Publications by authors named "Johannes Schramm"

186 Publications

Multi-scale image analysis and prediction of visual field defects after selective amygdalohippocampectomy.

Sci Rep 2021 Jan 14;11(1):1444. Epub 2021 Jan 14.

Department of Epileptology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.

Selective amygdalohippocampectomy is an effective treatment for patients with therapy-refractory temporal lobe epilepsy but may cause visual field defect (VFD). Here, we aimed to describe tissue-specific pre- and postoperative imaging correlates of the VFD severity using whole-brain analyses from voxel- to network-level. Twenty-eight patients with temporal lobe epilepsy underwent pre- and postoperative MRI (T1-MPRAGE and Diffusion Tensor Imaging) as well as kinetic perimetry according to Goldmann standard. We probed for whole-brain gray matter (GM) and white matter (WM) correlates of VFD using voxel-based morphometry and tract-based spatial statistics, respectively. We furthermore reconstructed individual structural connectomes and conducted local and global network analyses. Two clusters in the bihemispheric middle temporal gyri indicated a postsurgical GM volume decrease with increasing VFD severity (FWE-corrected p < 0.05). A single WM cluster showed a fractional anisotropy decrease with increasing severity of VFD in the ipsilesional optic radiation (FWE-corrected p < 0.05). Furthermore, patients with (vs. without) VFD showed a higher number of postoperative local connectivity changes. Neither in the GM, WM, nor in network metrics we found preoperative correlates of VFD severity. Still, in an explorative analysis, an artificial neural network meta-classifier could predict the occurrence of VFD based on presurgical connectomes above chance level.
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http://dx.doi.org/10.1038/s41598-020-80751-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809286PMC
January 2021

Pyramidal tract and alternate motor fibers complementarily mediate motor compensation in patients after hemispherotomy.

Sci Rep 2020 01 23;10(1):1010. Epub 2020 Jan 23.

Department of Epileptology, University of Bonn Medical Center, Bonn, 53127, Germany.

Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.
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http://dx.doi.org/10.1038/s41598-020-57504-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978326PMC
January 2020

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

J Neurosurg 2019 Oct 25:1-10. Epub 2019 Oct 25.

19Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Objective: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts.

Methods: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features.

Results: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation.

Conclusions: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.
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http://dx.doi.org/10.3171/2019.8.JNS191266DOI Listing
October 2019

Mendelian randomization provides support for obesity as a risk factor for meningioma.

Sci Rep 2019 01 22;9(1):309. Epub 2019 Jan 22.

Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.

Little is known about the causes of meningioma. Obesity and obesity-related traits have been reported in several epidemiological observational studies to be risk factors for meningioma. We performed an analysis of genetic variants associated with obesity-related traits to assess the relationship with meningioma risk using Mendelian randomization (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. We considered 11 obesity-related traits, identified genetic instruments for these factors, and assessed their association with meningioma risk using data from a genome-wide association study comprising 1,606 meningioma patients and 9,823 controls. To evaluate the causal relationship between the obesity-related traits and meningioma risk, we consider the estimated odds ratio (OR) of meningioma for each genetic instrument. We identified positive associations between body mass index (odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.03-1.56, P = 0.028) and body fat percentage (OR = 1.28, 95% CI = 1.01-1.63, P = 0.042) with meningioma risk, albeit non-significant after correction for multiple testing. Associations for basal metabolic rate, diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, total cholesterol, triglycerides and waist circumference with risk of meningioma were non-significant. Our analysis provides additional support for obesity being associated with an increased risk of meningioma.
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http://dx.doi.org/10.1038/s41598-018-36186-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343031PMC
January 2019

Cognitive features and surgical outcome of patients with long-term epilepsy-associated tumors (LEATs) within the temporal lobe.

Epilepsy Behav 2018 11 10;88:25-32. Epub 2018 Sep 10.

Dept. of Epileptology, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.

Objective: The objective of the study was to evaluate cognitive and epilepsy-related features in 166 surgically treated patients with epilepsy with long-term epilepsy-associated tumors (LEATs) located in the temporal lobe.

Method: Pre- and postsurgical cognitive as well as the one-year seizure outcome of adult patients with histopathologically confirmed LEATs (28 grade-I dysembryoplastic neuroepithelial tumors (DNET), 95 grade-I gangliogliomas (GG), 24 grade-I pilocytic astrocytomas (PA), 9 grade-II pleomorphic xanthoastrocytoma (PXA), 10 grade-II diffuse astrocytoma (DA)) who underwent epilepsy surgery in Bonn/Germany between 1988 and 2012 were evaluated.

Results: At baseline, tumor groups differed in regard to age at epilepsy onset and location within the temporal lobe. Postoperative seizure freedom was achieved most frequently (>77.8%) in DNET, GG, and DA, less often in PXA (62.5%) and the least in PA (56.5%). Preoperative memory was impaired in 67.1% of all patients, executive functions in 44.7%, and language in 45.5%. Patients with PA displayed the poorest cognitive performance. Individual significant memory decline that was observed in 27.1% of all patients was predicted by left-sided surgery, a mesial pathology, and extended hippocampal resection. Executive functions depended on antiepileptic drug (AED) load and remained stable (72.0%) or even improved (21.6%) after surgery. Language functions were unchanged in 89.5% of patients.

Conclusion: Patients with LEATs in the temporal lobe frequently show cognitive impairments. Predictors for pre- and postoperative cognition mostly correspond to what is known for temporal lobe epilepsy and resections in general. However, different tumor types appear to be associated with different cognitive and seizure outcomes with astrocytoma as the least benefitted group.
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http://dx.doi.org/10.1016/j.yebeh.2018.08.028DOI Listing
November 2018

Genome-wide association analysis identifies a meningioma risk locus at 11p15.5.

Neuro Oncol 2018 10;20(11):1485-1493

Division of Neuroepidemiology, Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.

Background: Meningiomas are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31.

Methods: To identify a susceptibility locus for meningioma, we conducted a meta-analysis of 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12081 controls.

Results: We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges.

Conclusions: This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.
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http://dx.doi.org/10.1093/neuonc/noy077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176799PMC
October 2018

Pediatric Temporal Lobe Epilepsy Surgery in Bonn and Review of the Literature.

Neurosurgery 2019 04;84(4):844-856

Department of Neurosurgery, Bielefeld Medical Center, Bielefeld, Germany.

Background: Epilepsy surgery is well established as safe and successful for children with temporal lobe epilepsy (TLE). Despite evidence from available data, there remains some reluctance to refer children with medically refractory epilepsy for preoperative evaluation and workup for possible surgery.

Objective: To present the largest case series of pediatric (TLE) patients thus far, in order to better understand the predictability of preoperative evaluation on seizure outcome, and to better understand longitudinal outcomes in a large pediatric cohort.

Methods: One hundred eighty-three pediatric patients with TLE who underwent surgical treatment between 1988 and 2012 were retrospectively reviewed. Preoperative seizure history, noninvasive and invasive preoperative evaluation, surgical results, pathological results, long-term seizure outcomes, and complications were evaluated. A review of pediatric TLE in the literature was also undertaken to better understand reported complications and long-term outcomes.

Results: Mean follow-up was 42 mo (range 12-152 mo); 155 patients had good seizure outcomes (Engel I/II; 84.8%) and 28 patients had poor seizure outcomes (Engel III/IV; 15.2%); 145 patients were Engel I (78.8%). Only 10 patients did not have worthwhile improvement (Engel class IV; 5.4%). A review of the literature identified 2089 unique cases of pediatric TLE. Satisfactory seizure outcomes occurred in 1629 patients (79%) with unsatisfactory outcomes in 433 patients (21%).

Conclusion: Pediatric patients benefit from surgery for medically refractory TLE with an acceptable safety profile regardless of histopathological diagnosis, seizure frequency, or seizure type. Seizure freedom appears to have extensive durability in a significant proportion of surgically treated patients.
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http://dx.doi.org/10.1093/neuros/nyy125DOI Listing
April 2019

DNA methylation-based classification of central nervous system tumours.

Nature 2018 03 14;555(7697):469-474. Epub 2018 Mar 14.

Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
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http://dx.doi.org/10.1038/nature26000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093218PMC
March 2018

Neuropsychological outcome after subtemporal versus transsylvian approach for selective amygdalohippocampectomy in patients with mesial temporal lobe epilepsy: a randomised prospective clinical trial.

J Neurol Neurosurg Psychiatry 2018 10 22;89(10):1057-1063. Epub 2017 Dec 22.

Department of Epileptology, University of Bonn-Medical Center, Bonn, Germany.

Objective: To compare the effects of different surgical approaches for selective amygdalohippocampectomy in patients with pharmacoresistant mesial temporal lobe epilepsy with regard to the neuropsychological outcome and to replicate an earlier study employing a matched-pair design.

Method: 47 patients were randomised to subtemporal versus transsylvian approaches. Memory, language, attentional and executive functions were assessed before and 1 year after surgery. Multivariate analyses of variance (MANOVAs) with presurgical and postsurgical assessments as within-subject variables and approach and side of surgery as between-subject factors were calculated. Additionally, the frequencies of individual performance changes based on reliable change indices were analysed.

Results: Seizure freedom International League Against Epilepsy (ILAE) 1a, was achieved in 62% of all patients without group difference. MANOVAs revealed no significant effects of approach on cognition. Tested separately for each parameter, verbal recognition memory declined irrespective of approach. Post hoc tests revealed that on group level, the subtemporal approach was associated with a worse outcome for verbal learning and delayed free recall as well as for semantic fluency. Accordingly, on individual level, more patients in the subtemporal group declined in verbal learning. Left side of surgery was associated with decline in naming regardless of approach.

Conclusion: The main analysis did not confirm the effects of approach on memory outcome seen in our previous study. Post hoc testing, however, showed greater memory losses with the subtemporal approach. Previous findings were replicated for semantic fluency. The discrepant results are discussed on the background of the different study designs.
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http://dx.doi.org/10.1136/jnnp-2017-316311DOI Listing
October 2018

How I do it - selective amygdalohippocampectomy via a navigated temporobasal approach, when veins forbid elevation of the temporal lobe.

Acta Neurochir (Wien) 2018 Mar 16;160(3):597-601. Epub 2017 Nov 16.

Department of Neurosurgery, RWTH Aachen University, Aachen, Germany.

Background: Selective amygdalohippocampectomy is an effective treatment option for mesial temporal lobe epilepsy associated with hippocampal sclerosis.

Methods: To describe and emphasize potential pitfalls during selective amygdalohippocampectomy via a modified navigated temporobasal approach, in cases, where temporal basal veins hinder the required elevation of the temporal lobe.

Conclusions: Selective amygdalohippocampectomy via navigated temporobasal approach is a safe procedure that can reduce the rate of visual field deficits by avoiding damage of optic radiation. The option of a small subpial corticotomy of the inferior temporal gyrus allows sufficient elevation of the temporal lobe in cases with difficult basal venous anatomy.
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http://dx.doi.org/10.1007/s00701-017-3386-7DOI Listing
March 2018

Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery.

N Engl J Med 2017 10;377(17):1648-1656

From the Departments of Neuropathology (I.B., G.H., R.C., K.K.) and Neurosurgery (K.R.) and the Epilepsy Center (H. Hamer, H.S.), University Hospital Erlangen, Erlangen, the Epilepsy Center Bethel, Krankenhaus Mara, Bielefeld (C.G.B., M.P.), the Departments of Epileptology (C.E., G.W.) and Neuropathology (A.B.), University of Bonn Medical Center, and Medical Faculty, University of Bonn (J.S.), Bonn, the Neuropediatric Clinic, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Vogtareuth (T.P., H. Holthausen, M.K., P.A.W.), the Epilepsy Center Berlin-Brandenburg, Berlin (H.J.M.), the Epilepsy Center (G.H., A.S.-B.) and Department of Neurosurgery (J.Z., D.H.H.), University Hospital, and the Department of Neuroradiology, Medical Center-University of Freiburg, and Faculty of Medicine, University of Freiburg (H.U.) Freiburg, Kork Epilepsy Center, Kehl-Kork (B.J.S., T.B.), the Departments of Neuropathology (S.V.) and Neurology (U.R.), University Hospital Greifswald, Greifswald, the Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tübingen, Tübingen (H.L., Y.W.), the Department of Neurology, University of Ulm, Ulm (H.L., Y.W.), the Epilepsy Center, Department of Neurology, Ludwig-Maximilians-University Hospital, Munich (S.N., E.H., P.A.W.), Sächsisches Epilepsiezentrum Radeberg, Radeberg (T.M., M.L.), Epilepsy Center Frankfurt Rhine-Main and the Department of Neurology, Goethe University, Frankfurt am Main (F.R., A.H.), the Epilepsy Center Hessen-Marburg, Philipps-University Marburg, Marburg (F.R., A.H.), and the Department of Social Medicine, Occupational and Environmental Dermatology, Heidelberg University, Heidelberg (T.L.D.) - all in Germany; the Clinical Epileptology and Experimental Neurophysiology Unit (R.S.) and the Department of Neurophysiology, Epilepsy Center (G.A.), IRCCS Foundation, Neurological Institute C. Besta, and the Claudio Munari Epilepsy Surgery Center, Niguarda Hospital (L.T., G.L.R.), Milan, and the Pediatric Neurology Unit and Laboratories, Children's Hospital A. Meyer-University of Florence, Florence (R.G., C.B.) - all in Italy; Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery (K.P.B., F.L.), and the Department of (Neuro)Pathology (E.A.), University Medical Center Utrecht, Utrecht, the Department of Neurosurgery, VU University Medical Center (J.C.B.), and the Department of (Neuro)Pathology, Academic Medisch Centrum, University of Amsterdam (E.A., A.M.), and the Department of (Neuro)Pathology, VU University Medical Center (E.A., A.M.), Amsterdam, Stichting Epilepsie Instellingen Nederland, Heemstede (E.A.), and the Department of Neurosurgery, Academic Center for Epileptology, Maastricht University Medical Center, Maastricht (O.S.) - all in the Netherlands; the Department of Neurosurgery, Sainte-Anne Hospital, and Paris Descartes University, Paris (F.C.), the Department of Neurology, Michallon Hospital, GIN INSERM Unité 836, Grenoble Alpes University, Grenoble (P. Kahane), and the Department of Clinical Epileptology, Sleep Disorders and Functional Neurology in Children, University Hospitals of Lyon, and the Brain Dynamics and Cognition team, Lyon Neurosciences Research Center, Lyon (A.A., A.U.-C.) - all in France; the Departments of Neuropathology (M.T.) and Clinical and Experimental Epilepsy (M.C.W., S.M.S., J.S.D., A.W.M.), UCL Institute of Neurology, and the Developmental Biology and Cancer Programme (T.S.J.) and Developmental Neurosciences Program (J.H.C.), UCL-Great Ormond Street Institute of Child Health, and the Department of Histopathology, Great Ormond Street Hospital for Children (T.S.J.), London, and Young Epilepsy, Lingfield (J.H.C.) - all in the United Kingdom; the Departments of Neurology (C.Ö.) and Pathology (B.O.), Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey; the Department of Pediatric Neurology, Motol Epilepsy Center, Charles University in Prague, and the 2nd Faculty of Medicine, Motol University Hospital, Prague, Czech Republic (P. Krsek); the Department of Anatomical Pathology, Hospital Pedro Hispano, Matosinhos (M.H.), and the Laboratory of Neuropathology, Department of Neurosciences, Hospital de Santa Maria-Centro Hospitalar de Lisboa Norte, Lisbon (J.P.) - both in Portugal; the Epilepsy Unit, Child Neurology Department, Hospital San Juan de Dios, Barcelona (A.A., A.U.-C.); the Department of Pediatrics, Medical University Vienna, Vienna (M.F., A.M.), the Departments of Neurology (E.T.) and Neurosurgery (P.A.W.), Christian Doppler Medical Center, Paracelsus Medical University, Center for Cognitive Neuroscience, Salzburg, and the Department of Neurology I, Neuromed Campus, Kepler Universitätsklinikum, Linz (T.J.O.) - all in Austria; the Swiss Epilepsy Center and Department of Neurology, University Hospital, Zurich, Switzerland (T.G.); the Department of Neurology, Hospital Ruber Internacional, Madrid (A.G.-N., R.T.D.); and the Neurosurgical Department (B.Z.) and Epilepsy Monitoring Unit (K.G.), St. Luke's Hospital, Thessaloniki, Greece.

Background: Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy.

Methods: We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%).

Results: The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients.

Conclusions: In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.).
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http://dx.doi.org/10.1056/NEJMoa1703784DOI Listing
October 2017

Seizures associated with cerebral arteriovenous malformations.

Authors:
Johannes Schramm

Handb Clin Neurol 2017 ;143:31-40

Department of Neurosurgery, University of Bonn, Bonn, Germany. Electronic address:

Various types of seizures and epilepsy are associated with 20-45% of cerebral arteriovenous malformations (AVMs). The necessity to differentiate between occasional seizures, epilepsy with repetitive seizures, and the much rarer drug-resistant epilepsy (DRE) is underlined. It is clear that where there is frequent seizures or DRE, vascular surgeons should take epilepsy surgery aspects into account. The epidemiology of AVM-associated seizures, assumed pathophysiologic mechanisms, most frequent seizures types, and medical treatment are described. Depending on the severity of the epilepsy, the diagnostic workup, including electroencephalogram (EEG), video-EEG, and, rarely, invasive evaluation, is explained. An invasive presurgical workup is only necessary in rare cases of DRE. The indication to extend the resection to more than just removal of the AVM is defined and the various specific resection techniques for this rare form are outlined. In the vast majority of AVM cases removal of the AVM with some adjoining gliotic or hemosiderotic rim of cortex will be sufficient, however. In the majority of cases with preoperative epilepsy, patients will be seizure-free after surgery. Patients who never had a seizure before AVM removal may develop de novo epilepsy postoperatively (5-15%). Rates of seizure freedom after different treatments (microsurgery, radiosurgery, endovascular) vary.
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http://dx.doi.org/10.1016/B978-0-444-63640-9.00004-7DOI Listing
March 2018

Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.

Nat Genet 2017 May 27;49(5):789-794. Epub 2017 Mar 27.

1st Medical Department, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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http://dx.doi.org/10.1038/ng.3823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558246PMC
May 2017

Integrated genomic analyses of de novo pathways underlying atypical meningiomas.

Nat Commun 2017 02 14;8:14433. Epub 2017 Feb 14.

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut 06510, USA.

Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state. Consistent with this observation, atypical meningiomas exhibit upregulation of EZH2, the catalytic subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks. Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas and potential therapeutic targets.
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http://dx.doi.org/10.1038/ncomms14433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316884PMC
February 2017

Prognostic relevance of miRNA-155 methylation in anaplastic glioma.

Oncotarget 2016 Dec;7(50):82028-82045

Department of General Neurology, University Hospital Tübingen, Germany.

The outcome of patients with anaplastic gliomas varies considerably depending on single molecular markers, such as mutations of the isocitrate dehydrogenase (IDH) genes, as well as molecular classifications based on epigenetic or genetic profiles. Remarkably, 98% of the RNA within a cell is not translated into proteins. Of those, especially microRNAs (miRNAs) have been shown not only to have a major influence on physiologic processes but also to be deregulated and prognostic in malignancies.To find novel survival markers and treatment options we performed unbiased DNA methylation screens that revealed 12 putative miRNA promoter regions with differential DNA methylation in anaplastic gliomas. Methylation of these candidate regions was validated in different independent patient cohorts revealing a set of miRNA promoter regions with prognostic relevance across data sets. Of those, miR-155 promoter methylation and miR-155 expression were negatively correlated and especially the methylation showed superior correlation with patient survival compared to established biomarkers.Functional examinations in malignant glioma cells further cemented the relevance of miR-155 for tumor cell viability with transient and stable modifications indicating an onco-miRNA activity. MiR-155 also conferred resistance towards alkylating temozolomide and radiotherapy as consequence of nuclear factor (NF)κB activation.Preconditioning glioma cells with an NFκB inhibitor reduced therapy resistance of miR-155 overexpressing cells. These cells resembled tumors with a low methylation of the miR-155 promoter and thus mir-155 or NFκB inhibition may provide treatment options with a special focus on patients with IDH wild type tumors.
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http://dx.doi.org/10.18632/oncotarget.13452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347671PMC
December 2016

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas.

Nat Genet 2016 10 22;48(10):1253-9. Epub 2016 Aug 22.

Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, Connecticut, USA.

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes, including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO, we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features.
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http://dx.doi.org/10.1038/ng.3651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114141PMC
October 2016

Microsurgery for cerebral arteriovenous malformations: subgroup outcomes in a consecutive series of 288 cases.

J Neurosurg 2017 Apr 10;126(4):1056-1063. Epub 2016 Jun 10.

Department of Neurosurgery, Medical School, University of Bonn, Bonn, Germany; and.

OBJECTIVE The objective of this study was to review the outcomes after microsurgical resection of cerebral arteriovenous malformations (AVMs) from a consecutive single-surgeon series. Clinical and imaging data were analyzed to address the following questions concerning AVM treatment in the post-ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) era. 1) Are the patients who present with unruptured or ruptured AVMs doing better at long-term follow-up? 2) Is the differentiation between Ponce Class A (Spetzler-Martin Grade I and II) patients versus Ponce Class B and C patients (Spetzler-Martin Grade III and IV) meaningful and applicable to surgical practice? 3) How did the ARUBA-eligible patients of this surgical series compare with the results reported in ARUBA? METHODS Two hundred eighty-eight patients with cerebral AVMs underwent microsurgical resection between 1983 and 2012 performed by the same surgeon (J.S.). This is a prospective case collection study that represents a consecutive series. The results are based on prospectively collected, early-outcome data that were supplemented by retrospectively collected, follow-up data for 94% of those cases. The analyzed data included the initial presentation, Spetzler-Martin grade, obliteration rates, surgical and neurological complications, and frequency of pretreatment with embolization or radiosurgery. The total cohort was compared using "small-AVM," Spetzler-Martin Grade I and II, and ARUBA-eligible AVM subgroups. RESULTS The initial presentation was hemorrhage in 50.0% and seizures in 43.1% of patients. The series included 53 Spetzler-Martin Grade I (18.4%), 114 Spetzler-Martin Grade II (39.6%), 90 Spetzler-Martin Grade III (31.3%), 28 Spetzler-Martin Grade IV (9.7%), and 3 Spetzler-Martin Grade V (1.0%) AVMs. There were 144 unruptured and 104 ARUBA-eligible cases. Preembolization was used in 39 cases (13.5%). The occlusion rates for the total series and small AVM subgroup were 99% and 98.7%, respectively. The mean follow-up duration was 64 months. Early neurological deterioration was seen in 39.2% of patients, of which 12.2% had permanent and 5.6% had permanent significant deficits, and the mortality rate was 1.7% (n = 5). Outcome was better for patients with AVMs smaller than 3 cm (permanent deficit in 7.8% and permanent significant deficit in 3.2% of patients) and Ponce Class A status (permanent deficit in 7.8% and significant deficit in 3.2% of patients). Unruptured AVMs showed slightly higher new deficit rates (but 0 instances of mortality) among all cases, and in the small AVM and Ponce Class A subgroups. Unruptured Spetzler-Martin Grade I and II lesions had the best outcome (1.8% permanent significant deficit), and ARUBA-eligible Spetzler-Martin Grade I and II lesions had a slightly higher rate of permanent significant deficits (3.2%). CONCLUSIONS Microsurgery has a very high cure rate. Focusing microsurgical AVM resection on unruptured lesions smaller than 3 cm or on Spetzler-Martin Grade I and II lesions is a good strategy for minimizing long-term morbidity. Well-selected microsurgical cases lead to better outcomes than with multimodal interventions, as in the ARUBA treatment arm, or conservative treatment alone. Long-term prospective data collection is valuable.
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http://dx.doi.org/10.3171/2016.4.JNS153017DOI Listing
April 2017

Vision after trans-sylvian or temporobasal selective amygdalohippocampectomy: a prospective randomised trial.

Acta Neurochir (Wien) 2016 09 6;158(9):1757-65. Epub 2016 Jun 6.

Department of Neurosurgery, University of Bonn, University Medical Centre, Bonn, Germany.

Background: Selective amygdalohippocampectomy (SAH) is an accepted surgical procedure for treatment of pharmacoresistant mesial temporal lobe epilepsy, but it may lead to postoperative visual field deficits (VFDs). Here we present a prospective randomised trial comparing the postoperative VFDs after either a trans-sylvian or temporobasal approach for SAH.

Method: Forty-eight patients were randomly assigned to trans-sylvian (n = 24) or temporobasal (n = 24) SAH. Postoperative VFD were quantitatively evaluated using automated static and kinetic perimetry. In 24 cases, diffusion tensor imaging-based deterministic fibre-tracking of the optic radiation was performed. The primary endpoint was absence of postoperative VFD. The secondary endpoint was seizure outcome and driving ability.

Results: Three patients (13 %) from the trans-sylvian group showed no VFD, compared to 11 patients (46 %) from the temporobasal group without VFD (p = 0.01, RR = 3.7; CI = 1.2-11.5). Fifteen patients from each group (63 %) became completely seizure-free (ILAE1). Among those seizure-free cases, five trans-sylvian (33 %) and ten temporobasal (66 %) patients could apply for a driving licence (NNT = 3) when VFDs were considered. Although the trans-sylvian group experienced more frequent VFDs, the mean functional visual impairment showed a tendency to be less pronounced compared with the temporobasal group. DTI-based tracking of the optic radiation revealed that a lower distance of optic radiation to the temporal base correlated with increased rate of VFD in the temporobasal group.

Conclusions: Temporobasal SAH shows significantly fewer VFDs and equal seizure-free rate compared with the trans-sylvian SAH. However, in patients in whom the optic radiation is close to the temporal base, the trans-sylvian approach may be a preferred alternative.
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http://dx.doi.org/10.1007/s00701-016-2860-yDOI Listing
September 2016

NOTCH4 gene polymorphisms as potential risk factors for brain arteriovenous malformation development and hemorrhagic presentation.

J Neurosurg 2017 May 27;126(5):1552-1559. Epub 2016 May 27.

Department of Neurosurgery.

OBJECTIVE Arteriovenous malformations (AVMs) of the brain are a frequent and important cause of intracranial hemorrhage in young adults. Little is known about the molecular-genetic pathomechanisms underlying AVM development. Genes of the NOTCH family control the normal development of vessels and proper arteriovenous specification. Transgenic mice with constitutive expression of active NOTCH4 frequently develop AVMs. Here, the authors report a genetic association study investigating possible associations between NOTCH4 gene polymorphisms and formation and clinical presentation of AVMs. METHODS After PCR amplification and direct DNA sequencing or restriction digests, 10 single-nucleotide polymorphisms (SNPs) of the NOTCH4 gene were used for genotyping 153 AVM patients and 192 healthy controls (i.e., blood donors). Pertinent clinical data were available for 129 patients. Uni- and multivariate single-marker and explorative haplotype analyses were performed to identify potential genetic risk factors for AVM development and for hemorrhagic or epileptic presentation. RESULTS Eleven calculated haplotypes consisting of 3-4 SNPs (most of which were located in the epidermal growth factor-like domain of the NOTCH4 gene) were observed significantly more often among AVM patients than among controls. Univariate analysis indicated that rs443198_TT and rs915895_AA genotypes both were significantly associated with hemorrhage and that an rs1109771_GG genotype was associated with epilepsy. The association between rs443198_TT and AVM bleeding remained significant in the multivariate regression analysis. CONCLUSIONS The authors' results suggest NOTCH4 SNPs as possible genetic risk factors for the development and clinical presentation of AVMs and a role of NOTCH4 in the pathogenesis of this disease.
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http://dx.doi.org/10.3171/2016.3.JNS151731DOI Listing
May 2017

The Simpson grading revisited: aggressive surgery and its place in modern meningioma management.

J Neurosurg 2016 09 29;125(3):551-60. Epub 2016 Jan 29.

Department of Neurosurgery, University Hospital of Bonn; and.

OBJECTIVE Recent advances in radiotherapy and neuroimaging have called into question the traditional role of aggressive resections in patients with meningiomas. In the present study the authors reviewed their institutional experience with a policy based on maximal safe resections for meningiomas, and they analyzed the impact of the degree of resection on functional outcome and progression-free survival (PFS). METHODS The authors retrospectively analyzed 901 consecutive patients with primary meningiomas (716 WHO Grade I, 174 Grade II, and 11 Grade III) who underwent resections at the University Hospital of Bonn between 1996 and 2008. Clinical and treatment parameters as well as tumor characteristics were analyzed using standard statistical methods. RESULTS The median follow-up was 62 months. PFS rates at 5 and 10 years were 92.6% and 86.0%, respectively. Younger age, higher preoperative Karnofsky Performance Scale (KPS) score, and convexity tumor location, but not the degree of resection, were identified as independent predictors of a good functional outcome (defined as KPS Score 90-100). Independent predictors of PFS were degree of resection (Simpson Grade I vs II vs III vs IV), MIB-1 index (< 5% vs 5%-10% vs >10%), histological grade (WHO I vs II vs III), tumor size (≤ 6 vs > 6 cm), tumor multiplicity, and location. A Simpson Grade II rather than Grade I resection more than doubled the risk of recurrence at 10 years in the overall series (18.8% vs 8.5%). The impact of aggressive resections was much stronger in higher grade meningiomas. CONCLUSIONS A policy of maximal safe resections for meningiomas prolongs PFS and is not associated with increased morbidity.
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http://dx.doi.org/10.3171/2015.9.JNS15754DOI Listing
September 2016

Quantifying the heritability of glioma using genome-wide complex trait analysis.

Sci Rep 2015 Dec 2;5:17267. Epub 2015 Dec 2.

Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.

Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) influencing glioma risk. While these SNPs only explain a small proportion of the genetic risk it is unclear how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we applied Genome-Wide Complex Trait Analysis (GCTA) to three GWAS datasets totalling 3,373 cases and 4,571 controls and performed a meta-analysis to estimate the heritability of glioma. Our results identify heritability estimates of 25% (95% CI: 20-31%, P = 1.15 × 10(-17)) for all forms of glioma - 26% (95% CI: 17-35%, P = 1.05 × 10(-8)) for glioblastoma multiforme (GBM) and 25% (95% CI: 17-32%, P = 1.26 × 10(-10)) for non-GBM tumors. This is a substantial increase from the genetic variance identified by the currently identified GWAS risk loci (~6% of common heritability), indicating that most of the heritable risk attributable to common genetic variants remains to be identified.
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http://dx.doi.org/10.1038/srep17267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667278PMC
December 2015

Integrated genomic characterization of IDH1-mutant glioma malignant progression.

Nat Genet 2016 Jan 30;48(1):59-66. Epub 2015 Nov 30.

Department of Neurosurgery, Acıbadem University School of Medicine, Istanbul, Turkey.

Gliomas represent approximately 30% of all central nervous system tumors and 80% of malignant brain tumors. To understand the molecular mechanisms underlying the malignant progression of low-grade gliomas with mutations in IDH1 (encoding isocitrate dehydrogenase 1), we studied paired tumor samples from 41 patients, comparing higher-grade, progressed samples to their lower-grade counterparts. Integrated genomic analyses, including whole-exome sequencing and copy number, gene expression and DNA methylation profiling, demonstrated nonlinear clonal expansion of the original tumors and identified oncogenic pathways driving progression. These include activation of the MYC and RTK-RAS-PI3K pathways and upregulation of the FOXM1- and E2F2-mediated cell cycle transitions, as well as epigenetic silencing of developmental transcription factor genes bound by Polycomb repressive complex 2 in human embryonic stem cells. Our results not only provide mechanistic insight into the genetic and epigenetic mechanisms driving glioma progression but also identify inhibition of the bromodomain and extraterminal (BET) family as a potential therapeutic approach.
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http://dx.doi.org/10.1038/ng.3457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829945PMC
January 2016

Genome-wide association study identifies multiple susceptibility loci for glioma.

Nat Commun 2015 Oct 1;6:8559. Epub 2015 Oct 1.

Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK.

Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project data as reference. After genotyping an additional 1,490 cases and 1,723 controls we identify new risk loci for glioblastoma (GBM) at 12q23.33 (rs3851634, near POLR3B, P=3.02 × 10(-9)) and non-GBM at 10q25.2 (rs11196067, near VTI1A, P=4.32 × 10(-8)), 11q23.2 (rs648044, near ZBTB16, P=6.26 × 10(-11)), 12q21.2 (rs12230172, P=7.53 × 10(-11)) and 15q24.2 (rs1801591, near ETFA, P=5.71 × 10(-9)). Our findings provide further insights into the genetic basis of the different glioma subtypes.
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http://dx.doi.org/10.1038/ncomms9559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600760PMC
October 2015

Health Literacy: Economic and Other Intricate Problems.

Authors:
Johannes Schramm

World Neurosurg 2016 Jan 2;85:28-9. Epub 2015 Sep 2.

Department of Neurosurgery, Medical Faculty, University of Bonn, Bonn, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2015.08.049DOI Listing
January 2016

Response to the future of the EANS neurosurgeons of Europe, unite!

Acta Neurochir (Wien) 2015 Nov 3;157(11):1829-30. Epub 2015 Sep 3.

Department of Neurosurgery, Charles University, Prague, Czech Republic.

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http://dx.doi.org/10.1007/s00701-015-2566-6DOI Listing
November 2015

Search for new loci and low-frequency variants influencing glioma risk by exome-array analysis.

Eur J Hum Genet 2016 May 12;24(5):717-24. Epub 2015 Aug 12.

Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, UK.

To identify protein-altering variants (PAVs) for glioma, we analysed Illumina HumanExome BeadChip exome-array data on 1882 glioma cases and 8079 controls from three independent European populations. In addition to single-variant tests we incorporated information on the predicted functional consequences of PAVs and analysed sets of genes with a higher likelihood of having a role in glioma on the basis of the profile of somatic mutations documented by large-scale sequencing initiatives. Globally there was a strong relationship between effect size and PAVs predicted to be damaging (P=2.29 × 10(-49)); however, these variants which are most likely to impact on risk, are rare (MAF<5%). Although no single variant showed an association which was statistically significant at the genome-wide threshold a number represented promising associations - BRCA2:c.9976A>T, p.(Lys3326Ter), which has been shown to influence breast and lung cancer risk (odds ratio (OR)=2.3, P=4.00 × 10(-4) for glioblastoma (GBM)) and IDH2:c.782G>A, p.(Arg261His) (OR=3.21, P=7.67 × 10(-3), for non-GBM). Additionally, gene burden tests revealed a statistically significant association for HARS2 and risk of GBM (P=2.20 × 10(-6)). Genome scans of low-frequency PAVs represent a complementary strategy to identify disease-causing variants compared with scans based on tagSNPs. Strategies to lessen the multiple testing burden by restricting analysis to PAVs with higher priors affords an opportunity to maximise study power.
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http://dx.doi.org/10.1038/ejhg.2015.170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677454PMC
May 2016

Seizure Outcomes in Patients With Surgically Treated Cerebral Arteriovenous Malformations.

Neurosurgery 2015 Nov;77(5):762-8

Department of Neurosurgery, University of Bonn Medical Centre, Bonn, Germany.

Background: Epilepsy is the second most common symptom in cerebral arteriovenous malformation (AVM) patients. The consecutive reduction of life quality is a clinically underrated problem because treatment usually focuses on the prevention of intracerebral hemorrhage.

Objective: To evaluate postoperative seizure outcome with the aim of more accurate counseling for postoperative seizure outcome.

Methods: From 1985 to 2012, 293 patients with an AVM were surgically treated by J.S. One hundred twenty-six patients with preoperative seizures or epilepsy could be identified; 103 of 126 had a follow-up of at least 12 months and were included in the analysis. The different epilepsy subtypes were categorized (sporadic seizures, chronic epilepsy, drug-resistant epilepsy [DRE]). Preoperative workup and surgical technique were evaluated. Seizure outcome was analyzed by using International League Against Epilepsy classification.

Results: Sporadic seizures were identified in 41% of patients (chronic epilepsy and DRE were identified in 36% and 23%, respectively). Detailed preoperative epileptological workup was done in 13%. Seizure freedom was achieved in 77% (79% at 5 years, 84% at 10 years). Outcome was significantly poorer in DRE cases. More extensive resection was performed in 11 cases with longstanding symptoms (>24 months) and resulted in better seizure outcome as well as the short duration of preoperative seizure history.

Conclusion: Patients presenting with AVM-associated epilepsy have a favorable seizure outcome after surgical treatment. Long-standing epilepsy and the progress into DRE markedly deteriorate the chances to obtain seizure freedom and should be considered an early factor in establishing the indication for AVM removal.
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http://dx.doi.org/10.1227/NEU.0000000000000919DOI Listing
November 2015

Role of Subdural Interhemispheric Electrodes in Presurgical Evaluation of Epilepsy Patients.

World Neurosurg 2015 Dec 22;84(6):1719-25.e1. Epub 2015 Jul 22.

Department of Neurosurgery, University of Bonn, University Medical Center, Germany.

Objective: Surgery is a well-established and safe treatment option for focal drug resistant epilepsy. However, difficulties are often encountered in diagnosing mesial cortical lesions. The aim of this study was to evaluate the usefulness and overall complication rate of subdural interhemispheric electrodes (IHEs) as part of an invasive presurgical evaluation of epilepsy patients.

Methods: A total of 100 patients who underwent implantation of subdural IHE were included in the study. Data on surgical complications, subdural electrodes and contacts, benefits of invasive electroencephalography recording, and final seizure outcome were collected and analyzed.

Results: A total of 343 subdural strip electrodes with a total of 1470 contacts were implanted. There were 6 perioperative/postoperative complications, none of them leading to a permanent neurologic deficit. An increased number of IHE (P = 0.005) and IHE-contacts (P = 0.03) also increased the rate of focus detection, while not significantly changing complication rate (P = 0.26). Two benefits of IHE (focus detection of interhemispheric lesions and mapping) in extratemporal resections were significantly associated with excellent seizure outcome (ILEA1) (P = 0.03, respectively P < 0.001). Other features associated with excellent seizure outcome are pure resections (w/o multiple subpial transection, P = 0.006), specific histology (P < 0.001), and a visible magnetic resonance imaging lesion (P = 0.002).

Conclusion: Implantation of IHE for the preoperative evaluation of epilepsy patients is an established surgical procedure with an acceptable complication profile. The benefits delivered from IHE can positively influence final seizure outcome in the challenging group of extratemporal resections due to interhemispheric lesions. Thus IHEs demonstrate a useful diagnostic utility for the presurgical evaluation of selected epilepsy patients.
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http://dx.doi.org/10.1016/j.wneu.2015.07.034DOI Listing
December 2015

Relevance of hippocampal integrity for memory outcome after surgical treatment of mesial temporal lobe epilepsy.

J Neurol 2015 Oct 3;262(10):2214-24. Epub 2015 Jul 3.

Department of Epileptology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.

Surgical treatment of unilateral mesial temporal lobe epilepsy (mTLE) particularly bears the risk of episodic memory decline. The present study investigates the role of the ipsilateral hippocampal integrity for postoperative change in material-specific memory performance. In 104 patients who had undergone epilepsy surgery for unilateral mTLE, we analyzed pre- to postoperative changes of verbal and figural memory as a function of segmental neuronal cell densities of the resected hippocampus (cornu ammonis, CA1-4; internal and external limb of the dentate gyrus, DG). Results were controlled for side of surgery and hemispheric dominance. Surgery caused significant memory decline, especially with regard to verbal memory after left temporal resections. Seizure freedom (65 % Engel Ia) did not affect memory outcome. Higher neuronal cell densities of the resected left hippocampus were associated with greater declines in verbal memory parameters (r = -0.27 to r = -0.39, p < 0.05), especially when excluding patients with atypical hemispheric dominance (r = -0.34 to r = -0.60, p < 0.05; significant correlations across all hippocampal subfields). There were no systematic correlations between neuronal cell densities of the resected right hippocampus and memory changes. The results emphasize the role of the structural and functional integrity of the hippocampus within the left dominant hemisphere for the degree of verbal memory decline after temporal lobe surgery. Presurgical verbal memory performance may be taken as a marker of ipsilateral left hippocampal integrity and may contribute to individual risk-benefit evaluations before epilepsy surgery. Finally, more precise neuropsychological markers of right hippocampal integrity are needed.
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http://dx.doi.org/10.1007/s00415-015-7831-3DOI Listing
October 2015