizure reduction, while in the remaining third there is little or no effect.3 There is only limited information on patients who become seizure-free. 3 The rate of seizure freedom shows a large variation across the studies which have provided any information at all about it, and ranged from 0% to 24%. [4][5][6][7][8][9][10][11][12][13] Despite increasing amounts of clinical data, it is still not possible to predict which patients will profit from VNS. 14 Determining prognostic factors is important in predicting seizure outcome of VNS and in counselling patients. Moreover, because of the invasive nature of the procedure, the possible hazards of chronic implantation, and the relatively high cost of the treatment, factors indicating a poor prognosis could favour other treatment options including the newer antiepileptic drugs, palliative e...

Extratemporal epilepsy surgery is effective according to findings on long-term follow-up. The outcome at the first 2-year follow-up visit is a reliable predictor of long-term Engel Class I postoperative outcome.

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Summary:  Purpose: Heat shock protein‐27 (HSP‐27) belongs to the group of small heat shock proteins that become induced in response to various pathologic conditions. HSP‐27 has been shown to protect cells and subcellular structures, particularly mitochondria, and serves as a carrier for estradiol. It is a reliable marker for tissues affected by oxidative stress. Oxidative stress and related cellular defence mechanisms are currently thought to play a major role during experimentally induced epileptic neuropathology. We addressed the question whether HSP‐27 becomes induced in the neocortex resected from patients with pharmacoresistant epilepsy. Methods: Human epileptic temporal neocortex was obtained during neurosurgery, and control tissue was obtained at autopsy from subjects without known neurologic diseases. The tissues were either frozen for Western blot analysis or fixed in Zamboni's fixative for the topographic detection of HSP‐27 at the cellular level by means of immunohistochemistry. Results: HSP‐27 was highly expressed in all epilepsy specimens and in the cortex of a patient who died in the final stage of multiple sclerosis (positive control), whereas only low amounts of HSP‐27 were detectable in control brains. In epilepsy patients, HSP‐27 was present in astrocytes and in the walls of blood vessels. The intracortical distribution patterns varied strongly among the epilepsy specimens. Conclusions: These results demonstrate that HSP‐27 becomes induced in response to epileptic pathology. Although the functional aspects of HSP‐27 induction during human epilepsy have yet to be elucidated, it can be concluded that HSP‐27 is a marker for cortical regions in which a stress response has been caused by seizures.