The Wada test in Austrian, Dutch, German, and Swiss epilepsy centers from 2000 to 2005: a review of 1421 procedures.

Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.

Intestinal expression of cytochrome P450 enzymes and ABC transporters and carbamazepine and phenytoin disposition.

OBJECTIVES: Interindividual variability in intestinal absorption and bioavailability might contribute to inadequate control of seizures under treatment with carbamazepine and phenytoin. We therefore correlated intestinal expression levels and genetics of CYP3A4, CYP2C9/19, MDR1 and MRP2 with dose requirement and plasma levels of carbamazepine and phenytoin. MATERIALS AND METHODS: Epileptic patients on carbamazepine (n = 29) or phenytoin (n = 15) were stratified into a 'high'-dose (carbamazepine > or =800 mg/day, phenytoin > or =300 mg/day) and a 'low'-dose group (carbamazepine < or =600 mg/day, phenytoin < or =200 mg/day). Duodenal biopsies and DNA were obtained for Western blotting and genotyping studies. RESULTS: Low carbamazepine plasma levels showed a trend towards higher intestinal MDR1 expression (P = 0.06). Furthermore, carbamazepine dose was positively correlated with MRP2 expression (P = 0.1). Moreover, MDR1 expression and carbamazepine and phenytoin dose requirement was influenced by the genotype in position 2677 and 3435 of the MDR1 gene. CONCLUSION: Differences in intestinal MDR1 and MRP2 expression may influence carbamazepine and phenytoin disposition and may account for interindividual pharmacokinetic variability.

Transient epileptic opercular syndrome.

Ictal transient opercular syndrome is rarely observed in benign epilepsy with centro-temporal spikes in children, and even more rarely in epilepsia partialis continua and symptomatic focal status epilepticus in adults. Here we report the ictal and interictal neuroimaging and electrophysiological findings in an adult female suffering from discontinuous focal status epilepticus presenting as a transient opercular syndrome. This patient was unusual insofar as the discharges were strictly unilateral, i.e., that even with extensive neuroimaging no structural abnormalities could be found.

Transient MR changes and symptomatic epilepsy following gamma knife treatment of a residual GH-secreting pituitary adenoma in the cavernous sinus.

OBJECTIVE: To report a rare side effect of gamma knife treatment of pituitary macroadenoma. CASE REPORT: In a forty-one-year old female patient acromegaly was diagnosed due to a growth hormone secreting pituitary macroadenoma. Following transsphenoidal surgery the patient underwent gamma knife treatment for persistent uncontrolled acromegaly activity of residual tumor, infiltrating the left cavernous sinus. 15 months later, complex partial seizures were diagnosed and 17 months after gamma knife treatment a gadolinium enhancing lesion was detected in her left medial temporal lobe. Radiation induced changes, radiation necrosis or a glioma were considered. Neuropsychological testing indicated potentially significant post-surgical deficits. Therefore, surgical action was postponed and anti-epileptic treatment was started. Four months later she was free of seizures and an MR scan showed an almost complete regression of the gadolinium enhancing lesion, indicating that it had been due to radiation induced changes. CONCLUSION: Gamma knife surgery of a pituitary adenoma may cause radiation induced MR changes of the mesial temporal lobe mimicking glioma or radionecrosis and cause symptomatic epileptic seizures. The awareness of this rare complication is important to avoid unnecessary and potentially harmful diagnostic or therapeutic interventions.

H2(15)O or 13NH3 PET and electromagnetic tomography (LORETA) during partial status epilepticus.

The authors evaluated the feasibility and source localization utility of H2(15)O or 13NH3 PET and low-resolution electromagnetic tomography (LORETA) in three patients with partial status epilepticus (SE). Results were correlated with findings from intraoperative electrocorticographic recordings and surgical outcomes. PET studies of cerebral blood flow and noninvasive source modeling with LORETA using statistical nonparametric mapping provided useful information for localizing the ictal activity in patients with partial SE.

[Neurotoxic encephalopathy caused by neuroleptics and lithium]. / Neurotoxische Enzephalopathie unter Neuroleptika und Lithium.

Treatment of psychiatric patients often necessitates overlapping neuroleptic medication. We report a 60-year-old woman suffering from a schizoaffective disorder who received temporarily three neuroleptics, together with lithium. She developed neurotoxic encephalopathy with symptoms of a malignant neuroleptic syndrome. It is unclear if irreversible brain damage will remain. We recommend frequent electroencephalographic controls for early detection of neurotoxicity.

Effects of vigabatrin on brain GABA+/Cr signals in focus-distant and focus-near brain regions monitored by 1H-NMR spectroscopy.

The new antiepileptic drug vigabatrin (VGB) increases gamma-aminobutyric acid (GABA) in the brain. We compared GABA+/Cr signals measured focus-near and focus-distant and correlated it with the degree of response to VGB. Brain GABA+/Cr signals were measured in 17 epileptic patients in structurally normal appearing tissue by nuclear proton magnetic resonance (1H-NMR) spectroscopy using a special editing sequence for GABA. In 11 patients the measurements were done in brain areas distant to focus and in six near to focus. Full-responders (seizure reduction of >or=50% at the end of the treatment phase) and partial-responders (seizure reduction of >or=50% at the end of the first month of treatment but

Future aspects of epilepsy research.

This contribution in honour of Prof. Gerhard Pendl first reviews some recent studies on resected tissue, migrational disorders, and Rasmussen's Syndrome. These areas of basic research profit from recent advances of molecular biology and genetics. On the clinical side, some studies dealing with proton magnetic resonance spectroscopy are reviewed. In order to highlight the progress in clinical epilepsy research using modern methods of structural and functional imaging, functional outcome prediction is also reviewed. This kind of advanced clinical research is dealt with by discussing risk factor assessment associated with postsurgical decrements in memory. With regard to motor functions, we compare the yield of functional MR and intraoperative cortical stimulation in patients with lesions in or close to the Rolandic cortex. Progress in the field of advanced EEG analysis is reviewed in the context of "seizure prediction" and cognitive event-related potentials. Finally some of the new epilepsy treatment options, such as Gamma Knife treatment, where Prof. Pendl's group made pioneering contributions, are dealt with.

Proton magnetic resonance spectroscopy characteristics of a focal cortical dysgenesis during status epilepticus and in the interictal state.

We report the magnetic resonance imaging and proton magnetic resonance spectroscopic findings ((1)HMRS) in a patient with a focal cortical dysgenesis in the right superior frontal gyrus during intermittent frontal status epilepticus (IFSE) with simple partial seizures, and after she had become seizure free. During the status epilepticus, demonstrated by simultaneous behavioural and electroencephalographic telemetric long-term monitoring with scalp electrodes and ictal SPECT, we performed a single voxel spectroscopy of the dysgenic cortex. The(1)HMRS was repeated after 20 days when the patient's seizures were controlled. The N-acetyl-aspartate concentration in the focal dysgenic cortex was decreased in the interictal state but more during IFSE. The creatine/phosphocreatine concentration was normal in both instances. There was a clear lactate signal during IFSE, which was no longer visible in the interictal state. To our knowledge this is the first report of a(1)HMRS study of a focal cortical dysgenesis during an intermittent status epilepticus. We interpret the observed changes as signs of histopathological changes inherent to a cortical malformation and of an impaired energy metabolism due to the partial status epilepticus.

Concentric visual field restriction under vigabatrin therapy: extent depends on the duration of drug intake.

Vigabatrin (VGB) is a novel antiepileptic drug which inhibits GABA-transaminase (GABA-T) and thus increases the level of GABA in the CNS and in its neurons. In the last few years, evidence has been presented that VGB intake may be associated with concentric visual field restrictions. The aim of this study was to estimate the prevalence of visual field constrictions and to determine if, and to what extent, they depend on the duration of VGB treatment. Visual fields of 15 patients who were taking VGB, and 12 matched control patients who had never been exposed to VGB, were investigated using a kinetic Goldmann perimeter. One of the 12 matched control patients had a slightly restricted visual field whereas nine of the 15 VGB patients (60%) showed a moderate to severe concentric visual field restriction. The extent of the outer isopters (V4, I4, I3, I2) depended on the duration of VGB intake. VGB treatment was clearly associated with a high prevalence of concentric visual field restriction. Moreover, the degree of visual field restriction depended on the duration of VGB intake. Further work, including longitudinal studies, is needed to clarify whether these lesions are reversible or not.

Topography of foramen ovale electrodes by 3D image reconstruction.

To date, the foramen ovale (FO) electrode recording technique has been used in 234 patients at our center to assist in the evaluation of epilepsy surgery. Most of the patients suffered from mesial temporal lobe epilepsy (MTLE) and were candidates for a selective amygdalohippocampectomy. Knowledge of the exact topography of the FO electrodes is mandatory for a more precise anatomo-electro-clinical correlation of seizures and for a better understanding of FO electrode recorded electroencephalogram (EEG) and evoked potentials generated in the hippocampal formation or in nearby thalamic relays or brainstem structures. Here, we describe and illustrate a 3D image reconstruction of FO electrodes in situ as an important step to better define the generators of MTLE seizures as well as of interictal spikes and physiological EEG signals recorded with FO electrodes.

Brain glutathione levels in patients with epilepsy measured by in vivo (1)H-MRS.

OBJECTIVE: Glutathione in its reduced form (GSH) is the most important free radical scavenging compound in the mammalian nervous system that prevents membrane lipid peroxidation. It is suspected that epileptic seizures are accompanied by a massive production of reactive oxygen species, i.e., oxidative stress. METHODS: Using an (1)H MRS technique developed at the authors' site, the authors measured glutathione levels in a volume of interest (VOI) of 25 x 25 x 25 mm placed in structurally normal-appearing tissue in the parietooccipital region of each hemispheres in patients with and without active epilepsy, and in a age-matched control group. RESULTS: The GSH/water ratio in patients with epilepsy was significantly reduced in the parietooccipital region of both hemispheres (1.6 +/- 1.0 x 10(-5)) compared to the GSH/water ratio in healthy controls (2.4 +/- 1.1 x 10(-5)). There was no significant difference between the hemisphere with epileptogenic focus and the hemisphere without epileptogenic focus. The GSH/water ratios of the patients without active epilepsy were not different from the GSH/water ratios of patients with active epilepsy. CONCLUSION: The authors found evidence for a widespread impairment of the glutathione system in patients with epilepsy independent from seizure activity.

Influence of pyridoxal 5'-phosphate alone and in combination with vigabatrin on brain GABA measured by 1H-NMR-spectroscopy.

Both iso-forms of the gamma-aminobutyric acid (GABA) synthesising enzyme and also the GABA degrading enzyme need pyridoxal 5'-phosphate (PP) as co-enzyme. The aim of the study was to investigate the influence of PP alone and in combination with various doses of vigabatrin (VGB) on brain GABA levels. In eight healthy subjects 300 mg/d PP and various doses of VGB (range, 1000 mg/d to 4000 mg/d) were given alone or in combination. The GABA+/creatine (Cr) signals in both occipital lobes were measured before treatment, during monotherapy with PP or VGB, and during combination of both using 1H-NMR-spectroscopy (1H-NMRS). PP alone did not change the GABA+/Cr signals. VGB alone increased the GABA+/Cr signals in both hemispheres. The combination PP and low-medium dosed VGB (1000-2000 mg/d) did not increase the GABA+/Cr signals. The effects of the combination of PP and high dosed (3000-4000 mg/d) VGB on the GABA+/Cr signals varied depending on the sequence of the drugs and dose of VGB. PP alone has no effect on the GABA+/Cr signals in healthy volunteers. The combination of PP and low-high dosed VGB had inconsistent effects on the GABA+/Cr signals compared to a VGB monotherapy because PP activates also the GABA-degrading enzyme GABA-transaminase.

Supracerebellar transtentorial approach to posterior temporomedial structures.

The supracerebellar transtentorial (SCTT) approach, a modification of the infratentorial supracerebellar approach, facilitates simple and minimally invasive access to posterior temporomedial structures without requiring retraction of the temporal or occipital lobe. The SCTT approach was used in 16 patients over a 3-year period. Eleven patients harbored tumors confined to, or located mainly within, the posterior hippocampal formation, three patients harbored aneurysms (one ruptured posterior cerebral artery [PCA] aneurysm at the P2-P3 junction, one ruptured giant PCA [P2] aneurysm, and one giant basilar artery-superior cerebellar artery aneurysm), one patient had juvenile-type moyamoya disease, and one patient suffered from medically intractable epilepsy. In these patients, the SCTT approach enabled tumor removal, aneurysm clipping, and vascular bypass procedures. The authors' experience suggests that this approach can be used routinely in treating lesions in the posterior temporomedial region.

Effects of vigabatrin on brain GABA+/CR signals in patients with epilepsy monitored by 1H-NMR-spectroscopy: responder characteristics.

PURPOSE: Vigabatrin (VGB) is a new antiepileptic drug that increases the human brain gamma-aminobutyric acid (GABA) level by irreversibly inhibiting GABA transaminase. Although some patients respond to VGB with a significant seizure reduction, others do not. The aim of this study was to identify possible responders before or in an early phase of VGB treatment by measuring the GABA and homocarnosine contaminated with macromolecules/creatine and phosphocreatine ratio (GABA+/Cr) signal by means of proton-nuclear magnetic resonance (1H NMR) spectroscopy. METHODS: Measurements were performed immediately before and after a titration period of 1 month (2 g/day during the past 2 weeks). A third measurement followed a maintenance period of 3 months (2 or 3 g/day). In 14 patients with drug-resistant temporal lobe epilepsy and 3 patients with occipital lobe epilepsy, GABA+/Cr was measured in the ipsilateral (i.e., epileptogenic) hemisphere and contralateral (i.e., nonepileptogenic) hemisphere in a volume of 8 cm3. RESULTS: Depending on the therapeutic efficacy of VGB, we defined three groups: (a) full responders (n = 7), (b) nonresponders (n = 7), and (c) partial responders (n = 3). The nonresponders had no significant change in the GABA+/Cr signal during the treatment compared with baseline. The full responders had a significant increase of the GABA+/Cr signal during the whole treatment phase and a lower ipsilateral level at baseline. The partial responders had also a lowered ipsilateral GABA+/Cr signal at baseline and an increase during treatment but a decrease when the seizures started again. CONCLUSIONS: Responders to VGB could be identified by a lower ipsilateral baseline GABA+/Cr signal and a steeper increase during VGB treatment. However, it was not possible to predict the duration of the response (full versus partial responder) with these criteria.

[Surgery of temporal lobe epilepsy]. / Temporallappen-Epilepsiechirurgie.

The need for and the most important categories of epilepsy surgery, as well as the evaluation of this kind of treatment by health care authorities in Switzerland is shortly discussed. Means for quality control and future developments of epilepsy surgery are mentioned. Indications and methods for the surgical treatment of the temporal lobe epilepsies are reviewed. Long-term results of the Zurich selective amygdalo-hippocampectomy series are briefly reported taking also into account the recently published proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery.

Recent advances in the diagnosis and treatment of epilepsy.

Recent advances in the diagnosis and treatment of epilepsies are discussed with special consideration of epidemiology and classification, progress in neuroimaging, electrophysiological studies using EEG and MEG, initiation of medical and surgical treatment, the role of new antiepileptic drugs and selected aspects of genetics of idiopathic epilepsies. In addition from conclusions obtained by the review of recent developments suggestions for future work in Europe are discussed. A constructive approach from multicenter studies requires homologous definitions, documentations and standardization of procedures of trials for European multicenter studies.

Mesial temporal lobe epilepsy versus amygdalar epilepsy: late seizure recurrence after initially successful amygdalotomy and regained seizure control following hippocampectomy.

We summarise the concept of mesial temporal lobe epilepsy and the pros and cons in order to define amygdala epilepsy. We present a patient with stereotactically proven right amygdalar seizure onset, associated with fear and vegetative autonomic signs and symptoms as the most prominent clinical ictal features. Following a right stereotactic amygdalotomy, the patient experienced an 11-year seizure-free period. Similar, but not identical, semeiology of complex partial seizures then recurred. A right-sided selective hippocampectomy and excision of the previously lesioned amygdala was performed. Except for 2 complex partial seizures associated with withdrawal of antiepileptic drugs, the patient remained seizure-free 9.5 years. This case underscores the important role of the amygdala in generating the semiology, and raises several questions concerning the existence of "amygdalar epilepsy". The 11-year seizure-free period following the stereotactic destruction of the amygdala is a strong argument for this notion. The late seizure recurrence requiring a second operation might, however, be seen as an argument for the important role of the hippocampal formation in the syndrome of mesial temporal lobe epilepsy even when the amygdala has been identified as the seizure onset zone. The role of stereotactic amygdalotomy is briefly reviewed.