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J Schramm

Publications and source records attributed to J Schramm.

At least 109 records · Page 6Linked to original sources
PubMed1999

Expression of 17beta-hydroxysteroid dehydrogenase types 1, 2, 3 and 4 in the human temporal lobe.

Sex steroid hormones exert important biological effects on the brain. Moreover, an extensive sex steroid metabolism occurs in the brain. In sex steroid metabolism 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) play essential roles in catalyzing the final steps in androgen and estrogen biosynthesis. Recently four types of human 17beta-HSDs and a pseudogene of the type 1 isoform were identified. To date, 17beta-HSD has not been extensively studied in the human brain. Therefore, we investigated the mRNA expression of the four isozymes of 17beta-HSD as well as the pseudogene of the type 1 isoform in the human temporal lobe to determine the predominant isoforms and, moreover, to elucidate the existence of possible sex and age differences. We studied biopsy materials from the temporal lobe of 34 women, 32 men and 10 children. Quantification of different mRNAs was achieved by competitive reverse transcription-PCR. 17beta-HSD 1, 17beta-HSD 3 and 17beta-HSD 4 were expressed in the human temporal lobe of children and adults, whereas 17beta-HSD 2 and the pseudogene of 17beta-HSD 1 were not expressed. In adults, 17beta-HSD 3 and 17beta-HSD 4 mRNA concentrations were significantly higher in the subcortical white matter (17beta-HSD 3: 14 591+/-3457 arbitrary units (aU), mean+/-s.e.m.; 17beta-HSD 4: 1201+/-212 aU) than in the cortex (17beta-HSD 3: 5428+/-1057 aU, P<0. 0002; 17beta-HSD 4: 675+/-74 aU, P<0.004). 17beta-HSD 1 concentrations did not differ significantly between the white matter (3860+/-1628 aU) and the cortex (2525+/-398 aU) of adults. In conclusion, the present study demonstrates the expression of 17beta-HSD 1, 3 and 4 mRNAs in the human temporal lobe. Together with CYP19AROM and 5alpha-reductase, known to be expressed in the human brain, the expression of 17beta-HSD 1, 3 and 4 mRNAs indicates the major importance of local steroid biosynthesis in the brain.

17-Hydroxysteroid Dehydrogenases↗
PubMed1999

Clinical relevance of amygdala sclerosis in temporal lobe epilepsy.

OBJECT: The goal of this study was to define the incidence and clinical significance of amygdala sclerosis (AS) in patients with temporal lobe epilepsy (TLE). METHODS: Surgical specimens of the lateral amygdaloid nucleus and the hippocampus excised from 71 patients who were treated for medically intractable TLE were quantitatively evaluated using a computer-assisted image-analysis system and compared with 10 normal autopsy specimens. Densities of neurons and reactive astrocytes in the patients with TLE were correlated with clinical, neuropsychological, and depth-electroencephalography data. The neuron counts of the lateral amygdaloid nucleus did not correlate with various presumed etiological factors of TLE including hereditary seizures, birth complications, febrile convulsions, traumatic brain injury, infections, seizure semiology, and epileptological outcome. However, patient age at surgery was significantly higher (mean difference 10 years) when AS was present, as compared with patients without AS (p < 0.01). Seizure origin, as determined by using amygdalohippocampal depth electrodes, did not correlate with the presence or absence of AS. Neuropsychologically, there was a significant correlation between the neuronal densities of the lateral amygdaloid nucleus and both preoperative visual recognition and postoperative deterioration of short-term verbal memory performance (p < 0.05). CONCLUSIONS: Except for the relatively long history of epilepsy, the presence of AS is not associated with specific clinical or electrocorticographic features of mesial TLE. However, patients without AS are particularly at risk for deterioration of short-term verbal memory following amygdalohippocampectomy.

Adolescent↗
PubMed1998

Polymorphic imprinting of the serotonin-2A (5-HT2A) receptor gene in human adult brain.

We have examined the imprinting status of the serotonin-2A (5-HT2A) receptor gene (HTR2A) in a series of 41 tissue samples from human adult brain. Using a HpaII RFLP polymorphism in the coding region, we obtained evidence of monoallelic expression of HTR2A in 4 out of 18 informative individuals. However, biallelic expression of HTR2A was observed in other individuals (14/18), suggesting that within the human population HTR2A imprinting in brain is polymorphic.

Alleles↗
PubMed1998

Electrophysiological characterization of Na+ currents in acutely isolated human hippocampal dentate granule cells.

1. Properties of voltage-dependent Na+ currents were investigated in forty-two dentate granule cells (DGCs) acutely isolated from the resected hippocampus of twenty patients with therapy-refractory temporal lobe epilepsy (TLE) using the whole-cell patch-clamp technique. 2. Depolarizing voltage commands elicited large, rapidly activating and inactivating Na+ currents (140 pS microm-2; 163 mM extracellular Na+) that were reduced in amplitude by lowering the Na+ gradient (43 mM extracellular Na+). At low temperatures (8-12 C), the time course of Na+ currents slowed and could be well described by the model of Hodgkin & Huxley. 3. Na+ currents were reversibly blocked by tetrodotoxin (TTX) and saxitoxin (STX) with a half-maximal block of 4.7 and 2.6 nM, respectively. In order to reduce series resistance errors, the Na+ current was partially blocked by low toxin concentrations (10-15 nM) in the experiments described below. Under these conditions, Na+ currents showed a threshold of activation of about -50 mV, and the voltages of half-maximal activation and inactivation were -29 and -55 mV, respectively. 4. The time course of recovery from inactivation could be described with a double-exponential function (time constants, 3-20 and 60-200 ms). The rapid and slow time constants showed a distinct voltage dependence with maximal values around -55 and -80 mV, respectively. These properties contributed to a reduction of the Na+ currents during repetitive stimulation that was more pronounced with higher stimulation frequencies and also showed a dependence on the holding potential. 5. In summary, the most striking features of DGC Na+ currents were the large current density and the presence of a current component showing a slow recovery from inactivation. Our data provide a basis for comparison with properties of Na+ currents in animal models of epilepsy, and for the study of drug actions in therapy-refractory epilepsy.

Adult↗
PubMed1998

PTEN mutations in gliomas and glioneuronal tumors.

Cytogenetic and loss of heterozygosity studies have suggested the presence of at least one tumor suppressor gene on chromosome 10 involved in the formation of high grade gliomas. Recently, the PTEN gene, also termed MMAC1 or TEP1, on chromosomal band 10q23 has been identified. Initial studies revealed mutations of PTEN in limited series of glioma cell lines and glioblastomas. In order to systematically evaluate the involvement of PTEN in gliomas, we have analysed the entire PTEN coding sequence by SSCP and direct sequencing in a series of 331 gliomas and glioneuronal tumors. PTEN mutations were detected in 20/142 glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic astrocytomas and 2/22 oligodendrogliomas. No PTEN mutations were detected in 52 astrocytomas, 37 oligoastrocytomas, three subependymal giant cell astrocytomas, four pleomorphic xanthoastrocytomas, 15 ependymomas, 16 gangliogliomas and one dysembryoplastic neuroepithelial tumor. In addition, all tumors were examined for the presence of homozygous deletions of the PTEN gene; these were detected in 7 glioblastomas that did not have PTEN mutations. Therefore, PTEN mutations occur in approximately 20% of glioblastomas but are rare in lower grade gliomas. These findings confirm that PTEN is one of the chromosome 10 tumor suppressor genes involved in the development of glioblastomas.

Female↗
PubMed1998

Expression of CYP19 (aromatase) mRNA in the human temporal lobe.

The conversion of androgens to estrogens by CYP19 (cytochrome P450AROM, aromatase) is an important step in the mechanism of androgen action in the brain. CYP19 expression has been demonstrated in various animal species, but studies in human postnatal brain tissue are lacking. Therefore, we investigated CYP19 mRNA expression in human temporal lobe tissues. We studied biopsy materials removed at neurosurgery from 34 women, 32 men and 10 children with temporal lobe epilepsy. Quantification of CYP19 mRNA was achieved by nested competitive reverse transcription-PCR. CYP19 mRNA concentrations did not differ significantly between women (2.6 +/- 0.6 arbitrary units, aU; mean +/- SEM) and men (1.6 +/- 0.3 aU) nor between cerebral cortex tissue (2.0 +/- 0.4 aU) and subcortical white matter tissue of adults (2.4 +/- 0.7 aU), but they were significantly lower in cerebral cortex specimens of children (0.9 +/- 0.6 aU) than in those of adults (p < 0.02). In conclusion, CYP19 mRNA is expressed in the temporal lobe of children and adults. CYP19 mRNA concentrations are significantly lower in specimens of children than in those of adults.

Adult↗
PubMed1998

Continuous external CSF drainage--a perpetual problem in neurosurgery.

BACKGROUND: Continuous external CSF drainage represents a well established procedure which has been improved by many technical contributions. We present our experience in a prospective study of 212 needle trephinations in 165 consecutive patients with a new screw fixation device. METHODS: The entire procedure is performed at the bedside under local anesthesia with a twist drill. The trephination needle is inserted into the self-tapping cannulated screw fixed to the skull. RESULTS: The mean operation time was 6 min, and the duration of ventricular drainage ranged from 2 h to 44 days. Ninety-one percent (N = 193) of ventricular needles in our series were placed at the first targeting attempt. ICP-monitoring and -therapy (88%) were the main indications for needle trephination in our study. During the study period we observed needle associated complications, such as intracerebral hemorrhages (N = 2, 1%) and infections (N = 17, 8%). CONCLUSIONS: Concerning infection, primary insufficient fixation, and general surgical handling, we found a clear learning curve during the course of our study. In spite of the initial problems at the time of introduction we have to emphasize the outstanding advantages of the new ventriculostomy device: It is a time-saving bedside procedure equipped with an optimum fixation device and it enables uncomplicated exchange of the needle in case of obstruction.

Adolescent↗
PubMed1998

Isoflurane plus nitrous oxide versus propofol for recording of motor evoked potentials after high frequency repetitive electrical stimulation.

The goal of this study was to test the influence of two widespread techniques of general anesthesia on motor evoked potentials (MEP) in response to transcranial and direct cortical high frequency repetitive electrical stimulation. Total intravenous anesthesia (TIVA) based on propofol and alfentanil was examined in 17 patients (group A), and balanced anesthesia (BA), based on nitrous oxide, isoflurane and fentanyl, was studied in 13 patients (group B). Distinct motor responses were available in 15 of 17 patients (88%) of group A, and in one of 13 patients (8%) of group B. Amplitudes increased significantly with increasing stimulus intensity and number of pulses under conditions of TIVA. At the same time, latencies decreased significantly with increasing stimulus intensity and decreasing interstimulus interval, but not with increasing number of pulses. It is hypothesized that propofol suppresses corticospinal I-waves at the cortical level, resulting in a conduction block at the level of the alpha-motoneuron, and that this effect may be overcome by high frequency repetitive stimulation. In contrast, nitrous oxide and isoflurane seem to have an additional suppressive effect on corticospinal D-waves, which may be overcome by higher stimulation intensity. In conclusion, transcranial high frequency repetitive stimulation and TIVA provide a feasible setting for intraoperative MEP monitoring, while higher doses of nitrous oxide and isoflurane are not compatible with recording of muscular activity elicited by the stimulation technique as described.

Adolescent↗
PubMed1998

Analysis of the PTEN gene in human meningiomas.

Previous observations demonstrated that the neurofibromatosis type 2 gene (NF2) plays an important role in the pathogenesis of the transitional, fibroblastic and malignant variants of human meningiomas. No specific genes have been associated with the pathogenesis of meningothelial meningiomas and with the progression to anaplastic meningiomas. However, allelic losses on chromosomal arms 1p, 10q and 14q have been implicated in the process of malignant progression. Recently, PTEN (phosphatase and tensin homolog deleted on chromosome ten) also termed MMAC1 (mutated in multiple advanced cancers 1) or TEP1 (TGF--regulated and epithelial cell-enriched phosphatase), emerged as a candidate gene on chromosome 10q23.3. Initial studies revealed mutations of PTEN in limited series of glioblastomas, breast, kidney and prostate carcinomas mainly as cell lines. In order to evaluate the involvement of PTEN in the development of meningiomas, we have analysed the entire coding sequence of the gene in a series of 55 meningiomas (WHO grade I). 10 atypical meningiomas (WHO grade II) and 10 anaplastic meningiomas (WHO grade III). No PTEN mutations were seen in the WHO grade I meningiomas. However, one of the anaplastic meningiomas carried a somatic mutation. In addition, all tumours were examined for the presence of homozygous deletions of PTEN but these were not detected in any of the meningiomas. Our data suggest that mutations in PTEN are not involved in the formation of low grade meningiomas, but may contribute to malignant progression in a fraction of anaplastic meningiomas.

Chromosomes, Human, Pair 10↗
PubMed1998

Physiological steal around AVMs of the brain is not equivalent to cortical ischemia.

To challenge the concept of steal rendering the surrounding cortex ischemic, we examined patterns of nutritive capillary flow in the vicinity of AVMs. With a spectrophotometer (EMPHO, BGT) capillary O2 saturation (O2 satn.) was intraoperatively scanned around AVMs in n = 44 patients and in n = 42 controls. 130,000 O2 satn. values before AVM resection were calculated as medians, ratio of critical values (< 25% O2 satn.), coefficients of variance and compared via ANOVA (p < 0.05). n = 40 AVM patients had no postoperative complication (group A), while in n = 4 cases a hyperperfusion syndrome occurred (group B). Physiological variables were comparable among groups A, B and C (controls). Medians (A: 52.9+/-16.3, B: 44.2+/-17.1, C: 51.9+/-11.5% O2 satn.) and the ratio of critical values (A: 6.5+/-5.1, B: 14.7+/-11.1, C: 7.1+/-4.9 O2 satn.) were identical in groups A and C, but significantly different in group B, indicating exhausted compensation. Decreased flow heterogeneity in group A (A: 20.2+/-12.7, B: 27.9+/-12.4, C: 26.8+/-10.9 O2 satn.) kept median cortical perfusion identical to group C. These results confirm recent findings, that cerebrovascular adaption by capillary recruitment keeps CBF at normal levels in the majority of cases and that chronic noninfarctional cerebral hypoperfusion is eventually the equivalent of steal around AVMs. Only around AVMs predisposed to hemodynamic derangement some areas of local low flow anoxia may exist.

Adult↗
PubMed1998

Altered patterns of Ca2+/calmodulin-dependent protein kinase II and calcineurin immunoreactivity in the hippocampus of patients with temporal lobe epilepsy.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) and calcineurin represent neuronal Ca2+-dependent enzymes which dynamically modify several common substrates in the mammalian brain via phosphorylation/dephosphorylation cycles. Studies in animal models indicate that altered expression and activity of these enzymes may be involved in epilepsy. We have analyzed their immunohistochemical distribution in hippocampi of 28 temporal lobe epilepsy (TLE) patients and 13 controls. TLE specimens were classified as Ammon's horn sclerosis (AHS) or focal lesions without alteration of hippocampal cytoarchitecture. Compared to control and lesion-associated TLE specimens, striking changes in the distribution pattern of both enzymes were found in the dentate gyrus (DG) of AHS specimens: Whereas CaMKII labeling was significantly increased in the granule cell somata and their proximal dendrites, calcineurin immunoreactivity was significantly reduced in the granule cell somata. Furthermore, calcineurin staining in controls showed high levels in the inner molecular layer with a sharp demarcation towards the outer molecular layer. In AHS, calcineurin staining was reduced in the inner molecular layer, with partial loss of this demarcation. These findings raise the possibility, that an up-regulation of CaMKII with a concomitant down-regulation of calcineurin in the DG of AHS specimens may cause a pathogenetically relevant imbalance of neuronal Ca2+/calmodulin-dependent phosphorylation/dephosphorylation systems.

Adult↗
PubMed1998

Electrophysiological considerations regarding electrical stimulation of motor cortex and brain stem in humans.

OBJECTIVE: To provide information about activation of descending motor pathways in humans, motor evoked potentials were obtained from 16 patients without any sensorimotor deficit, after both cortical and brain stem stimulation. METHOD: Total anesthesia was achieved in all patients through intravenous administration. Short trains of one to five electrical pulses were delivered separately to the motor cortex and the brain stem. Compound muscle action potentials were recorded from the contralateral upper extremity. Threshold intensity, stimulus polarity, latencies, and effect of increased stimulus intensity on latencies were analyzed. RESULTS: The threshold intensity was significantly lower when stimulating the brain stem than when stimulating the cortex. A monophasic anodal stimulus was better for cortical stimulation than for brain stem stimulation. Conversely, a monophasic cathodal stimulus was more effective for brain stem stimulation. The rate of unsuccessful stimulations was higher with brain stem stimulation and with increased stimulation intensity. The variability of latencies was so high that a calculation of the conduction velocity of the motor pathways was not possible. CONCLUSION: The results indicate that cortical surface and brain stem stimulation act on different nervous elements. Because of the condensation of motor pathway fibers at the brain stem level, much less stimulus intensity for eliciting compound muscle action potentials was necessary. On the other hand, the higher rate of unsuccessful brain stem stimulations may be caused by a block of conduction at either the anterior horn cell pool or the neuromuscular junction. Thus, for cortical and for brain stem stimulation, different stimulating parameters seemed to be necessary with the patient under general anesthesia.

Action Potentials↗
PubMed1998

Depth electrode implantation in the length axis of the hippocampus for the presurgical evaluation of medial temporal lobe epilepsy: a computed tomography-based stereotactic insertion technique and its accuracy.

OBJECTIVE: An individualized computed tomography-based stereotactic technique for the longitudinal insertion of intrahippocampal electrodes is presented and its accuracy described. METHODS: The technique makes use of one well reproducible target in the hippocampal head and of the approximate inclination of the anteroposterior length axis of the hippocampus, for which the orbital floor is taken as an auxiliary landmark. It was used in 141 patients with medically intractable complex partial seizures. In 106 patients, magnetic resonance imaging (MRI) was available for assessment of implantation accuracy. Each of the 212 electrodes was plotted on topographic drawings and its goodness of fit rated. RESULTS: Whereas hippocampal head and body were hit by 97 and 96% of the electrodes, respectively, the amygdala was hit by only 75% of the electrodes and mainly at its basal margin. For 93% of the electrodes, the inclination in a sagittal plane corresponded exactly to that of the hippocampus. The implantation morbidity amounted to 5.7%, whereas permanent neurological deficit occurred in one (0.7%) of the 141 patients. CONCLUSION: This computed tomography-based protocol proved to be reliable and hence can be considered as an adequate alternative to MRI-based stereotactic implantation if MRI is not available or if a single MRI-based stereotactic set-up is unreliable because of intolerable distortions.

Amygdala↗
PubMed1998

Effects of phenytoin, carbamazepine, and gabapentin on calcium channels in hippocampal granule cells from patients with temporal lobe epilepsy.

PURPOSE: The anticonvulsants phenytoin (PHT), carbamazepine (CBZ), and gabapentin (GBP) are commonly used in the treatment of temporal lobe epilepsy. Ca2+ current modulation has been proposed to contribute to the antiepileptic activity of these drugs. The purpose of this study was to determine the effects of these anticonvulsants on voltage-dependent calcium channels in pathologically altered neurons from patients with chronic temporal lobe epilepsy. METHODS: Acutely isolated human hippocampal granule cells were examined by using the whole-cell configuration of the patch-clamp technique. RESULTS: PHT and CBZ produced a reversible, concentration-dependent inhibition of high-voltage-activated (HVA) Ca2+ currents without affecting voltage-dependent activation. The concentration-response curves of PHT and CBZ indicated maximal inhibition of 35 and 65%, respectively, with half-maximal inhibition being obtained at 89 and 244 microM, respectively. At therapeutic cerebrospinal fluid (CSF) concentrations, HVA currents were not significantly altered by PHT and CBZ. However, PHT but not CBZ showed a reduction of HVA currents of 16% at a therapeutic whole-brain concentration of 80 microM. In contrast to CBZ, PHT produced a small hyperpolarizing shift in the voltage dependence of steady-state inactivation. PHT, 80 microM, shifted the potential of half-maximal inactivation by -3.1 +/- 0.5 mV (p < 0.05). GBP, which was recently found to bind to the alpha2delta subunit of a neuronal Ca2+ channel, showed no modulation of Ca2+ conductances. CONCLUSIONS: These results suggest that, in contrast to GBP and CBZ, modulation of postsynaptic Ca2+ channels can contribute to the anticonvulsant action of PHT in human hippocampal granule cells.

Acetates↗
PubMed1998

Treatment of accidental high dose intraventricular mezlocillin application by cerebrospinal fluid exchange.

An accidental high dose of intraventricular mezlocillin was given during antibiotic treatment for pneumonia in a patient admitted because of severe traumatic brain injury and occlusive hydrocephalus. Because of serial epileptic seizures not responsive to antiepileptic drug treatment, CSF exchange was performed. The CSF was drained through a ventricular catheter, while mock CSF was infused into the lumbar subarachnoid space. The patient soon recovered to her clinical status previous to intraventricular mezlocillin application. Side effects of CSF exchange were not seen. Under continued antiepileptic medication no more seizures occurred. It is concluded that high doses of intraventricular mezlocillin have proconvulsive effects. In this patient CSF exchange was a suitable means of preventing putatively permanent impairment of brain function caused by serial epileptic seizures due to intraventricular mezlocillin application.

Adult↗