141 results on '"Woermann FG"'
Search Results
2. Posterior disconnection in epilepsy surgery – correlations with seizure outcome in26 patients
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Kalbhenn, T, Woermann, FG, Coras, R, Blümcke, I, Polster, T, Simon, M, and Bien, CG
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Objective: Multilobar resective epilepsy surgery especially in young children poses significant challenges and is often not successful. In 2004 Daniel et al. described operative disconnection of the posterior quadrant of the brain (i.e. the temporal, parietal and occipital lobes) as a surgical option[for full text, please go to the a.m. URL], 69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie
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- 2018
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3. Hippocampal but not amygdalar volume affects contextual fear conditioning in humans
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Pohlack ST, Nees F, Liebscher C, Cacciaglia R, Diener SJ, Ridder S, Woermann FG, and Flor H
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Both animal and human studies have identified a critical role of the hippocampus in contextual fear conditioning. In humans mainly functional magnetic resonance imaging has been used. To extend these findings to volumetric properties, 58 healthy participants underwent structural magnetic resonance imaging and participated in a differential fear conditioning paradigm with contextual stimuli. Ratings of emotional valence, arousal, and contingency as well as skin conductance responses (SCRs) were used as indicators of conditioning. Twenty-nine participants with the smallest hippocampal volumes were compared with 29 persons with the largest hippocampal volumes. Persons with larger hippocampal volume (especially on the right side) learned to discriminate between two conditioned contexts, whereas those with small hippocampal volumes did not, as indicated by SCRs. Further analyses showed that these results could not be explained by amygdalar volumes. In contrast, the participant answers on the self-report measures were not significantly influenced by hippocampal or amygdalar, but by total brain volume, suggesting a role of cortical structures in these more cognitive evaluation processes. Reanalysis of the self-report data using partial hippocampal volumes revealed a significant influence of the posterior but not anterior subvolumes, which is in accordance with theories and empirical findings on hippocampal functioning. This study shows the relevance of hippocampal volume for contextual fear conditioning in healthy volunteers and may have important implications for anxiety disorders.
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- 2012
4. Multiple pterygium syndrome, bilateral periventricular nodular heterotopia and epileptic seizures--a syndrome?
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Boenigk He, Holtmann M, and Woermann Fg
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Male ,Pathology ,medicine.medical_specialty ,X Chromosome ,Eye disease ,Choristoma ,Pterygium ,Cerebral Ventricles ,Central nervous system disease ,Diagnosis, Differential ,Epilepsy ,Intellectual Disability ,medicine ,Elbow ,Humans ,Abnormalities, Multiple ,Knee ,Sex Chromosome Aberrations ,Arthrogryposis ,Cerebral Cortex ,Neurons ,Brain Diseases ,business.industry ,Bilateral Periventricular Nodular Heterotopia ,Infant ,General Medicine ,Syndrome ,medicine.disease ,Magnetic Resonance Imaging ,eye diseases ,Developmental disorder ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,sense organs ,Neurology (clinical) ,Multiple pterygium syndrome ,Epilepsies, Partial ,medicine.symptom ,business ,Follow-Up Studies - Abstract
We present the clinical, neurophysiological and radiographic findings in a boy with coexisting multiple pterygium syndrome, bilateral periventricular nodular heterotopia (BPNH), mental retardation and epileptic seizures. This constellation has not been previously reported. We discuss the possibility of a new BPNH syndrome associated with multiple pterygium syndrome in our patient.
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- 2001
5. Analysis of reoperation in mesial temporal lobe epilepsy with hippocampal sclerosis
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Schulz, R, Hoppe, M, Pannek, HW, Woermann, FG, May, T, Ebner, A, Schulz, R, Hoppe, M, Pannek, HW, Woermann, FG, May, T, and Ebner, A
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- 2010
6. Reproducible localisation of interictal activation in epilepsy patients using spike-triggered f-MRI
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Krakow, K, primary, Symms, MR, additional, Woermann, FG, additional, Allen, PJ, additional, Polizzi, G, additional, and Fish, DR, additional
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- 1998
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7. Functional MRI correlates of the recall of unresolved life events in borderline personality disorder.
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Beblo T, Driessen M, Mertens M, Wingenfeld K, Piefke M, Rullkoetter N, Silva-Saavedra A, Mensebach C, Reddemann L, Rau H, Markowitsch HJ, Wulff H, Lange W, Berea C, Ollech I, and Woermann FG
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Background. Patients with borderline personality disorder (BPD) frequently report unresolved life events but it is still poorly understood, how these experiences are represented in the brain. Using functional magnetic resonance imaging (fMRI), the present study aimed at investigating the neural correlates of the recall of unresolved life events in patients with BPD and healthy controls.Method. Twenty female BPD patients and 21 healthy control subjects underwent fMRI. During measurement subjects recalled unresolved and resolved negative life events. Individual cue words were used to stimulate autobiographical memory. After scanning, subjects rated their emotional states during the recall of both types of memories.Results. When contrasting unresolved and resolved life events, patients showed significant bilateral activation of frontotemporal areas including the insula, amygdala, and the anterior cingulate cortex, the left posterior cingulate cortex, right occipital cortex, the bilateral cerebellum and the midbrain. In healthy subjects, no differential brain activation was related to these conditions. The 2x2 factorial analysis (DeltaBPD-Deltacontrols) revealed similar results with bilateral activation of the frontal cortex including parts of the insula and of the orbitofrontal cortex, temporal activation including the amygdala, activation of the right occipital cortex, and parts of the cerebellum. Patients but not controls reported higher levels of anxiety and helplessness during the unresolved versus resolved memory condition.Conclusions. The activation of both, the amygdala and prefrontal areas, might reflect an increased effortful but insufficient attempt to control intensive emotions during the recall of unresolved life events in patients with BPD. [ABSTRACT FROM AUTHOR]
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- 2006
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8. Amygdala fMRI lateralizes temporal lobe epilepsy.
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Schacher M, Haemmerle B, Woermann FG, Okujava M, Huber D, Grunwald T, Krämer G, and Jokeit H
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- 2006
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9. Transient lesion in the splenium of the corpus callosum and antiepileptic drug withdrawal.
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Gürtler S, Ebner A, Tuxhorn I, Ollech I, Pohlmann-Eden B, and Woermann FG
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- 2005
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10. Epileptic activity influences the speech organization in medial temporal lobe epilepsy.
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Janszky J, Jokeit H, Heinemann D, Schulz R, Woermann FG, and Ebner A
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- 2003
11. Quantitative MRI in patients with idiopathic generalized epilepsy: evidence of widespread cerebral structural changes.
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Woermann FG, Sisodiya SM, Free SL, and Duncan JS
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- 1998
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12. Language lateralization by Wada test and fMRI in 100 patients with epilepsy.
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Woermann FG, Jokeit H, Luerding R, Freitag H, Schulz R, Guertler S, Okujava M, Wolf P, Tuxhorn I, Ebner A, Woermann, F G, Jokeit, H, Luerding, R, Freitag, H, Schulz, R, Guertler, S, Okujava, M, Wolf, P, Tuxhorn, I, and Ebner, A
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- 2003
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13. Right hippocampal sclerosis is more common than left after febrile seizures.
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Janszky J, Woermann FG, Barsi P, Schulz R, Halász P, Ebner A, Janszky, J, Woermann, F G, Barsi, P, Schulz, R, Halász, P, and Ebner, A
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- 2003
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14. LGI1 encephalitis: potentially complement-activating anti-LGI1-IgG subclasses 1/2/3 are associated with the development of hippocampal sclerosis.
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Bien CG, Rada A, Mertens M, Bien CI, Bauer J, Hagemann A, and Woermann FG
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- Humans, Female, Male, Middle Aged, Aged, Retrospective Studies, Adult, Encephalitis immunology, Magnetic Resonance Imaging, Hippocampal Sclerosis, Hippocampus pathology, Sclerosis etiology, Autoantibodies blood, Autoantibodies cerebrospinal fluid, Intracellular Signaling Peptides and Proteins immunology, Immunoglobulin G blood
- Abstract
Two-thirds of published patients with anti-leucine rich, glioma inactivated 1 (LGI1) encephalitis develop hippocampal sclerosis (HS). It is likely that this contributes to residual cognitive long-term deficits and the risk of epilepsy. Almost all patients harbor anti-LGI1-immunoglobulin G-(IgG-) subclass 4, which is considered a "benign", non-destructive subclass. In contrast, neuropathological case studies have suggested that the classical complement cascade may contribute to mediotemporal cell death in patients with LGI1 antibodies. IgG subclasses 1, 2, or 3 are required to initiate this cascade. We hypothesized that patients with these anti-LGI1-IgG1/2/3 in addition to IgG4 have a higher risk of developing HS than patients with anti-LGI1-IgG4 alone. We retrospectively assessed all anti-LGI1 encephalitis patients from this center with anti-LGI1-IgG-subclass information and follow-up MRI available. Nine out of 20 patients had developed HS (45%). Volumetric FreeSurfer analysis confirmed the visual HS diagnoses. HS and a lower hippocampal volume were associated with anti-LGI1-IgG1/2/3. All six patients with this IgG subclass status developed HS. There was no association with older or younger age at onset, female sex, longer latency from disease onset to start of immunotherapy, less intense immunotherapy, higher serum titers of LGI1 antibodies, LGI1 antibodies in CSF or higher LGI1-specific antibody indices. There was no association between anti-LGI1-IgG1/2/3 status and neuropsychological performance, epilepsy, or general neurological performance. This confirms our hypothesis that anti-LGI1-IgG1/2/3 in serum puts patients at risk of developing HS. If these findings can be confirmed and clinically corroborated, patients with anti-LGI1-IgG1/2/3 might become candidates for anti-complement-directed immunological treatments., (© 2024. The Author(s).)
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- 2024
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15. A complex case with generalized epilepsy, probable focal seizures, and functional seizures.
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Elshetihy A, Nergiz L, Cloppenborg T, Woermann FG, Müffelmann B, and Bien CG
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In this patient, now 42 years old, genetic generalized epilepsy (juvenile myoclonic epilepsy) manifested itself at the age of 13. At the age of 39, she experienced a status episode with prolonged ICU treatment. She was left with a left-sided hippocampal sclerosis and probably focal seizures. In addition, since the age of 24, the patient also experiences functional seizures on the background of a borderline personality disorder. While generalized epileptic seizures could be controlled with antiseizure medication (ASM), the patient was multiple times admitted to Emergency Departments for her functional seizures with subsequent intensive care treatments, including intubation. As a complication, the patient developed critical illness polyneuropathy and myopathy, resulting in wheelchair dependence. Additionally, she acquired a complex regional pain syndrome after extravasation of ASM. The report demonstrates the uncommon development of hippocampal sclerosis after a generalized tonic-clonic status epilepticus and the poor treatability of functional seizures as compared to generalized and focal seizures., 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., (© 2024 The Author(s).)
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- 2024
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16. MRI evidence for material-specific encoding deficits and mesial-temporal alterations in presurgical frontal lobe epilepsy patients.
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Doll A, Wegrzyn M, Woermann FG, Labudda K, Bien CG, and Kissler J
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- Humans, Memory physiology, Seizures, Temporal Lobe diagnostic imaging, Temporal Lobe surgery, Temporal Lobe physiology, Memory Disorders diagnostic imaging, Memory Disorders complications, Magnetic Resonance Imaging methods, Epilepsy, Frontal Lobe diagnostic imaging, Epilepsy, Frontal Lobe surgery, Epilepsy, Frontal Lobe complications
- Abstract
Objective: Neuroimaging studies reveal frontal lobe (FL) contributions to memory encoding. Accordingly, memory impairments are documented in frontal lobe epilepsy (FLE). Still, little is known about the structural or functional correlates of such impairments. Particularly, material specificity of functional changes in cerebral activity during memory encoding in FLE is unclear., Methods: We compared 24 FLE patients (15 right-sided) undergoing presurgical evaluation with 30 healthy controls on a memory fMRI-paradigm of learning scenes, faces, and words followed by an out-of-scanner recognition task as well as regarding their mesial temporal lobe (mTL) volumes. We also addressed effects of FLE lateralization and performance level (normal vs. low)., Results: FLE patients had poorer memory performance and larger left hippocampal volumes than controls. Volume increase seemed, however, irrelevant or even dysfunctional for memory performance. Further, functional changes in FLE patients were right-sided for scenes and faces and bilateral for words. In detail, during face encoding, FLE patients had, regardless of their performance level, decreased mTL activation, while during scene and word encoding only low performing FLE patients had decreased mTL along with decreased FL activation. Intact verbal memory performance was associated with higher right frontal activation in FLE patients but not in controls., Significance: Pharmacoresistant FLE has a distinct functional and structural impact on the mTL. Effects vary with the encoded material and patients' performance levels. Thus, in addition to the direct effect of the FL, memory impairment in FLE is presumably to a large part due to functional mTL changes triggered by disrupted FL networks., Plain Language Summary: Frontal lobe epilepsy (FLE) patients may suffer from memory impairment. Therefore, we asked patients to perform a memory task while their brain was scanned by MRI in order to investigate possible changes in brain activation during learning. FLE patients showed changes in brain activation during learning and also structural changes in the mesial temporal lobe, which is a brain region especially relevant for learning but not the origin of the seizures in FLE. We conclude that FLE leads to widespread changes that contribute to FLE patients' memory impairment., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
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- 2024
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17. Hemispherotomy in children: A retrospective analysis of 152 surgeries at a single center and predictors for long-term seizure outcome.
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Kalbhenn T, Cloppenborg T, Woermann FG, Hagemann A, Polster T, Coras R, Blümcke I, Bien CG, and Simon M
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- Humans, Child, Child, Preschool, Adolescent, Retrospective Studies, Treatment Outcome, Seizures diagnostic imaging, Seizures surgery, Magnetic Resonance Imaging, Electroencephalography, Hemispherectomy methods, Epilepsy diagnostic imaging, Epilepsy surgery, Epilepsy pathology
- Abstract
Objective: Completeness as a predictor of seizure freedom is broadly accepted in epilepsy surgery. We focused on the requirements for a complete hemispherotomy and hypothesized that the disconnection of the insula contributes to a favorable postoperative seizure outcome. We analyzed surgical and nonsurgical predictors influencing long-term seizure outcome before and after a modification of our hemispherotomy technique., Methods: We retrospectively studied surgical procedures, electroclinical parameters, magnetic resonance imaging (MRI) results, and follow-up data in all children who had undergone hemispherotomy between 2001 and 2018 at our institution. We used logistic regression models to analyze the influence of different factors on seizure outcome., Results: A total of 152 patients were eligible for seizure outcome analysis only. Of these, 140 cases had complete follow-up data for ≥24 months and provide the basis for the following results. The median age at surgery was 4.3 years (range = .3-17.9 years). Complete disconnection (including the insular tissue) was achieved in 63.6% (89/140). At 2-year follow-up, seizure freedom (Engel class IA) was observed in 34.8% (8/23) with incomplete insular disconnection, whereas this was achieved in 88.8% (79/89) with complete surgical disconnection (p < .001, odds ratio [OR] = 10.41). In the latter group (n = 89), a potentially epileptogenic contralateral MRI lesion was the strongest predictor for postoperative seizure recurrence (OR = 22.20)., Significance: Complete surgical disconnection is the most important predictor of seizure freedom following hemispherotomy and requires disconnection of the insular tissue at the basal ganglia level. Even if the hemispherotomy is performed surgically completely, a potentially epileptogenic contralateral lesion on preoperative MRI significantly reduces the chances of postoperative seizure freedom., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
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- 2023
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18. Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the SLC35A2 Gene.
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Barba C, Blumcke I, Winawer MR, Hartlieb T, Kang HC, Grisotto L, Chipaux M, Bien CG, Heřmanovská B, Porter BE, Lidov HGW, Cetica V, Woermann FG, Lopez-Rivera JA, Canoll PD, Mader I, D'Incerti L, Baldassari S, Yang E, Gaballa A, Vogel H, Straka B, Macconi L, Polster T, Grant GA, Krsková L, Shin HJ, Ko A, Crino PB, Krsek P, Lee JH, Lal D, Baulac S, Poduri A, and Guerrini R
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- Humans, Brain diagnostic imaging, Brain surgery, Brain pathology, Seizures pathology, Retrospective Studies, Treatment Outcome, Electroencephalography, Drug Resistant Epilepsy genetics, Drug Resistant Epilepsy surgery, Drug Resistant Epilepsy pathology, Epilepsy genetics, Epilepsy surgery, Epilepsy diagnosis
- Abstract
Background and Objectives: The SLC35A2 gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic SLC35A2 gene variants., Methods: This is a retrospective multicenter study where we performed a descriptive analysis and classical hypothesis testing. We included the variables of interest significantly associated with the outcomes in the generalized linear models., Results: Two main phenotypes were associated with brain somatic SLC35A2 variants: (1) early epileptic encephalopathy (EE, 39 patients) with epileptic spasms as the predominant seizure type and moderate to severe intellectual disability and (2) drug-resistant focal epilepsy (DR-FE, 8 patients) associated with normal/borderline cognitive function and specific neuropsychological deficits. Brain MRI was abnormal in all patients with EE and in 50% of those with DR-FE. Histopathology review identified mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy in 44/47 patients and was inconclusive in 3. The 47 patients harbored 42 distinct mosaic SLC35A2 variants, including 14 (33.3%) missense, 13 (30.9%) frameshift, 10 (23.8%) nonsense, 4 (9.5%) in-frame deletions/duplications, and 1 (2.4%) splicing variant. Variant allele frequencies (VAFs) ranged from 1.4% to 52.6% (mean VAF: 17.3 ± 13.5). At last follow-up (35.5 ± 21.5 months), 30 patients (63.8%) were in Engel Class I, of which 26 (55.3%) were in Class IA. Cognitive performances remained unchanged in most patients after surgery. Regression analyses showed that the probability of achieving both Engel Class IA and Class I outcomes, adjusted by age at seizure onset, was lower when the duration of epilepsy increased and higher when postoperative EEG was normal or improved. Lower brain VAF was associated with improved postoperative cognitive outcome in the analysis of associations, but this finding was not confirmed in regression analyses., Discussion: Brain somatic SLC35A2 gene variants are associated with 2 main clinical phenotypes, EE and DR-FE, and a histopathologic diagnosis of MOGHE. Additional studies will be needed to delineate any possible correlation between specific genetic variants, mutational load in the epileptogenic tissue, and surgical outcomes., (© 2022 American Academy of Neurology.)
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- 2023
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19. Neural correlates of emotion acceptance and suppression in borderline personality disorder.
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Fernando SC, Beblo T, Lamers A, Schlosser N, Woermann FG, Driessen M, and Toepper M
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Background: Emotion dysregulation is a central feature of borderline personality disorder (BPD). Since impaired emotion regulation contributes to disturbed emotion functioning in BPD, it is crucial to study underlying neural activity. The current study aimed at investigating the neural correlates of two emotion regulation strategies, namely emotion acceptance and suppression, which are both important treatment targets in BPD., Methods: Twenty-one women with BPD and 23 female healthy control participants performed an emotion regulation task during functional magnetic resonance imaging (fMRI). While watching fearful movie clips, participants were instructed to either accept or to suppress upcoming emotions compared to passive viewing., Results: Results revealed acceptance-related insular underactivation and suppression-related caudate overactivation in subjects with BPD during the emotion regulation task., Conclusion: This is a first study on the neural correlates of emotion acceptance and suppression in BPD. Altered insula functioning during emotion acceptance may reflect impairments in emotional awareness in BPD. Increased caudate activity is linked to habitual motor and cognitive processes and therefore may accord to the well-established routine in BPD patients to suppress emotional experiences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fernando, Beblo, Lamers, Schlosser, Woermann, Driessen and Toepper.)
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- 2023
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20. Transient Global Amnesia (TGA): Sex-Specific Differences in Blood Pressure and Cerebral Microangiopathy in Patients with TGA.
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Rogalewski A, Beyer A, Friedrich A, Zuhorn F, Klingebiel R, Woermann FG, Oertelt-Prigione S, and Schäbitz WR
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Transient global amnesia (TGA) is defined by an acute memory disturbance of unclear aetiology for a period of less than 24 h. Observed psychological, neuroanatomical and hormonal differences between the sexes in episodic memory suggest sex-specific differences in memory disorders such as TGA. The aim of this study was to determine sex-specific differences in cardiovascular risk profiles, recurrences and magnetic resonance imaging (MRI). In total, 372 hospitalised TGA patients between 01/2011 and 10/2021 were retrospectively analysed. Comparisons were made between female and male TGA patients and compared to 216 patients with acute stroke. In our sample, women were overrepresented (61.8%), especially compared to the general population in the 65−74 age category (χ2 = 10.6, p < 0.02). On admission, female TGA patients had significantly higher systolic blood pressure values and a higher degree of cerebral microangiopathy compared to male TGA patients, whereas acute stroke patients did not. No sex-specific differences were observed with respect to recurrences or hippocampal DWI lesions. Our data demonstrate sex-specific differences in TGA. The higher blood pressure on admission and different degree of cerebral microangiopathy in female TGA patients supports the theory of blood pressure dysregulation as a disease trigger. Distinct precipitating events in female and male patients could lead to differences in the severity and duration of blood pressure abnormalities, possibly explaining the higher incidence in female patients.
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- 2022
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21. Face processing and efficient recognition of facial expressions are impaired following right but not left anteromedial temporal lobe resections: Behavioral and fMRI evidence.
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Reisch LM, Wegrzyn M, Mielke M, Mehlmann A, Woermann FG, Bien CG, and Kissler J
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- Emotions physiology, Humans, Magnetic Resonance Imaging, Recognition, Psychology, Temporal Lobe diagnostic imaging, Temporal Lobe physiology, Temporal Lobe surgery, Facial Expression, Facial Recognition
- Abstract
Anteromedial temporal lobe structures seem to support processing of faces and facial expressions. However, differential effects of unilateral left or right temporal lobe resections (TLR) on face processing, recognition of facial expressions, and on BOLD response to faces in intact brain areas are not yet fully understood. Therefore, we compared 39 patients with unilateral TLR (18 left, 21 right) and 20 healthy controls regarding recognition of facial identity and emotional facial expressions as well as BOLD response to fearful and neutral faces. We found impaired recognition of facial identity following right TLR, which was paralleled by reduced BOLD response to faces irrespective of expression in the right fusiform and lingual gyrus in postsurgical fMRI. Right TLR patients also exhibited subtle impairments of emotion recognition as they needed higher intensity of facial expressions for correct responses in a morphing task. Accuracy of emotion recognition and subjective appraisals of facial expressions did not differ between groups. There was no specific reduction of BOLD response to fearful versus neutral faces in either patient group. Our results underline the specific role of the right anteromedial temporal lobe in processing of faces and facial expressions by showing changes in face processing following right TLR in behavioral as well as imaging data., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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22. Effects of left and right medial temporal lobe resections on hemodynamic correlates of negative and neutral scene processing.
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Reisch LM, Wegrzyn M, Mielke M, Mehlmann A, Woermann FG, Kissler J, and Bien CG
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- Emotions physiology, Hemodynamics, Humans, Magnetic Resonance Imaging methods, Photic Stimulation methods, Amygdala diagnostic imaging, Amygdala physiology, Amygdala surgery, Temporal Lobe diagnostic imaging, Temporal Lobe physiology, Temporal Lobe surgery
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Enhanced visual cortex activation by negative compared to neutral stimuli is often attributed to modulating feedback from the amygdala, but evidence from lesion studies is scarce, particularly regarding differential effects of left and right amygdala lesions. Therefore, we compared visual cortex activation by negative and neutral complex scenes in an event-related fMRI study between 40 patients with unilateral temporal lobe resection (TLR; 19 left [lTLR], 21 right [rTLR]), including the amygdala, and 20 healthy controls. We found preserved hemodynamic emotion modulation of visual cortex in rTLR patients and only subtle reductions in lTLR patients. In contrast, rTLR patients showed a significant decrease in visual cortex activation irrespective of picture content. In line with this, healthy controls showed small emotional modulation of the left amygdala only, while their right amygdala was activated equally by negative and neutral pictures. Correlations of activation in amygdala and visual cortex were observed for both negative and neutral pictures in the controls. In both patient groups, this relationship was attenuated ipsilateral to the TLR. Our results support the notion of reentrant mechanisms between amygdala and visual cortex and suggest laterality differences in their emotion-specificity. While right medial temporal lobe structures including the amygdala seem to influence visual processing in general, the left medial temporal lobe appears to contribute specifically to emotion processing. Still, effects of left TLR on visual emotion processing were relatively subtle. Therefore, hemodynamic correlates of visual emotion processing are likely supported by a distributed cerebral network, challenging an amygdalocentric view of emotion processing., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
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- 2022
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23. Diagnostic challenges in patients with temporal lobe seizures and features of autoimmune limbic encephalitis.
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Ismail FS, Spatola M, Woermann FG, Popkirov S, Jungilligens J, Bien CG, Wellmer J, and Schlegel U
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- Autoantibodies, Autoimmune Diseases, Humans, Magnetic Resonance Imaging methods, Memory Disorders complications, Seizures complications, Seizures etiology, Temporal Lobe diagnostic imaging, Epilepsy, Temporal Lobe complications, Epilepsy, Temporal Lobe diagnostic imaging, Limbic Encephalitis diagnosis, Limbic Encephalitis diagnostic imaging
- Abstract
Background and Purpose: Consensus criteria for autoimmune limbic encephalitis (ALE) allow for a diagnosis even without neuronal antibodies (Abs), but it remains unclear which clinical features should prompt neuronal Ab screening in temporal lobe epilepsy patients. The aim of the study was to investigate whether patients with temporal lobe seizures associated with additional symptoms or signs of limbic involvement may harbor neuronal Abs, and which clinical features should prompt neuronal Ab screening in these patients., Methods: We identified 47 patients from a tertiary epilepsy center with mediotemporal lobe seizures and additional features suggestive of limbic involvement, including either memory deficits, psychiatric symptoms, mediotemporal magnetic resonance imaging (MRI) hyperintensities or inflammatory cerebrospinal fluid (CSF). Neuronal Ab testing was carried out at two independent reference laboratories (Bielefeld-Bethel, Germany, and Barcelona, Spain). All brain MRI scans were assessed by two reviewers independently., Results: Temporal lobe seizures were accompanied by memory deficits in 35/46 (76%), psychiatric symptoms in 27/42 (64%), and both in 19/42 patients (45%). Limbic T2/fluid-attenuated inversion recovery signal hyperintensities were found in 26/46 patients (57%; unilateral: n = 22, bilateral: n = 4). Standard CSF studies were abnormal in 2/37 patients (5%). Neuronal Abs were confirmed in serum and/or CSF in 8/47 patients (17%) and were directed against neuronal cell-surface targets (leucine-rich glioma inactivated protein 1: n = 1, contactin-associated protein-2: n = 1, undetermined target: n = 3) or glutamic acid decarboxylase in its 65-kD isoform (n = 3, all with high titers). Compared to Ab-negative patients, those who harbored neuronal Abs were more likely to have uni- or bilateral mediotemporal MRI changes (8/8, 100% vs. 18/38, 47%; p = 0.01, Fisher's exact test)., Conclusions: In patients with temporal lobe seizures and additional limbic signs, 17% had neuronal Abs affirming ALE diagnosis. Mediotemporal MRI changes were found in all Ab-positive cases and had a positive likelihood ratio of 2.11 (95% confidence interval 1.51-2.95)., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
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- 2022
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24. Hypochondroplasia and temporal lobe epilepsy - A series of 4 cases.
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Ahmadi M, Herting A, Mueffelmann B, Woermann FG, Abou Jamra R, Bien CG, Polster T, and Brandt C
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- Bone and Bones abnormalities, Electroencephalography, Female, Humans, Limb Deformities, Congenital, Lordosis, Magnetic Resonance Imaging, Male, Mutation, Receptor, Fibroblast Growth Factor, Type 3 genetics, Dwarfism, Epilepsy, Temporal Lobe complications, Epilepsy, Temporal Lobe diagnostic imaging
- Abstract
Hypochondroplasia is a skeletal dysplasia syndrome with an autosomal dominant inheritance. It may be associated with temporal lobe epilepsy. We present a series of four patients (two female, two male) with hypochondroplasia who presented at our center with drug refractory epilepsy. Clinical details and EEG and MRI findings led to a diagnosis of temporal lobe epilepsy in all four cases. The MRI findings indicate the epilepsy in hypochondroplasia may be associated with bilateral temporal lobe dysgenesis., Competing Interests: Declaration of Competing Interest AH obtained honoraria as a speaker from Desitin. CB obtained honoraria as a speaker or for consulting from Arvelle Therapeutics/ Angelini Pharma, Desitin, Eisai, GW Pharmaceuticals, UCB, Zogenix. CGB receives research support from the Deutsche Forschungsgemeinschaft (German Research Council, Bonn, Germany) and Gerd-Altenhof-Stiftung (Deutsches Stiftungs-Zentrum, Essen, Germany). TP obtained honoraria as speaker or consultant from Zogenix, Desitin and Novartis and research support from Zogenix. BM, FGW, MA, and RAJ had no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2022
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25. Relative Source Power: A novel method for localizing epileptiform EEG discharges.
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Scherg M, Schulz R, Berg P, Cho JH, Bornfleth H, Kural MA, Woermann FG, Bien CG, and Beniczky S
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- Adolescent, Adult, Brain Mapping methods, Electroencephalography, Epilepsy surgery, Female, Humans, Male, Middle Aged, Young Adult, Brain physiopathology, Epilepsy physiopathology
- Abstract
Objective: To validate relative source power (RSP) imaging of extratemporal interictal epileptiform discharges (IEDs)., Methods: The accuracy of RSP was validated in a cohort of patients with extratemporal focal epilepsy and a confined epileptogenic lesion (<19 cm
3 ) using distance to the lesion, concordance with resected area and postoperative outcome. Performance was compared with three conventional methods: voltage maps, equivalent current dipole and a distributed source model., Results: Thirty-three of 41 consecutive patients (80%) had IED averages suitable for analysis. While the peak negativity in voltage maps localized above the epileptogenic lesion only in 18 cases, RSP-maps matched in 29 cases (88%, p < 0.0026). Source localization showed a median distance of 9.8 mm from the lesion. Source-regions with 20 mm radius included 98% of all source-to-lesion distances. In the 21 surgical cases, outcome showed a sensitivity of 82.35% and specificity of 50% without significant differences between the three source imaging methods., Conclusions: RSP-maps provide a rapid, intuitive and more accurate source estimation than voltage maps. At sublobar level, RSP localizes with an accuracy similar to conventional methods and results of previous studies., Significance: The definition of a source region with 20 mm radius helps in guiding further exploration in extratemporal focal epilepsy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.S., P.B., J-H.C and H.B. are employees of BESA GmbH, Gräfelfing, Germany; M.S. is also shareholder of BESA GmbH. S.B. reports personal fees from Natus and Epihunter, outside the submitted work. The remaining authors have no financial or other conflicts of interest to declare., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)- Published
- 2022
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26. Clinical characteristics and postoperative seizure outcome in patients with mild malformation of cortical development and oligodendroglial hyperplasia.
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Gaballa A, Woermann FG, Cloppenborg T, Kalbhenn T, Blümcke I, Bien CG, and Fauser S
- Subjects
- Adolescent, Adult, Child, Preschool, Electroencephalography methods, Humans, Hyperplasia surgery, Magnetic Resonance Imaging methods, Retrospective Studies, Treatment Outcome, Epilepsy, Seizures etiology, Seizures surgery
- Abstract
Objective: We describe for the first time clinical characteristics in a series of 20 pre-surgically investigated patients with mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) who were operated on in our epilepsy center. We aimed to better diagnose this entity and help surgical planning., Methods: Data on 20 patients with histologically confirmed MOGHE were retrospectively evaluated as to age at epilepsy onset and operation, seizure semiology, magnetic resonance imaging (MRI) localization, electroencephalography (EEG) patterns, extent of the operative resection, and postoperative seizure outcome., Results: Epilepsy began mainly in early childhood; however, symptoms did not manifest until adolescence or adulthood in 30% of patients. All patients had pathologic MRI findings. In 45% of patients the lesion was initially overlooked. Most commonly, the lesion was seen in the frontal lobe. Seizure semiology was characterized as follows: (1) epileptic spasms at epilepsy onset were common and (2) nocturnal hyperkinetic seizures during the course of the disease were rare. EEG always showed frequent interictal epileptic discharges. Two peculiar patterns were observed: (1) during sleep stage I-II, sub-continuous repetitive (0.5-1.5/s) unilateral plump spike/polyspike slow waves were seen and (2) during wakefulness, unilateral paroxysms of 2-2.5/s spike-wave complexes occurred. In total, 60% of patients were seizure-free 1 year postoperatively. Postoperative seizure outcome was positively correlated with the extent of resection, age at epilepsy onset, and age at operation. Postoperative long-term outcomes remained stable in patients undergoing larger operations., Significance: MRI, EEG, and semiology already contribute to the diagnosis of probable MOGHE preoperatively. Because postoperative seizure outcomes depend on the extent of the resection, prior knowledge of a probable MOGHE helps to plan the resection and balance the risks and benefits of such an intervention. In patients undergoing larger operations, epilepsy surgery achieved good postoperative results; the first long-term outcome data were stable in these patients., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
- Published
- 2021
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27. Transient Global Amnesia (TGA): Younger Age and Absence of Cerebral Microangiopathy Are Potentially Predisposing Factors for TGA Recurrence.
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Rogalewski A, Beyer A, Friedrich A, Plümer J, Zuhorn F, Klingebiel R, Woermann FG, Bien CG, Greeve I, and Schäbitz WR
- Abstract
Background: Transient global amnesia (TGA) is defined by an acute memory disturbance of unclear etiology for a period of less than 24 h. TGA occurs as a single event in most cases. Prevalence rates of recurrent TGA vary widely from 5.4 to 27.1%. This retrospective study aimed to determine predictors for TGA recurrence. Methods: Cardiovascular risk profile and magnetic resonance imaging (MRI) of 340 hospitalized TGA patients between 2011 and 2020 were retrospectively analyzed. The median follow-up period amounted to 4.5 ± 2.7 years. Comparisons were made between TGA patients with and without subsequent recurrence. Results: TGA patients with subsequent recurrence were significantly younger (recurrent vs. single episode, 63.6 ± 8.6 years vs. 67.3 ± 10.5 years, p = 0.032) and showed a lower degree of cerebral microangiopathy compared to TGA patients without recurrence. The mean latency to recurrence was 3.0 years ± 2.1 years after the first episode. In a subgroup analysis, patients with at least five years of follow-up ( N = 160, median follow-up period 7.0 ± 1.4 years) had a recurrence rate of 11.3%. A 24.5% risk of subsequent TGA recurrence in the following five years was determined for TGA patients up to 70 years of age without microangiopathic changes on MRI (Fazekas' score 0). Conclusion: Younger TGA patients without significant microangiopathy do have an increased recurrence risk. In turn, pre-existing cerebrovascular pathology, in the form of chronic hypertension and cerebral microangiopathy, seems to counteract TGA recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rogalewski, Beyer, Friedrich, Plümer, Zuhorn, Klingebiel, Woermann, Bien, Greeve and Schäbitz.)
- Published
- 2021
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28. Reading and the visual word form area (VWFA) - Management and clinical experience at one epilepsy surgery center.
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Cloppenborg T, Mertens M, Hopf JL, Kalbhenn T, Bien CG, Woermann FG, and Polster T
- Abstract
Objective: Presurgical evaluation has no established routine to assess reading competence and to identify essential "not to resect" reading areas. Functional models describe a visual word form area (VWFA) located in the midfusiform gyrus in the dominant ventral occipito-temporal cortex (vOTC) as essential for reading. We demonstrate the relevance and feasibility of invasive VWFA-mapping., Methods: Four patients with epilepsy received invasive VWFA-mapping via left temporo-basal strip-electrodes. Co-registration of the results and additional data from the literature led to the definition of a region of interest (ROI) for a retrospective assessment of postoperative reading deficits by a standardized telephone-interview in patients with resections in this ROI between 2004 and 2018., Results: Electrical cortical stimulation disturbed whole word recognition and reading in four patients with structural epilepsy. Stimulation results showed distribution in the basal temporal lobe (dorsal mesencephalon to preoccipital notch). We identified 34 patients with resections in the ROI of the dominant hemisphere. Of these, 15 (44.1%) showed a postoperative reading deficit with a mean duration of 18.2 months (+/-32.4, 0.5-122). Six patients suffered from letter-by-letter (LBL) reading. Two patients had permanent LBL reading after resection in the ROI., Significance: We present evidence on the functional relevance of the vOTC for reading by (1) extra-operative cortical stimulation of the VWFA and by (2) a retrospective case study of reading deficits in patients operated in this area. Reading assessments and data concerning essential reading structures should be included in the presurgical evaluation of patients with lesions in the left vOTC., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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29. Transient Global Amnesia (TGA): Influence of Acute Hypertension in Patients Not Adapted to Chronic Hypertension.
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Rogalewski A, Beyer A, Friedrich A, Plümer J, Zuhorn F, Greeve I, Klingebiel R, Woermann FG, Bien CG, and Schäbitz WR
- Abstract
Objective: Transient global amnesia (TGA) is defined by an acute memory disturbance of unclear etiology for a period of <24 h. Several studies showed differences in vascular risk factors between TGA compared to transient ischemic attack (TIA) or healthy controls with varying results. This retrospective and cross-sectional study compares the cardiovascular risk profile of TGA patients with that of acute stroke patients. Methods: Cardiovascular risk profile and MR imaging of 277 TGA patients was retrospectively analyzed and compared to 216 acute ischemic stroke patients (26% TIA). Results: TGA patients were significantly younger and predominantly female compared to stroke patients. A total of 90.6% of TGA patients underwent MRI, and 53% of those showed hippocampal diffusion-weighted imaging (DWI) lesions. Scores for cerebral microangiopathy were lower in TGA patients compared to stroke patients. After statistical correction for age, TGA patients had higher systolic and diastolic blood pressure, higher cholesterol levels, lower HbA1c, as well as blood glucose levels, and lower CHA
2 DS2 -VASc scores. Stroke patients initially displayed higher CRP levels than TIA and TGA patients. TGA patients without DWI lesions were older and showed higher CHA2 DS2 -VASc scores compared to TGA patients with DWI lesions. Conclusion: This study revealed significant differences between TGA and stroke patients in regard to the cardiovascular risk profile. Our main findings show a strong association between acute hypertensive peaks and TGA in patients not adapted to chronic hypertension, indicating a vascular cause of the disease., Competing Interests: CB receives research support from the Deutsche Forschungsgemeinschaft (German Research Council, Bonn, Germany) and Gerd-Altenhof-Stiftung (Deutsches Stiftungs-Zentrum, Essen, Germany). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rogalewski, Beyer, Friedrich, Plümer, Zuhorn, Greeve, Klingebiel, Woermann, Bien and Schäbitz.)- Published
- 2021
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30. Stereotactic depth electrode placement surgery in paediatric and adult patients with the Neuromate robotic device: Accuracy, complications and epileptological results.
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Kalbhenn T, Cloppenborg T, Coras R, Fauser S, Hagemann A, Omaimen H, Polster T, Yasin H, Woermann FG, Bien CG, and Simon M
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Electrodes, Implanted, Electroencephalography, Humans, Imaging, Three-Dimensional, Middle Aged, Stereotaxic Techniques, Young Adult, Robotic Surgical Procedures adverse effects
- Abstract
Objective: The number of patients requiring depth electrode implantation for invasive video EEG diagnostics increases in most epilepsy centres. Here we report on our institutional experience with frameless robot-assisted stereotactic placement of intracerebral depth electrodes using the Neuromate® stereotactic robot-system., Methods: We identified all patients who had undergone robot-assisted stereotactic placement of intracerebral depth electrodes for invasive extra-operative epilepsy monitoring between September 2013 and March 2020. We studied technical (placement) and diagnostic accuracy of the robot-assisted procedure, associated surgical complications and procedural time requirements., Results: We evaluated a total of 464 depth electrodes implanted in 74 patients (mean 6 per patient, range 1-12). There were 27 children and 47 adults (age range: 3.6-64.6 yrs.). The mean entry and target point errors were 1.82±1.15 and 1.98±1.05 mm. Target and entry point errors were significantly higher in paediatric vs. adult patients and for electrodes targeting the temporo-mesial region. There were no clinically relevant haemorrhages and no infectious complications. Mean time for the placement of one electrode was 37±14 min and surgery time per electrode decreased with the number of electrodes placed. 55 patients (74.3%) underwent definitive surgical treatment. 36/51 (70.1%) patients followed for >12 months or until seizure recurrence became seizure-free (ILAE I)., Conclusion: Frameless robot-guided stereotactic placement of depth electrodes with the Neuromate® stereotactic robot-system is safe and feasible even in very young children, with good in vivo accuracy and high diagnostic precision. The surgical workflow is time-efficient and further improves with increasing numbers of implanted electrodes., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2021
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31. Hyperkinetic Seizures with Ictal Fear as Localizing Ictal Signs in MRI-Negative Medial Frontal Lobe Epilepsy.
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Cloppenborg T, Albers K, Kalbhenn T, Woermann FG, Bien CG, and Polster T
- Subjects
- Child, Electrocorticography, Epilepsy, Frontal Lobe diagnostic imaging, Epilepsy, Frontal Lobe surgery, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Malformations of Cortical Development diagnostic imaging, Malformations of Cortical Development surgery, Neurosurgical Procedures, Epilepsy, Frontal Lobe physiopathology, Fear physiology, Malformations of Cortical Development pathology
- Abstract
Purpose: Hyperkinetic seizures are described as seizure onset in the frontal or temporal lobe. Additional localizing information is important for diagnostic workup and surgical therapy. We describe diagnostic workup and surgical outcomes in three patients with pharmacoresistant focal emotional seizures with hyperkinetic elements., Methods/results: High-resolution 3 Tesla (T) magnetic resonance imaging (MRI) did not reveal clear-cut lesions. Invasive video-electroencephalography (EEG) with depth electrodes along the cingulate sulcus (bilateral; patients 1 and 3), right; patient 2 provided congruent results for a circumscribed seizure onset zone within the medial frontal lobe (right: patients 1 and 2; left: patient 3). Topectomies were performed in all patients. Histopathology revealed a small focal cortical dysplasia in the three cases (focal cortical dysplasia [FCD] IIA: patient 1; FCD IIB: patients 2 and 3). All patients remained completely seizure-free since surgery (Engel 1A; follow-up: 9-28 months)., Conclusion: Ictal fear associated with hyperkinetic semiology points to a seizure-onset zone within the anteromedial frontal lobe (anterior cingulate gyrus). Ictal semiology is crucial for the placement of depth electrodes, especially in MRI-negative cases. These cases illustrate a clinical advantage to the new International League against Epilepsy (ILAE) seizure classification, emphasizing initial clinical symptoms., Competing Interests: C.G.B. obtained honoraria for speaking engagements from UCB (Monheim, Germany), Desitin (Hamburg, Germany), and Euroimmun (Lübeck, Germany). He received research support from Deutsche Forschungsgemeinschaft (German Research Council, Bonn, Germany) and Gerd-Altenhof-Stiftung (Deutsches Stiftungs-Zentrum, Essen, Germany).T.C. was supported by a stipend from the Epilepsy Academy Berlin-Bethel, and from the von-Bodelschwingh Foundation in Bielefeld-Bethel. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Thieme. All rights reserved.)
- Published
- 2021
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32. Whole-brain functional correlates of memory formation in mesial temporal lobe epilepsy.
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Doll A, Wegrzyn M, Benzait A, Mertens M, Woermann FG, Labudda K, Bien CG, and Kissler J
- Subjects
- Brain, Functional Laterality, Hippocampus, Humans, Magnetic Resonance Imaging, Neuropsychological Tests, Temporal Lobe diagnostic imaging, Epilepsy, Temporal Lobe diagnostic imaging, Memory, Episodic
- Abstract
The mesial temporal lobe is a key region for episodic memory. Accordingly, memory impairment is frequent in patients with mesial temporal lobe epilepsy. However, the functional relevance of potentially epilepsy-induced reorganisation for memory formation is still not entirely clear. Therefore, we investigated whole-brain functional correlates of verbal and non-verbal memory encoding and subsequent memory formation in 56 (25 right sided) mesial temporal lobe epilepsy patients and 21 controls. We applied an fMRI task of learning scenes, faces, and words followed by an out-of-scanner recognition test. During encoding of faces and scenes left and right mesial temporal lobe epilepsy patients had consistently reduced activation in the epileptogenic mesial temporal lobe compared with controls. Activation increases in patients were apparent in extra-temporal regions, partly associated with subsequent memory formation (left frontal regions and basal ganglia), and patients had less deactivation in regions often linked to the default mode and auditory networks. The more specific subsequent memory contrast indicated only marginal group differences. Correlating patients' encoding activation with memory performance both within the paradigm and with independent clinical measures demonstrated predominantly increased contralateral mesio-temporal activation supporting intact memory performance. In left temporal lobe epilepsy patients, left frontal activation was also correlated with better verbal memory performance. Taken together, our findings hint towards minor extra-temporal plasticity in mesial temporal lobe epilepsy patients, which is in line with pre-surgical impairment and post-surgical memory decline in many patients. Further, data underscore the importance of particularly the contralateral mesial temporal lobe itself, to maintain intact memory performance., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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33. Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay.
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Kobow K, Jabari S, Pieper T, Kudernatsch M, Polster T, Woermann FG, Kalbhenn T, Hamer H, Rössler K, Mühlebner A, Spliet WGM, Feucht M, Hou Y, Stichel D, Korshunov A, Sahm F, Coras R, Blümcke I, and von Deimling A
- Subjects
- DNA Copy Number Variations physiology, Drug Resistant Epilepsy complications, Drug Resistant Epilepsy genetics, Female, Humans, Male, Polymicrogyria complications, Polymicrogyria genetics, Seizures pathology, Brain pathology, Chromosomes metabolism, Drug Resistant Epilepsy pathology, Malformations of Cortical Development pathology, Polymicrogyria pathology
- Abstract
Polymicrogyria (PMG) is a developmental cortical malformation characterized by an excess of small and frustrane gyration and abnormal cortical lamination. PMG frequently associates with seizures. The molecular pathomechanisms underlying PMG development are not yet understood. About 40 genes have been associated with PMG, and small copy number variations have also been described in selected patients. We recently provided evidence that epilepsy-associated structural brain lesions can be classified based on genomic DNA methylation patterns. Here, we analyzed 26 PMG patients employing array-based DNA methylation profiling on formalin-fixed paraffin-embedded material. A series of 62 well-characterized non-PMG cortical malformations (focal cortical dysplasia type 2a/b and hemimegalencephaly), temporal lobe epilepsy, and non-epilepsy autopsy controls was used as reference cohort. Unsupervised dimensionality reduction and hierarchical cluster analysis of DNA methylation profiles showed that PMG formed a distinct DNA methylation class. Copy number profiling from DNA methylation data identified a uniform duplication spanning the entire long arm of chromosome 1 in 7 out of 26 PMG patients, which was verified by additional fluorescence in situ hybridization analysis. In respective cases, about 50% of nuclei in the center of the PMG lesion were 1q triploid. No chromosomal imbalance was seen in adjacent, architecturally normal-appearing tissue indicating mosaicism. Clinically, PMG 1q patients presented with a unilateral frontal or hemispheric PMG without hemimegalencephaly, a severe form of intractable epilepsy with seizure onset in the first months of life, and severe developmental delay. Our results show that PMG can be classified among other structural brain lesions according to their DNA methylation profile. One subset of PMG with distinct clinical features exhibits a duplication of chromosomal arm 1q.
- Published
- 2020
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34. Negative content enhances stimulus-specific cerebral activity during free viewing of pictures, faces, and words.
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Reisch LM, Wegrzyn M, Woermann FG, Bien CG, and Kissler J
- Subjects
- Adolescent, Adult, Amygdala diagnostic imaging, Cerebral Cortex diagnostic imaging, Emotions physiology, Facial Expression, Facial Recognition physiology, Female, Humans, Magnetic Resonance Imaging, Male, Young Adult, Amygdala physiology, Brain Mapping, Cerebral Cortex physiology, Pattern Recognition, Visual physiology, Reading
- Abstract
Negative visual stimuli have been found to elicit stronger brain activation than do neutral stimuli. Such emotion effects have been shown for pictures, faces, and words alike, but the literature suggests stimulus-specific differences regarding locus and lateralization of the activity. In the current functional magnetic resonance imaging study, we directly compared brain responses to passively viewed negative and neutral pictures of complex scenes, faces, and words (nouns) in 43 healthy participants (21 males) varying in age and demographic background. Both negative pictures and faces activated the extrastriate visual cortices of both hemispheres more strongly than neutral ones, but effects were larger and extended more dorsally for pictures, whereas negative faces additionally activated the superior temporal sulci. Negative words differentially activated typical higher-level language processing areas such as the left inferior frontal and angular gyrus. There were small emotion effects in the amygdala for faces and words, which were both lateralized to the left hemisphere. Although pictures elicited overall the strongest amygdala activity, amygdala response to negative pictures was not significantly stronger than to neutral ones. Across stimulus types, emotion effects converged in the left anterior insula. No gender effects were apparent, but age had a small, stimulus-specific impact on emotion processing. Our study specifies similarities and differences in effects of negative emotional content on the processing of different types of stimuli, indicating that brain response to negative stimuli is specifically enhanced in areas involved in processing of the respective stimulus type in general and converges across stimuli in the left anterior insula., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
- Published
- 2020
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35. Genetic generalized epilepsies with frontal lesions mimicking migratory disorders on the epilepsy monitoring unit.
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Fauser S, Cloppenborg T, Polster T, Specht U, Woermann FG, and Bien CG
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Objective: Some patients with genetic generalized epilepsy (GGE) may present with ambiguous and atypical findings and even focal brain abnormalities. Correct diagnosis may therefore be difficult., Methods: We retrospectively collected six patients investigated on the epilepsy monitoring unit with MRI abnormalities mimicking focal cortical dysplasia (FCD-like) or heterotopias, but with semiology and EEG features of GGE. We compared them to four additional patients with GGE and nonmigratory abnormalities., Results: All six patients presented with frontal MRI lesions: radial ("transmantle," n = 4), cortical-subcortical (n = 1), and periventricular heterotopia (n = 1). Five had positive family histories. Semiologic lateralizing signs compatible with the lesion were seen in four. Five patients had 3/s spike-wave complexes, with an asymmetric appearance in three. Regional EEG changes matched with the side of the abnormality in three patients. Invasive EEG (n = 2) or postoperative outcomes (n = 3) argued against an ictogenic role of the MRI abnormalities. Histology showed mild malformation of cortical development, but no focal cortical dysplasia. The six patients were finally diagnosed with juvenile myoclonic epilepsy (n = 2), juvenile absence epilepsy (n = 2), or GGE not further specified (nfs, n = 2). Compared to these patients, the other four (final diagnoses: childhood absence epilepsy, n = 1; perioral myoclonia with absences, n = 1; and GGE nfs, n = 2) had no lateralizing EEG findings., Significance: Patients with GGE may have coincidental MRI abnormalities. These cases are challenging as frontal epilepsy and GGE can present with similar semiologies. GGE with coincidental FCD-like lesions/heterotopias is in particular difficult to diagnose as patients have more lateralizing features (in semiology and EEG) than those with tumors. A detailed noninvasive presurgical evaluation may be justified. We point out red flags that may help to distinguish GGE from frontal epilepsy, even in the presence of brain abnormalities: 3/s spike waves (even if asymmetric), changing lateralizing signs at different times, and a positive family history hinting at GGE., Competing Interests: CGB obtained honoraria for speaking engagements from UCB (Monheim, Germany), Desitin (Hamburg, Germany), and Euroimmun (Lübeck, Germany). He receives research support from Deutsche Forschungsgemeinschaft (German Research Council, Bonn, Germany) and Gerd‐Altenhof‐Stiftung (Deutsches Stiftungszentrum, Essen, Germany). US received financial support from Desitin (Hamburg, Germany) for serving on scientific advisory boards and obtained honoraria for speaking engagements from Desitin, UCB (Monheim, Germany), and Eisai (Frankfurt, Germany). He received research support from Desitin. TP received personal fees from Desitin, Novartis, Shire, UCB, and Zogenix outside the submitted work. The remaining authors have no conflicts of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. The study has been approved by the Ethics Committee in Münster (2019‐576‐f‐S)., (© 2020 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.)
- Published
- 2020
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36. Rhinal and hippocampal contributions to spontaneous inter-item binding and verbal memory recall: Evidence from temporal lobe epilepsy.
- Author
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Grewe P, Neu D, Aengenendt J, Woermann FG, Mertens M, Bien CG, and Kissler J
- Subjects
- Hippocampus diagnostic imaging, Humans, Magnetic Resonance Imaging, Memory, Mental Recall, Temporal Lobe diagnostic imaging, Epilepsy, Temporal Lobe
- Abstract
The medial temporal lobes (MTL) play a prominent role in associative memory processing. Still, it is unclear to what extent specific structures within the MTL sub-serve distinct aspects of associative memory. Here, the role of the MTL in forming spontaneous associations in a "naturalistic" setting is investigated applying a word-list memory test not presenting items in an associative fashion. This allows for the differential investigation of item recall and associative binding. Participants included patients with medial temporal lobe epilepsy (mTLE, n = 79) and healthy controls (n = 58). Memory performance in a verbal list-learning paradigm was analyzed by (1) inter-trial repetitions ("binding", i.e., number of word-pairs consistently recalled over two consecutive trials), and (2) single item recall. In patients, behavioral results were correlated with rhinal cortex and hippocampal volumetric data. Results showed that binding was specifically diminished for patients with mTLE during learning and delayed recall. Moreover, binding predicted behavioral differences in item recall. Notably, hippocampal volumes were correlated with item recall during delayed recall, whereas rhinal cortex volumes were correlated with binding during learning. Our results provide evidence that diminished verbal memory in patients with mTLE at least partly can be attributed to functional reductions in spontaneous inter-trial stimulus binding. Moreover, they demonstrate a process-dependent functional dissociation between rhinal cortex and hippocampus for verbal encoding and recall: While the rhinal cortex is mainly engaged in detecting novel associations, the hippocampus primarily subserves consolidation and recall of associations between stimuli. Our study thus advances current models of the sub-specialization of MTL structures and offers novel evidence that memory formation in the MTL is mediated by associative item-processing, even when stimuli are not presented in an associative fashion per se. Thus, our results provide valuable qualitative insights into mechanisms of memory formation and memory failures in patients with MTL dysfunctions., Competing Interests: Declaration of Competing Interest CGB obtained honoraria for speaking engagements from UCB (Monheim, Germany), Desitin (Hamburg, Germany), and Euroimmun (Lübeck, Germany). He receives research support from Deutsche Forschungsgemeinschaft (Bonn, Germany) and Gerd-Altenhof-Stiftung (Deutsches Stiftungs-Zentrum, Essen, Germany). The remaining authors have no conflict of interest to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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37. Quantifying the Confidence in fMRI-Based Language Lateralisation Through Laterality Index Deconstruction.
- Author
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Wegrzyn M, Mertens M, Bien CG, Woermann FG, and Labudda K
- Abstract
In epilepsy patients, language lateralisation is an important part of the presurgical diagnostic process. Using task-based fMRI, language lateralisation can be determined by visual inspection of activity patterns or by quantifying the difference in left- and right-hemisphere activity using variations of a basic formula [(L-R)/(L+R)]. However, the values of this laterality index (LI) depend on the choice of activity thresholds and regions of interest. The diagnostic utility of the LI also depends on how its continuous values are translated into categorical decisions about a patient's language lateralisation. Here, we analysed fMRI data from 712 epilepsy patients who performed a verbal fluency task. Each fMRI data set was evaluated by a trained human rater as depicting left-sided, right-sided, or bilateral lateralisation or as being inconclusive. We used data-driven methods to define the activity thresholds and regions of interest used for LI computation and to define a classification scheme that allowed us to translate the LI values into categorical decisions. By deconstructing the LI into measures of laterality (L-R) and strength (L+R), we also modelled the relationship between activation strength and conclusiveness of a data set. In a held-out data set, predictions reached 91% correct when using only conclusive data and 82% when inconclusive data were included. Although only trained on human evaluations of fMRIs, the approach generalised to the prediction of language Wada test results, allowing for significant above-chance accuracies. Compared against different existing methods of LI-computation, our approach improved the identification and exclusion of inconclusive cases and ensured that decisions for the remaining data could be made with consistently high accuracies. We discuss how this approach can support clinicians in assessing fMRI data on a single-case level, deciding whether lateralisation can be determined with sufficient certainty or whether additional information is needed.
- Published
- 2019
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38. Biallelic mutations in PIGP cause developmental and epileptic encephalopathy.
- Author
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Krenn M, Knaus A, Westphal DS, Wortmann SB, Polster T, Woermann FG, Karenfort M, Mayatepek E, Meitinger T, Wagner M, and Distelmaier F
- Subjects
- Brain diagnostic imaging, Brain physiology, Electroencephalography, Female, Glycosylphosphatidylinositols genetics, Hexosyltransferases chemistry, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging, Male, Membrane Proteins chemistry, Mutation, Hexosyltransferases genetics, Membrane Proteins genetics, Spasms, Infantile genetics, Spasms, Infantile physiopathology
- Abstract
Developmental and epileptic encephalopathies are characterized by infantile seizures and psychomotor delay. Glycosylphosphatidylinositol biosynthesis defects, resulting in impaired tethering of various proteins to the cell surface, represent the underlying pathology in some patients. One of the genes involved, PIGP , has recently been associated with infantile seizures and developmental delay in two siblings. Here, we report the second family with a markedly overlapping phenotype due to a homozygous frameshift mutation (c.456delA;p.Glu153Asnfs*34) in PIGP . Flow cytometry of patient granulocytes confirmed reduced expression of glycosylphosphatidylinositol-anchored proteins as functional consequence. Our findings corroborate PIGP as a monogenic disease gene for developmental and epileptic encephalopathy., Competing Interests: The authors declare that they have no conflict of interest related to the content of this article.
- Published
- 2019
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39. Very long-term outcome in resected and non-resected patients with temporal lobe epilepsy with medial temporal lobe sclerosis: A multiple case-study.
- Author
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Grewe P, Schulz R, Woermann FG, Brandt C, Doll A, Hoppe M, Tomka-Hoffmeister M, and Bien CG
- Subjects
- Aged, Cognition, Depression, Epilepsy, Temporal Lobe psychology, Female, Follow-Up Studies, Humans, Male, Memory, Memory Disorders etiology, Middle Aged, Postoperative Complications, Quality of Life, Seizures drug therapy, Seizures psychology, Seizures surgery, Time Factors, Treatment Outcome, Epilepsy, Temporal Lobe drug therapy, Epilepsy, Temporal Lobe surgery
- Abstract
Purpose: To investigate the very long-term (i.e., ≥15 years) seizure, cognitive and psycho-social outcomes in resected patients (RP) with TLE compared to control patients not having undergone epilepsy surgery., Methods: We applied a multiple case-study design including three non-resected patients (NRP) who were compared to a group of six RP. The latter were matched to the NRP according to clinical-demographic data. Outcome measures were various seizure, cognitive, and psycho-social variables., Results: Patients were 56-72 years old. Seizure and AED outcome was more favourable among RP. RP reported better self-perceived overall health but higher subjective memory complaints. Upon formal neuropsychological testing, RP presented with lower verbal memory scores. Very long-term memory decline was evident in left-sided RP with good baseline memory scores, while RP with lower baseline performance, right-sided RP and NRP remained stable. Seizure-freedom had remarkable effects on the relationship between objective and subjective outcome: seizure-free patients, in general, subjectively reported the best psychosocial and cognitive outcome - irrespective of neuropsychological test results., Conclusion: Our study suggests positive effects of TLE surgery in the very long-term course of ≥15 years postoperatively. Long-term seizure-freedom appears to have the strongest impact on patients' subjectively perceived psycho-social and cognitive outcome and may even outweigh actual memory disturbances and/or decline. Overall, our data do not support the assumption of a generally accelerated cognitive decline in patients with TLE., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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40. Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014.
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Cloppenborg T, May TW, Blümcke I, Fauser S, Grewe P, Hopf JL, Kalbhenn T, Polster T, Schulz R, Woermann FG, and Bien CG
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Electroencephalography adverse effects, Epilepsy, Temporal Lobe pathology, Female, Follow-Up Studies, Hemispherectomy methods, Humans, Male, Malformations of Cortical Development complications, Retrospective Studies, Temporal Lobe pathology, Temporal Lobe surgery, Treatment Outcome, Epilepsy surgery, Epilepsy, Temporal Lobe surgery, Hemispherectomy trends, Malformations of Cortical Development surgery
- Abstract
Objective: Surgical volumes at large epilepsy centers are decreasing. Pediatric cohorts, however, show a trend toward more resections and superior outcome. Differences in pediatric and adult epilepsy surgery were investigated in our cohort., Methods: The Bethel database between 1990 and 2014 was retrospectively analyzed., Results: A total of 1916 adults and 1300 children underwent presurgical workup. The most common etiologies were medial temporal sclerosis (35.4%) in adults, and focal cortical dysplasias (21.1%) and diffuse hemispheric pathologies (14.7%) in children. Only 1.4% of the total cohort had normal histopathology. A total of 1357 adults (70.8%) and 751 children (57.8%) underwent resections. Surgery types for children were more diverse and showed a higher proportion of extratemporal resections (32.8%) and functional hemispherectomies (20.8%). Presurgical evaluations increased in both groups; surgical numbers remained stable for children, but decreased in the adult group from 2007 on. The patients' decision against surgery in the adult nonoperated cohort increased over time (total = 44.9%, 27.4% in 1995-1998 up to 53.2% in 2011-2014; for comparison, in children, total = 22.1%, stable over time). Postsurgical follow-up data were available for 1305 adults (96.2%) and 690 children (91.9%) 24 months after surgery. The seizure freedom rate was significantly higher in children than in adults (57.8% vs 47.5%, P < 0.001) and significantly improved over time (P = 0.016)., Significance: Pediatric epilepsy surgery has stable surgical volumes and renders more patients seizure-free than epilepsy surgery in adults. A relative decrease in hippocampal sclerosis, the traditional substrate of epilepsy surgery, changes the focus of epilepsy surgery toward other pathologies., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)
- Published
- 2019
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41. The hidden identity of faces: a case of lifelong prosopagnosia.
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Wegrzyn M, Garlichs A, Heß RWK, Woermann FG, and Labudda K
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- Adult, Brain pathology, Emotions, Face, Female, Humans, Prosopagnosia pathology, Prosopagnosia physiopathology
- Abstract
Background: Not being able to recognize a person's face is a highly debilitating condition from which people with developmental prosopagnosia (DP) suffer their entire life. Here we describe the case of J, a 30 year old woman who reports being unable to recognize her parents, her husband, or herself in the mirror., Case Presentation: We set out to assess the severity of J's prosopagnosia using tests with unfamiliar as well as familiar faces and investigated whether impaired configural processing explains her deficit. To assess the specificity of the impairment, we tested J's performance when evaluating emotions, intentions, and the attractiveness and likability of faces. Detailed testing revealed typical brain activity patterns for faces and normal object recognition skills, and no evidence of any brain injury. However, compared to a group of matched controls, J showed severe deficits in learning new faces, and in recognizing familiar faces when only inner features were available. Her recognition of uncropped faces with blurred features was within the normal range, indicating preserved configural processing when peripheral features are available. J was also unimpaired when evaluating intentions and emotions in faces. In line with healthy controls, J rated more average faces as more attractive. However, she was the only one to rate them as less likable, indicating a preference for more distinctive and easier to recognize faces., Conclusions: Taken together, the results illustrate both the severity and the specificity of DP in a single case. While DP is a heterogeneous disorder, an inability to integrate the inner features of the face into a whole might be the best explanation for the difficulties many individuals with prosopagnosia experience.
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- 2019
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42. Thought experiment: Decoding cognitive processes from the fMRI data of one individual.
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Wegrzyn M, Aust J, Barnstorf L, Gippert M, Harms M, Hautum A, Heidel S, Herold F, Hommel SM, Knigge AK, Neu D, Peters D, Schaefer M, Schneider J, Vormbrock R, Zimmer SM, Woermann FG, and Labudda K
- Subjects
- Adult, Comprehension physiology, Humans, Male, Rest physiology, Spatial Memory physiology, Brain physiology, Cognition physiology, Magnetic Resonance Imaging methods
- Abstract
Cognitive processes, such as the generation of language, can be mapped onto the brain using fMRI. These maps can in turn be used for decoding the respective processes from the brain activation patterns. Given individual variations in brain anatomy and organization, analyzes on the level of the single person are important to improve our understanding of how cognitive processes correspond to patterns of brain activity. They also allow to advance clinical applications of fMRI, because in the clinical setting making diagnoses for single cases is imperative. In the present study, we used mental imagery tasks to investigate language production, motor functions, visuo-spatial memory, face processing, and resting-state activity in a single person. Analysis methods were based on similarity metrics, including correlations between training and test data, as well as correlations with maps from the NeuroSynth meta-analysis. The goal was to make accurate predictions regarding the cognitive domain (e.g. language) and the specific content (e.g. animal names) of single 30-second blocks. Four teams used the dataset, each blinded regarding the true labels of the test data. Results showed that the similarity metrics allowed to reach the highest degrees of accuracy when predicting the cognitive domain of a block. Overall, 23 of the 25 test blocks could be correctly predicted by three of the four teams. Excluding the unspecific rest condition, up to 10 out of 20 blocks could be successfully decoded regarding their specific content. The study shows how the information contained in a single fMRI session and in each of its single blocks can allow to draw inferences about the cognitive processes an individual engaged in. Simple methods like correlations between blocks of fMRI data can serve as highly reliable approaches for cognitive decoding. We discuss the implications of our results in the context of clinical fMRI applications, with a focus on how decoding can support functional localization., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
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43. Partial resection of presurgical fMRI activation is associated with a postsurgical loss of language function after frontal lobe epilepsy surgery.
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Labudda K, Mertens M, Kalbhenn T, Schulz R, and Woermann FG
- Subjects
- Adult, Epilepsy, Frontal Lobe surgery, Female, Humans, Language, Male, Middle Aged, Young Adult, Brain Mapping methods, Epilepsy, Frontal Lobe diagnostic imaging, Magnetic Resonance Imaging methods, Neurosurgical Procedures adverse effects, Postoperative Complications psychology, Speech Disorders etiology
- Abstract
We describe five patients with frontal lobe epilepsy who underwent electrocortical stimulation (ES) for language localization and language functional magnetic resonance imaging (fMRI) prior to epilepsy surgery. Six months after surgery, three patients suffered from a drop of verbal fluency. In all of them, frontal areas with presurgical language fMRI activity were resected. Our results suggest that resection in regions of areas with presurgical fMRI activation is not without risk for a postsurgical loss of function, even when ES results were negative for language function in these areas. Using fMRI activations might be specifically helpful to plan the resection when ES delivered inconclusive results.
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- 2017
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44. Lesional cerebellar epilepsy: a review of the evidence.
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Foit NA, van Velthoven V, Schulz R, Blümcke I, Urbach H, Woermann FG, and Bien CG
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- Animals, Cerebellar Diseases diagnosis, Cerebellar Diseases therapy, Cerebellum diagnostic imaging, Epilepsies, Partial diagnosis, Epilepsies, Partial therapy, Humans, Cerebellar Diseases pathology, Cerebellar Diseases physiopathology, Cerebellum pathology, Cerebellum physiopathology, Epilepsies, Partial pathology, Epilepsies, Partial physiopathology
- Abstract
Classical teaching in epileptology localizes the origins of focal seizures solely in the cerebral cortex, with only inhibitory effects attributed to subcortical structures. However, electrophysiological and neuroimaging studies over the last decades now provide evidence for an initiation of epileptic seizures within subcortical structures. Intrinsic epileptogenicity of hypothalamic hamartoma has already been established in recognition of subcortical epilepsy, whereas a seizure-generating impact of dysplastic cerebellar lesions remains to be clarified. Herein, we examine the supportive evidence and clinical presentation of cerebellar seizures and review therapy options.
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- 2017
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45. Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes.
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Cloppenborg T, May TW, Blümcke I, Grewe P, Hopf LJ, Kalbhenn T, Pfäfflin M, Polster T, Schulz R, Woermann FG, and Bien CG
- Subjects
- Adolescent, Adult, Aged, Brain Neoplasms epidemiology, Brain Neoplasms surgery, Child, Child, Preschool, Cohort Studies, Cross-Sectional Studies, Epilepsy, Temporal Lobe epidemiology, Epilepsy, Temporal Lobe surgery, Female, Follow-Up Studies, Germany, Humans, Infant, Infant, Newborn, Male, Malformations of Cortical Development, Group I epidemiology, Malformations of Cortical Development, Group I surgery, Middle Aged, Outcome Assessment, Health Care, Treatment Outcome, Treatment Refusal trends, Utilization Review trends, Young Adult, Epilepsy epidemiology, Epilepsy surgery, Neurosurgical Procedures statistics & numerical data, Neurosurgical Procedures trends
- Abstract
Introduction: Despite the success of epilepsy surgery, recent reports suggest a decline in surgical numbers. We tested these trends in our cohort to elucidate potential reasons., Patients and Methods: Presurgical, surgical and postsurgical data of all patients undergoing presurgical evaluation in between 1990 and 2013 were retrospectively analysed. Patients were grouped according to the underlying pathology., Results: A total of 3060 patients were presurgically studied, and resective surgery was performed in 66.8% (n=2044) of them: medial temporal sclerosis (MTS): n=675, 33.0%; benign tumour (BT): n=408, 20.0%; and focal cortical dysplasia (FCD): n=284, 13.9%. Of these, 1929 patients (94.4%) had a follow-up of 2 years, and 50.8% were completely seizure free (Engel IA). Seizure freedom rate slightly improved over time. Presurgical evaluations continuously increased, whereas surgical interventions did not. Numbers for MTS, BT and temporal lobe resections decreased since 2009. The number of non-lesional patients and the need for intracranial recordings increased. More evaluated patients did not undergo surgery (more than 50% in 2010-2013) because patients were not suitable (mainly due to missing hypothesis: 4.5% in 1990-1993 up to 21.1% in 2010-2013, total 13.4%) or declined from surgery (maximum 21.0% in 2010-2013, total 10.9%). One potential reason may be that increasingly detailed information on chances and risks were given over time., Conclusions: The increasing volume of the presurgical programme largely compensates for decreasing numbers of surgically remediable syndromes and a growing rate of informed choice against epilepsy surgery. Although comprehensive diagnostic evaluation is offered to a larger group of epilepsy patients, surgical numbers remain stable., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
- Published
- 2016
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46. Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series.
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Dogan Onugoren M, Deuretzbacher D, Haensch CA, Hagedorn HJ, Halve S, Isenmann S, Kramme C, Lohner H, Melzer N, Monotti R, Presslauer S, Schäbitz WR, Steffanoni S, Stoeck K, Strittmatter M, Stögbauer F, Trinka E, von Oertzen TJ, Wiendl H, Woermann FG, and Bien CG
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Retrospective Studies, Autoantibodies blood, Limbic Encephalitis immunology, Receptors, AMPA immunology, Receptors, GABA-B immunology
- Abstract
Background: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABA(B)R) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement., Methods: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABA(B)R or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled., Results: In 10 patients, we detected abs to GABA(B)R. Median age was 70 years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABA(B)R ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patients tumour treatment and three both therapies. Three patients died, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7 years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level., Discussion: GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2015
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47. Volume of hippocampal substructures in borderline personality disorder.
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Kreisel SH, Labudda K, Kurlandchikov O, Beblo T, Mertens M, Thomas C, Rullkötter N, Wingenfeld K, Mensebach C, Woermann FG, and Driessen M
- Subjects
- Adolescent, Adult, Borderline Personality Disorder epidemiology, Comorbidity, Diagnostic and Statistical Manual of Mental Disorders, Female, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Organ Size, Stress Disorders, Post-Traumatic epidemiology, Stress Disorders, Post-Traumatic pathology, Stress Disorders, Post-Traumatic psychology, Young Adult, Borderline Personality Disorder pathology, Borderline Personality Disorder psychology, Hippocampus pathology
- Abstract
Borderline personality disorder (BPD) may be associated with smaller hippocampi in comparison to hippocampal size in controls. However, specific pathology in hippocampal substructures (i.e., head, body and tail) has not been sufficiently investigated. To address hippocampal structure in greater detail, we studied 39 psychiatric inpatients and outpatients with a DSM-IV diagnosis of BPD and 39 healthy controls. The hippocampus and its substructures were segmented manually on magnetic resonance imaging scans. The volumes of hippocampal substructures (and total hippocampal volume) did not differ between BPD patients and controls. Exploratory analysis suggests that patients with a lifetime history of posttraumatic stress disorder (PTSD) may have a significantly smaller hippocampus - affecting both the hippocampal head and body - in comparison to BPD patients without comorbid PTSD (difference in total hippocampal volume: -10.5%, 95%CI -2.6 to -18.5, significant). Also, patients fulfilling seven or more DSM-IV BPD criteria showed a hippocampal volume reduction, limited to the hippocampal head (difference in volume of the hippocampal head: -16.5%, 95%CI -6.1 to -26.8, significant). Disease heterogeneity in respect to, for example, symptom severity and psychiatric comorbidities may limit direct comparability between studies; the results presented here may reflect hippocampal volumes in patients who are "less" affected or they may simply be a chance finding. However, there is also the possibility that global effects of BPD on the hippocampus may have previously been overestimated., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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48. Disturbed spatial cognitive processing of body-related stimuli in a case of a lesion to the right fusiform gyrus.
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Grewe P, Woermann FG, Bien CG, and Piefke M
- Subjects
- Adolescent, Cognition Disorders complications, Dominance, Cerebral, Epilepsy complications, Humans, Male, Neuropsychological Tests, Body Image, Cognition Disorders pathology, Spatial Processing physiology, Temporal Lobe pathology
- Abstract
The fusiform gyrus (FG) is well known as one of the main neural sites of human face and body processing. We report the case of a young male patient with epilepsy and a circumscribed lesion in the right FG who presented with isolated impairments in spatial cognitive processing of body-related stimuli. However, he did not show any clinical signs of prosopagnosia. In particular, handling/processing of body and face stimuli was impaired, when stimuli were presented in unconventional views and orientations, thus requiring additional spatial cognitive operations. In this case study, we discuss the patient's selective impairment from the view of current empirical and theoretical work on the segregation of functions in the FG.
- Published
- 2015
- Full Text
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49. Going beyond seizure control: can pharmacotherapy help to restore cognitive network function?
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Cendes F and Woermann FG
- Subjects
- Female, Humans, Levetiracetam, Male, Piracetam therapeutic use, Anticonvulsants therapeutic use, Brain drug effects, Epilepsy, Temporal Lobe drug therapy, Epilepsy, Temporal Lobe pathology, Piracetam analogs & derivatives
- Published
- 2014
- Full Text
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50. The impact of age on prefrontal cortex integrity during spatial working memory retrieval.
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Toepper M, Markowitsch HJ, Gebhardt H, Beblo T, Bauer E, Woermann FG, Driessen M, and Sammer G
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Neuropsychological Tests, Reaction Time physiology, Signal Processing, Computer-Assisted, Young Adult, Aging physiology, Memory, Short-Term physiology, Prefrontal Cortex physiology, Spatial Memory physiology
- Abstract
Healthy aging is accompanied by a decline in spatial working memory that is related to functional cerebral changes within the spatial working memory network. In the last decade, important findings were presented concerning the location (e.g., prefrontal), kind (e.g., 'underactivation,' 'overactivation'), and meaning (e.g., functional deficits, compensation) of these changes. Less is known about how functional connections between specific brain regions are affected by age and how these changes are related to behavioral performance. To address these issues, we used functional magnetic resonance imaging to examine retrieval-related brain activation and functional connectivity in 18 younger individuals and 18 older individuals. We assessed working memory with a modified version of the Corsi Block-Tapping test, which requires the storage and reproduction of spatial target sequences. Analyses of group differences in brain activation and functional connectivity included comparisons between younger individuals, older individuals, older high-performers, and older low-performers. In addition, we conducted a functional connectivity analysis by using a seed region approach. In comparison to younger individuals, older individuals showed lower right-hemispheric dorsolateral prefrontal activation and lower functional connectivity between the right dorsolateral prefrontal cortex and the bilateral orbitofrontal cortex. Older high-performers showed higher right dorsolateral and anterior prefrontal cortex activation than older low-performers, as well as higher functional connectivity between these brain regions. The present results suggest age-related reductions of prefrontal activation during spatial working memory retrieval. Moreover, task-related functional connectivity appears to be lower in older adults. Performance accuracy in older adults is associated with right dorsolateral and anterior prefrontal cortex activation, and with the functional connection between these regions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
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