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.

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.

Depth recorded limbic seizures and psychopathology.

Chronically performed stereotaxic depth recordings in medically intractable epileptics offer a unique chance to study the correlation of epileptic discharges with changes of higher mental functions as well as behavioral and emotional alterations. From a quantitative study using 213 complex partial seizures from 29 selected patients with partial drug resistant epilepsy and from the observation of other patients with well defined epileptic perturbations of the limbic system and related sensory brain areas a good correlation between ictal signs and chronotopographical seizure patterns was obtained. The special role of mesiobasal limbic structures, i.e., amygdala and hippocampus, and its connections to hypothalamic and frontobasal-cingulate areas is highlighted by tracing the seizures. It is concluded that besides the short-lived ictal abberations of mental state and emotional sphere ("psychical seizures") also some of the more prolonged behavior and personality changes seen frequently in patients with bitemporal basal spike foci might be attributed to narrowly confined limbic seizure discharges or to a "limbic dyscontrol syndrome" based on the altered activity of limbic structures due to the spike foci.

Mesiobasal versus lateral temporal lobe epilepsy: metabolic differences in the temporal lobe shown by interictal 18F-FDG positron emission tomography.

Metabolic abnormalities in the temporal lobe (TL) of 25 patients suffering from temporal lobe epilepsy of mesiobasal or lateral TL origin have been investigated using interictal [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). The epileptogenic area was determined by ictal EEG recordings using foramen ovale and scalp electrodes in 20 patients, and by the use of stereo-electroencephalography in one patient. Four patients with structural lesions on their MRIs had noninvasive ictal surface EEG recordings. Sixteen patients had a clear-cut mesiobasal seizure onset, and in five patients the seizures originated from the lateral temporal neocortex. Twenty-four patients underwent selective surgery. Patients with temporal limbic seizures associated with mesial gliosis (n = 15) had the lowest FDG uptake in the entire TL, followed by patients with lateral temporal seizure origin (n = 5). Patients with tumors located in the mesiobasal TL (n = 5) showed, in general, only a slight decrease of glucose metabolism in all TL structures. There was no clear-cut correlation between the degree of hypometabolism and the location of EEG-defined epileptogenic focus. The metabolic pattern, however, differed between the patient groups and allowed a discrimination between patients of mesial temporal and lateral temporal seizure onset.

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.

Preoperative and postoperative glucose consumption in mesiobasal and lateral temporal lobe epilepsy.

We have studied 25 patients with interictal 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) before and after selective surgery for temporal lobe epilepsy (TLE). Based on the findings of the presurgical evaluation, including ictal intracranial EEGs, histopathologic findings, and the postoperative outcome, we classified the patients in three subgroups: (1) patients with TLE of lateral temporal origin (n = 5), (2) patients with mesiobasal limbic TLE associated with mesial gliosis (n = 14), and (3) patients with mesiobasal limbic TLE and small mesial tumors (n = 6). Postoperatively, patients with mesiobasal limbic TLE and mesial gliosis and five of six patients with mesiobasal limbic TLE and mesial tumors were seizure-free; the remaining sixth patient had one generalized seizure. Patients with TLE of lateral temporal origin had more than 90% reduction of seizure frequency. The main postoperative metabolic findings were as follows: (1) marked increase of regional cerebral metabolic rate of glucose (rCMRglu), both in the ipsilateral and, significantly, in the contralateral hemisphere in patients with mesiobasal limbic TLE and mesial gliosis-the changes of brain metabolism were characteristic for patients with the syndrome of "mesial temporal lobe epilepsy" (MTLE); (2) decrease of rCMRglu values in the contralateral mesiobasal temporal lobe (TL) cortex in all patient groups--the reduction of rCMRglu in homologous brain structures contralateral to the operated side provides evidence for stronger interhemispheric connections between both mesial TL structures than were hitherto supposed; and (3) a trend toward a normalization of rCMRglu values in the ipsilateral temporal neocortex 12 months after surgery in patients with MTLE syndrome.

Musical consonances and dissonances: are they distinguished independently by the right and left hippocampi?

Our study sought to determine whether, where and how the consonance or dissonance of musical intervals might be reflected in the electrical activity (depth EEG) of the human brain. Presenting an adequate musical test program to a patient with depth electrodes implanted within the planum temporale (near Heschl's gyrus) and the hippocampal formations of both sides, we found that the reactions shown by the depth EEG of the limbic system correspond in precise and distinctly differing patterns to the consonances and dissonances presented. The main findings are: the EEG of the left hippocampus reflects the consonance-dissonance dichotomy; the activity of the left hippocampus but not the right is affected by a previous sequence of dissonances in responding to a single consonance; the EEG activity of the right Heschl's gyrus (the left Heschl's gyrus was not analyzed), but neither the left nor the right hippocampus, responded differently to a given succession of intervals and its pitch inversion. These results may help to understand the different emotional responses which usually arise in response to consonant or dissonant musical intervals.

Untroubled musical judgement of a performing organist during early epileptic seizure of the right temporal lobe.

The case of a professional musician with a right temporal lobe epilepsy is presented. Whilst playing an organ concert (John Stanley's Voluntary VIII, Op. 5), he suffered a complex partial seizure. The recorded concert performance (with the seizure) was analysed and compared with other available exercise records and with the composition. The musical analysis of the seizure-induced variations reveals that at the beginning of the seizure, the left hand started to become unprecise in time and deviated from the score, whereas the right hand remained faultless at this time. With increasing duration of the seizure discharge, the dissociation of both hands from the score increased but the right hand compensated for the errors of the left hand in a musically meaningful way, i.e. with the aim to compensate for the seizure-induced errors of the left hand. The case illustrates untroubled musical judgement during epileptic activity in the right temporal lobe at the beginning of the seizure. Whereas the temporal formation of the performance was markedly impaired, the ability of improvisation-in the sense of a 'perfect musical solution' to errors of the left hand-remained intact.

Functional inhibition and release: unilateral tachistoscopic performance and stereoelectroencephalographic activity in a case with left limbic status epilepticus.

During prolonged nonconvulsive unilateral left limbic status epilepticus, a natural model of functional hemispheric inhibition, we performed two tachistoscopic experiments, a lexical decision task associated with a RVF (left hemisphere) superiority and a facial matching task associated with a LVF (right hemisphere) superiority. We found that epileptic activity in the left hemisphere, especially rhythmic high-frequency "tonic" discharges, inhibited performance on the lexical task but not on the facial matching task. This suggests that only cognitive activity in the discharging hemisphere is inhibited. Strikingly, the best performance of the right hemisphere was obtained while the left hemisphere was most inhibited, suggesting a functional balance of inhibition and release.

Learning and retention of words and designs following excision from medial or lateral temporal-lobe structures.

We sought to elucidate the contributions of the amygdala, hippocampus and temporal neocortex to learning and memory for verbal and visuospatial material. Two matched learning tasks, using abstract words versus abstract designs, were administered to patients with unilateral neocorticectomy (NCE; Dublin), selective amygdalohippocampectomy (AHE; Zurich) or anterior temporal-lobe resection invading the amygdala and hippocampus (ATL; Montreal). Data were analysed according to side and type of resection. Learning and recall for words was impaired in groups with resection from the left temporal lobe, irrespective of whether mediobasal structures were spared or temporal neocortex was spared. All right-resection groups were unimpaired. Learning for abstract designs was impaired across all trials in the right AHE and NCE groups, and on the last two trials in the right ATL group. Restricted deficits of lower magnitude were observed on some trials in left-resection groups. These results show a partial dissociation between side of excision and type of material, but the finding of similar deficits in all resection types was unexpected. We propose that excision from either the hippocampal region or temporal neocortex may result in a disconnection, giving a similar functional outcome, as both types of resection interrupt a circuit likely to be essential for normal storage and retrieval of information.

A highly sensitive immunofluorescence procedure for analyzing the subcellular distribution of GABAA receptor subunits in the human brain.

We designed a protocol to improve the immunohistochemical analysis of human brain structures, which overcomes the limited detection sensitivity, high background, and intense autofluorescence commonly associated with human tissue. This procedure was evaluated by using antibodies against major GABAA receptor subunits (alpha1, alpha2, alpha3, gamma2) in autopsy and surgical specimens. Tissue blocks were briefly fixed by immersion and pretreated with microwave irradiation in sodium citrate buffer. Immunoperoxidase staining revealed a marked enhancement of cell surface immunoreactivity and reduction of background in microwave-irradiated tissue, irrespective of its origin. For confocal laser scanning microscopy, immunofluorescence staining was optimized with the tyramide signal amplification (TSA) technique. This procedure not only dramatically increased the sensitivity for antigen detection but also totally suppressed autofluorescence, thus revealing the cellular and subcellular distribution of GABAA receptor subunits. A distinct neuron-specific expression pattern of the alpha-subunit variants was observed in cerebral cortex and hippocampal formation, along with widespread expression of the gamma2-subunit. Of particular interest was the prominent alpha2- and alpha3-subunit staining on the initial axon segment of pyramidal neurons. This protocol represents a major improvement for high-resolution studies of human brain tissue aimed at investigating morphological alterations underlying neurological diseases.

Excitatory amino acid AMPA receptor mRNA localization in several regions of normal and neurological disease affected human brain. An in situ hybridization histochemistry study.

In situ hybridization histochemistry was used to localize the mRNAs coding for four alpha-aminoisoxazole propionic acid-sensitive glutamate receptor subunits in human brain (age range 51-95 years, postmortem delay 4.5-10 h). High levels of the B receptor subunit mRNA were present in all the studied regions, followed by the A-subunit and the C-subunit. Only very low levels of the D-subunit mRNA were detected. In hippocampus, the mRNA coding for the B-subunits of the glutamate receptor was observed in granule cells of dentate gyrus and in the pyramidal cells of Ammon's horn. In cortex, the highest levels of glutamate receptor subunit mRNAs were found in layer I and layers III-IV of entorhinal and temporal cortex, although significant levels were also observed in the other cell layers. A differential distribution was seen in cerebellum where the A-subunit mRNA is expressed mainly by Purkinje cells, while the B-subunit mRNA is present in the internal granule cell layer. These results correlate well with previous data from autoradiographic studies on the localization of excitatory amino acid binding sites in human brain and pinpoint the cells where these receptors are synthesized. In situ hybridization in the hippocampus of patients affected by Alzheimer's disease (age range 77-82 years, postmortem delay 19-25.5 h) revealed a decrease on the content of the mRNAs coding for these excitatory amino acid receptors, while an increase was detected in surgically dissected epileptic human hippocampi. These results corroborate and extend the previous data from in vitro autoradiography and suggest alteration of the excitatory amino acid disfunction during these neurodegenerative processes.

Intracranial temperature across 24-hour sleep-wake cycles in humans.

The 24 h time course of intracranial temperature, recorded subdurally at the parahippocampal gyrus in six patients (19 24 h periods), exhibited a prominent 24 h rhythm with its crest located at 20-21 h. The declining trend of intracranial temperature between lights off and sleep onset persisted in the first nonREM sleep episode (studied in two patients, seven sleep episodes). The correlation between EEG slow-wave activity (SWA) in nonREM sleep and the change in temperature explained < 25% of the variance. Although the change in temperature tended to be more positive in REM sleep episodes than in nonREM sleep episodes, no significant increase was observed in REM sleep. The data indicate that intracranial temperature exhibits a marked 24 h rhythm, the time course of which is only slightly affected by nonREM/REM sleep and EEG synchronization.

Analysis of EEG data from weak-field magnetic stimulation of mesial temporal lobe epilepsy patients.

Ten patients suffering from mesial temporal lobe epilepsy were exposed to weak, DC magnetic field stimulation following computer-controlled protocols established in previous studies. Poisson statistical analysis of the ten patients undergoing semi-invasive (foramen ovale) electrode monitoring reveals that for at least one experimental protocol, application of DC magnetic fields alters interictal epileptiform spike activity in five of ten patients. Similar results also have been observed in the analysis of both human and rat brains by employing weak, alternating magnetic field stimulation. Further study is necessary in order to optimize the magnetic field exposure protocol.

[Clinical observations on hydrocephalus with special regard to the posttraumatic malresorptive form (author's transl)]. / Beitrag zur Klinik des Hydrocephalus mit besonderer Berücksichtigung des posttraumatischen Hydrocephalus male resorptivus und der Shuntindikation

100 cases of Spitz-Holter shunts performed for hydrocephalus over a period of 3 years were analyzed; 17 of these were of posttraumatic origin and are discussed in regard to pathogenesis, clinical symptoms, diagnostic methods, and therapy. Half of these 17 had severe traffic accidents. The rapidity and degree of ventricular dilatation were positively correlated with the duration of unconsciousness. When the unconsciousness had lasted more than 10 days hydrocephalus was recognized early, and the shunt was performed on an average 2 months after the trauma. Two thirds of the patients improved after the shunt operation. Pathogenetically we believe the important factors in the acute stages are increased CSF pressure, disturbed CSF dynamics, brain swelling and vascular circulation disorder; in the chronic stages, parenchymous atrophy. The following 3 types of posttraumatic hydrocephalus were differentiated on the basis of the clinical features: --symmetrical communicating internal hydrocephalus with malresorption, especially after subarachnoid hemorrhage, --communicating internal hydrocephalus alone, or in combination with external hydrocephalus resulting from atrophy, --internal occlusive hydrocephalus after trauma. The following posttraumatic clinical features were found to be indications that hydrocephalus may be present: in the acute stages inadequately long symptom resolution considering the severity of the trauma, secondary changes for the worse, an apallic syndrome which does not improve; in late stages, the presence of an Adams-Hakim syndrome charaterized by dementia, a spastic gait and loss of sphincter control. The most successful diagnostic methods were found to be pneumencephalography with 24 and 48 h delayed exposures, cisternoscintigraphy and continuous intracranial pressure monitoring in combination with the spinal infusion test. The most important intracranial shunting procedures and the indications for shunting are discussed.

Effect of L-cycloserine on cortical neurons in the rat.

L-Cycloserine but not D-cycloserine, depressed the firing of neurons in the sensorimotor cortex of the rat with a relatively slow time course when administered by microionophoresis or i.p. injection. The effects of GABA applied by microionophoresis or released synaptically were not modified by i.p. injections and microionophoretic administration of L-cycloserine. It is concluded that L-cycloserine depresses cell firing not by potentiation of the action of GABA but by elevating GABA-levels.

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.

On the sensitivity of the human brain to magnetic fields: evocation of epileptiform activity.

Evocation of epileptiform activity by DC magnetic fields of between 0.9 and 1.8 millitesla (mT) has been demonstrated in 6 epileptic patients undergoing presurgical evaluation. The activity was monitored by electroencephalography (EEG) recording from both electrodes attached to the scalp as well as from intracranial electrodes inserted via the foramen ovale. Epileptiform activity evoked by the magnetic field application was distinguished from background levels by comparing the number of epileptiform discharges in the 10-s intervals before and after field applications. In nearly all cases, a delay of up to several seconds was observed between the application of the magnetic field and the onset of epileptiform firing. Removal of the field also appeared to cause firing in some instances, but this has not yet been investigated systematically. In all 6 patients, subsequent seizures confirmed that the epileptiform activity monitored during the experiments was originating from the primary epileptogenic zones of the patients.

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.

Comparison of valproate concentrations in human plasma, CSF and brain tissue after administration of different formulations of valproate or valpromide.

The concentration of valproate was measured in plasma, CSF and brain tissue of patients who underwent resective surgical treatment because of severe temporal lobe epilepsy after pretreatment with either a sustained release formulation of valproate (Depakine Chrono; 5 patients), the conventional formulation of valproate (Depakine; 6 patients) or valpromide (Depamide; 2 patients). With a mean serum value for all 13 patients of 32.3 micrograms/g valproate, the mean brain/serum ratio was 15.1% (SD 6.1%). The valproate concentration of the hippocampus was significantly higher than that of the amygdala and patients who had the sustained release formulation had significantly higher valproate concentration in the CSF and in the hippocampal formation than those patients who had the conventional valproate. Since a few patients had tumors, whereas others had varying degrees of gliosis, it cannot be ruled out that these differences are the result of different histopathological conditions with related differences in blood-brain barrier functions.