Biomedical subjects

Johannes Schramm

Publications and source records attributed to Johannes Schramm.

At least 19 recordsLinked to original sources

PubMed2003

Cellular pathology of amygdala neurons in human temporal lobe epilepsy.

The amygdala complex substantially contributes to the generation and propagation of focal seizures in patients suffering from temporal lobe epilepsy (TLE). A cellular substrate for increased excitability in the human amygdala, however, remains to be identified. Here, we analyzed the three-dimensional morphology of 264 neurons from different subregions of the amygdaloid complex obtained from 17 "en bloc" resected surgical specimens using intracellular Lucifer Yellow (LY) injection and confocal laser scanning microscopy. Autopsy samples from unaffected individuals ( n=3, 20 neurons) served as controls. We have identified spine-laden, spine-sparse and aspinous cells in the lateral, basal, accessory basal and granular nuclei. Semiquantitative analysis points to significant changes in neuronal soma size, number of dendrites and spine densities in specimens from epilepsy patients compared to controls. Neuronal somata in the epilepsy group were smaller compared to controls ( P<0.01), neurons had fewer first-order dendrites ( P<0.01), whereas the maximum density of spines per dendritic segment in these cells was increased in TLE patients ( P<0.01). There were also dendritic alterations such as focal constrictions or spine bifurcations. These changes were consistent between amygdaloid subregions. The dendritic morphology of amygdaloid neurons in TLE patients points to substantial changes in synaptic connectivity and would be compatible with altered neuronal circuitries operating in the epileptic human amygdala. Although the morphological alterations differ from those described in hippocampal subregions of a similar cohort of TLE patients, they appear to reflect a characteristic pathological substrate associated with seizure activity/propagation within the amygdaloid complex.

Adult↗

PubMed2003

Patterns of cortical oxygen saturation changes during CO2 reactivity testing in the vicinity of cerebral arteriovenous malformations.

BACKGROUND AND PURPOSE: The aim of this study was to test the hypothesis that patterns of cerebrovascular reactivity (CVR) in the vicinity of cerebral arteriovenous malformations (AVMs) before and after resection are not specific for this disease. METHODS: With a microspectrophotometer, cortical oxygen saturation (So2) was measured under steady-state conditions (Paco2, 33 mm Hg) before and after removal of 22 AVMs and in 30 control subjects before and after transsylvian amygdalohippocampectomy. Intraoperative vasoreactivity tests were performed by induced changes of end-tidal CO2 (25, 45, and 25 mm Hg) with simultaneous recording of local So2 in all patients. CVR patterns were established by linear regression analysis (P<0.05) to define parallel (positive) versus inverse (negative) behavior, and reactivity indexes were calculated to define their degree. RESULTS: Cortical oxygenation under steady-state conditions increased significantly (P<0.05) from preoperative to postoperative levels equally in both groups (preoperative AVM, 54.8+/-10.4%So2; postoperative AVM, 73.1+/-10.1%So2; preoperative control, 52.7+/-9.1%So2; postoperative control, 73.6+/-8.9%So2). The rate of inverse CVR patterns increased significantly (P<0.05) from before to after resection without showing statistically significant differences between groups. CONCLUSIONS: Local CVR patterns on presumably normal human cortex of control subjects are heterogeneous, including inverse behavior, and are similar to those of AVM patients before surgery. After surgery, cortical hyperemia is present in both groups, and a significant increase in inverse reactivity patterns interpreted as microvascular steal is noted. An AVM-specific CVR pattern could not convincingly be proved.

Adolescent↗

PubMed2003

Changes in splice variant expression and subunit assembly of AMPA receptors during maturation of hippocampal astrocytes.

Astrocytes in the hippocampus express glutamate receptors of the AMPA subtype. An increasing body of evidence suggests a contribution of astroglial AMPA receptors to a direct signaling between neurons and glial cells in vivo. Here, we have combined functional analysis with singlecell RT-PCR to investigate whether hippocampal astrocytes express Ca(2+)-permeable AMPA receptors. We show that by postnatal day 5, a mosaic of Ca(2+)-permeable and less Ca(2+)-permeable AMPA receptors coexists in individual astrocytes, while receptors with a more uniform, low divalent permeability dominate in older cells. Moreover, we report an upregulation of the flip form of the GluR2 subunit during maturation, while the splicing status of GluR1 and GluR4 remains unchanged. Due to its specific properties, Ca(2+)-permeable AMPA receptors in astrocytes might strengthen neuron-to-glia signaling and enable proper formation of structural and functional connections between glial cells and glutamatergic synapses in the developing hippocampus.

Alternative Splicing↗

PubMed2003

The spectrum of long-term epilepsy-associated tumors: long-term seizure and tumor outcome and neurosurgical aspects.

PURPOSE: To describe the histologic spectrum and clinical characteristics of patients with neuroepithelial tumors and drug-resistant epilepsy and to analyze clinical data and treatment related to seizure outcome and survival. METHODS: Data were analyzed from 207 consecutive patients with intractable epilepsy (aged 2-54 years), who between 1988 and 1999 had >or=50% resection of supratentorial, neuroepithelial tumors. Extent of resection was assessed on postoperative magnetic resonance imaging (MRI); seizure outcome was classified according to Engel's outcome scale; and follow-up data were prospectively updated. RESULTS: Median follow-up was eight years (range, 2-14 years). Histologic examination revealed 154 classic epilepsy-associated tumors (ganglioglioma, dysembryoplastic neuroepithelial tumor, pleomorphic xanthoastrocytoma, and pilocytic astrocytomas) and 53 others (astrocytomas and oligodendrogliomas). Four World Health Organization (WHO) grade III tumors were found (astrocytoma, n = 3; ganglioglioma, n = 1). After surgery, 82% of the patients were seizure free (class I). The following factors were associated with improved seizure outcome: Short duration of epilepsy before surgery, single EEG focus, absence of additional hippocampal sclerosis or cortical dysplasia, transsylvian approach, other than astrocytomas, and complete tumor resection. After 5 years, only nine (4%) patients had tumor recurrence, four (2%) with malignant transformation and death. None of the four patients with anaplastic tumors died. Even patients with astrocytomas of WHO grade II or III showed 10-year recurrence of only 25% and 10-year survival of 90%. CONCLUSIONS: Tumors associated with long-term epilepsy should be removed early for two different reasons: high rate of seizure freedom and rare but potential risk of malignant tumor progression. The unexpected long survival of these astrocytomas should be investigated by using immunohistochemistry and molecular biology.

Adolescent↗

PubMed2002

Mutational and expression analysis of the reelin pathway components CDK5 and doublecortin in gangliogliomas.

Gangliogliomas represent highly differentiated glioneuronal tumors frequently occurring in young patients with focal epilepsies. Dysplastic neurons are a neuropathological hallmark of this neoplasm. Here, we have analyzed two major components of the reelin pathway associated with neuronal migration and cortical cytoarchitecture in gangliogliomas, i.e., cyclin-dependent kinase 5 (CDK5) and doublecortin (DCX). The genomic structure of human CDK5 was identified by an " in silico" cloning approach using the "high throughput genomic sequencing" (htgs) databank, NCBI BLAST 2.1. DNA sequence analysis of CDK5 and DCX was carried out in tissue samples obtained from 23 patients and compared with control DNA from non-affected individuals ( n=100). For gene expression analysis of CDK5 and DCX, a quantitative real time reverse transcription-PCR TaqMan assay was used with mRNA from gangliogliomas ( n=22) and non-lesional central nervous tissue control tissue ( n=7). The human CDK5 gene is located on chromosome 7q36 and contains 12 exons. Its coding sequence reveals 90.1% homology to the mouse counterpart. A novel pseudogene of CDK5 was found on chromosome 8. While the mutational analysis of CDK5 and DCX did not reveal any sequence alterations in gangliogliomas, a lower expression was observed for both genes in tumor compared to control tissue samples. The present data indicate that mutations of CDK5 and DCX genes are not involved in the development of gangliogliomas. A novel pseudogene on chromosome 8 has to be taken into account for future studies on CDK5.

Animals↗

PubMed2002

Epilepsy surgery in patients with additional psychogenic seizures.

OBJECTIVE: To assess whether surgery to reduce or control epileptic seizures is safe and effective in patients known to have additional psychogenic seizures. DESIGN: We reviewed our computerized database of 1342 patients examined for epilepsy surgery and identified 13 patients with both epileptic and psychogenic seizures on whom postoperative outcome data were available. Data were gathered from the patients' records. Mean postoperative follow-up was 56 months. RESULTS: Epilepsy surgery led to clinically relevant improvements in 11 of 13 patients. Seven patients became free of epileptic and psychogenic seizures, 2 patients became free of epileptic seizures but continued to have infrequent psychogenic seizures, 1 patient reported more than an 80% improvement in epileptic seizure frequency and an abolishment of psychogenic attacks, and in 1 patient nondisabling epileptic seizures persisted at lower frequency but psychogenic seizures stopped. In 2 of 13 patients, epilepsy surgery failed to produce notable improvements. Although 1 patient became free of epileptic attacks and the other had fewer than 3 epileptic seizures per year, the severity or frequency of psychogenic seizures and pseudo-status epilepticus increased postoperatively. One of these patients had a preoperative diagnosis of somatization disorder; in the other, pathological illness behavior had been noted. CONCLUSION: A diagnosis of additional psychogenic seizures should not be considered an absolute contraindication to epilepsy surgery, although patients should undergo careful preoperative psychiatric evaluation.

Adolescent↗

PubMed2002

Destruction of neurons by cytotoxic T cells: a new pathogenic mechanism in Rasmussen's encephalitis.

Rasmussen's encephalitis is a progressive epileptic disorder characterized by unihemispheric lymphocytic infiltrates, microglial nodules, and neuronal loss leading to the destruction of the affected hemisphere. In this study, immunohistochemical evaluation of specimens from 11 patients revealed lymphocytic infiltrates that consisted mainly of CD3(+)CD8(+) T cells. Of these cells, 7.0% lay in direct apposition to MHC class I(+) neurons. Confocal laser microscopy revealed that these lymphocytes contained granzyme B in a polar orientation toward these perikarya. Single neurons underwent apoptosis. These findings indicate that a T-cell-mediated cytotoxic reaction induces neuronal death in Rasmussen's encephalitis. This study directly shows, for what we believe is the first time, that a cytotoxic T-cell mechanism contributes to loss of neurons in human brain disease.

Adolescent↗

PubMed2002

Focal cortical dysplasia of Taylor's balloon cell type: mutational analysis of the TSC1 gene indicates a pathogenic relationship to tuberous sclerosis.

Focal cortical dysplasia (FCD) is characterized by a localized malformation of the neocortex and underlying white matter. Balloon cells, similar to those observed in tuberous sclerosis, are present in many cases (FCD(bc)). In these patients, a hyperintense funnel-shaped subcortical lesion tapering toward the lateral ventricle was the characteristic finding on fluid-attenuated inversion recovery magnetic resonance imaging scans. Surgical lesionectomy results in complete seizure relief. Although the pathogenesis of FCD(bc) remains uncertain, histopathological similarities indicate that FCD(bc) may be related pathogenetically to tuberous sclerosis. Here, we studied alterations of the TSC1 and TSC2 genes in a cohort of patients with chronic, focal epilepsy and histologically documented FCD(bc) (n = 48). DNA was obtained after microdissection and laser-assisted isolation of balloon cells, dysplastic neurons, and nonlesional cells from adjacent normal brain tissue. Sequence alterations resulting in amino acid exchange of the TSC1 gene product affecting exons 5 and 17 and silent base exchanges in exons 14 and 22 were increased in patients with FCD(bc) compared with 200 control individuals (exon 5, 2.3% FCD(bc) vs 0% C; exon 17, 35% FCD(bc) vs 1.0% C; exon 14, 37.8% FCD(bc) vs 15% C; exon 22, 45% FCD(bc) vs 23.8% C). Sequence alterations could be detected in FCD(bc) and in adjacent normal cells. In 24 patients, DNA was suitable to study loss of heterozygosity at the TSC1 gene locus in microdissected FCD(bc) samples compared with control tissue. Eleven FCD(bc) cases exhibited loss of heterozygosity. In the TSC2 gene, only silent polymorphisms were detected at similar frequencies as in controls. Our findings indicate that FCD(bc) constitutes a clinicopathological entity with distinct neuroradiological, neuropathological, and molecular genetic features. These data also suggest a role of the TSC1 gene in the development of FCD(bc) and point toward a pathogenic relationship between FCD(bc) and the tuberous sclerosis complex.

Amino Acid Substitution↗

PubMed2002

Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets.

Oligoastrocytomas are heterogeneous tumors that have molecular features that overlap with either oligodendrogliomas or astrocytomas. Differences in the frequency of chromosomal losses of 1p and 19q in oligodendrogliomas are related to tumor location, with a low rate of allelic loss in tumors of the temporal and a high rate in tumors of the frontal, parietal, and occipital lobes. To test the possibility of regional molecular heterogeneity in oligoastrocytoma, we examined a series of 203 gliomas including 68 oligoastrocytomas and two control groups of 73 oligodendrogliomas and 62 astrocytomas for allelic losses of chromosomal arms 1p and 19q, and TP53 mutations, and compared these data with tumor localization. Common molecular alterations were found in oligodendrogliomas and oligoastrocytomas arising in extratemporal sites. In respect to the molecular parameters analyzed, temporal oligoastrocytomas were either indistinguishable from astrocytoma or similar to temporal oligodendrogliomas. Oligodendroglial neoplasms can thus be separated into three molecular subsets, two of which include lesions with the morphological features of oligodendrogliomas and oligoastrocytomas and one resembling temporal oligoastrocytoma. Molecular subclassification thus unifies previous findings about prognosis, behavior, response to therapy, genotype, and location in oligodendroglial tumors.

Astrocytoma↗

PubMed2002

Hemispherectomy techniques.

Hemispherectomy techniques have undergone multiple changes. Because of these changes, several current alternatives are described. The need for an extensive procedure in young children with special pediatric requirements is the background for the development of newer and more microsurgically oriented techniques aimed at reducing the intraoperative problems and late postoperative complications. This article reviews the strengths and the disadvantages of the currently used procedures in light of special requirements for hemispheric dysplasias.

Cerebral Cortex↗

PubMed2002

Combined surgery, radiation, and PCV chemotherapy for astrocytomas compared to oligodendrogliomas and oligoastrocytomas WHO grade III.

The time to tumor progression (TTP), time to death (TTD) and complications were studied prospectively in a cohort of patients treated by surgery and adjuvant radio- and intensified PCV chemotherapy for astrocytomas (AIII), oligodendrogliomas (OIII) and oligoastrocytomas (OAIII) WHO grade III. The treatment was carried out in 48 patients: 24 AIII, 20 OAIII and four OIII, at the same medical institution. OIII and OAIII were grouped together (OIIIOAIII). With the exception of age (mean age 48.5 years for AIII and 38.5 years for OIIIOAIII, respectively) and number of PCV cycles completed (median of three cycles for AIII and 4.75 for OIIIOAIII respectively), the patients' characteristics at study entry (gender, Karnofsky Performance Score (KPS), tumor localization) and at completion of therapy (extent of tumor resection, dose of adjuvant radiotherapy) were not statistically different between the two patient groups. The median TTP and TTD for AIII were 26.8 and 27.9 months, respectively. The median TTP and TTD for OIIIOAIII were not reached yet. The 75th percentile of TTP and TTD for OIIIOAIII was reached at 49.4 and 51.5 months, respectively. The Kaplan-Meier analysis showed significantly longer TTP (p = 0.009) and TTD (p = 0.002) for OIIIOAIII as compared to AIII. A new neurological deficit, following surgery, occurred in 14.5% of the patients. Brain radiation necrosis occurred in one patient. The most significant toxicity of PCV-chemotherapy was hematologic and reached WHO grade III and IV in 30% of the patients. This study compared for the first time the outcome of AIII with OIIIOAIII when treated with combined surgery, radiotherapy, and intensified PCV chemotherapy: longer TTP and TTD were observed in anaplastic glioma with oligodendroglial components WHO grade III as compared to pure astrocytoma WHO grade III. This is in accordance with results in patients treated by surgery with adjuvant radiation alone. The efficacy of additional adjuvant PCV chemotherapy in prolonging TTP and TTD has to be verified in prospective controlled studies.

Adult↗

PubMed2002

Conditional expression of the tumor suppressor p16 in a heterotopic glioblastoma model results in loss of pRB expression.

We have expressed the tumor suppressor p16 under the control of a tetracycline-sensitive promoter in two human glioblastoma cell lines which do not contain endogenous p16. Ectopic p16 expression led to a stable but reversible G1 phase cell cycle arrest, reduced the growth of both cell lines in cell culture, and almost abolished their in vitro tumorigenicity. U-87MG-tTA-p16 glioblastoma cells consistently formed tumors after subcutaneous injection into the flanks of nude mice. p16 expression in these tumors was strictly dependent on the presence or absence of tetracycline in the drinking water. Ectopic p16 reduced the tumor take rate (in vivo tumorigenicity) of U-87MG-tTA-p16 cells from 18/20 (90%) to 5 tumors/12 (42%) tumor cell injections. p16 positive and negative tumors differed with respect to their Ki67 labeling indices (34 +/- 4% vs. 52 +/- 6% , P < 0.001, student's t-test). These data are consistent with an in vitro and in vivo glioma suppressor role for p16. Interestingly, we observed a secondary reduction of pRB expression in tumors (and cell cultures) exposed to p16 for > or = 10 (6) days. pRB is p16's major downstream target. Hence, this finding might explain, why p16 expression neither significantly affected the morphology nor led to a reduction of size or growth rate of the tumors. Loss of pRB following p16 expression might severely limit the potential benefit of p16 gene therapy for glioblastoma.

Animals↗

PubMed2002

Selective middle cerebral artery Wada tests as a part of presurgical evaluation in patients with drug-resistant epilepsies.

PURPOSE: To analyze the role of selective middle cerebral artery (MCA) Wada tests in the presurgical workup of patients with drug-resistant focal epilepsies. METHODS: Twenty MCA Wada test procedures were performed to identify eloquent cortex (a) in nine patients with hemispheric lesions involving the motor cortex (connatal MCA infarct, n = 5; unilateral cortical dysplasia, n = 3; Rasmussen encephalitis, n = 1), (b) five patients with circumscribed neoplastic or nonneoplastic lesions adjacent to the motor cortex or classic language areas, and (c) for purely electrophysiologic reasons, in two patients with electrical status epilepticus in sleep (ESES). Sodium amobarbital and [99mTc]-HMPAO were simultaneously injected via a microcatheter into the distal M1 segment (n = 7), the inferior MCA trunk (n = 3), or into MCA branches (n = 10). RESULTS: Co-registered single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI;n = 18) showed that sodium amobarbital did not reach the target area in three procedures. Temporary neurologic deficits occurred in 12 procedures. Eleven patients were operated on with the following surgical approaches: functional hemispherectomy, n = 3; partial or extended lesionectomy, n = 4; anterior temporal lobectomy, n = 1; and multiple subpial transsections, n = 3. Seizure freedom (Engel class I) was achieved in five patients. CONCLUSIONS: Selective MCA Wada tests can contribute to risk assessment concerning postsurgical motor deficits before functional hemispherectomy. Other indications are less clear: The identification of language areas is targeted primarily by electrical-stimulation mapping after subdural grid implantations, and selective MCA Wada tests in ESES patients yet have to be validated in larger patient groups.

Adolescent↗

PubMed2002

Memory outcome after selective amygdalohippocampectomy: a study in 140 patients with temporal lobe epilepsy.

PURPOSE: The technique of selective amygdalohippocampectomy (SAH) was originally developed in epilepsy surgery to spare unaffected brain tissue from surgery, thus minimizing the cognitive consequences of temporal lobe surgery. The results of previous studies, however, are equivocal in this regard. This study evaluated memory after SAH in a large sample of patients with mesial temporal lobe epilepsy. METHODS: The 140 patients received material-specific memory tests before and 3 months after unilateral SAH. RESULTS: Significant declines in all aspects of verbal learning and memory were found particularly for the left resected group. With reliability-of-change indices, a high number of patients showed postoperative verbal memory declines, < or = 51% in left SAH and < or = 32% in right SAH. For left SAH, a higher preoperative verbal memory performance, a lower preoperative nonverbal memory score, an older age at surgery, and a later onset of epilepsy predicted a stronger decline in verbal memory. After right SAH, the risk for a verbal memory decline was slightly increased when patients had surgical complications or a presurgical evaluation with bilateral intrahippocampal depth electrodes. Results concerning nonverbal memory were less clear. CONCLUSIONS: The results clearly indicate, that particularly left SAH can lead to a significant decline in memory functions. Predictors of postoperative verbal memory were similar to those reported for temporal lobectomy. Postoperative deteriorations were broader and stronger in our study than in previous studies. We discuss methodologic differences (sample size, retest interval, extent of resection) and other factors as possible reasons.

Adult↗

PubMed2002

Multiple subpial transection for intractable partial epilepsy: an international meta-analysis.

PURPOSE: Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected. METHODS: A meta-analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty-three patients underwent MST without resection. RESULTS: In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%). CONCLUSIONS: These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand-alone procedure to allow further development of criteria and predictive factors for outcome.

Epilepsies, Partial↗

PubMed2002

Focal cortical dysplasia of Taylor's balloon cell type: a clinicopathological entity with characteristic neuroimaging and histopathological features, and favorable postsurgical outcome.

BACKGROUND AND PURPOSE: Focal cortical dysplasia of Taylor's balloon-cell type (FCD-BC) are a frequent cause of pharmacoresistant epilepsy in young patients. In order to characterize FCD-BC, we coupled MRI and histopathology, and analyzed the clinical outcome following epilepsy surgery. METHODS: From an epilepsy data bank with 547 histological specimens, 17 FCD-BC were re-evaluated of which high resolution MRI was available. Five additional FCD-BC were prospectively identified by MRI. Histopathological and immunohistochemical features were related to MRI. Outcome following lesionectomy was analyzed as determined on routine examinations 3, 6 and 12 months following surgery. RESULTS: All but one lesion were located outside the temporal lobe. A markedly hyperintense funnel-shaped subcortical zone tapering towards the lateral ventricle was the characteristic finding on FLAIR MRI. Histopathologically, the subcortical zone of the FCD-BC displayed hypomyelinated white matter with radially oriented balloon cells and gliosis. Dysplastic neurons were found in the adjacent, disorganized cortex. All patients with complete lesionectomy were seizure free one year following surgery. CONCLUSION: Focal cortical dysplasias of Taylor's balloon-cell type (FCD-BC) have characteristic MRI and histopathological findings. MRI recognition is important, since outcome following resective surgery is favorable.

Adolescent↗

PubMed2002

Changes in flip/flop splicing of astroglial AMPA receptors in human temporal lobe epilepsy.

PURPOSE: Recent data suggested a role for glial cells in epilepsy. This study sought to identify and functionally characterize AMPA receptors expressed by astrocytes in human hippocampal tissue resected from patients with intractable temporal lobe epilepsy. METHODS: Patch-clamp and fast application methods were combined to investigate astrocytes in situ and after fresh isolation from the stratum radiatum of the hippocampal CA1 subfield. Relying on presurgical and histopathologic analysis, we divided human specimens into two groups, Ammon's horn sclerosis (AHS) and lesion-associated epilepsy. RESULTS: Fast application of glutamate and kainate evoked receptor currents in all cells studied. Reversal-potential analysis revealed an intermediate Ca2+ permeability of the receptor channels that did not vary between the two groups of patients. However, preapplication of the AMPA receptor-specific modulator, cyclothiazide, disclosed differences in flip-flop splicing. This treatment considerably enhanced the receptor conductance, with potentiation being significantly stronger in cells from AHS specimens compared with lesion-associated cells, suggesting upregulation of AMPA receptor flip splice variants in astrocytes of the sclerotic tissue. CONCLUSIONS: Compelling evidence has been accumulated showing direct and rapid signaling between neurons and glial cells. Our data suggest that in AHS patients, neuronally released glutamate will lead to an enhanced and prolonged depolarization of astrocytes, which might be involved in seizure generation and spread in this particular condition of human temporal lobe epilepsy.

Astrocytes↗

PubMed2002

The natural history of Rasmussen's encephalitis.

Rasmussen's encephalitis (RE) is a chronic inflammatory disease of unknown origin, usually affecting one brain hemisphere. In the present study, a comprehensive assessment of the natural history of the disorder is presented. Seizure frequency, degree of hemiparesis and degree of cerebral hemiatrophy in 13 patients with histopathologically proven RE are analysed over the time course prior to resective epilepsy surgery or introduction of long-term immunosuppressive pharmacotherapy. For the assessment of the degree of cerebral hemiatrophy, on defined slices comprising the Sylvian fissure of hard copies of serial MRI investigations, the hemispheric ratio (HR) was determined. The data show an initial prodromal phase with an intermediate frequency of focal onset seizures and mostly no hemiparesis. The occurrence of this stage was mainly observed in the adolescent and adult patients. All patients went through an acute phase with a median duration of 8 months. During this stage, there were frequent simple partial motor seizures, development of hemiparesis and volume loss of the affected hemisphere. After this, the patients passed into a residual stage with a marked decrease in seizure frequency. Twelve months after the onset of the acute stage, the average HR was 0.72. These data allow an estimation of the prognosis of newly affected patients, and demonstrate that most of the brain damage in RE occurs during the first 8-12 months. These findings should be taken into consideration when future therapeutic approaches to RE are evaluated.

Adolescent↗