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J Schramm

Publications and source records attributed to J Schramm.

At least 19 recordsLinked to original sources
PubMed2006

Present practice and perspective of evaluation and surgery for temporal lobe epilepsy.

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.

Anticonvulsants↗
PubMed2006

Firing pattern and calbindin-D28k content of human epileptic granule cells.

In the hippocampus of chronic temporal lobe epilepsy, many abnormalities in structure and function have been described but their pathophysiological relevance often is poorly understood. In this study, we asked whether there may be a link between changes in the firing pattern and the loss of the calcium binding protein calbindin-D28k in epileptic hippocampal granule cells. Using the perforated patch-clamp technique, we investigated granule cells in slices prepared from human hippocampi removed for the treatment of pharmacoresistant temporal lobe epilepsy. Granule cells in hippocampi without significant signs of structural damage (lesion group) displayed a firing pattern indistinguishable from that of rodent granule cells and were strongly labeled with anti-calbindin-D28k antibodies. In contrast, half of granule cells in sclerotic hippocampi (HS group) showed an altered firing pattern and a severe loss of calbindin-D28k. While these cells show passive membrane properties comparable to cells of the rodent and lesion group, they lack the medium afterhyperpolarization and display only a weak spike frequency adaptation. On the other hand, granule cells in the HS group have an increased action potential threshold and an enlarged fast afterhyperpolarization. Applying post-recording immunohistochemistry to individual electrophysiologically characterized granule cells, we show that the loss of calbindin-D28k is not causally related to any of the changes in firing pattern. Both alterations seem to occur during the course of temporal lobe epilepsy, with the firing pattern being affected earlier than the calbindin-D28k content. In conclusion, we propose that it is the combination of the altered intrinsic excitability of granule cells with the amplified and prolonged synaptic input from perforant path fibers previously described in the epileptic dentate area which promotes tonic, non-adapting, high frequency firing of granule cells and thereby strongly augments the excitability of the hippocampus.

Action Potentials↗
PubMed2006

Frequent loss of chromosome 9, homozygous CDKN2A/p14(ARF)/CDKN2B deletion and low TSC1 mRNA expression in pleomorphic xanthoastrocytomas.

The molecular pathogenesis of pleomorphic xanthoastrocytoma (PXA), a rare astrocytic brain tumor with a relatively favorable prognosis, is still poorly understood. We characterized 50 PXAs by comparative genomic hybridization (CGH) and found the most common imbalance to be loss on chromosome 9 in 50% of tumors. Other recurrent losses affected chromosomes 17 (10%), 8, 18, 22 (4% each). Recurrent gains were identified on chromosomes X (16%), 7, 9q, 20 (8% each), 4, 5, 19 (4% each). Two tumors demonstrated amplifications mapping to 2p23-p25, 4p15, 12q13, 12q21, 21q21 and 21q22. Analysis of 10 PXAs with available high molecular weight DNA by high-resolution array-based CGH indicated homozygous 9p21.3 deletions involving the CDKN2A/p14(ARF)/CDKN2B loci in six tumors (60%). Interphase fluorescence in situ hybridization to tissue sections confirmed the presence of tumor cells with homozygous 9p21.3 deletions. Mutational analysis of candidate genes on 9q, PTCH and TSC1, revealed no mutations in PXAs with 9q loss and no evidence of TSC1 promoter methylation. However, PXAs consistently showed low TSC1 transcript levels. Taken together, our study identifies loss of chromosome 9 as the most common chromosomal imbalance in PXAs and suggests important roles for homozygous CDKN2A/p14(ARF)/CDKN2B deletion as well as low TSC1 mRNA expression in these tumors.

Adolescent↗
PubMed2006

Correlation of health-related quality of life after surgery for mesial temporal lobe epilepsy with two seizure outcome scales.

PURPOSE: 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)). METHOD: 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. RESULTS: 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 P<0.001, respectively), whereas the social aspects were not significantly dependent on seizure outcome (P=0.06). CONCLUSION: 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.

Adolescent↗
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

DNA methylation and allelic losses on chromosome arm 14q in oligodendroglial tumours.

Cytogenetic and molecular genetic studies have shown frequent losses on the long arm of chromosome 14 in different types of human gliomas. Using differential methylation hybridization as a genome-wide screening approach to determine DNA methylation patterns in gliomas, we recently identified two DNA fragments in 14q23.1 (CGI-clone musical sharp396) and 14q32.12 (CGI-clone musical sharp519) that were differentially methylated between astrocytic gliomas and mixed oligoastrocytomas. To validate this observation, we examined these 14q32.12 locus for methylation in an extended series of 43 astrocytic and oligodendroglial gliomas. All tumours were additionally investigated for loss of heterozygosity (LOH). Microsatellite analysis showed LOH in seven of 28 (25%) oligodendroglial tumours and three of 15 (20%) astrocytic tumours. Seven tumours demonstrated LOH at all informative 14q loci whereas three tumours carried partial deletions defining a commonly deleted region at 14q22.3-q32.1 between the microsatellite markers D14S282 and D14S995. Methylation-specific PCR analysis of the 14q32.12 locus revealed hypermethylation in 12 of 43 gliomas (28%). Hypermethylation was restricted to tumours with oligodendroglial differentiation (12 of 28 tumours, 43%). However, none of the hypermethylated tumours demonstrated LOH on 14q and vice versa. In total, 19 of 28 oligodendroglial tumours (68%) showed either hypermethylation at the 14q32.12 locus or LOH at 14q22.3-q32.2. Taken together, our data lend further support for the location of one or more yet to be identified glioma-associated tumour suppressor gene(s) on 14q. In addition, the restriction of 14q32.12 methylation to oligodendroglial tumours suggests a role for epigenetic DNA modifications in these particular gliomas.

Adolescent↗
PubMed2005

Interinstitutional variance of postoperative radiotherapy and follow up for meningiomas in Germany: impact of changes of the WHO classification.

OBJECTIVE: To document and critically analyse the impact of the revised WHO 2000 histological classification for meningiomas on postoperative radiotherapy/radiosurgery indications and MRI follow up protocols. METHODS: The current (2000) WHO classification was used to grade 57 meningiomas treated surgically at one institution. These had been reviewed previously in 1999. All German neurosurgical departments carrying out intracranial microsurgery were asked to detail their guidelines for radiation therapy and follow up for meningiomas of different WHO grades. RESULTS: Use of the current criteria downgraded seven of 15 atypical meningiomas (WHO grade II, MII) to grade I (MI), and four of six anaplastic tumours (WHO grade III, MIII) to grade II. Indications for radiotherapy/radiosurgery and MRI follow up protocols varied substantially with the histological grade and between institutions--for example, after an incomplete resection, radiotherapy/radiosurgery recommendations differed between MI and MII in 30 of 58 units (52%), and between MII and MIII in 34 of 56 units (61%). CONCLUSIONS: Correlative studies combining treatment and outcome data with a standardised histopathological analysis are warranted to define properly the indications for radiotherapy/radiosurgery and follow up protocols after surgery for meningiomas of different histological grades. The use of changing grading paradigms during recent years renders decision making based on local and published experience difficult. The relatively large number of meningiomas classified as atypical/WHO grade II in current practice would argue against an uncritically aggressive approach to these tumours.

Adult↗
PubMed2005

Greater functional recovery after temporal lobe epilepsy surgery in children.

The purpose of our study is to evaluate whether children recover better than adults from memory deficits as a consequence of temporal lobe surgery. We compared 3 and 12 month outcomes obtained in children and adults with medically refractory epilepsy. Each candidate underwent temporal lobe resection for seizure control and children were matched with regard to pathology, onset of epilepsy, side of surgery and type of surgery with adults (N = 30 for each group, mean age at surgery 13 versus 30 years). Three months after surgery, both left-resected groups displayed a significant decline in verbal learning capacity. During the following 9 months, only the children recovered and were able to reach their preoperative level 1 year after surgery. The left-resected adults remained, for the most part, on their low level and one year after surgery, they were still significantly worse than at the time of their preoperative examination. The right-resected adults experienced a deterioration in visual memory 1 year after surgery relative to the results of the short-term follow-up; the children improved. The children also had a better outcome with regard to attentional functions and, as a trend, a better seizure outcome (Engel Outcome I--1 year after surgery: 63% adults, 80% paediatric patients). Our neuropsychological data provide evidence of greater plasticity and compensational capacity in childhood. The results can be taken as a strong argument for early surgical intervention.

Adolescent↗
PubMed2005

[Familial cavernous malformations of the central nervous system. A clinical and genetic study of 15 German families].

In 1928, Hugo Friedrich Kufs reported on a family with cerebral, retinal, and cutaneous cavernous malformations. Since then, more than 300 families with inherited cavernous malformations have been reported. Genetic studies showed three loci, on chromosomes 7q21-q22 (with the gene CCM1), 7p15-p13 (CCM2), and 3q25.2-q27 (CCM3). The gene product of CCM1 is Krit 1 (Krev interaction trapped 1), a protein interacting with angiogenesis by various mechanisms. Recently, CCM2 has also been identified; its product is a protein which might have a function similar to that of Krit 1. However, the CCM3 gene has still not been found. In this study, we present clinical and genetic findings on 15 German families.

Adult↗
PubMed2004

Expression analysis of metabotropic glutamate receptors I and III in mouse strains with different susceptibility to experimental temporal lobe epilepsy.

Increased hippocampal excitability constitutes a pathogenetic hallmark of pharmacoresistant human temporal lobe epilepsy (TLE). Metabotropic glutamate receptors (mGluRs) can be subdivided into three classes based on sequence homologies, mechanisms of signal transduction as well as pharmacological characteristics. Generally, class I mGluRs mediate neuronal excitation whereas activation of class II and III mGluRs decreases synaptic transmission. Changes in expression of class I and III mGluR subunits have been described in human TLE. It remains to be determined whether altered mGluR expression relates to differences in seizure susceptibility or hippocampal damage. Here, we examine the transcription levels of mGluRs class I (mGluR1 and 5) and III (mGluR4 and 7) in experimental TLE and correlate differential mGluR subunit expression with mouse-strain-dependent susceptibility to TLE induced by pilocarpine. Expression of mGluRs 1, 4, 5 and 7 was determined in epileptic dentate gyrus granule cells (DG) in CD1, C57BL/6 and FVB/N mice by real time RT-PCR. FVB/N mice appear significantly more vulnerable to pilocarpine-induced seizures than C57BL/6 and CD1 strains. RT-PCR analysis demonstrates an increased expression of inhibitory mGluR 4 and downregulation of excitatory mGluR 1 in epileptic CD1 mice and a decrease of the excitatory mGluRs 1 and 5 in C57BL/6 (p<0.05, n=6 each) but not in the FVB/N strain. These results correlate differential expression of excitatory class mGluR I and inhibitory class mGluR III to seizure susceptibility and hippocampal damage. Our data suggest mGluRs class I and III as interesting potential therapeutic targets to interfere with hippocampal epileptogenesis and hyperexcitability.

Animals↗
PubMed2004

Motor evoked potential monitoring for the surgery of brain tumours and vascular malformations.

Brain surgery incurs a significant risk of a new motor deficit in lesions within or adjacent to the motor areas and pathways which, for the patient, presents one of the most disabling complications of such operations. It is a major concern of intracranial procedures to delineate and monitor motor regions in order to preserve their structural and functional integrity, while still achieving maximal cytoreduction. The technique of motor evoked potential recording has had to be adapted to intraoperative recording conditions under general anaesthesia, but has been available for clinical use now for almost ten years. This contribution summarizes the current technique and related methods, as well as our clinical experience in some 400 cases of MEP monitoring in supratentorial tumors, lesions in and around the brainstem, and aneurysm surgery. Intraoperative MEP recordings have been shown to reliably reflect an impending new motor deficit. Irreversible MEP deterioration heralds new paresis, and unaltered recordings predict preserved motor function. This is also true in aneurysm surgery where conventional SEP monitoring may yield false-negative results with regard to development of a new motor deficit. Moreover, if MEP deterioration can be reversed, or halted by early surgical intervention, the presence of only a transient motor deficit, or even the lack of a new postoperative deficit, indicates the success of the MEP monitoring method in the prevention of a significant motor impairment. Certain complicated lesions can only be operated on at all because MEP monitoring is available. In conclusion, intraoperative MEP monitoring is a useful aid in brain surgery with which to avoid a new motor deficit without compromise to the surgical result. Controlled prospective studies will be required to verify the clinical value of the method.

Brain Mapping↗
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

Immediate postoperative angiography after aneurysm clipping--implications for quality control and guidance of further management.

BACKGROUND: To determine the impact of postoperative angiography after aneurysm clipping on quality control and further management. METHODS: A recent consecutive series of n = 296 patients (186 females, 110 males, mean age 51 yrs) who underwent 324 craniotomies to clip 384 aneurysms was reviewed. New irregularities on postoperative angiographies were categorized as unrelated (e. g. vasospasm) or related (= vessel occlusion/residuum) to clipping and expected or unexpected by the surgeon. Therapies prompted by these findings as well as subsequent negative sequelae were analyzed. Factors related to negative events were identified by logistic regression (p < 0.05). RESULTS: Twenty-six (8%) unrelated findings prompted medical or intravascular therapy. Of 36 (9.4%) clip-related findings (n = 17 occlusions, n = 19 residua), 14 (3.6%) were unexpected (n = 9 occlusions, n = 5 residua). This was followed by 9 (2.3%, n = 4 occlusions, n = 5 residua) clip readjustments and 6 aggressive medical therapies. Nine patients were scheduled for angiographic follow-up, of which in five performed so far no change of aneurysm remnants was noted. Permanent sequelae from vessel occlusion occurred in 9 cases. Major premature rupture (p < 0.005), giant size/fusiform configuration (p < 0.001), posterior circulation aneurysms (p < 0.05) and ophthalmic segment location (p < 0.008) were significantly related to adverse postoperative findings. The use of microvascular Doppler significantly reduced the rate of unexpected vessel occlusion (3.3 vs. 0.9%). CONCLUSIONS: Apart from the need for quality control in aneurysm clipping--especially with respect to coiling--our results stress the importance of postoperative angiography, because a small, but significant subset of patients will benefit from immediate intervention and/or deserves long-term follow-up.

Angiography↗
PubMed2004

Characterization of hemorrhagic complications after surgery for temporal lobe epilepsy.

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.

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↗