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Radiographic shunt series are still the imaging technique of choice for radiologic evaluation of VP-shunt complications. Radiographic shunt series are associated with high radiation exposure and have a low diagnostic performance. Our aim was to investigate the diagnostic performance of whole-body ultra-low-dose CT for detecting mechanical ventriculoperitoneal shunt complications.This retrospective study included 186 patients (mean age, 54.8 years) who underwent whole-body ultra-low-dose CT (100 kV[peak]; reference, 10 mAs). Two radiologists reviewed the images for the presence of ventriculoperitoneal shunt complications, image quality, and diagnostic confidence. On a 5-point Likert scale, readers scored image quality and diagnostic confidence (1 = very low, 5 = very high). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Radiation dose estimation of whole-body ultra-low-dose CT was calculated and compared with the radiation dose of a radiographic shunt series.34 patients positive for VP-shunt complications were correctly identified on whole-body ultra-low-dose CT by both readers. No false-positive or -negative cases were recorded by any of the readers, yielding a sensitivity of 100% (95% CI, 87.3%-100%), a specificity of 100% (95% CI, 96.9%-100%), and perfect agreement (κ = 1). Positive and negative predictive values were high at 100%. Shunt-specific image quality and diagnostic confidence were very high (median score, 5; range, 5-5). Interobserver agreement was substantial for image quality (κ = 0.73) and diagnostic confidence (κ = 0.78). The mean radiation dose of whole-body ultra-low-dose CT was significantly lower than the radiation dose of a conventional radiographic shunt series (0.67 [SD, 0.4] mSv versus 1.57 [SD, 0.6] mSv; 95% CI, 0.79-1.0 mSv;Whole-body ultra-low-dose CT allows detection of ventriculoperitoneal shunt complications with excellent diagnostic accuracy and diagnostic confidence. With concomitant radiation dose reduction on contemporary CT scanners, whole-body ultra-low-dose CT should be considered an alternative to the radiographic shunt series.

Der MKG-Chirurg 14(2), 125-129 (2021). doi:10.1007/s12285-021-00303-8 special issue: "Zystische Veränderungen im Kiefer und Weichgewebe der Kopf-Hals-Region", Published by Springer, Berlin

Objective Due to the proximity of eloquent areas of the brain, the surgical treatment of insular lesions causing refractory epilepsy is considered difficult. We report here on our experience in this field. Methods We identified 24 patients (age: 1–62 years, mean 27) who underwent epilepsy surgery for an insular lesion from the epilepsy surgery data bank. We analyzed the preoperative diagnostics, surgical strategy and postoperative follow-up (duration: 12–168 months, mean 37.5) for functional morbidity and seizure outcome. Results Eight patients had strictly insular lesions while, in 16 cases, the lesion extended into the frontal (n = 3) or temporal (n = 8) lobe, or was multilobar (n = 5). Sixteen resections (66.7%) were right-sided. Six patients required invasive EEG with implanted electrodes, while three had the aid of intraoperative electrocorticography. In 12 patients, continuous electrophysiological monitoring was used intraoperatively (phase reversal, motor evoked potentials) and, in seven, neuronavigation. In seven patients, only subtotal resection of the insular lesion was possible due to involvement of eloquent areas, and two patients required repeat surgery to complete the resection. Thirteen patients had glial/glioneural tumours (WHO grades I–III), 11 from non-neoplastic lesions. Postoperatively, two patients (8.3%) had a transient neurological deficit (hemiparesis and dysphasia, respectively). One patient had permanent hemihypaesthesia, another had permanent deterioration of preexistent hemiparesis and two had hemianopia as calculated deficit (16.6% rate of mild permanent morbidity). According to the International League against Epilepsy (ILAE) classification, 15 patients were totally seizure-free (62.5%, ILAE 1) and 79.2% had a satisfactory seizure outcome (ILAE 1–3). Conclusion In selected patients, an individually tailored lesionectomy of insular lesions can be performed, with acceptable safety, to provide a high rate of satisfactory seizure relief. Indeed, even subtotal resection can result in effective seizure control.

Summary Purpose: Electrical stimulation mapping (ESM) is the gold standard for identifying language-relevant cortex prior to neurosurgical resections near the eloquent cortex. However, its application mode is not standardized, as some procedures rely on a single task, whereas others depend on task batteries. In this study, we examine whether multitask ESM is necessary, quantify the information loss that occurs from restricting the number of applied tasks, and search for a procedure that allows for time-efficient, multitask ESM. Methods: Thirty-eight epilepsy and 11 brain tumor patients with subdural grid electrodes receive extraoperative ESM for language cortex at 1,890 stimulation sites. The applied test battery includes counting, naming, repeating, reading, Token Test, and body commands. Correlation analysis and principal component analysis are used to identify the functional overlap between tasks. Sensitivity analysis is the basis for determining the optimal task order, which requires a minimum number of stimulations for identifying language loci. Results: Correlation coefficients between tasks are −0.17 to 0.63; frontal and temporoparietal language cortex are organized differently. Naming is the most sensitive task, but 31% (temporoparietal) to 43% (frontal) of language sites remained undetected after naming alone. The optimal procedure starts with naming and the Token Test and differs thereafter between frontal and temporoparietal cortex. Omitting the Token Test and body commands from the battery results in up to 26% information loss. Discussion: Despite considerable overlap between different tasks, multitask ESM appears necessary to avoid missing language relevant cortex. Applying the tasks in an optimal order allows economizing the procedure.

Objective Aim of the study was a comparison of cranioplasty using the Tutoplast technology for autogenic bone processing and conventional polymethylmethacrylate (PMMA) calvarial re- construction. Patients and methods A retrospective analysis was carried out in a consecutive series of 61 plastic reconstructions for skull defects, the largest measuring more than 12 cm. Cranioplasty was either performed with PMMA or with the patient's own bone graft which had been recycled using the Tutoplast process. Results 36 patients with a mean age of 44 (range 10-68) years underwent freehand PMMA cranioplasty following craniectomy for increased intracranial pressure (19 patients, 52.8%), infection (15 patients, 41.7%), or traumatic bone destruction (2 patients, 5.6%). Bilateral procedures were performed in 10 patients (27.8%). Mean follow-up was 44 months. Four patients (11.1%) died, 14 (38.9%) remained severely disabled, and 18 (50%) made a satisfactory recovery. Two patients (5.6%) had PMMA-related complications and required removal. 26 patients exhibited at least satisfactory cosmetic results (83.9%), in 5 patients the results were not satisfactory (16.1%) and in 5 the results are unknown. Twenty-five patients with a mean age of 42 (range 2-68) years received Tutoplast processed autografts following craniectomy for elevated intracranial pressure. Bilateral procedures were performed in 3 patients (12%). Mean follow-up was 15 months. One patient (4%) died, 18 (72%) remained severely disabled, and 6 (24%) made a satisfactory recovery. All patients had satisfactory cosmetic results, but 2 patients (8.3%) required removal at a later stage, one due to infection (4.2%) and one for bone resorption (4.2%). In the 18 patients with follow-up >0.5 years significant resorption occurred in all 5 children and adolescents (100%) and in two adult patients (15.4%). Conclusion Cosmetic results were more satisfactory with Tutoplast processed autografts, and the operating time for unilateral surgery was shorter. Complication rates were similar. Resorption occurred in all children and adolescents, but was rare in adults. Thus, Tutoplast processed autogenic bone grafts can be a reasonable alternative to other methods of cranioplasty in adult patients with large craniotomy defects. Cranioplasty in children and adolescents remains an unsolved problem.

Background: Studies of long term outcome after epilepsy surgery for cortical malformations are rare. In this study, we report our experience with surgical treatment and year to year long term outcome for a subgroup of patients with focal cortical dysplasia (FCD). Methods: We retrospectively analysed the records of 49 patients (females n = 26; males n = 23; mean age 25 (11) years) with a mean duration of epilepsy of 18 years (range 1–45). Preoperative MRI, histological results based on the Palmini classification and clinical year to year follow-up according to the International League Against Epilepsy (ILAE) classification were available in all patients. Results: 98% of patients had a lesion on preoperative MRI. In addition to lobectomy (n = 9) or lesionectomy (n = 40), 14 patients had multiple subpial transections of the eloquent cortex. The resected tissue was classified as FCD type II b in 41 cases with an extratemporal (88%) and FCD type II a in 8 cases with a temporal localisation (100%). After a mean follow-up of 8.1 (4.5) years, 37 patients (76%) were seizure free, a subgroup of 23 patients (47%) had been completely seizure free since surgery (ILAE class 1a) and 4 patients (8%) had only auras (ILAE class 2). Over a 10 year follow-up, the proportion of satisfactory outcomes decreased, mainly within the first 3 years. During long term follow-up, 48% stopped antiepileptic drug treatment, 34% received a driver’s license and 57% found a job or training. Conclusion: Surgical treatment of epilepsy with FCD is not only successful in the short term but also has a satisfying long term outcome which remains constant after 3 years of follow-up but is not associated with better employment status or improvement in daily living.

Surgery for temporal lobe epilepsy refractory to medical treatment is a promising treatment option. After a short overview of historical developments in this field, we describe the present practice of presurgical evaluation and resection strategies as practiced at our institution and review the corresponding publications from other centers. We will be trying to outline major future developments for the surgical therapy of temporal lobe epilepsy based on present trends.

The objective of this study was to correlate health-related quality of life (HRQOL) after surgery for mesial temporal lobe epilepsy, as revealed by a postoperative screening tool, to different modalities of seizure outcome classification (Engel, International League Against Epilepsy (ILAE)).One hundred twenty-eight of one hundred forty consecutive patients returned a HRQOL questionnaire at a mean of 36 months after selective amygdalohippocampectomy. Patients answered in two ways: with an absolute estimation (values 1-4) and with a self-rated relative change (-1, 0, +1) after surgery.Eighty patients were seizure- and aura-free (63.3% ILAE 1), 16 continued to have auras (12.5% ILAE 2), and 13 experienced 1-3 seizure days per year after surgery (10.2% ILAE 3). Ninety-two patients were classified seizure-free (71.9% Engel I), and 17 had two or fewer seizures per year (13.3% Engel II). Of 110 patients in ILAE 1-3, 100 (91%) stated good or even very good postoperative HRQOL, and 99 (90.0%) reported improvements in HRQOL. Only 9 of the remaining 18 (50%) reported good or very good HRQOL after surgery (P=0.01). Corresponding results were obtained with Engel classes I and II, suggesting a trend toward ILAE 1-3 and Engel I and II as overall satisfactory outcomes. A more detailed HRQOL assessment yielded lowest scores in the cognitive domain, and a significant correlation of self-rated changes in cognitive functioning with seizure control (P=0.01). Changes in physical capabilities and mood were significantly better with satisfactory seizure outcome (P=0.006 and P0.001, respectively), whereas the social aspects were not significantly dependent on seizure outcome (P=0.06).Correlation of HRQOL and seizure control suggested that ILAE 1-3 and Engel I and II most likely represent overall satisfactory outcome. Subdomain analyses revealed cognitive abilities as the most critical feature associated with seizure control, whereas social aspects remained mainly stable.

Spondylodiscitis is a rare disease which is associated with high mortality. No guidelines for treatment exist and the available studies are not homogeneous. Attempts have been made in recent years to structure therapy using algorithms. Early recognition of the disease is above all important for its later outcome. Therapy takes place in not only orthopaedic/trauma surgery clinics but also in neurosurgical clinics.We sent an online survey on this subject to orthopaedic clinics, trauma surgery and neurosurgery clinics in Germany. The aim was to ascertain current care strategies in Germany. A further objective was to elicit differences between the specialist fields.A total of 164 clinics responded to the survey. The response rate was 16% of the orthopaedic/trauma surgery clinics and 32% of the neurosurgical clinics. Differences between the two specialist fields can be found particularly in the use of systemic and local antibiotics, in the choice of surgical access to the thoracic spine and the lumbar spine and in post-operative imaging. In both specialist fields, patients with neurological dysfunctions are treated primarily in clinics with high case numbers. In terms of surgery, 2/3 of the responding clinics choose a one-stage operative treatment. Minimally invasive procedures and the use of cages are widespread. The participants estimate that, on the whole, a better outcome and higher patient satisfaction tend to exist after operative treatment.The lack of homogeneity regarding treatment strategies which is indicated here clearly shows the need for therapy guidelines as an aid to orientation. This will be a challenge for the future due to the low incidence and the situation regarding currently available studies.

Objectives: To assess the significance of symptomatic hemorrhagic complications occurring after different temporal resections for temporal lobe epilepsy (TLE) and to compare this data to findings with postoperative hematomas after temporal surgery for mostly glial or metastatic tumors.Patients and Methods: Patient charts were retrospectively reviewed for 442 patients who underwent surgery for refractory TLE between 1995 and 2000. Procedures were 247 transsylvian amygdalohippocampectomies (AH), 40 transcortical AH, 57 anterior temporal lobectomies (ATL), 23 lesionectomies plus AH, and 75 lesionectomies without AH. All patients with delayed awakening or new neurological deficits due to hemorrhages were included in the study. An identical procedure was performed to detect symptomatic hemorrhages after 208 procedures for temporal tumor resection during the same time period.Results: Symptomatic postoperative hemorrhages were found in 17 patients (3.8 %) undergoing epilepsy surgery, while the incidence was 3.0 % in a group with space-occupying temporal tumors (six patients). Hemorrhages showed a characteristic distribution after epilepsy surgery: in eight patients they were located remote from the site of surgery in the upper cerebellar vermis and foliae. Five typical hemorrhages associated with dysphasia were found in the left frontal operculum, only three patients had hematomas in the resection cavity, and one was located epidurally. Two patients had more than one location of hemorrhage. Transsylvian AH and ATL had a similar risk for postoperative hemorrhage, whereas none was found after lateral lesionectomies or transcortical AH. Intraoperative manipulations were associated with opercular hemorrhages; the only predisposing factor for resection site hematomas was older age, whereas cerebellar hemorrhages were associated with cerebrospinal fluid (CSF) loss during AH and ATL. There was no mortality in the TLE group, and 0.75 % permanent mild deficits. Seizure outcome did not differ from the rest of the group (82.5 % satisfactory seizure control).In contrast, all intraaxial hematomas after tumor surgery (N = 4, incidence 1.9 %) were located in or adjacent to the resection cavity. Prognosis was much worse with parenchymal hemorrhages after tumor surgery: three of four patients died, one survived with a severe hemiparesis, only two patients with extraaxial hematomas (incidence 1 %) had a complete recovery. The 3 % incidence of symptomatic hemorrhages was only insignificantly lower compared to the TLE group, patients with tumor surgery were older than TLE patients (49 versus 33 years), and in five of six patients only incomplete tumor resection was achieved.Conclusion: Although associated with a low permanent morbidity, features of postoperative hemorrhages after TLE surgery are characteristically different to complications after surgery for other indications, which has to be kept in mind for patient counseling and obtaining informed consent. Einleitung: Die Untersuchung der Bedeutung symptomatischer Blutungskomplikationen nach unterschiedlichen Resektionen bei Temporallappenepilepsie (TLE) und der Vergleich mit Nachblutungen nach Resektionen temporaler zumeist glialer metastatischer Tumoren.Patienten und Methode: Aufzeichnungen von 442 Patienten, deren OP wegen refraktarer TLE zwischen 1995 und 2000 erfolgte, wurden retrospektiv evaluiert. Es wurden 247 transsylvische Amygdalohippokampektomien (AH), 40 transkortikale AH, 57 vordere Temporallappenresektionen mit AH (ATL), 23 Lasionektomien mit AH und 75 Lasionektomien ohne AH durchgefuhrt. Alle Patienten mit verzogertem Aufwachen oder neuen neurologischen Ausfallen wurden in die Studie eingeschlossen. Ein gleichartiges Vorgehen erfolgte in einer zeitgleichen Gruppe von 208 Operationen bei temporalen Tumoren.Ergebnisse: Bei 17 TLE Patienten (3,8 %) wurden symptomatische Blutungen gefunden, die Inzidenz betrug 3 % (6 Patienten) in der Tumorgruppe. Nach TLE Chirurgie zeigte sich eine charakteristische Verteilung der Blutungen: bei acht Patienten entfernt vom Ort der Operation im oberen Kleinhirnwurm und den Folien. Funf mit Dysphasie aufgefallene Blutungen waren im linken frontalen Operkulum, lediglich drei Patienten hatten Blut in der Resektionshohle und einer im Epiduralraum. Zwei Patienten wiesen Einblutungen an mehr als einer Stelle auf. Transsylvische AH und ATL wiesen ein vergleichbares Risiko fur Nachblutungen auf, wohingegen keine Blutungen nach lateralen Lasionektomien oder transkortikaler AH auftraten. Intraoperative Manipulationen schienen mit den operkularen Hamatomen im Zusammenhang zu stehen, ein hoheres Alter mit Blutungen in die Resektionshohle, wohingegen zerebellare Einblutungen eher mit Liquorverlust bei AH und ATL korreliert waren. In der TLE-Gruppe gab es keine Mortalitat und in 0,7 % permanente Morbiditat. Das Anfallsoutcome unterschied sich nicht von der Gesamtgruppe (82,5 % befriedigende Anfallskontrolle).Dagegen waren alle intraaxialen Hamatome nach Tumor-OP (N = 4, Inzidenz 1,9 %) in der Gegend der Resektion lokalisiert, verbunden mit einer erheblich schlechteren Prognose: drei von vier Patienten verstarben, einer uberlebte mit schwerer Hemiparese, nur zwei Patienten mit extraaxialen Blutungen (Inzidenz 1,0 %) erholten sich vollstandig. Die Blutungsinzidenz war mit 3 % nur insignifikant geringer als in der TLE-Gruppe, die Patienten der Tumorgruppe waren im Mittel alter als in der TLE-Gruppe (49 versus 33 Jahre), bei funf von sechs Patienten war die Tumorentfernung lediglich inkomplett moglich.Schlussfolgerung: Obwohl hier nur mit geringer permanenter Morbiditat assoziiert, weichen die Charakteristika der Blutungen nach TLE Chirurgie deutlich von denen nach Operationen fur andere Indikationen ab. Dies sollte bei der Beratung und Aufklarung der Patienten berucksichtigt werden.

Human temporal lobe epilepsy is characterized by strong synaptic reorganization that leads to abnormal recurrent excitatory synaptic connections among hippocampal neurons. In addition, electrophysiological studies show that synaptic activity of the main afferent input to the hippocampus, the perforant path, is prolonged and amplified by changes in postsynaptic glutamate receptors. The current view is that these morphological and physiological abnormalities contribute significantly to the hyperexcitability seen in the hippocampus of temporal lobe epilepsy. Recently, it was found that presynaptic inhibitory metabotropic glutamate receptors are an important negative feedback mechanism that controls synaptic release of glutamate in the hippocampus. In this study, we assessed the functionality of this feedback system by investigating the metabotropic glutamate receptor mediated depression of excitatory synaptic transmission in surgically removed hippocampi from patients with marked synaptic reorganization (Ammon's horn sclerosis group) and from patients without detectable reorganization (lesion group). We report here that this control of synaptic transmission is lost in hippocampi from the Ammon's horn sclerosis group whereas this control is preserved in hippocampi from the lesion group. The data presented here suggest that the loss of feedback inhibition mediated by metabotropic glutamate receptors could be a further, previously not recognized, mechanism in the pathophysiology of temporal lobe epilepsy.

The functional consequences of lesions of the entorhinal cortex of rats were studied by analysing laminar distributions of stimulus induced field potentials in the dentate gyrus with a subsequent current source density analysis. Stimulation of the inner molecular layer elicits large excitatory postsynaptic potentials with small if any population spikes in the stratum granulare both in normal and lesioned animals. In lesioned animals middle molecular layer stimulation causes large excitatory sinks in the stratum moleculare without generation of population spikes in stratum granulare, while the same stimulation in slices from normal animals readily induces population spikes. The current source density analysis revealed a shift of current sinks induced by stimulation of either the inner or the middle molecular layer to common site. The N-methyl-D-aspartate receptor contribution to the current sink and source was found to be more prominent after middle molecular layer stimulation in comparison to inner molecular layers stimulation in the control group, while such a distinction could not be made in the lesioned group. Activation of mossy fibers did not reveal any significant differences between normal and lesioned animals. Following entorhinal cortex lesion sprouting of remaining afferents (e.g. commissural fibers) into the termination zones of the degenerated perforant path has been reported suggesting a compensatory replacement of excitatory synaptic input. However, persistent transneuronal dendritic alterations of neurons in the dentate gyrus have been observed which might result in altered dentate gyrus function. Our findings suggest that the reorganization process after entorhinal cortex lesion does not lead to full functional compensation of the lost perforant path input, resulting in an altered balance between excitation and inhibition.

Objective: We report on a patient with pituicytoma, i.e. a rare neoplasm of the neurohypophysis, with unusual anamnestic manifestation. Case material: After a car accident, the patient suffered from severe persisting headaches. Diagnostic procedures revealed a minor visual impairment and restriction of the gonado- and somatotropic pituitary axis. MRI showed an architecturally solid, well demarcated and homogenous suprasellar lesion. Due to the challenging location of the lesion with a small intrasellar mass and larger suprasellar part within the hypophyseal stalk, a subtotal resection was carried out to save the pituitary function and for neuropathological assessment comprising numerous stainings and immunohistochemical reactions. We observed a highly differentiated, low proliferative, rather cellular and in individual parts moderately pleomorphic tumor with cells arranged in storiform or whorled patterns, that strongly expressed S-100 protein, microtubulus-associated protein 2 (MAP2) and vimentin. Postoperative visual field testing was inconspicuous, but pituitary malfunction was persistent. With respect to the accidental discovery of this pituicytoma, it remains unresolved whether the persisting headache was due solely to the head trauma or was additive with the effects of the pituicytoma. Conclusion: To date less than 30 bona fide examples have been described and typically present symptoms due to mass effects such as visual disturbances, hypopituitarism as well as interference with hypothalamic dopamine release, resulting in subsequent hyperprolactinemia accompanied by decreased libido and amenorrhea in females. These neoplasms represent an important differential diagnosis with respect to suprasellar lesions and a clinical and neuropathological challenge. Language: en

Surgical treatment of deep-seated insular lesions causing refractory epilepsy is thought to be difficult due to the complicated accessibility and close proximity of eloquent areas. Here we report our experience with insular lesionectomies. Twenty-four patients (range 1-62 years, mean 27) who underwent epilepsy-surgery for a lesion involving the insular region, were identified from the epilepsy surgery data bank. We analysed pre-surgical diagnostics, surgical strategy and postoperative follow up concerning functional morbidity and seizure outcome (range 12-168 months, mean 37.5). Eight patients had pure insular lesions, in 16 cases the lesion extended either to the frontal (n = 3) or temporal lobe (n = 8) or was multilobar (n = 5). Sixteen resections (66.7%) were done on the right side. Six patients required invasive EEG-recording, three patients received intra-operative electrocorticography. In seven patients only subtotal resection of the insular lesion was possible due to involvement of eloquent areas. Thirteen patients suffered from glial/glioneural tumours (WHO grades I-III), 11 from non-neoplastic lesions. Postoperatively, one patient had a hemihypesthesia and one patient had a deterioration of a pre-existing hemiparesis; two patients had a hemianopia as calculated deficit (mild permanent morbidity 16.6%). According to the ILAE-classification, 15 patients were completely seizure free (62.5%, ILAE 1). Around 79.2% had satisfactory seizure outcome (ILAE 1-3). In selected patients an individually tailored lesionectomy of insular lesions can be performed, which is acceptably safe and provides a high rate of satisfactory seizure relief. Even subtotal resection can result in good seizure control.

Highly selective epilepsy surgery in temporal lobe epilepsy is intended to achieve seizure freedom at a lower cognitive risk than standard en bloc resections, but bears the risk of collateral cortical damage resulting from the surgical approach.To investigate cortical damage associated with selective amygdalo-hippocampectomy (SAH).34 epileptic patients were evaluated. They were randomly assigned to SAH using either a sylvian (9 left/10 right) or a transcortical surgical approach (5 left/10 right). Postoperative MRI signal intensity changes adjacent to the approach were correlated with performance changes in serial word and design list learning.Losses in verbal learning and recognition memory were positively related to signal intensity changes, independent of the side of the resection, the surgical approach, or the extent of the mesial resection. Losses in consolidation/retrieval (memory) were greater after left sided surgery. Losses in design learning were related to right sided surgery and signal intensity changes. Seizure outcome (85% seizure-free) did not differ depending on the side or type of surgery.Collateral damage to cortical tissues adjacent to the surgical approach contributes to postoperative verbal and figural memory outcome after SAH. Controlling for collateral damage may clarify the controversial memory outcomes after SAH reported by different surgical centres.

Activation of presynaptic metabotropic glutamate receptors (mGluRs) leads to a powerful inhibition of glutamate release from many synaptic terminals throughout the CNS. mGluRs as autoreceptors are believed to provide a negative feedback system that prevents potentially toxic accumulation of glutamate in the extracellular space during synchronous synaptic activity such as epileptic seizures. In this study we analyzed the function of presynaptic mGluR8 on terminals of the lateral perforant pathway in the pilocarpine model of limbic epilepsy. Field excitatory postsynaptic potentials (fEPSPs) recorded in hippocampal slices of rats that developed spontaneous recurrent seizures after pilocarpine-induced status epilepticus (SRS group) showed a significantly reduced sensitivity to Group III mGluR agonists and severe mossy fiber sprouting. The Group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 10 microM) depressed fEPSPs in the SRS group only by 26 +/- 21% compared to 50 +/- 18% in untreated rats. Similarly, the mGluR8 preferring agonist (R,S)-4-phosphonophenylglycine (PPG, 5 microM) was significantly less effective in slices from SRS rats (43 +/- 4% vs. 83 +/- 5%). Concentration-response curves for L-AP4 revealed that the EC(50) values were not different between the control and SRS group (13 +/- 7 microM vs. 9 +/- 9 microM), while the maximal depressing effect was significantly reduced. The remaining depressing effect of L-AP4 in the SRS group could be blocked by the Group III specific antagonists (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) and alpha-methyl-L-AP4 (MAP4). Rats that did not develop SRS following pilocarpine-induced status epilepticus were indistinguishable from control rats: fEPSPs were highly sensitive to L-AP4 and there was no mossy fiber sprouting. The results show that pilocarpine-induced status epilepticus can lead to a downregulation of mGluR8 and suggest that the condition of SRS is associated with a deteriorated autoregulation of glutamate release.

SUMMARY Epilepsy surgery has been established as a successful treatment in patients with drug-resistant focal epilepsies. Different standardized surgical approaches were developed for resective or functional treatment. Successful surgical treatment, however, necessitates a careful presurgical evaluation. Although there are international standards for non invasive and invasive presurgical procedures most centers differ in their diagnostic strategy. This article gives a survey of the Bonn Epilepsy surgery program within which more than 1300 patients have been treated. After the method of patient selection different we describe tools of non invasive and invasive evaluation. This article serves only as a description of current practice in one center with a relatively large volume of cases. It presents just one opinion of a specific group within a wide spectrum of possible algorithms for presurgical evaluation that have briefly been outlined for 33 centers in Engels book [4].

Rat or human neocortical synaptosomes were used to study the role of voltage-gated Ca(2+) channels and the Na(+)/Ca(2+) exchanger in (45)Ca(2+) influx into nerve terminals. K(+) depolarization-induced (45)Ca(2+) influx through voltage-gated Ca(2+) channels into rat or human synaptosomes was completely blocked by mibefradil 30 microM or Cd(2+) 100 microM but was not affected by tetrodotoxin 1 microM. It was reduced by omega-agatoxin IVA 0.2 microM by 68% in synaptosomes of either species, whereas omega-conotoxin GVIA 0.1 microM and nifedipine 1 microM had no effect. Veratridine-induced (45)Ca(2+) entry into rat neocortical synaptosomes was completely blocked by mibefradil 30 microM, reduced by 80% by Cd(2+) 100 microM, by 90% by tetrodotoxin 1 microM and by 53% by omega-agatoxin IVA 0.2 microM but not by omega-conotoxin GVIA 0.1 microM or nifedipine 1 microM. Na(+)/Ca(2+) exchanger-mediated (45)Ca(2+) uptake into rat neocortical synaptosomes evoked by replacement of Na(+) by choline(+) in the incubation buffer was reduced by KB-R7943 (3-50 microM), an inhibitor of the Na(+)/Ca(2+) exchanger, in a concentration-dependent manner (maximal inhibition by 46% at 50 microM; IC(23%)=7.1 microM). Mibefradil also inhibited the Na(+)/Ca(2+) exchanger-mediated Ca(2+) uptake, although at 3.7 times lower potency (IC(23%)=26 microM). It is concluded that in rat and human neocortical nerve terminals Ca(2+) entry is mediated under physiological conditions by P/Q-type, but not by N- or L-type Ca(2+) channels or the Na(+)/Ca(2+) exchanger. If the cytosolic Na(+) concentration is increased, Ca(2+) is also taken up via the Na(+)/Ca(2+) exchanger. In addition to the ability of mibefradil to block all voltage-operated Ca(2+) channels, this drug is a low potency inhibitor of the Na(+)/Ca(2+) exchanger.

Human temporal lobe epilepsy is characterized by strong synaptic reorganization that leads to abnormal recurrent excitatory synaptic connections among hippocampal neurons. In addition, electrophysiological studies show that synaptic activity of the main afferent input to the hippocampus, the perforant path, is prolonged and amplified by changes in postsynaptic glutamate receptors. The current view is that these morphological and physiological abnormalities contribute significantly to the hyperexcitability seen in the hippocampus of temporal lobe epilepsy. Recently, it was found that presynaptic inhibitory metabotropic glutamate receptors are an important negative feedback mechanism that controls synaptic release of glutamate in the hippocampus. In this study, we assessed the functionality of this feedback system by investigating the metabotropic glutamate receptor mediated depression of excitatory synaptic transmission in surgically removed hippocampi from patients with marked synaptic reorganization (Ammon's horn sclerosis group) and from patients without detectable reorganization (lesion group). We report here that this control of synaptic transmission is lost in hippocampi from the Ammon's horn sclerosis group whereas this control is preserved in hippocampi from the lesion group. The data presented here suggest that the loss of feedback inhibition mediated by metabotropic glutamate receptors could be a further, previously not recognized, mechanism in the pathophysiology of temporal lobe epilepsy.

The entorhinal cortex- hippocampus complex has particular features not only with respect to synaptic plasticity but also with respect to the readiness to develop progressive epilepsy. It might well be that this particular feature depends on the impressive plastic properties of the involved structures. A model for the progression of epilepsy is the kindling epilepsy. It is caused by stimuli (1 s, 50 Hz) of a type which also elicits long term potentiation [1]. Such stimulation induces generalized seizures when the stimuli are repeated in daily intervals [4]. The number of stimulations required to induce the kindling epilepsy is dependent on structure and varies between roughly 20 and more than 100.