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3. Histopathological findings in brain tissue obtained during epilepsy surgery

Author

Blümcke, I., Spreafico, R., Haaker, G., Coras, R., Kobow, K., Bien, C.G., Pfäfflin, M., Elger, C., Widman, G., Schramm, J., Becker, A., Braun, K.P.J., Leijten, F.S.S., Baayen, J.C., Aronica, E., Chassoux, F., Hamer, H., Stefan, H., Rössler, K., Thom, M., Walker, M.C., Sisodiya, S.M., Duncan, J.S., McEvoy, A.W., Pieper, T., Holthausen, H., Kudernatsch, M., Meencke, H.J., Kahane, P., Schulze-Bonhage, A., Zentner, J., Heiland, D., Urbach, H., Steinhoff, B.J., Bast, T., Tassi, L., Lo Russo, G., Ozkara, C., Oz, B., Krsek, P., Vogelgesang, S., Runge, U., Lerche, H., Weber, Y., Honavar, M., Pimentel, J., Arzimanoglou, A., Ulate-Campos, A., Noachtar, S., Hartl, E., Schijns, O.E.M.G., Guerrini, R., Barba, C., Jacques, T.S., Cross, J.H., Feucht, M., Mühlebner, A., Grunwald, T., Trinka, E., Winkler, P.A., Gil-Nagel, A., Toledano Delgado, R., Mayer, T., Lutz, M., Zountsas, B., Garganis, K., Rosenow, F., Hermsen, A., Örtzen, T.J. von, Diepgen, T.L., Avanzini, G., Aparicio, J., Bento, C., Beckervordersandforth, J., Buccoliero, A.M., Cabral, P., Chamadoira, C., Colon, A.J., Chabardès, S., Carpenter, S., Czech, T., Dressler, A., Deleo, F., Dílio, A., Dings, J., Devaux, B., De Tisi, J., De Bellescize, J., Ebner, A., Franke, K., Groeppel, G., Giordano, F., Gozzo, F., Garbelli, R., Guenot, M., García‐Morales, I., Gómez‐Angulo, J.C., Garcia, G., Hainfellner, J.A., Höfler, J., Hoogland, G., Hendriks, M.P.H., Hofman, P., Harding, B., Huppertz, H.J., Herms, J., Hilkman, D.M.W., Hamelin, S., Idema, S., Jansen, F.E., Jahodova, A., Keeley, A., Kalss, G., Kudr, M., Kroell, J., Kokkinos, V., Keo Kosal, P., Kalbhenn, T., Leitinger, M., Landré, E., Melo Pires, M., Matas, A., Mann, M.W., Ostrowsky‐Coste, K., Prinz, M., Puttinger, G., Peraud, A., Rangel Pinho, R., Romero, C., Rego, R., Rouhl, R.P.W., Ryvlin, P., Rumia, J., Rampp, S., Scholl, T., Schulz, R., Stone, T.J., Streichenberger, N., Tisdall, M., Turak, B., Taipa, R., Uzan, M., Kranen‐Mastenbroek, V. van, Varlet, P., Vlooswijk, M.C.G., Wagner, L., Weis, S., Blümcke, I., Spreafico, R., Haaker, G., Coras, R., Kobow, K., Bien, C.G., Pfäfflin, M., Elger, C., Widman, G., Schramm, J., Becker, A., Braun, K.P.J., Leijten, F.S.S., Baayen, J.C., Aronica, E., Chassoux, F., Hamer, H., Stefan, H., Rössler, K., Thom, M., Walker, M.C., Sisodiya, S.M., Duncan, J.S., McEvoy, A.W., Pieper, T., Holthausen, H., Kudernatsch, M., Meencke, H.J., Kahane, P., Schulze-Bonhage, A., Zentner, J., Heiland, D., Urbach, H., Steinhoff, B.J., Bast, T., Tassi, L., Lo Russo, G., Ozkara, C., Oz, B., Krsek, P., Vogelgesang, S., Runge, U., Lerche, H., Weber, Y., Honavar, M., Pimentel, J., Arzimanoglou, A., Ulate-Campos, A., Noachtar, S., Hartl, E., Schijns, O.E.M.G., Guerrini, R., Barba, C., Jacques, T.S., Cross, J.H., Feucht, M., Mühlebner, A., Grunwald, T., Trinka, E., Winkler, P.A., Gil-Nagel, A., Toledano Delgado, R., Mayer, T., Lutz, M., Zountsas, B., Garganis, K., Rosenow, F., Hermsen, A., Örtzen, T.J. von, Diepgen, T.L., Avanzini, G., Aparicio, J., Bento, C., Beckervordersandforth, J., Buccoliero, A.M., Cabral, P., Chamadoira, C., Colon, A.J., Chabardès, S., Carpenter, S., Czech, T., Dressler, A., Deleo, F., Dílio, A., Dings, J., Devaux, B., De Tisi, J., De Bellescize, J., Ebner, A., Franke, K., Groeppel, G., Giordano, F., Gozzo, F., Garbelli, R., Guenot, M., García‐Morales, I., Gómez‐Angulo, J.C., Garcia, G., Hainfellner, J.A., Höfler, J., Hoogland, G., Hendriks, M.P.H., Hofman, P., Harding, B., Huppertz, H.J., Herms, J., Hilkman, D.M.W., Hamelin, S., Idema, S., Jansen, F.E., Jahodova, A., Keeley, A., Kalss, G., Kudr, M., Kroell, J., Kokkinos, V., Keo Kosal, P., Kalbhenn, T., Leitinger, M., Landré, E., Melo Pires, M., Matas, A., Mann, M.W., Ostrowsky‐Coste, K., Prinz, M., Puttinger, G., Peraud, A., Rangel Pinho, R., Romero, C., Rego, R., Rouhl, R.P.W., Ryvlin, P., Rumia, J., Rampp, S., Scholl, T., Schulz, R., Stone, T.J., Streichenberger, N., Tisdall, M., Turak, B., Taipa, R., Uzan, M., Kranen‐Mastenbroek, V. van, Varlet, P., Vlooswijk, M.C.G., Wagner, L., and Weis, S.

Abstract

Item does not contain fulltext, 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.)

Published
2017

5. D-galactose Supplementation for the Treatment of Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE): A Pilot Trial of Precision Medicine After Epilepsy Surgery.

Author

Aledo-Serrano Á, Valls-Carbó A, Fenger CD, Groeppel G, Hartlieb T, Pascual I, Herraez E, Cabal B, García-Morales I, Toledano R, Budke M, Beltran-Corbellini Á, Baldassari S, Coras R, Kobow K, Herrera DM, Del Barrio A, Dahl HA, Del Pino I, Baulac S, Blumcke I, Møller RS, and Gil-Nagel A

Subjects
Humans, Precision Medicine, Hyperplasia, Pilot Projects, Quality of Life, Seizures, Electroencephalography methods, Galactose, Epilepsy therapy
Abstract

MOGHE is defined as mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Approximately half of the patients with histopathologically confirmed MOGHE carry a brain somatic variant in the SLC35A2 gene encoding a UDP-galactose transporter. Previous research showed that D-galactose supplementation results in clinical improvement in patients with a congenital disorder of glycosylation due to germline variants in SLC35A2. We aimed to evaluate the effects of D-galactose supplementation in patients with histopathologically confirmed MOGHE, with uncontrolled seizures or cognitive impairment and epileptiform activity at the EEG after epilepsy surgery (NCT04833322). Patients were orally supplemented with D-galactose for 6 months in doses up to 1.5 g/kg/day and monitored for seizure frequency including 24-h video-EEG recording, cognition and behavioral scores, i.e., WISC, BRIEF-2, SNAP-IV, and SCQ, and quality of life measures, before and 6 months after treatment. Global response was defined by > 50% improvement of seizure frequency and/or cognition and behavior (clinical global impression of "much improved" or better). Twelve patients (aged 5-28 years) were included from three different centers. Neurosurgical tissue samples were available in all patients and revealed a brain somatic variant in SLC35A2 in six patients (non-present in the blood). After 6 months of supplementation, D-galactose was well tolerated with just two patients presenting abdominal discomfort, solved after dose spacing or reduction. There was a 50% reduction or higher of seizure frequency in 3/6 patients, with an improvement at EEG in 2/5 patients. One patient became seizure-free. An improvement of cognitive/behavioral features encompassing impulsivity (mean SNAP-IV - 3.19 [- 0.84; - 5.6]), social communication (mean SCQ - 2.08 [- 0.63; - 4.90]), and executive function (BRIEF-2 inhibit - 5.2 [- 1.23; - 9.2]) was observed. Global responder rate was 9/12 (6/6 in SLC35A2-positive). Our results suggest that supplementation with D-galactose in patients with MOGHE is safe and well tolerated and, although the efficacy data warrant larger studies, it might build a rationale for precision medicine after epilepsy surgery., (© 2023. The American Society for Experimental Neurotherapeutics, Inc.)

Published
2023
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6. Tuberous Sclerosis Complex: new criteria for diagnostic work-up and management.

Author

Samueli S, Abraham K, Dressler A, Groeppel G, Jonak C, Muehlebner A, Prayer D, Reitner A, and Feucht M

Subjects
Algorithms, Austria, Registries standards, Case Management standards, Immunosuppressive Agents administration & dosage, Practice Guidelines as Topic, Symptom Assessment standards, Tuberous Sclerosis diagnosis, Tuberous Sclerosis therapy
Abstract

Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder, characterized by predominantly benign tumors in potentially all organ systems. System involvement, severity of clinical symptoms and the response to treatment are age-dependent and heterogeneous. Consequently, the disorder is still not recognized in a considerable number of patients. The diagnostic criteria and the guidelines for surveillance and management of patients with TSC were revised, and the establishment of specialized TSC-centers was strongly recommended during an International Consensus Conference in 2012. TOSCA (TuberOus SClerosis registry to increase disease Awareness), an international patient registry, was started to allow new insights into the causes of different courses. Finally, there are-since the approval of the mTOR inhibitor Everolimus-promising new therapeutic approaches.This review focuses on the various TSC related symptoms occurring at different ages, the novel recommendations for diagnosis and treatment as well as the need for multidisciplinary follow-up.

Published
2015
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7. Beneficial effect of epilepsy surgery in a case of childhood non-paraneoplastic limbic encephalitis.

Author

Muehlebner A, Groeppel G, Pahs G, Hainfellner JA, Prayer D, Czech T, and Feucht M

Subjects
Adolescent, Female, Hippocampus pathology, Humans, Limbic Encephalitis complications, Limbic Encephalitis pathology, Magnetic Resonance Imaging, Sclerosis complications, Sclerosis pathology, Sclerosis surgery, Seizures etiology, Seizures pathology, Treatment Outcome, Hippocampus surgery, Limbic Encephalitis surgery, Seizures surgery
Abstract

This 15-year-old girl had subacute onset of secondary generalized seizures, confusion, and subsequent memory decline. MRI showed bilateral hippocampal swelling progressing to unilateral mesial temporal sclerosis (MTS) within 12 months. Epilepsy surgery was performed, and laboratory data were consistent with non-paraneoplastic limbic encephalitis. 18 months after epilepsy surgery, the patient is seizure-free with stable cognitive functions.

Published
2010
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