Biomedical subjects

I Blümcke

Publications and source records attributed to I Blümcke.

At least 19 recordsLinked to original sources

PubMed2006

Periventricular nodular heterotopia: A challenge for epilepsy surgery.

Pharmacoresistant focal epilepsies due to periventricular nodular heterotopia are a diagnostic and therapeutic challenge because of the need of invasive presurgical diagnostics and the selection of an optimal surgical approach. Invasive investigations in previous studies showed that focal epileptic activity can be correlated predominantly either with one of the nodular heterotopia or with neocortical epileptogenic zones distant to the periventricular nodules. Up to now, invasive recordings were required for localization of epileptic activity and its correlation to heterotopia. The following case presentation reports on a non-invasive approach using magnetic source imaging (MSI) combined with intraoperative ECoG. MSI combines preoperative data from magnetic resonance imaging (MRI) with magnetoencephalography (MEG). The MSI data for definition of the localization of the epileptic activity and functional important areas were coregistered with the intraoperative high-field-MRI and diffusion tensor imaging-based fiber tracking (DTI) of the visual pathway using a neuronavigational system. A neuronavigation-guided surgical resection of the epileptogenic area was performed leaving the heterotopia and the visual tract fibers intact. Postoperatively preservation of the visual fields was documented and the frequency of seizures was markedly reduced.

Brain Diseases↗

PubMed2006

Deficient memory acquisition in temporal lobe epilepsy is predicted by hippocampal granule cell loss.

BACKGROUND: The hippocampal formation is essentially involved in the formation of conscious memories for facts and events and neurologic diseases affecting the hippocampus associate with severe memory deficits, i.e., temporal lobe epilepsies. METHODS: We studied the degree of declarative memory dysfunction in 24 human subjects with unilateral mesial temporal lobe epilepsy, using the unique possibility to access memory performance of each isolated hippocampus by intracarotid amobarbital anesthesia. Subsequently, hippocampal specimens from the same patients were available for neuropathologic analysis following surgical treatment of intractable seizures. RESULTS: Neuronal cell loss in the dentate gyrus and all hippocampal subfields correlated with memory performance with the exception of CA2. Moreover, multiple regression and partial correlation analyses identified neuronal cell loss within the internal limb of the dentate gyrus, a developmentally distinct subregion of the hippocampal formation known to generate new neurons throughout life, as highly significant predictor for the patient's ability to learn and recall memories. CONCLUSIONS: In accordance with animal studies, the dentate gyrus may play a critical role in the neuronal network associated with memory formation.

Adult↗

PubMed2006

Low-grade gliomas -- current concepts.

Diffuse astrocytomas, oligodendrogliomas, and oligoastrocytomas (mixed gliomas) WHO grade II, pleomorphic xanthoastrocytomas (PXAs), pilocytic astrocytomas, and subependymal giant cell astrocytomas (SEGAs) are often referred to as low-grade gliomas. WHO grade II astrocytomas, oligodendrogliomas, and mixed gliomas are characterized by their infiltrative growth, frequent tumor recurrence and a more than 50 % risk for malignant progression. In contrast, pilocytic astrocytomas and SEGAs are circumscribed tumors amenable to a (radio)surgical cure. There are few universally accepted guidelines for the treatment of low-grade gliomas. In this review, three neurosurgeons, a neurologist, a neuropathologist, and a radiation oncologist discuss some of the difficult issues surrounding the diagnosis and treatment of low-grade gliomas from their individual points of view (i. e., classification and neuropathology, MR imaging, stereotactic biopsy, microsurgery, interstitial radiotherapy/brachytherapy, radiotherapy, wait and see strategy).

Brain Neoplasms↗

PubMed2006

Immunohistochemical profile and chromosomal imbalances in papillary tumours of the pineal region.

The histopathology of papillary tumours of the pineal region (PTPR) closely resembles that of ependymomas and choroid plexus tumours. Therefore, immunohistochemical staining profiles were investigated in a series of 15 PTPR. In addition to cytokeratin, synaptophysin and glial fibrillary acidic protein expression, PTPR were examined for the presence of dot- or ring-like epithelial membrane antigen (EMA) immunoreactivity typically encountered in ependymoma, staining for inwardly rectifying potassium channel Kir7.1 and stanniocalcin-1 (specifically expressed in choroid plexus tumours) as well as microtubule-associated protein-2 (MAP-2). Furthermore, comparative genomic hybridization was performed in five PTPR. Cytokeratin was expressed in all PTPR examined, whereas glial fibrillary acidic protein and synaptophysin staining were absent. Dot- or ring-like EMA immunoreactivity was only observed in 1 out of 15 PTPR. Membranous Kir7.1 and cytoplasmic stanniocalcin-1 staining were present in the minority of PTPR (3/15 and 4/15, respectively). In contrast, MAP-2 immunoreactivity was encountered in 13 out of 15 PTPR, but was significantly less frequently observed in a series of choroid plexus tumours (7/37). PTPR mainly presented with chromosomal losses affecting chromosomes 10 (4/5 cases) and 22q (3/5 cases) as well as gains on chromosomes 4 (4/5 cases), 8 (3/5 cases), 9 (3/5 cases) and 12 (3/5 cases). To conclude, the majority of PTPR can be distinguished from ependymomas and choroid plexus tumours by absent staining for epithelial membrane antigen, Kir7.1 and staniocalcin-1 as well as the presence of distinct MAP-2 immunoreactivity. Antibodies directed against these antigens are thus expected to be valuable markers in the diagnosis of papillary tumours located in the vicinity of the third ventricle.

Adenocarcinoma, Papillary↗

PubMed2005

[Brain tumors and epilepsy].

Improved tumor and epilepsy treatment requires long-term care of patients with symptomatic epilepsies caused by tumors. Pathophysiology, epidemiology, prognosis, drugs, and surgical treatment are discussed with special emphasis on seizure control, side effects, and quality of life. Because of the long-term course -- often 10 to 20 years -- optimal treatment strategies have to be selected individually. These should consider possibilities of new techniques of co-registering imaging and electrophysiology, surgery, and the interaction of anticonvulsive and chemotherapeutic drugs, cognition, and mood.

Anticonvulsants↗

PubMed2004

[Supratentorial cavernoma and epileptic seizures. Are there predictors for postoperative seizure control?].

For cavernous haemangiomas, it is the aim of surgical treatment to control epilepsy and eliminate potential sources of intracerebral haematomas. In the following investigation, it was attempted to find indicators for seizure freedom after surgery. Success of therapy was assessed according to three patterns of classification. Thirty patients underwent tailored resection based on findings from preoperative investigations and intraoperative electrocorticography. Follow-up averaged 4 years. Lesionectomy, extended lesionectomy, and modified lobe resection were carried out in 13, 11, and six patients, respectively. For all procedures, including microsurgical lesionectomy, the firm gliotic layer unequivocally differed in colour and consistency from normal brain and was removed. Further tissue resection was carried out only if the electrocortical course suggested persistent spike activity around the resection cavity or if presurgical MRI evaluation (e.g. hippocampal atrophy) or electrophysiology also pointed to pathology distant from the lesion. Of the patients, 53.3% became completely seizure-free (Engel I), and one additional patient had only occasional isolated auras. Dramatic reductions in seizure frequency and severity were exhibited by 26.7%. Outcome in respect to seizure control was not associated with resection procedure, comparing pure lesionectomy with lesionectomy plus cortectomy. In the group of patients with epilepsy surgery, those with hippocampectomy had significantly better outcome than those without. Important prognostic factors were early operation after seizure manifestation (91.7% operated upon within 2 years of seizure onset became seizure-free). Another prognostic factor was unifocal seizure onset (bilateral or multifocal seizure onset was found in care of the ten patients with unfavourable outcome). None of the four patients harbouring multiple cavernomas became seizure-free after resection of one lesion, which was believed to be mostly attributable to the epileptic focus that was removed.

Adult↗

PubMed2004

The reelin pathway components disabled-1 and p35 in gangliogliomas--a mutation and expression analysis.

Focal epilepsies in young patients are frequently associated with differentiated glioneuronal tumours. Dysplastic neurones represent a characteristic neuropathological feature of gangliogliomas, the most common entity encountered in this group. Here, we have analysed two major components of the reelin pathway involved in neuronal migration and cortical development, that is, p35 and disabled-1 (dab1), in gangliogliomas. Genomic structures of human dab1 and p35 were identified 'in silico' using the HTGS databank, NCBI BLAST 2.1. DNA sequence analysis was carried out in gangliogliomas obtained from 29 epilepsy patients vs. peripheral blood DNA from non-affected control individuals (n = 100). Gene expression of dab1 and p35 was determined by real-time RT-PCR (reverse transcriptase polymerase chain reaction) in gangliogliomas (n = 14) vs. non-neoplastic central nervous system tissue (n = 20). The human dab1 gene contains 13 coding exons and is located on chromosome 1p31-32. A single coding exon constitutes the human p35 gene, which is located on chromosome 17q11.2. A novel homologueous genomic region on chromosome 2 has to be taken into account for future studies on p35. One ganglioglioma patient showed a unique polymorphism in the p35 gene. The single base exchange (C to A) at nucleotide 904 of the p35 cDNA (GenBank X80343, start ATG, codon 302) results in a leucine-isoleucine amino acid substitution. No mutations of the dab1 and p35 genes in gangliogliomas were observed. However, significantly lower levels of dab1 and p35 gene transcripts were detected in gangliogliomas compared to controls (dab1 28.24%, t-test P < 0.001; p35 21.28%, t-test P < 0.001, in gangliogliomas vs. controls). Our data suggest that mutational events of dab1 and p35 are not involved in the molecular pathogenesis of gangliogliomas. A potential functional role of these developmentally regulated genes for the formation of epileptogenic glioneuronal lesions remains to be elucidated.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Magnetoencephalography (MEG) predicts focal epileptogenicity in cavernomas.

OBJECTIVE: The aim of this study was to identify the irritative epileptic zone in patients with cavernomas by means of magnetoencephalography (MEG). METHOD: Among 82 patients operated for epilepsy, whose presurgical evaluation had included MEG, histological assessment of the tissue removed had confirmed cavernomas in eight. These eight patients had epilepsy since 18.6 (SD 12.7) years on average. The monitoring lasted about 2.1 (SD 1.3) hours and a median 20.9 (SD 14.3) spikes per hour were recorded. Spontaneous brain activity was recorded by means of a 74 channel dual unit MEG system (Magnes II, 4-D Neuroimaging) with simultaneous EEG recording (31 scalp electrodes). Spike analysis was performed using different source (moving dipole, current density reconstruction) and head models (spherical shells, BEM). Co-registration of neurophysiological and imaging data (MRI) was based upon anatomical landmarks. RESULTS: In 6/8 patients co-localisation from the cavernoma and epileptic zone was found. In two patients the focus was localised in the parieto-occipital lobe, in three patients in the frontal lobe and in three patients in the temporal lobe. In one case of temporal and one case of frontal lobe focus localisation there was no spatial relationship to the cavernoma. CONCLUSION: In cases of focal seizures due to a single cavernoma, MEG may precisely delineate the epileptogenic tissue bordering the lesion. In patients with multiple cavernomas or dual pathology, MSI may reveal the complexity of the case, and contribute to the decision about further invasive diagnostics and more sophisticated therapeutic measures. MEG is a promising method for prediction of the epileptic zone in cavernoma related epilepsies, and thus it can contribute to decision making about and planning of epilepsy surgery.

Adolescent↗

PubMed2004

Lesional mesial temporal lobe epilepsy and limited resections: prognostic factors and outcome.

OBJECTIVES: To evaluate the influence of clinical, investigational, surgical, and histopathological factors on postoperative seizure relief in patients with mesial temporal lobe epilepsy (MTLE) due to lesions other than ammonshornsclerosis (AHS). METHODS: Of 738 patients operated for TLE, 78 patients underwent limited resections for lesional MTLE (1990-2000). Seventy four patients with a follow up of more than one year were included. The preoperative clinical, neuropsychological, electroencephalogram, and neuroimaging characteristics were prospectively collected in a database. The histopathological material was re-examined. RESULTS: The mean follow up was 49 months. Fifty eight patients were classified as seizure free (78.4% Class I), and six as almost seizure free (8.1% Class II), grouped together as satisfactory seizure control (64 patients, 86.5%). Five patients (6.8%) were categorised in Classes III and IV, respectively. These were grouped as unsatisfactory seizure control (10 patients, 13.5%). Surgical procedures were: 32 amygdalohippocampectomies (AH), 17 partial anterior AH, 15 AH plus polar resection, seven AH plus basal resection, and three AH plus extended temporal lesionectomy. There was no mortality and 2.7% mild permanent morbidity. Seizure relief did neither differ significantly with these approaches, nor with different classes of pathological findings (43 developmental tumours, 12 glial tumours, 10 dysplasias, and nine others). Even operation of dysplasias resulted in 80% satisfactory seizure control. Seizure onset during childhood proved to be a negative predictor for seizure relief (p = 0.020). MRI revealed 73 suspected lesions (98.6%), one dysembryoplastic neuroepithelial tumour was missed, in four cases no structural abnormalities could be confirmed with histopathological exam. Additionally, multifactorial regression revealed the factors "seizure onset after 10 years of age", "presence of complex partial seizures", "absence of a neurological deficit", and a "correlating neuropsychological deficit" as predictive for satisfactory seizure control. CONCLUSIONS: "Preoperative tailoring" resulting in limit resections has proven to be safe and to provide a very good chance for satisfactory seizure relief in patients with lesional MTLE.

Adolescent↗

PubMed2003

Outcome of epilepsy surgery in focal cortical dysplasia.

OBJECTIVE: To describe the outcome of surgery in patients with drug resistant epilepsy and a histopathological diagnosis of focal cortical dysplasia. METHODS AND SUBJECTS: Analysis of histories and presurgical and follow up data was carried out in 53 patients with a histological diagnosis of focal cortical dysplasia. Their mean age was 24.0 years (range 5 to 46), and they included 14 children and adolescents. Mean age at seizure onset was 12.4 years (0.4 to 36) and mean seizure duration was 11.6 years (1 to 45). RESULTS: The presurgical detection rate of focal cortical dysplasia with magnetic resonance imaging (MRI) was 96%. There were 24 temporal and 29 extratemporal resections; additional multiple subpial transections were done in 12 cases to prevent spread of seizure discharges. There was a 6% rate of complications with permanent neurological deficit, but no deaths. All resected specimens were classified by neuropathological criteria as focal cortical dysplasia. Balloon cells were seen in most cases of extratemporal focal cortical dysplasia. After a mean follow up of 50 months, 38 patients (72%) were seizure-free, two (4%) had less than two seizures a year, nine (17%) had a reduction of seizure frequency of more than 75%, and four (8%) had no improvement. Seizure outcome was similar after temporal and extratemporal surgery. The patients in need of multilobar surgery had the poorest outcome. CONCLUSIONS: Circumscribed lesionectomy of focal dysplastic lesions provides seizure relief in patients with chronic drug resistant temporal and extratemporal epilepsy. There was a trend for the best seizure outcome to be in patients with early presurgical evaluation and early surgery, and in whom lesions were identified on the preoperative MRI studies.

Adolescent↗

PubMed2002

Expression of the CD34 antigen in pleomorphic xanthoastrocytomas.

Pleomorphic xanthoastrocytoma (PXA) is a rare, superficially located astrocytic glioma of children and young adults, which is associated with a relatively favorable prognosis. Here we report on the expression of the hematopoietic progenitor cell and vascular endothelial cell associated antigen CD34 in PXAs. We found CD34 immunoreactivity in various fractions of tumor cells in 44 of 60 PXAs investigated (73%). CD34 expression was more common in PXAs of WHO grade II (37 of 44 tumors, 84%) than in PXAs with anaplastic features (7 of 16 tumors, 44%). Immunoreactivity for CD34 was also commonly detected in single or clustered dysplastic neural cells within the cerebral cortex adjacent to the PXAs. Reverse transcription-PCR revealed that PXAs express the full-length CD34 transcript and a known splice variant encoding a truncated form of CD34. Both transcripts were detectable at higher levels in PXAs as compared to diffuse astrocytomas and non-neoplastic brain tissue. Taken together, our findings demonstrate that PXAs frequently express CD34 not only in vascular endothelial cells but also in tumor cells and in dysplastic cells of the adjacent cortex. Therefore, immunostaining for CD34 may be a helpful tool for the histological differential diagnosis of PXAs.

Adolescent↗

PubMed2002

Time-efficient T2 relaxometry of the entire hippocampus is feasible in temporal lobe epilepsy.

OBJECTIVE: To test the clinical usefulness and reliability of a new dual-echo turbo-spin-echo (TSE) sequence for rapid and regional hippocampal T2 relaxometry. METHODS: Hippocampal T2 relaxation time (HRT) was determined by a TSE sequence on three to four consecutive coronal images in 16 control subjects and 12 patients with mesial temporal lobe epilepsy. HRT was related to neuropathology findings in hippocampal specimens including neuronal cell density (ND), results of visual analysis of MR images, clinical outcome after epilepsy surgery, and hippocampal volumetry. RESULTS: Rapid HRT differentiated patients from control subjects; all cases of hippocampal sclerosis (HS; n = 10) were correctly diagnosed. HRT showed a strong correlation with ND in CA1 (p < 0.02) and CA3 (p < 0.05). Diagnoses based on rapid relaxometry concurred fully with results of visual inspection. Mean HRT was prolonged ipsilaterally in all patients with excellent postoperative seizure outcome and bilaterally prolonged or normal in patients with poorer outcome. Rapid HRT was concordant with hippocampal volumetry in 10 of 12 patients. Regional HRT of control subjects revealed significantly higher values in the anterior than posterior hippocampus. In patients with unilateral HS, this gradient was absent. The gradient was also absent contralaterally to HS, although surgical outcome was excellent. CONCLUSIONS: Hippocampal dual-echo TSE-relaxometry can be regarded a reliable technique to detect and quantify HS. With a scan time of 3.31 minutes and immediate off-line analysis lasting a few minutes only, TSE-T2 relaxometry is easy to integrate in the routine diagnostic assessment of hippocampal morphology in large numbers of patients.

Adolescent↗

PubMed2002

[The new WHO classification of tumors of the nervous system 2000. Pathology and genetics].

New developments in neuro-oncology have prompted an update of the World Health Organization (WHO) classification of tumors of the nervous system. Major changes include the addition of new entities and the refinement of criteria for the diagnosis and grading of various neoplasms, in particular the meningiomas. As novel clinico-pathological entities, the chordoid glioma of the third ventricle, the atypical teratoid/rhabdoid tumor (AT/RT), the solitary fibrous tumor, and the perineurioma have been listed. The former lipomatous medulloblastoma of the cerebellum, previously incorporated in the family of embryonal tumors, is now classified as cerebellar liponeurocytoma. The term mixed pineocytoma/pineoblastoma has been replaced by pineal parenchymal tumor of intermediate differentiation. Furthermore, the large cell medulloblastoma and the tanycytic ependymoma were established as novel tumor variants. A separate chapter on the peripheral neuroblastic tumors has now been included in the classification. Substantial revisions were introduced in the meningioma chapter. For both atypical meningioma WHO grade II and anaplastic meningioma WHO grade III, histopathological criteria are now precisely defined. An important new addition to the WHO 2000 classification of nervous system tumors is the inclusion of molecular pathology findings. With this combination of pathology and genetics it has set the stage for a new format of the WHO tumor classification series.

Astrocytoma↗

PubMed2001

Messenger RNA of steroid 21-hydroxylase (CYP21) is expressed in the human hippocampus.

21-hydroxylase converts progesterone to 11-deoxycorticosterone and 17-hydroxyprogesterone to 11-deoxycortisol, the substrates which are required for the production of the main adrenal steroids, corticosterone, aldosterone, and cortisol. As 21-hydroxylase activity has been detected in rodent and fetal human brain, we studied whether and to what extent 21-hydroxylase mRNA is expressed in hippocampal tissue specimens from patients undergoing epilepsy surgery (n=42). 21-hydroxylase mRNA was detected in the hippocampus with an expression 10 000 times lower than in adrenal gland tissue. There was no significant difference in expression levels between women (9.5+/-2.7 arbitrary units (aU); mean+/-SEM) and men (8.0+/-2.2 aU); however, mRNA concentrations in the hippocampus of children (n=4, 1.8+/-0.5 aU) were considerably lower than in adults (n=38, 8.6+/-1.7 aU). The expression of 21-hydroxylase mRNA in the hippocampus suggests that this human brain area has the enzymatic capability to convert progesterone to 11-deoxycorticosterone and 17-hydroxyprogesterone to 11-deoxycortisol.

Adult↗

PubMed2001

Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy.

A considerable potential for neurogenesis has been identified in the epileptic rat hippocampus. Here, we explore this feature in human patients suffering from chronic mesial temporal lobe epilepsy. Immunohistochemical detection of the neurodevelopmental antigen nestin was used to detect neural precursor cells, and cell-type specific markers were employed to study their histogenetic origin and potential for neuronal or glial differentiation. The ontogenetic regulation of nestin-positive precursors was established in human control brains (week 19 of gestation-15 years of age). A striking increase of nestin-immunoreactive cells within the hilus and dentate gyrus could be observed in a group of young patients with temporal lobe epilepsy (TLE) and surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resembled nestin-immunoreactive granule-cell progenitors transiently expressed during prenatal human hippocampus development. An increased Ki-67 proliferation index and clusters of supragranular nestin-immunoreactive cells within the molecular layer of the dentate gyrus were also noted in the group of young TLE patients. Confocal studies revealed colocalization of nestin and the betaIII isoform of tubulin, indicating a neuronal fate for some of these cells. Vimentin was consistently expressed in nestin-immunoreactive cells, whereas cell lineage-specific markers, i.e., glial fibrillary acidic protein, MAP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric patients with early onset of temporal lobe epilepsy and/or point towards a delay in hippocampal maturation in a subgroup of patients with TLE.

Adolescent↗

PubMed2001

Quality management in neuropathology.

Quality management will have an increasing impact on the field of clinical neurosciences. The neuropathological examination of surgical or autopsy samples obtained from the central nervous system (CNS) and related structures, cerebrospinal fluid, peripheral nerve or skeletal muscle serves three major purposes: to identify a structural correlate of the disease, provide a reliable basis for treatment strategies and to investigate underlying pathogenic mechanisms. In order to achieve histopathological diagnosis at a consistent quality, quality management and control have to be implemented at different levels. At the local site, these concern neuropathological services, such as acquisition of tissue specimens, handling and staining procedures as well as diagnostic examination. Training programs offered in slide seminars and diagnostic workshops are important tools to highlight new developments and maintain high standards. National reference centers for brain tumors, neurodegenerative disorders, prion or muscle and nerve diseases assist with a second opinion in difficult cases and support epidemiological as well as clinical therapy trials. An international panel of neuropathologists has established guidelines for the classification of brain tumors, recently updated during a WHO 2000 consensus conference. Finally, the standardized histopathological and cytological diagnosis of CNS disorders plays also an important role in providing quality control for associated fields of the clinical neurosciences, such as neuroradiology, neurology, psychiatry and neurosurgery.

Brain Neoplasms↗

PubMed2001

Postsurgical outcome of children and adolescents with medically refractory frontal lobe epilepsies.

OBJECTS: In the adult population surgical treatment is generally less favorable for refractory frontal lobe epilepsy (FLE) than for temporal lobe epilepsy (TLE). Predictive factors and outcome of FLE surgery had not previously been described for the pediatric and adolescent population. Therefore, 32 children and adolescents who underwent FLE surgery were analyzed in this study. METHODS: Medical records were reviewed for demographic data, presurgical evaluation procedures, surgical procedures, pathological findings and follow-up. RESULTS: Mean age at operation was 10.8 years, with seizure onset at 4.6 years. Excellent outcomes were observed in 21 of the 32 patients following evaluation a mean of 34.5 months after surgery. Nineteen of 22 patients became seizure free after tailored resections, versus 2 out of 10 after lobectomy. Transient neurological and surgical complications occurred in 4 patients. Focal neoplastic lesions detectable by MRI were associated with a favorable outcome. CONCLUSIONS: As seen in adult FLE series, the detection of a resectable ictal neoplastic lesion on preoperative MRI is associated with an excellent outcome comparable to that of TLE surgery.

Adolescent↗

PubMed2001

Neuroactive steroids and seizure susceptibility.

There is increasing clinical and experimental evidence that hormones, in particular sex steroid hormones, influence neuronal excitability and other brain functions. The term 'neuroactive steroids' has been coined for steroids that interact with neurotransmitter receptors. One of the best characterized actions of neuroactive steroids is the allosteric modulation of GABA(A)-receptor function via binding to a putative steroid-binding site. Since neuroactive steroids may interact with a variety of other membrane receptors, excitatory as well as inhibitory, they may have an impact on the excitability of specific brain regions. Neuronal excitability is enhanced by estrogen, whereas progesterone and its metabolites exert anticonvulsant effects. Testosterone and corticosteroids have less consistent effects on seizure susceptibility. Apart from these particular properties, neuroactive steroids may regulate gene expression via progesterone receptors. Based on their molecular properties, these compounds appear to have a promising therapeutical profile for the treatment of different neuropsychiatric diseases including epilepsy. This review focuses on the effects of neuroactive steroids on neuronal excitability and their putative impact on the physiology of epileptic disorders.

Adrenal Cortex Hormones↗