Biomedical subjects

Johannes Schramm

Publications and source records attributed to Johannes Schramm.

At least 19 recordsLinked to original sources

PubMed2007

A new clinico-pathological classification system for mesial temporal sclerosis.

We propose a histopathological classification system for hippocampal cell loss in patients suffering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subfields CA1-CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The first group comprised hippocampi with neuronal cell densities not significantly different from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subfields excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subfields (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury (IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the first event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was significantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%). Our classification system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.

Adult↗

PubMed2007

Axo-somatic inhibition of projection neurons in the lateral nucleus of amygdala in human temporal lobe epilepsy: an ultrastructural study.

Here, we report ultrastructural alterations in the synaptic circuitry of the human amygdala related to neuronal cell densities in surgical specimens of patients suffering from temporal lobe epilepsy (TLE). The neuronal cell densities quantified in the basolateral complex of amygdala were significantly reduced only in the lateral nucleus (LA) of TLE patients as compared to autopsy or non-Ammon's horn sclerosis (AHS) controls (Nissl staining, immunostaining against the neuronal marker NeuN). For this reason, we focussed on the LA to perform a more detailed quantitative ultrastructural analysis, which revealed an inverse correlation between the number of axo-somatic inhibitory synaptic profiles at the somata of glutamic acid decarboxylase (GAD)-negative projection neurons and the extent of perisomatic fibrillary gliosis. In contrast, the density of GAD-immunoreactive interneurons positively correlated with the number of axo-somatic inhibitory synaptic profiles. The fibrillary material in perisomatic glial cell processes was preferentially labeled by the astroglial marker S100B. In addition, a qualitative study of the dendrites of GAD- and parvalbumin (PARV)-containing interneurons showed that they were often contacted by asymmetrical excitatory synapses. Our results are in line with anatomical data from rodents and cats, which show that amygdalar interneurons form axo-somatic inhibitory synapses on GAD-negative projection neurons, whereas the interneurons themselves receive excitatory input from recurrent collaterals of projection neurons and from cortico- and thalamo-amygdalar afferents. The structural reorganization patterns observed in the GABAergic circuitry are compatible with a reduced feedback or feed forward inhibition of amygdalar projection neurons in human TLE.

Adult↗

PubMed2006

Comparison of manual tracing versus a semiautomatic radial measurement method in temporal lobe MRI volumetry for pharmacoresistant epilepsy.

INTRODUCTION: The aim of this study was to test a modified radial semiautomated volumetry technique (radial divider technique, RDT) versus the manual volumetry technique (MVT) for proportionality of temporal subvolumes in 30 patients with drug-resistant temporal lobe epilepsy. METHODS: Included in the study were 30 patients (15 female, 15 male; mean age 39.6 years) with pharmacoresistant epilepsy (mean duration 26.6 years). MRI studies were performed preoperatively on a 1.5-T scanner. All image processing steps and volume measurements were performed using ANALYZE software. The volumes of six subregions were measured bilaterally; these included the superior temporal gyrus (STG), middle + inferior temporal gyrus (MITG), fusiform gyrus (FG), parahippocampal gyrus (PHG), amygdala (AM), and hippocampus (HP). Linear regression was used to investigate the relationship between the comparable subvolumes obtained with MVT and RDT. RESULTS: Very high correlations (R (2) >0.95) between RDT and MVT were observed for the STG + MITG and the STG + MITG + FG, but low correlations for the PHG subvolumes and the combined PHG + HP + AM subvolumes. These observations were independent of the side of the pathology and of hemisphere. CONCLUSION: The two measurement techniques provided highly reliable proportional results. This series in a homogeneous group of TLE patients suggests that the much quicker RDT is suitable for determining the volume of temporolateral and laterobasal temporal lobe compartments, of both the affected and the non-affected side and the right and left hemisphere.

Adolescent↗

PubMed2006

Transsylvian functional hemispherectomy.

OBJECTIVE: To describe the technique of transsylvian-transventricular functional hemispherectomy developed at our institution. METHODS: We review appropriate patient selection and evaluation, timing of surgery, selection of surgical approach, preoperative preparation, details of operative procedure, and postoperative management. CONCLUSIONS: The transsylvian "keyhole" functional hemispherectomy technique involves a smaller craniotomy than other functional hemispherectomy techniques and consists of transsylvian exposure, resection of mesial temporal structures, transventricular frontobasal disconnection, callosotomy, and occipitoparietal disconnection. The key advantages of this approach compared to the Rasmussen's "classic" functional hemispherectomy are smaller exposure, shorter operative time, and lower blood loss. The efficacy of functional hemispherectomy procedures in achieving seizure freedom appears to be at least as good compared to resective procedures. The long-term complication rate will require longer follow-up times.

Cerebral Cortex↗

PubMed2006

Surgical treatment for refractory temporal lobe epilepsy in the elderly: seizure outcome and neuropsychological sequels compared with a younger cohort.

PURPOSE: Surgical treatment of refractory temporal lobe epilepsy (TLE) is promising for selected patients, but only little experience has been acquired in operating on older patients, especially with limited resections. We intend to delineate clinical and surgical factors influencing outcome in patients older than 50 years at operation and to compare the results with those of a younger patient cohort. METHODS: Fifty-two patients older than 50 years were operated on for intractable mesial or combined mesiolateral TLE between 1991 and 2002. The mean age at operation was 55 years, and the mean duration of epilepsy was 33 years. Forty selective amygdalohippocampectomies (33 for hippocampal sclerosis, seven for removal of a mesiotemporal lesion), five lateral temporal lesionectomies plus amygdalohippocampectomy, and seven anterior temporal lobectomies were performed. Eleven (21%) patients had undergone invasive presurgical video-EEG monitoring. The mean follow-up period was 33 months. We compared the results with those of a younger cohort operated on in the same time period. RESULTS: Thirty-seven older patients attained complete seizure control (71% class I), and 10 patients had only rare postoperative seizures (19% class II). Four patients improved >75% (8% class III), and one patient did not improve (2% class IV). The same rate of seizure control was attained by 11 patients older than 60 years at surgery. These results were not significantly different from those in a younger patient group. A trend toward better seizure control was noted in 16 patients with an epilepsy duration of <30 years (all class I or II), and in 20 patients with a seizure frequency of fewer than five seizures per month (all class I or II). No mortality resulted from a total of 65 diagnostic and therapeutic procedures. A 3.8% permanent neurologic morbidity (dysphasia and hemiparesis) was noted. Hemianopia occurred in three (5.9%) patients. Neuropsychological testing revealed low preoperative performances and some gradual further deterioration after surgery. CONCLUSIONS: Results of surgery for TLE with mainly limited resections are promising in patients older than 50 years and older 60 years, despite the long seizure history. As expected, the risk of complications is somewhat higher compared with that in a younger control group. The impact of low neuropsychological performance is a concern.

Adult↗

PubMed2006

Assessment of the long-term effects of epilepsy surgery with three different reference groups.

PURPOSE: It is difficult to validly assess the long-term effect of epilepsy surgery. Here, this is attempted by comparing the outcome of surgically treated pharmacoresistant epilepsy patients to three different nonoperated comparison groups regarding seizure control, antiepilepsy drug (AED) usage, and health related quality of life (QOL). METHODS: One hundred thirty-one operated patients (group 1, mean follow-up since presurgical assessment 6.9 years), 105 patients awaiting presurgical assessment (group 2, mean follow-up after assignment to waiting list 0.8 years), 99 patients considered to be presurgical candidates who chose to withdraw from waiting for presurgical assessment (group 3, mean follow-up after assignment to waiting list 5.5 years), and 49 patients who were not deemed to be eligible for surgery after comprehensive assessment (group 4, mean follow-up since presurgical assessment 6.5 years) were studied. The patients completed a questionnaire on seizures, AED usage, and QOL (ESI-55). RESULTS: The surgical patients had a better outcome than all three comparison groups regarding seizure frequency, seizure freedom rate, and number of AEDs used. They scored higher than groups 2, 3, and 4 on 7/11, 6/11, and 3/11 ESI-55 domains, respectively. CONCLUSIONS: The superior long-term outcome of the operated patients was most marked if compared to the patients awaiting surgery. This is compatible with the assumption that patients present for presurgical candidacy selection and assessment at a "nadir" of their disease course. After several years, a regression to the mean occurs which reduces (but does not abolish) the differences between nonoperated and operated patients.

Adult↗

PubMed2006

FLAIR-/T1-/T2-co-registration for image-guided diagnostic and resective epilepsy surgery.

OBJECTIVE: For technical reasons, T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences do not allow morphological orientation with high anatomic resolution, but they may show small epileptogenic lesions. Considering the peculiarities of diagnostic and resective epilepsy surgery the present study focused on the co-registration of various magnetic resonance sequences for guided epilepsy surgery. METHODS: Fifty patients (24 men; 26 women) aged 2 to 74 years (mean, 32 yr), in whom epileptogenic lesions were not readily identifiable on three-dimensional T1-weighted MRI scans underwent additional two-dimensional T2-weighted and FLAIR sequences before diagnostic and/or resective epilepsy surgery. FLAIR and/or T2-weighted images were co-registered to the T1-weighted data set and were displayed on the navigation station on site for guided invasive diagnostics and for resection according to an individualized resection plan. Postoperative MRI scanning was routinely performed for assessment of resection extent. RESULTS: Co-registered T1- and FLAIR-/T2-images allowed for image-guided intraoperative identification of all lesions (n = 50). Control MRI scans revealed that complete resection was performed as planned before the operation in 49 patients and incomplete resection was performed in one patient. Preliminary seizure outcome with a mean follow up of 14 months (range, 7-24 mo) was assigned according to the Engel classification: Class I, 78%; Class II, 12%; Class III, 4%; Class IV, 6%. CONCLUSION: Image guidance on the basis of image fusion/co-registration of T1- and FLAIR-/T2-images allows for intraoperative identification of otherwise poorly visible lesions on standard MRI sequences in good spatial resolution. Recall of this information during surgery from the navigation system's screen assists in achieving the goal of precise electrode placement, or complete resection of the lesion as well as of the perilesional epileptogenic tissue and improves the surgeon's intraoperative orientation.

Adolescent↗

PubMed2006

Stimulation mapping via implanted grid electrodes prior to surgery for gliomas in highly eloquent cortex.

OBJECTIVE: To evaluate whether preoperative mapping of higher cortical functions with subdural grid electrodes can help to maximize resection in functional areas and avoid permanent injury. METHODS: A consecutive series of 16 patients (female: n = 7, male: n = 9, mean age of 38 yr) with a history of seizures and without focal deficit was reviewed, harboring gliomas located in the dominant hemisphere adjacent to or in the F3 gyrus/Broca area (n = 11), parietal/perisylvian area (n = 5) and additionally the pre- or postcentral area (n = 15). All patients in this series were operated for cytoreductive purposes only and not for treatment of intractable seizures. To preoperatively define and intraoperatively tailor the extent of resection all patients had a presurgical grid implantation for functional brain mapping. RESULTS: No permanent morbidity/mortality was observed after grid implantation and resective surgery. On postoperative MRI the resection was complete (100%), nearly complete (>90%) in n = 9 and subtotal (60% to <90%) in n = 5 cases. Twice, only biopsies were taken according to the results of mapping. All patients with high-grade gliomas had adjuvant treatment with radiation and chemotherapy. After a mean follow up of 20.4 months, no tumor relapse or growth was seen in all cases of resection. CONCLUSION: Preoperative grid mapping is a safe and precise instrument to evaluate language and/or associated left perisylvian functions in patients with gliomas. It may be considered a valid alternative to awake craniotomy to maximize safe resection.

Adolescent↗

PubMed2006

Variant of the CHEK2 gene as a prognostic marker in glioblastoma multiforme.

OBJECTIVE: Germline mutations of the CHEK2 tumor suppressor gene have been found in families with the Li-Fraumeni syndrome (LFS). Patients with LFS experience a variety of cancers, including malignant astrocytomas. We investigated a potential role for a CHEK2 gene polymorphism in glioblastomas. METHODS: A genetic polymorphism of the CHEK2 gene (CHEK2 SNP rs2017309 A/T) was genotyped in a series of glioblastoma patients (n = 213) and population controls (n = 192). Subsets of tumors were analyzed for loss of heterozygosity 22q(n = 66), loss of heterozygosity CHEK2 (n = 53), CHEK2 expression (n = 21), and CHEK2 coding sequence alterations (n = 18). CHEK2 SNP rs2017309 genotyping findings and traditional clinicopathological parameters were correlated with the patients' prognoses. RESULTS: No association between the CHEK2 SNP and glioblastoma formation was observed. No CHEK2 coding sequence aberrations or tumors completely lacking CHEK2 protein were identified. However, the presence of the CHEK2 rs2017309 A allele was significantly associated with an adverse prognosis (P = 0.034), particularly among patients undergoing postoperative chemotherapy and radiotherapy (n = 28, median survival 10.5 versus 15.5 mo, P = 0.008). We could confirm the patients' age, Karnofsky Performance Scale score, and postoperative radiotherapy and chemotherapy (all P < 0.0001, log-rank test) as decisive prognostic factors. CONCLUSION: Our data suggest that a CHEK2 gene polymorphism might correlate with the prognosis of glioblastoma patients. These findings may point to an as yet unrecognized role for the CHEK2 gene in glioblastomas.

Biomarkers↗

PubMed2006

Skull base chordomas: management and results.

Growth patterns of skull base chordomas are related to important neurovascular structures. Local invasiveness results in "clinically malignant" behavior. A high rate of transient neurological deficits occurs following radical surgery. At our institution, the principle of radical removal is not followed at any price. This study compared the results of our management with recent series. Eleven patients, five females and six males aged 24-65 years (mean 41 years), underwent removal of skull base chordoma with size one <3 cm, five 3-5 cm, and five >5 cm. Mostly, standard operative approaches were chosen. All patients underwent postoperative radiotherapy. Resection was subtotal/partial in seven patients and total in four with no mortality. Neurological deterioration occurred due to transient cranial nerve deficits in six patients. Temporary surgical morbidity (including cranial nerve deficits) was observed in seven patients. Median Karnofsky performance status score improved compared to preoperative (80), early postoperative (70), and latest assessment (90) (median 36 months). Five patients underwent reoperation due to tumor recurrence after 4-48 months (mean 24 months). Most patients undergoing removal of skull base chordomas suffer from transient neurological deficits which are mainly nonsignificant as the patients return to preoperative functional status. The apparently high rate of incomplete tumor resection (64%) reflects the infiltrative behavior and relationship with neurovascular structures. The operative strategy should not be excessively aggressive at any price, but rather take into account the options of radiotherapy and observation of residual tumor.

Adult↗

PubMed2006

Association of a polymorphism of the ACVRL1 gene with sporadic arteriovenous malformations of the central nervous system.

OBJECT: Important central nervous system (CNS) manifestations in patients with hereditary hemorrhagic telangiectasia (HHT) include arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs). Hereditary hemorrhagic telangiectasia is caused by germline mutations of two genes: ENG (HHT Type 1) and ACVRL1 (HHT Type 2). The ENG gene variations have been associated with the formation of intracranial aneurysms. The authors studied whether sequence variations in ACVRL1 or ENG are associated with the development of clinically sporadic arteriovenous dysplasias and aneurysms of the CNS. METHODS: The coding sequence (in 44 patients with AVMs and 27 with aneurysms) and the 5' end and the polyA site (in 53 patients with AVMs) of the ACVRL1 gene were analyzed for sequence variations using direct sequencing and single-strand conformational polymorphism analysis. One ENG and three ACVRL1 gene polymorphisms were genotyped using restriction enzyme-based analysis in 101 patients with sporadic AVMs and DAVFs of the CNS, 79 patients treated for intracranial aneurysms, and 202 control volunteers. The authors identified a statistically significant association between the IVS3 -35A/T polymorphism in intron 3 of the ACVRL1 gene and the development of AVMs and DAVFs (p = 0.004; odds ratio [OR] 1.73; 95% confidence interval [CI] 1.19-2.51; after adjustments for age and sex), but not aneurysms (crude OR 0.82; 95% CI 0.55-1.18). CONCLUSIONS: The results of this study link ACVRL1 (HHT Type 2 gene) to the formation of the clinically sporadic variants of vascular malformations of the CNS most commonly seen in patients with HHT, that is, AVMs and DAVFs.

Activin Receptors, Type II↗

PubMed2005

Mutational and immunohistochemical analysis of ezrin-, radixin-, moesin (ERM) molecules in epilepsy-associated glioneuronal lesions.

Glioneuronal lesions are frequently observed in biopsy specimens obtained from patients with pharmacoresistant epilepsies, comprising focal cortical dysplasias (FCD) and gangliogliomas. Recent findings point to the phosphoinositide 3-kinase (PI3K) pathway and tuberin/hamartin signaling cascade as being compromised in these lesions. Ezrin, radixin and moesin (ERM-/band-4.1 proteins) genes represent downstream effectors of the PI3K pathway, are involved in cytoskeleton-membrane interference, cell growth, migration and differentiation, and harbor tumor suppressor motifs. Accumulation of band-4.1 proteins has been identified in cortical tubers of tuberous sclerosis patients, which share neuropathological similarities with FCD and gangliogliomas. Here, we have studied the immunohistochemical distribution pattern of ERMs, as well as allelic variants, occurring in gangliogliomas (n=20) and FCDs (FCD(IIa), n=7; FCD(IIb), n=37). Aberrant accumulation of ERMs was observed in dysplastic neurons of FCDs and gangliogliomas as well as in balloon cells. Adjacent brain tissue without structural abnormalities was used as control and showed only faint neuropil staining. Mutational screening revealed silent polymorphisms in the ezrin gene in two individuals suffering from FCD(IIb). A transition from G to A in radixin exon 2 resulted in an exchange of valine by isoleucine at codon 50 in an additional FCD(IIb) specimen. Such sequence alterations were not found in controls. The present data suggest accumulation of ERM expression in dysplastic cellular components but do not favor mutational events of ERM in the pathogenesis of FCDs or gangliogliomas. Aberrant expression of ERMs is, however, compatible with compromised PI3K-pathway signaling in glioneuronal lesions characterized by abnormal cellular differentiation and aberrant network formation.

Brain Diseases↗

PubMed2005

Molecular and functional properties of neurons in the human lateral amygdala.

Neuronal properties were investigated through patch-clamp recording in situ in surgical specimens of the human lateral amygdala (LA) obtained from patients with intractable temporal lobe epilepsy. Projection neurons displayed spiny dendrites, action potentials with varying degree of frequency adaptation, and an inwardly rectifying K+ (Kir) conductance coupled to GABA(B) receptors. In interneurons, dendrites were spineless or sparsely spiny, action potentials were shorter than those in projection neurons and often occurred spontaneously, and GABA(B) receptor-mediated responses were lacking. Single-cell RT-PCR demonstrated expression of Kir channel subunits Kir3.1 and Kir3.2 and of vesicular glutamate transporters VGLUT1 and VGLUT2 in projection neurons. It is concluded that projection neurons and interneurons of the human LA can be distinguished based upon morphological, electrophysiological, and molecular biological criteria. The most striking difference relates to the expression of postsynaptic GABA(B) receptors coupled to Kir3 channels in projection neurons and the lack of functional GABA(B) receptors in interneurons.

Action Potentials↗

PubMed2005

Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach.

Abnormalities in regional cerebral blood flow (rCBF) have been reported to characterize depressive episodes; they are at least partly reversed by antidepressant treatment. Treatment-specific as well as response-related changes in rCBF have been reported. We explored the changes in rCBF induced by vagus nerve stimulation (VNS), a recently proposed antidepressant strategy, by application of single photon emission-computed tomography with (99m)Tc-hexamethyl-propylene amine oxime in otherwise treatment-refractory patients. Both region-of-interest (ROI) and statistical parametric mapping (SPM) analytic approaches were used. Decreases of rCBF in the amygdala, left hippocampus, left subgenual cingulate cortex, left and right ventral anterior cingulum, right thalamus and brain stem were observed; the only increase of rCBF was found by SPM analysis in the middle frontal gyrus. This pattern shares features with changes of rCBF previously associated with the administration of selective serotonin reuptake inhibitors. Similarities to other brain-stimulation strategies in antidepressant treatment were less pronounced.

Adult↗

PubMed2005

Comparison of programmable shunt valves vs standard valves for communicating hydrocephalus of adults: a retrospective analysis of 407 patients.

BACKGROUND: The aim of the present study was to clarify whether programmable shunt valves are advantageous in the treatment of adults with communicating hydrocephalus with respect to valve-related shunt complications and surgical shunt revisions, in comparison with standard valves. METHODS: Adult patients with communicating hydrocephalus treated with Codman Hakim programmable (CHP) valves or Hakim (H) standard valves during 12 years were retrospectively studied. Patients were analyzed for demographic data, implantation diagnosis, valve type, opening pressure at implantation, opening pressure adjustments, and incidence of shunt complications, especially valve-related complications. The end point of the study was a surgical shunt revision. RESULTS: In 407 patients, 247 CHP valves and 160 H valves were implanted. Median opening pressure of CHP at implantation was 110 mm H(2)O, while 3 low-pressure, 153 medium-pressure, and 4 high-pressure H valves were implanted. Opening pressure adjustments were performed in 39% of CHP patients--1.44 adjustments per adjusted valve. Overall complication rate as well as the rate of surgical revisions for infections and catheter- and valve-related problems did not show any significant difference between CHP and H valves. The incidence of nontraumatic subdural hematomas and hygromas was significantly higher in the CHP group; however, the rate of surgical decompressions did not differ. CONCLUSIONS: The advantage of reprogramming of CHP did not translate into a reduction in surgical shunt revisions. Therefore, in conjunction with the present data, we believe it is still justified to implant H standard valves in adult patients with communicating hydrocephalus.

Adult↗

PubMed2005

Distinct allelic variants of TSC1 and TSC2 in epilepsy-associated cortical malformations without balloon cells.

Epilepsy-associated malformations of cortical development (MCDs) comprise a variety of dysplastic and neoplastic lesions of yet undetermined molecular pathology. Histopathologic similarities between MCDs and dysplastic brain lesions in the autosomal inherited neurocutaneous phacomatosis tuberous sclerosis (TSC), which affects the TSC1 and/or TSC2 genes, suggest common pathogenetic mechanisms. Previous studies revealed different alterations of TSC1 and TSC2 in epilepsy-associated malformations and glio-neuronal tumors despite histopathologic similarities. In order to examine current clinico-pathologic classification systems of cortical malformations on the molecular level, we carried out a mutational analysis of TSC1 and TSC2 in a series of surgical specimens obtained from patients with FCD without Taylor type balloon cells (FCDIIa; n = 20), architectural dysplasias (FCDI; n = 15), nodular cortical heterotopias (NCH; n = 4), and heterotopic white matter neurons (WMNH; n = 19). In FCDIIa, abundant genomic polymorphisms were detected in TSC2 (intron 4) but no allelic variants observed in exon 17 of TSC1. This allelic distribution pattern is in contrast to findings in FCDI and WMNH but also to those previously reported in FCDIIb (Taylor's balloon cell type). The latter revealed increased frequencies of specific alleles only in TSC1. The determination of characteristic molecular genetic alterations in specific epilepsy-associated malformations will support a comprehensive clinico-pathologic classification system and help to identify molecular pathways with potential pathogenetic relevance. Our work is supported by DFG (SFB TR3 [AJB], DFG Bl 421/1-1 [IB]), BONFOR, and Deutsche Krebshilfe.

Alleles↗

PubMed2005

Recurrent laryngeal nerve palsy during anterior cervical spine surgery: a prospective study.

OBJECT: Recurrent laryngeal nerve (RLN) palsy is a well-known complication of cervical spine surgery. Nearly all previous studies were performed without laryngoscopy in asymptomatic patients. This prospective study was undertaken to discern the true incidence of RLN palsy. Because not every RLN palsy is associated with hoarseness, the authors conducted a prospective study involving the use of pre- and postoperative laryngoscopy. METHODS: Prior to anterior cervical spine surgery preoperative indirect laryngoscopy was performed in 123 patients to evaluate the status of the vocal cords as a sign of function of the RLN. To assess postoperative status in 120 patients laryngoscopy was repeated, and in cases of vocal cord malfunction follow-up examination was conducted 3 months later. In the group of 120 patients who attended follow-up examination, two (1.6%) had experienced a preoperative RLN palsy without hoarseness. Postoperatively the rate of clinically symptomatic RLN palsy was 8.3%, and the incidence of RLN palsy not associated with hoarseness (that is, clinically unapparent without laryngoscopy) was 15.9% (overall incidence 24.2%). At 3-month follow-up evaluation the rate had decreased to 2.5% in cases with hoarseness and 10.8% without hoarseness. Thus, the overall rate of early persisting RLN palsy was 11.3%. CONCLUSIONS: Laryngoscopy revealed that the true incidence of initial and persisting RLN palsy after anterior cervical spine surgery was much higher than anticipated. Especially in cases without hoarseness this could be proven, but the initial incidence of hoarseness was higher than expected. Only one third of new RLN palsy cases could be detected without laryngoscopy. Resolution of hoarseness was approximately 70% in those with preoperative hoarseness. The true rate of RLN palsy underscores the necessity to reevaluate the surgery- and intubation-related techniques for anterior cervical spine surgery and to reassess the degree of presurgical patient counseling.

Cervical Vertebrae↗

PubMed2004

Supratentorial gangliogliomas: histopathologic grading and tumor recurrence in 184 patients with a median follow-up of 8 years.

BACKGROUND: Supratentorial gangliogliomas (GGs) are rare tumors of the central nervous system and are commonly associated with chronic seizures. To date, only case reports and small series of patients with short-term follow-up have been available for the assessment of the potential of GGs to recur and progress. METHODS: Data from 184 patients who underwent resection of GGs between 1988 and 2001 were available from the University of Bonn Epilepsy Surgery Center (Bonn, Germany). Analysis of factors that influenced tumor recurrence and patient survival, such as preoperative history, age at operation, tumor location, histopathologic findings (including immunohistochemical findings), extent of tumor resection, and recurrence evaluated on postoperative magnetic resonance imaging (MRI), was performed. RESULTS: The median follow-up period was 8 years (range, 1-14 years). One hundred seventy-eight patients (97%) presented with long-term seizures (> or = 2 years). The median age at surgery was 26 years (range, 2-65 years). Tumor location was temporal in 79% of patients and frontal in 12% of patients. Eleven tumors (6%) were classified as World Health Organization (WHO) Grade 2 lesions, and 2 tumors were classified as anaplastic WHO Grade 3 lesions. For 38 patients (21%), postoperative MRIs revealed residual tumors. Two years after surgery, 5 patients (3%) experienced tumor recurrence, which resulted in malignant progression in 3 patients (2%) and death in 2 patients (1%). Eighty-four percent of patients with epilepsy had complete and sustained seizure relief. The calculated 7.5-year recurrence-free survival rate was 97%. Lower rates of recurrence were found in patients with tumors classified as WHO Grade 1 lesions (P < 0.0001), patients with temporal lesions (P < 0.0001), patients who underwent complete tumor resection (P = 0.0278), and patients with long-standing epilepsy (P < 0.0001). CONCLUSIONS: Supratentorial GGs are benign tumors, and the surgical goal for patients with GG should be complete resection. Residual tumor masses, frontal tumor location, and WHO Grade 2 or 3 lesions are associated with a greater risk of recurrence or malignant progression. Patients with such characteristics should be considered for long-term clinical follow-up using MRI. .

Adolescent↗