Search

Your search keyword '"Widman G"' showing total 141 results
Start Over Author "Widman G"
141 results on '"Widman G"'

2. Quantification of depth of anesthesia by nonlinear time series analysis of brain electrical activity

Author

Widman, G., Schreiber, T., Rehberg, B., Hoeft, A., and Elger, C. E.

Subjects
Nonlinear Sciences - Chaotic Dynamics, Quantitative Biology
Abstract

We investigate several quantifiers of the electroencephalogram (EEG) signal with respect to their ability to indicate depth of anesthesia. For 17 patients anesthetized with Sevoflurane, three established measures (two spectral and one based on the bispectrum), as well as a phase space based nonlinear correlation index were computed from consecutive EEG epochs. In absence of an independent way to determine anesthesia depth, the standard was derived from measured blood plasma concentrations of the anesthetic via a pharmacokinetic/pharmacodynamic model for the estimated effective brain concentration of Sevoflurane. In most patients, the highest correlation is observed for the nonlinear correlation index D*. In contrast to spectral measures, D* is found to decrease monotonically with increasing (estimated) depth of anesthesia, even when a "burst-suppression" pattern occurs in the EEG. The findings show the potential for applications of concepts derived from the theory of nonlinear dynamics, even if little can be assumed about the process under investigation., Comment: 7 pages, 5 figures

Published
2000
Full Text
View/download PDF

7. The importance of early immunotherapy in patients with faciobrachial dystonic seizures

Author

Thompson, J, Bi, M, Murchison, AG, Makuch, M, Bien, CG, Chu, K, Farooque, P, Gelfand, JM, Geschwind, MD, Hirsch, LJ, Somerville, E, Lang, B, Vincent, A, Leite, MI, Waters, P, Irani, SR, Dogan-Onugoren, M, Rae-Grant, A, Illes, Z, Szots, M, Malter, M, Widman, G, Surges, R, Archibald, N, Reid, J, Duncan, C, Richardson, A, Lilleker, J, Iorio, R, Blaabjerg, M, Abeler, K, Shin, Y, Thompson, J, Bi, M, Murchison, AG, Makuch, M, Bien, CG, Chu, K, Farooque, P, Gelfand, JM, Geschwind, MD, Hirsch, LJ, Somerville, E, Lang, B, Vincent, A, Leite, MI, Waters, P, Irani, SR, Dogan-Onugoren, M, Rae-Grant, A, Illes, Z, Szots, M, Malter, M, Widman, G, Surges, R, Archibald, N, Reid, J, Duncan, C, Richardson, A, Lilleker, J, Iorio, R, Blaabjerg, M, Abeler, K, and Shin, Y

Abstract

Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment. awx323media1 5681705685001

Published
2018

9. 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

10. Suspected antibody negative autoimmune limbic encephalitis: outcome of immunotherapy

Author

von Rhein, B., Wagner, J., Widman, G., Malter, M. P., Elger, C. E., Helmstaedter, C., von Rhein, B., Wagner, J., Widman, G., Malter, M. P., Elger, C. E., and Helmstaedter, C.

Abstract

Objectives - Whether and when to immunologically treat epilepsy patients with suggested autoantibody (AB)-negative limbic encephalitis (LE) is clinically challenging. Therefore, we evaluated the clinical outcome and eventual outcome predictors of immunotherapy in a group of AB-negative patients with recent-onset temporal lobe epilepsy (TLE), magnetic resonance imaging (MRI) indicators of LE, subjective cognitive decline, and/or psychiatric symptoms. Methods - This retrospective, observational, uncontrolled study monitored 28 TLE patients with suggested AB-negative LE along with methylprednisolone immunotherapy. Results - All patients had seizures, amygdala and/or - hippocampal enlargement, subjective cognitive decline and/or behavioral problems. Eighty-six percent (24/28) were impaired in executive or memory functions, 39% (10/25) depressed, 81% were on antiepileptic drugs when pulse therapy started. After a median follow-up of 18 months, 46% (13/28) of the patients were seizure free (>2 months), 48% (13/27) showed MRI improvements (amygdala and/or hippocampal volume reduction), cognition improved in 57% (16/28), worsened in 32% (9/28), mood improved in 14% (4/25), and deteriorated in 11% (3/25). Immunotherapy was discontinued in 75% (21/28). Clinical changes did not correlate to each other. Outcomes could not be predicted. Conclusion - Immunological treatment of suggested AB-negative LE showed reasonable seizure control, MRI and cognitive improvements. Treatment success was not predictable from clinical features, nor definitely attributable to immunological treatment. Lacking biomarkers for the reliable diagnosis of AB-negative LE, we suggest that in presence of mild manifestations, and after initiating antiepileptic drug therapy, negative dynamics in MRI, seizures, cognition, and behavior should be documented before immunosuppressive treatment is initiated.

Published
2017

11. Histopathological findings in brain tissue obtained during epilepsy surgery

Author

Zorglijn FNE Medisch, UMC Utrecht, ZL Kinder Ner en Nec Medisch, Brain, Pathologie, Blumcke, I., Spreafico, R., Haaker, G., Coras, Roland, Kobow, K., Bien, Christian G., Pfäfflin, M., Elger, C.E., Widman, G., Schramm, J., Becker, A., Braun, K. P., Leijten, F., Baayen, Johannes C, Aronica, E., Chassoux, F., Hamer, H.M., Stefan, H., Rössler, K., Thom, M., Walker, M. C., Sisodiya, Sanjay M., Duncan, J.S., McEvoy, A. W., Pieper, T., Holthausen, Hans, Kudernatsch, M., Meencke, H. J., Kahane, P., Schulze-Bonhage, A., Zentner, J., Heiland, D. H., Urbach, H., Steinhoff, Bernhard J, Bast, Thomas, Tassi, L., Russo, Maria Giovanna, Özkara, Cigdem, Oz, B., Krsek, Pavel, Vogelgesang, S., Runge, U., Lerche, H., Weber, Y.G., Honavar, M., Pimentel, J., Arzimanoglou, A., Ulate-Campos, A., Noachtar, S., Hartl, E., EEBB Consortium, Zorglijn FNE Medisch, UMC Utrecht, ZL Kinder Ner en Nec Medisch, Brain, Pathologie, Blumcke, I., Spreafico, R., Haaker, G., Coras, Roland, Kobow, K., Bien, Christian G., Pfäfflin, M., Elger, C.E., Widman, G., Schramm, J., Becker, A., Braun, K. P., Leijten, F., Baayen, Johannes C, Aronica, E., Chassoux, F., Hamer, H.M., Stefan, H., Rössler, K., Thom, M., Walker, M. C., Sisodiya, Sanjay M., Duncan, J.S., McEvoy, A. W., Pieper, T., Holthausen, Hans, Kudernatsch, M., Meencke, H. J., Kahane, P., Schulze-Bonhage, A., Zentner, J., Heiland, D. H., Urbach, H., Steinhoff, Bernhard J, Bast, Thomas, Tassi, L., Russo, Maria Giovanna, Özkara, Cigdem, Oz, B., Krsek, Pavel, Vogelgesang, S., Runge, U., Lerche, H., Weber, Y.G., Honavar, M., Pimentel, J., Arzimanoglou, A., Ulate-Campos, A., Noachtar, S., Hartl, E., and EEBB Consortium

Published
2017

17. Brain-Computer Interfaces for Communication in Paralysis: A Clinical Experimental Approach

Author

Hinterberger, T., Nijboer, F., Kübler, A., Matuz, T., Furdea, A., Mochty, U., Jordan, M., Lal, T., Hill, J., Meilinger, J., Bensch, M., Tangermann, M., Widman, G., Elger, C., Rosenstiel, W., Schölkopf, B., and Birbaumer, N.

Abstract

An overview of different approaches to brain-computer interfaces (BCIs) developed in our laboratory is given. An important clinical application of BCIs is to enable communication or environmental control in severely paralyzed patients. The BCI “Thought-Translation Device (TTD)” allows verbal communication through the voluntary self-regulation of brain signals (e.g., slow cortical potentials (SCPs)), which is achieved by operant feedback training. Humans' ability to self-regulate their SCPs is used to move a cursor toward a target that contains a selectable letter set. Two different approaches were followed to developWeb browsers that could be controlled with binary brain responses. Implementing more powerful classification methods including different signal parameters such as oscillatory features improved our BCI considerably. It was also tested on signals with implanted electrodes. Most BCIs provide the user with a visual feedback interface. Visually impaired patients require an auditory feedback mode. A procedure using auditory (sonified) feedback of multiple EEG parameters was evaluated. Properties of the auditory systems are reported and the results of two experiments with auditory feedback are presented. Clinical data of eight ALS patients demonstrated that all patients were able to acquire efficient brain control of one of the three available BCI systems (SCP, µ-rhythm, and P300), most of them used the SCP-BCI. A controlled comparison of the three systems in a group of ALS patients, however, showed that P300-BCI and the µ-BCI are faster and more easily acquired than SCP-BCI, at least in patients with some rudimentary motor control left. Six patients who started BCI training after entering the completely locked-in state did not achieve reliable communication skills with any BCI system. One completely locked-in patient was able to communicate shortly with a ph-meter, but lost control afterward.

Published
2007

18. Suspected antibody negative autoimmune limbic encephalitis: outcome of immunotherapy.

Author

Rhein, B., Wagner, J., Widman, G., Malter, M. P., Elger, C. E., and Helmstaedter, C.

Subjects
TREATMENT of encephalitis, IMMUNOGLOBULINS, AUTOIMMUNE diseases, IMMUNOTHERAPY, PEOPLE with epilepsy, TEMPORAL lobe epilepsy, THERAPEUTICS
Abstract

Objectives Whether and when to immunologically treat epilepsy patients with suggested autoantibody ( AB)-negative limbic encephalitis ( LE) is clinically challenging. Therefore, we evaluated the clinical outcome and eventual outcome predictors of immunotherapy in a group of AB-negative patients with recent-onset temporal lobe epilepsy ( TLE), magnetic resonance imaging ( MRI) indicators of LE, subjective cognitive decline, and/or psychiatric symptoms. Methods This retrospective, observational, uncontrolled study monitored 28 TLE patients with suggested AB-negative LE along with methylprednisolone immunotherapy. Results All patients had seizures, amygdala and/or -hippocampal enlargement, subjective cognitive decline and/or behavioral problems. Eighty-six percent (24/28) were impaired in executive or memory functions, 39% (10/25) depressed, 81% were on antiepileptic drugs when pulse therapy started. After a median follow-up of 18 months, 46% (13/28) of the patients were seizure free (>2 months), 48% (13/27) showed MRI improvements (amygdala and/or hippocampal volume reduction), cognition improved in 57% (16/28), worsened in 32% (9/28), mood improved in 14% (4/25), and deteriorated in 11% (3/25). Immunotherapy was discontinued in 75% (21/28). Clinical changes did not correlate to each other. Outcomes could not be predicted. Conclusion Immunological treatment of suggested AB-negative LE showed reasonable seizure control, MRI and cognitive improvements. Treatment success was not predictable from clinical features, nor definitely attributable to immunological treatment. Lacking biomarkers for the reliable diagnosis of AB-negative LE, we suggest that in presence of mild manifestations, and after initiating antiepileptic drug therapy, negative dynamics in MRI, seizures, cognition, and behavior should be documented before immunosuppressive treatment is initiated. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

19. Methods Towards Invasive Human Brain Computer Interfaces

Author

Lal, T., Hinterberger, T., Widman, G., Schröder , M., Hill, J., Rosenstiel, W., Elger, C., Schölkopf, B., and Birbaumer, N.

Abstract

During the last ten years there has been growing interest in the development of Brain Computer Interfaces (BCIs). The field has mainly been driven by the needs of completely paralyzed patients to communicate. With a few exceptions, most human BCIs are based on extracranial electroencephalography (EEG). However, reported bit rates are still low. One reason for this is the low signal-to-noise ratio of the EEG. We are currently investigating if BCIs based on electrocorticography (ECoG) are a viable alternative. In this paper we present the method and examples of intracranial EEG recordings of three epilepsy patients with electrode grids placed on the motor cortex. The patients were asked to repeatedly imagine movements of two kinds, e.g., tongue or finger movements. We analyze the classifiability of the data using Support Vector Machines (SVMs) and Recursive Channel Elimination (RCE).

Published
2005

22. Antiepileptic drugs interact with folate and vitamin B12 serum levels

Author

Linnebank, M, Moskau, S, Semmler, A, Widman, G, Stoffel-Wagner, B, Weller, M, Elger, C E, Linnebank, M, Moskau, S, Semmler, A, Widman, G, Stoffel-Wagner, B, Weller, M, and Elger, C E

Abstract

OBJECTIVE: Antiepileptic drugs (AEDs) are important for the treatment of epilepsy, psychiatric diseases, and pain syndromes. Small studies have suggested that AED treatment reduces serum levels of folate and vitamin B12. METHODS: This prospective monocenter study aimed at testing the hypothesis that AED treatment is associated with folate and vitamin B12 serum levels in a large population. A total of 2730 AED-treated and 170 untreated patients with epilepsy and 200 healthy individuals were enrolled. RESULTS: Treatment with carbamazepine, gabapentin, oxcarbazepine, phenytoin, primidone, or valproate was associated with lower mean serum folate levels or with a higher frequency of folate levels below the reference range in comparison with the entire group of patients, untreated patients, or controls. Treatment with phenobarbital, pregabalin, primidone, or topiramate was associated with lower vitamin B12 levels compared with the entire group of patients. Vitamin B12 serum levels were higher in patients treated with valproate compared with the entire group of patients, untreated patients, and healthy controls. Folate or vitamin B12 levels below the reference range were associated with higher mean corpuscular volume (MCV) and higher homocysteine plasma levels. Vitamin substitution for 3 months in 141 patients with folate or vitamin B12 levels below the reference range yielded normal vitamin levels in 95% of the supplemented patients and reduced MCV and homocysteine plasma levels. INTERPRETATION: Treatment with most of the commonly used AEDs is associated with reduced folate or vitamin B12 serum levels and is a risk factor for hyperhomocysteinemia. Oral substitution is effective to restore vitamin, MCV, and homocysteine levels. Ann Neurol 2011

Published
2011

25. Classifying EEG and ECoG signals without subject training for fast BCI implementation: comparison of nonparalyzed and completely paralyzed subjects

Author

Hill, N.J., primary, Lal, T.N., additional, Schroder, M., additional, Hinterberger, T., additional, Wilhelm, B., additional, Nijboer, F., additional, Mochty, U., additional, Widman, G., additional, Elger, C., additional, Scholkopf, B., additional, Kubler, A., additional, and Birbaumer, N., additional

Published
2006
Full Text
View/download PDF

40. Is it possible to anticipate seizure onset by non-linear analysis of intracerebral EEG in human partial epilepsies?

Author

Lehnertz, K., Widman, G., Ralph Gregor Andrzejak, Arnhold, J., and Elger, Ce

Subjects
Predictive Value of Tests, Seizures, Animals, Humans, Electroencephalography, Epilepsies, Partial
Abstract

Detection of electrophysiological features preceding and indicative of imminent seizures in patients with epilepsy would be a major breakthrough with immense scientific and clinical implications. The definition of a "pre-ictal state" several minutes prior to seizure onset would open a new time window for studying mechanisms of seizure generation as well as for possible therapeutic interventions. In this review we present recent findings from nonlinear time series analysis of intracranially recorded EEG that may allow to forecast seizure onset in patients with partial epilepsy.

43. SPINAL ANAESTHESIA WITH GLUCOSE-FREE 0.5% BUPIVACAINE: EFFECTS OF DIFFERENT VOLUMES

Author

AXELSSON, K. H., EDSTRÖM, H. H., and WIDMAN, G. B.

Abstract

The effects of different volumes (1.5, 2, 3, and 4ml) of glucose-free 0.5% bupivacaine used for spinal anaesthesia were compared in 40 patients scheduled for urological surgery. The blocks were performed with the patients in the sitting position. The time to maximum cephalad spread of analgesia varied between 13 and 18.5 min. A significant difference was found in cephalad spread between the 1.5-and 2-ml groups and the 3-and 4-ml groups. The duration of analgesia increased, the time to complete motor blockade of the lower limbs decreased and the frequency of complete motor blockade increased with increasing volume. Spinal anaesthesia with 3–4ml of glucose-free 0.5% bupivacaine proved satisfactory for transurethral resection of the prostate.

Published
1984
Full Text
View/download PDF

44. A DOUBLE-BLIND STUDY OF MOTOR BLOCKADE IN THE LOWER LIMBS: Studies During Spinal Anaesthesia with Hyperbaric and Glucose-free 0.5% Bupivacaine

Author

AXELSSON, K. H., WIDMAN, G. B., SUNDBERG, A. E. A., and HALLGREN, S.

Abstract

Sensory and motor blockade were studied double-blind during spinal anaesthesia in 20 urology patients who received 0.5% bupivacaine solution 4 ml with or without glucose. Using a new method for determining muscle strength, motor blockade during anaesthesia was recorded quantitatively for flexion of the hip, extension of the knee and plantar flexion of the big toe. Movements of the lower part of the thoracic cage were recorded at the same time. Complete motor blockade of longer duration was observed for all three movements following the administration of the glucose-free solution compared with the solution containing glucose. During the regression phase, the muscle strength returned significantly later (knee extension and hip flexion) when glucose-free bupivacaine solution was given. There was no significant difference between the two anaesthetic solutions regarding plantar flexion of the big toe during this phase. For hip flexion (L1-L3) there was no noteworthy difference between the levels of analgesia and the motor blockade, whereas for plantar flexion of the big toe (L5-S2) the level of analgesia was 2–3 segments higher than the level of motor blockade. Thoracic movements (maximal inspiration to normal expiration) did not appear to be notably influenced by the level of analgesia. Complete regression of motor blockade was not observed for any of the movements at grade O of a modified Bromage scale. Not until 1.5–2 h after the attainment of this grade was the muscle strength of all movements restored (90% of control value).

Published
1985
Full Text
View/download PDF

46. Cenobamate: real-world data from a retrospective multicenter study.

Author

Lauxmann S, Heuer D, Heckelmann J, Fischer FP, Schreiber M, Schriewer E, Widman G, Weber Y, Lerche H, Alber M, Schuh-Hofer S, and Wolking S

Subjects
Humans, Male, Female, Retrospective Studies, Adult, Middle Aged, Young Adult, Nitriles, Adolescent, Aged, Germany, Tetrazoles, Anticonvulsants adverse effects, Drug Resistant Epilepsy drug therapy, Carbamates adverse effects, Carbamates therapeutic use, Chlorophenols adverse effects
Abstract

Background: Clinical trials have shown that cenobamate (CNB) is an efficacious and safe anti-seizure medication (ASM) for drug-resistant focal epilepsy. Here, we analyzed one of the largest real-world cohorts, covering the entire spectrum of epilepsy syndromes, the efficacy and safety of CNB, and resulting changes in concomitant ASMs., Methods: We conducted a retrospective observational study investigating CNB usage in two German tertiary referral centers between October 2020 and June 2023 with follow-up data up to 27 months of treatment. Our primary outcome was treatment response. Secondary outcomes comprised drug response after 12 and 18 months, seizure freedom rates, CNB dosage and retention, adverse drug reactions (ADRs), and changes in concomitant ASMs., Results: 116 patients received CNB for at least two weeks. At 6 months, 98 patients were eligible for evaluation. Thereof 50% (49/98) were responders with no relevant change at 12 and 18 months. Seizure freedom was achieved in 18.4% (18/98) at 6 months, 16.7% (11/66), and 3.0% (1/33) at 12 and 18 months. The number of previous ASMs did not affect the seizure response rate. Overall, CNB was well-tolerated, however, in 7.7% (9/116), ADRs led to treatment discontinuation. The most frequent changes of concomitant ASMs included the discontinuation or reduction of sodium channel inhibitors, clobazam reduction, and perampanel discontinuation, while brivaracetam doses were usually left unchanged., Conclusions: CNB proved to be a highly effective and generally well-tolerated ASM in patients with severe drug-resistant epilepsy, comprising a broad array of epilepsy syndromes beyond focal epilepsy., (© 2024. The Author(s).)

Published
2024
Full Text
View/download PDF

47. A genome-wide association study in autoimmune neurological syndromes with anti-GAD65 autoantibodies.

Author

Strippel C, Herrera-Rivero M, Wendorff M, Tietz AK, Degenhardt F, Witten A, Schroeter C, Nelke C, Golombeck KS, Madlener M, Rüber T, Ernst L, Racz A, Baumgartner T, Widman G, Doppler K, Thaler F, Siebenbrodt K, Dik A, Kerin C, Räuber S, Gallus M, Kovac S, Grauer OM, Grimm A, Prüss H, Wickel J, Geis C, Lewerenz J, Goebels N, Ringelstein M, Menge T, Tackenberg B, Kellinghaus C, Bien CG, Kraft A, Zettl U, Ismail FS, Ayzenberg I, Urbanek C, Sühs KW, Tauber SC, Mues S, Körtvélyessy P, Markewitz R, Paliantonis A, Elger CE, Surges R, Sommer C, Kümpfel T, Gross CC, Lerche H, Wellmer J, Quesada CM, Then Bergh F, Wandinger KP, Becker AJ, Kunz WS, Meyer Zu Hörste G, Malter MP, Rosenow F, Wiendl H, Kuhlenbäumer G, Leypoldt F, Lieb W, Franke A, Meuth SG, Stoll M, and Melzer N

Subjects
Humans, Proteome genetics, Histocompatibility Antigens Class II, HLA Antigens, Haplotypes, Alleles, Autoantibodies, HLA-DRB1 Chains genetics, Genome-Wide Association Study, Genetic Predisposition to Disease genetics
Abstract

Autoimmune neurological syndromes (AINS) with autoantibodies against the 65 kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis, including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes mellitus, which has a strong genetic susceptibility conferred by human leukocyte antigen (HLA) and non-HLA genomic regions. We investigated the genetic predisposition in patients with anti-GAD65 AINS. We performed a genome-wide association study (GWAS) and an association analysis of the HLA region in a large German cohort of 1214 individuals. These included 167 patients with anti-GAD65 AINS, recruited by the German Network for Research on Autoimmune Encephalitis (GENERATE), and 1047 individuals without neurological or endocrine disease as population-based controls. Predictions of protein expression changes based on GWAS findings were further explored and validated in the CSF proteome of a virtually independent cohort of 10 patients with GAD65-AINS and 10 controls. Our GWAS identified 16 genome-wide significant (P < 5 × 10-8) loci for the susceptibility to anti-GAD65 AINS. The top variant, rs2535288 [P = 4.42 × 10-16, odds ratio (OR) = 0.26, 95% confidence interval (CI) = 0.187-0.358], localized to an intergenic segment in the middle of the HLA class I region. The great majority of variants in these loci (>90%) mapped to non-coding regions of the genome. Over 40% of the variants have known regulatory functions on the expression of 48 genes in disease relevant cells and tissues, mainly CD4+ T cells and the cerebral cortex. The annotation of epigenomic marks suggested specificity for neural and immune cells. A network analysis of the implicated protein-coding genes highlighted the role of protein kinase C beta (PRKCB) and identified an enrichment of numerous biological pathways participating in immunity and neural function. Analysis of the classical HLA alleles and haplotypes showed no genome-wide significant associations. The strongest associations were found for the DQA1*03:01-DQB1*03:02-DRB1*04:01HLA haplotype (P = 4.39 × 10-4, OR = 2.5, 95%CI = 1.499-4.157) and DRB1*04:01 allele (P = 8.3 × 10-5, OR = 2.4, 95%CI = 1.548-3.682) identified in our cohort. As predicted, the CSF proteome showed differential levels of five proteins (HLA-A/B, C4A, ATG4D and NEO1) of expression quantitative trait loci genes from our GWAS in the CSF proteome of anti-GAD65 AINS. These findings suggest a strong genetic predisposition with direct functional implications for immunity and neural function in anti-GAD65 AINS, mainly conferred by genomic regions outside the classical HLA alleles., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2023
Full Text
View/download PDF

48. Evaluation of a Rapid Topiramate Titration Scheme for the Early Detection of Cognitive Side Effects.

Author

Witt JA, Widman G, Hansen N, von Wrede R, Elger CE, and Helmstaedter C

Subjects
Humans, Topiramate adverse effects, Retrospective Studies, Bayes Theorem, Fructose adverse effects, Cognition, Anticonvulsants adverse effects, Epilepsy drug therapy
Abstract

Background: Topiramate (TPM) is effective for treating epilepsy, but executive dysfunction is a common side effect that could significantly affect everyday life. Additionally, previous studies have suggested that patients might be unaware of these changes., Objective: To evaluate a rapid TPM titration scheme for the early detection of adverse cognitive side effects., Methods: In this retrospective study, we assessed changes in objective cognitive performance (EpiTrack ® ) after rapidly titrating TPM (50 mg per day during an inpatient stay) in 49 epilepsy patients and compared those results with an outpatient control group that underwent the recommended standard titration (n = 23 with 25-50 mg per week)., Results: Using Bayesian statistics, analyses revealed decisive evidence of a negative effect on cognitive performance when TPM was introduced (BF 31480000000) independent of the titration speed (BF 0.739). When using a fast titration rate, deficits in executive function increased from a baseline of 53.1 to 73.5% at follow-up, and 55.1% experienced a statistically significant intraindividual decline. When using the standard titration scheme, impairments increased from 52.2 to 65.2%, with an intraindividual deterioration found in 52.2% of the patients., Conclusion: Physicians might be able to detect adverse cognitive side effects sooner in epilepsy patients if TPM is administered using a faster titration rate while applying repeated cognitive assessments within days. This approach might help prevent any unnoticed intolerance and eventual negative consequences for the patient. Therefore, we recommend monitoring early on for adverse changes instead of withholding a potentially effective treatment option because of anticipated side effects., (© 2022. The Author(s).)

Published
2022
Full Text
View/download PDF

49. Increased T- and B-cells associated with the phenotype of autoimmune limbic encephalitis with mainly memory dysfunction.

Author

Hansen N, Widman G, Önder D, Schwing K, Leelaarporn P, Prusseit I, von Wrede R, Surges R, Becker AJ, Witt JA, Elger CE, and Helmstaedter C

Abstract

Background: Our goal is to investigate the autoantibodies' presence and immune cells in the bioprobes of autoimmune encephalitis (AE) patients with distinct phenotypes as a promising target in AE., Methods: We retrospectively analyzed immune cells via flow cytometry, serum and cerebrospinal fluid (CSF) autoantibodies, electroencephalography, magnetic resonance imaging in 94 AE patients with suspected temporal lobe epilepsy and classified neuropsychological phenotypes according to their occurrence., Results: We detected different phenotypes in 94 AE patients [10.6% with isolated memory dysfunction (MEM), 11.7% with mood-dysfunction, 12.7% with mood and memory dysfunction, 13.8% with memory and attention dysfunction, 18.1% with memory, mood and attention disturbances and 20.2% with no mood, memory or attention dysfunction]. We did discern a relevant association of phenotypes and CSF antibody-positivity on CSF CD4 + T-cells, CD8+T-cells and HLADR + CD8+T-cells in our patients with MEM presenting elevated CD8+T-cells and HLADR + CD8+T-cells. Furthermore, CSF CD19+B-cells differed significantly between phenotypes in patients with MEM., Discussion: Taken together, the phenotypes in combination with CSF antibody-positivity are biomarkers for stratifying patients. Furthermore, our results confirm the role of CD4 + T-cells, CD8+T-cells and CD19+B-cells in AE patients with a memory dysfunction, providing insights into AE pathogenesis. Our preliminary results should be confirmed by larger-scale investigations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Published
2022
Full Text
View/download PDF

50. Impact of T cells on neurodegeneration in anti-GAD65 limbic encephalitis.

Author

Dik A, Widman G, Schulte-Mecklenbeck A, Witt JA, Pitsch J, Golombeck KS, Wagner J, Gallus M, Strippel C, Hansen N, Mönig C, Räuber S, Wiendl H, Elger CE, Surges R, Meuth SG, Helmstaedter C, Gross CC, Becker AJ, and Melzer N

Subjects
Adult, Autoimmune Diseases blood, Autoimmune Diseases cerebrospinal fluid, Cross-Sectional Studies, Female, Humans, Limbic Encephalitis blood, Limbic Encephalitis cerebrospinal fluid, Magnetic Resonance Imaging, Male, Middle Aged, Young Adult, Autoimmune Diseases immunology, Autoimmune Diseases pathology, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Glutamate Decarboxylase immunology, Limbic Encephalitis immunology, Limbic Encephalitis pathology
Abstract

Objective: Direct pathogenic effects of autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GAD65) in autoimmune limbic encephalitis (LE) have been questioned due to its intracellular localization. We therefore hypothesized a pathogenic role for T cells., Methods: We assessed magnet resonance imaging, neuropsychological and peripheral blood, and CSF flow cytometry data of 10 patients with long-standing GAD65-LE compared to controls in a cross-sectional manner. These data were related to each other within the GAD65-LE group and linked to neuropathological findings in selective hippocampectomy specimen from another two patients. In addition, full-resolution human leukocyte antigen (HLA) genotyping of all patients was performed., Results: Compared to controls, no alteration in hippocampal volume but impaired memory function and elevated fractions of activated HLADR + CD4 + and CD8 + T cells in peripheral blood and cerebrospinal fluid were found. Intrathecal fractions of CD8 + T cells negatively correlated with hippocampal volume and memory function, whereas the opposite was true for CD4 + T cells. Consistently, antigen-experienced CD8 + T cells expressed increased levels of the cytotoxic effector molecule perforin in peripheral blood, and perforin-expressing CD8 + T cells were found attached mainly to small interneurons but also to large principal neurons together with wide-spread hippocampal neurodegeneration. 6/10 LE patients harbored the HLA-A*02:01 allele known to present the immunodominant GAD65 114-123 peptide in humans., Interpretation: Our data suggest a pathogenic effect of CD8 + T cells and a regulatory effect of CD4 + T cells in patients with long-standing GAD65-LE., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results