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Article ; Online: Big Data - Big Trouble: The two faces of publishing results from big data studies based on cohorts with poor clinical definition.

von Wrede, Randi / Witt, Juri-Alexander / Helmstaedter, Christoph

2023 Volume 111, Page(s) 21–22

Language	English
Publishing date	2023-07-21
Publishing country	England
Document type	Editorial
ZDB-ID	1137610-7
ISSN	1532-2688 ; 1059-1311
ISSN (online)	1532-2688
ISSN	1059-1311
DOI	10.1016/j.seizure.2023.07.015
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Book ; Online ; Thesis: Über die Beeinflussung dynamischer epileptischer Hirnnetzwerke durch die transkutane aurikuläre Vagusnervstimulation

Freifrau von Wrede, Randi Désirée [Verfasser] / Surges, Rainer [Akademischer Betreuer]

2023

Author's details	Randi Désirée Freifrau von Wrede ; Betreuer: Rainer Surges
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Universitäts- und Landesbibliothek Bonn
Publishing place	Bonn
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Impact of biological rhythms on the importance hierarchy of constituents in time-dependent functional brain networks.

Bröhl, Timo / von Wrede, Randi / Lehnertz, Klaus

Frontiers in network physiology

2023 Volume 3, Page(s) 1237004

Abstract: Biological rhythms are natural, endogenous cycles with period lengths ranging from less than 24 h (ultradian rhythms) to more than 24 h (infradian rhythms). The impact of the circadian rhythm (approximately 24 h) and ultradian rhythms on spectral ... ...

Abstract	Biological rhythms are natural, endogenous cycles with period lengths ranging from less than 24 h (ultradian rhythms) to more than 24 h (infradian rhythms). The impact of the circadian rhythm (approximately 24 h) and ultradian rhythms on spectral characteristics of electroencephalographic (EEG) signals has been investigated for more than half a century. Yet, only little is known on how biological rhythms influence the properties of EEG-derived evolving functional brain networks. Here, we derive such networks from multiday, multichannel EEG recordings and use different centrality concepts to assess the time-varying importance hierarchy of the networks' vertices and edges as well as the various aspects of their structural integration in the network. We observe strong circadian and ultradian influences that highlight distinct subnetworks in the evolving functional brain networks. Our findings indicate the existence of a vital and fundamental subnetwork that is rather generally involved in ongoing brain activities during wakefulness and sleep.
Language	English
Publishing date	2023-08-29
Publishing country	Switzerland
Document type	Journal Article
ISSN	2674-0109
ISSN (online)	2674-0109
DOI	10.3389/fnetp.2023.1237004
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Article ; Online: Epileptic-network-based prediction and control of seizures in humans.

Lehnertz, Klaus / Bröhl, Timo / Wrede, Randi von

Neurobiology of disease

2023 Volume 181, Page(s) 106098

Abstract: Epilepsy is now conceptualized as a network disease. The epileptic brain network comprises structurally and functionally connected cortical and subcortical brain regions - spanning lobes and hemispheres -, whose connections and dynamics evolve in time. ... ...

Abstract	Epilepsy is now conceptualized as a network disease. The epileptic brain network comprises structurally and functionally connected cortical and subcortical brain regions - spanning lobes and hemispheres -, whose connections and dynamics evolve in time. With this concept, focal and generalized seizures as well as other related pathophysiological phenomena are thought to emerge from, spread via, and be terminated by network vertices and edges that also generate and sustain normal, physiological brain dynamics. Research over the last years has advanced concepts and techniques to identify and characterize the evolving epileptic brain network and its constituents on various spatial and temporal scales. Network-based approaches further our understanding of how seizures emerge from the evolving epileptic brain network, and they provide both novel insights into pre-seizure dynamics and important clues for success or failure of measures for network-based seizure control and prevention. In this review, we summarize the current state of knowledge and address several important challenges that would need to be addressed to move network-based prediction and control of seizures closer to clinical translation.
MeSH term(s)	Humans ; Electroencephalography/methods ; Seizures ; Epilepsy ; Brain ; Brain Mapping/methods
Language	English
Publishing date	2023-03-29
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2023.106098
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Article ; Online: The time-evolving epileptic brain network: concepts, definitions, accomplishments, perspectives.

Bröhl, Timo / Rings, Thorsten / Pukropski, Jan / von Wrede, Randi / Lehnertz, Klaus

Frontiers in network physiology

2024 Volume 3, Page(s) 1338864

Abstract: Epilepsy is now considered a network disease that affects the brain across multiple levels of spatial and temporal scales. The paradigm shift from an epileptic focus-a discrete cortical area from which seizures originate-to a widespread epileptic network- ...

Abstract	Epilepsy is now considered a network disease that affects the brain across multiple levels of spatial and temporal scales. The paradigm shift from an epileptic focus-a discrete cortical area from which seizures originate-to a widespread epileptic network-spanning lobes and hemispheres-considerably advanced our understanding of epilepsy and continues to influence both research and clinical treatment of this multi-faceted high-impact neurological disorder. The epileptic network, however, is not static but evolves in time which requires novel approaches for an in-depth characterization. In this review, we discuss conceptual basics of network theory and critically examine state-of-the-art recording techniques and analysis tools used to assess and characterize a time-evolving human epileptic brain network. We give an account on current shortcomings and highlight potential developments towards an improved clinical management of epilepsy.
Language	English
Publishing date	2024-01-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2674-0109
ISSN (online)	2674-0109
DOI	10.3389/fnetp.2023.1338864
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Short-term effects of transcutaneous auricular vagus nerve stimulation on T-wave alternans in people with focal epilepsy - An exploratory pilot study.

Pukropski, Jan / Baumann, Jan / Jordan, Arthur / Bausch, Marcel / von Wrede, Randi / Surges, Rainer

Epilepsy & behavior reports

2024 Volume 26, Page(s) 100657

Abstract: High levels of T-wave alternans (TWA) are linked to an increased risk of sudden cardiac death. People with epilepsy display elevated TWA levels that are decreased by chronic vagus nerve stimulation via implanted devices after 2-4 weeks or later. Our ... ...

Abstract	High levels of T-wave alternans (TWA) are linked to an increased risk of sudden cardiac death. People with epilepsy display elevated TWA levels that are decreased by chronic vagus nerve stimulation via implanted devices after 2-4 weeks or later. Our objective was to explore short-term effects of transcutaneous auricular vagus nerve stimulation (tVNS) on TWA. Five patients (3 female) with focal epilepsy undergoing video-EEG monitoring were included. TWA levels were determined using a one-channel modified lead I ECG via an open-source TWA-algorithm on two consecutive days, 1 h before, during and after tVNS via the left auricle. Data are given as mean ± SE. Mean TWA at baseline was 3.8 ± 0.4 µV and 3.0 ± 0.6 µV during stimulation on day 2. Stimulations on the second day were associated with TWA reductions by 22 ± 13 % that exceeded stimulation effects on the first day relative to baseline (p < 0.05). Linear mixed-models revealed effects of both stimulation (p < 0.05) and stimulation number (p < 0.005). Normalized TWA showed reproducible peak reductions at both days within 35 min after the initiation of tVNS (p < 0.05). Our observations suggest that tVNS has short-term effects on TWA, supporting the notion that vagus nerve stimulation has a beneficial impact on electrical cardiac properties.
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ISSN	2589-9864
ISSN (online)	2589-9864
DOI	10.1016/j.ebr.2024.100657
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Article ; Online: Value of drug level concentrations of brivaracetam, lacosamide, and perampanel in care of people with epilepsy.

Hentschel, Matthias / Stoffel-Wagner, Birgit / Surges, Rainer / von Wrede, Randi / Dolscheid-Pommerich, Ramona Christina

Epilepsia

2024 Volume 65, Issue 3, Page(s) 620–629

Abstract: Objective: The aim of this study was to determine whether clinical efficacy and reported adverse effects (AEs) of the newer antiseizure medications (ASMs) brivaracetam (BRV), lacosamide (LCM), and perampanel (PER) have been associated with plasma levels ...

Abstract	Objective: The aim of this study was to determine whether clinical efficacy and reported adverse effects (AEs) of the newer antiseizure medications (ASMs) brivaracetam (BRV), lacosamide (LCM), and perampanel (PER) have been associated with plasma levels of these ASMs. We also investigated whether plasma levels outside the reference range has led to dose adjustments. Methods: Plasma levels of 300 people with epilepsy (PWE) seen at our tertiary epilepsy center were determined by liquid chromatography-tandem mass spectrometry. PWE received BRV (n = 100), LCM (n = 100), or PER (n = 100), in most cases in polytherapy. Demographic and clinical data were retrospectively analyzed and related to plasma levels. Clinical efficacy of BRV, LCM, or PER was assessed retrospectively by comparing seizure frequency at the time of current blood draw with seizure frequency at the time of first administration. AEs were also recorded and, if reported, compared retrospectively with the time of first administration. Results: No significant associations were found between plasma levels of BRV, LCM, or PER and seizure freedom (BRV, p = 1.000; LCM, p = .243; PER, p = .113) or responder status (BRV, p = .118; LCM, p = .478; PER, p = .069) at presentation. There was also no pattern between plasma levels and the occurrence of AEs. In the majority of cases, drug levels outside the reference ranges have not led to adjustments in the daily doses of BRV (93.5%), LCM (93.9%), or PER (89.1%). Significance: Plasma levels at a given time point did not allow conclusions to be drawn about seizure control or the occurrence of AEs. Our findings indicate that efficacy and tolerability cannot be predicted based on averaged data from a single plasma measurement due to high interindividual variability. Instead, individual reference values should be established when sufficient clinical data are available, in line with the 2008 International League Against Epilepsy position paper on therapeutic drug monitoring.
MeSH term(s)	Humans ; Lacosamide/therapeutic use ; Anticonvulsants/adverse effects ; Retrospective Studies ; Epilepsy/drug therapy ; Epilepsy/chemically induced ; Pyrrolidinones/adverse effects ; Seizures/drug therapy ; Seizures/chemically induced ; Treatment Outcome ; Drug Therapy, Combination ; Nitriles ; Pyridones
Chemical Substances	Lacosamide (563KS2PQY5) ; perampanel (H821664NPK) ; brivaracetam (U863JGG2IA) ; Anticonvulsants ; Pyrrolidinones ; Nitriles ; Pyridones
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17873
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Zs.A 517: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Transcutaneous vagus nerve stimulation in the treatment of drug-resistant epilepsy.

von Wrede, Randi / Surges, Rainer

Autonomic neuroscience : basic & clinical

2021 Volume 235, Page(s) 102840

Abstract: Epilepsy is a common chronic neurological disease with a high burden of illness. Invasive vagus nerve stimulation (iVNS) is a well-established treatment option in patients with epilepsy (PWE). More recently, transcutaneous vagus nerve stimulation (tVNS) ... ...

Abstract	Epilepsy is a common chronic neurological disease with a high burden of illness. Invasive vagus nerve stimulation (iVNS) is a well-established treatment option in patients with epilepsy (PWE). More recently, transcutaneous vagus nerve stimulation (tVNS) was introduced, an alternative option which is particularly interesting because it does not require surgery and is instantaneously removable. Here, we thoroughly reviewed clinical data on efficacy and safety of tVNS in epilepsies. Five prospective trials in 118 patients with drug-resistant epilepsies and 3 randomized controlled trials in 280 patients with drug-resistant epilepsies were carried out. Study protocols were heterogeneous in terms of patients' characteristics, used device, stimulation parameters, study duration and endpoints. Seizure reduction amounted up to 64%, with responder rates (seizure reduction ≥50%) up to 65%. Seizure freedom was reached in up to 24%, and even to 31% in a small pediatric study group. Seizure severity scores were provided in 4 studies, showing significant improvement in two of them. Adverse side effects were mostly headache, ear pain and skin alteration and rated as mild to moderate. Drowsiness might be depend on stimulation intensity. Quality of life scores reflecting burden of illness showed significant improvement in two studies. Efficacy and safety of tVNS in PWE has to be interpreted as promising. Multicenter randomized double-blind clinical trials with standardized stimulation protocols and long-term follow-up studies are necessary to finally assess tVNS treatment outcome in drug-resistant epilepsies.
MeSH term(s)	Child ; Epilepsy/therapy ; Humans ; Pharmaceutical Preparations ; Prospective Studies ; Quality of Life ; Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Vagus Nerve ; Vagus Nerve Stimulation
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2021-06-30
Publishing country	Netherlands
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	2020105-9
ISSN	1872-7484 ; 1566-0702
ISSN (online)	1872-7484
ISSN	1566-0702
DOI	10.1016/j.autneu.2021.102840
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Article ; Online: The time-evolving epileptic brain network

Timo Bröhl / Thorsten Rings / Jan Pukropski / Randi von Wrede / Klaus Lehnertz

Frontiers in Network Physiology, Vol

concepts, definitions, accomplishments, perspectives

2024 Volume 3

Abstract: Epilepsy is now considered a network disease that affects the brain across multiple levels of spatial and temporal scales. The paradigm shift from an epileptic focus—a discrete cortical area from which seizures originate—to a widespread epileptic network— ...

Abstract	Epilepsy is now considered a network disease that affects the brain across multiple levels of spatial and temporal scales. The paradigm shift from an epileptic focus—a discrete cortical area from which seizures originate—to a widespread epileptic network—spanning lobes and hemispheres—considerably advanced our understanding of epilepsy and continues to influence both research and clinical treatment of this multi-faceted high-impact neurological disorder. The epileptic network, however, is not static but evolves in time which requires novel approaches for an in-depth characterization. In this review, we discuss conceptual basics of network theory and critically examine state-of-the-art recording techniques and analysis tools used to assess and characterize a time-evolving human epileptic brain network. We give an account on current shortcomings and highlight potential developments towards an improved clinical management of epilepsy.
Keywords	epilepsy ; epileptic network ; epileptic focus ; seizure ; seizure-prediction ; seizure-control ; Electronic computers. Computer science ; QA75.5-76.95
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modifying functional brain networks in focal epilepsy by manual visceral-osteopathic stimulation of the vagus nerve at the abdomen.

Lehnertz, Hendrik / Broehl, Timo / Rings, Thorsten / von Wrede, Randi / Lehnertz, Klaus

Frontiers in network physiology

2023 Volume 3, Page(s) 1205476

Abstract: Non-invasive transcutaneous vagus nerve stimulation elicits similar therapeutic effects as invasive vagus nerve stimulation, offering a potential treatment alternative for a wide range of diseases, including epilepsy. Here, we present a novel, non- ... ...

Abstract	Non-invasive transcutaneous vagus nerve stimulation elicits similar therapeutic effects as invasive vagus nerve stimulation, offering a potential treatment alternative for a wide range of diseases, including epilepsy. Here, we present a novel, non-invasive stimulation of the vagus nerve, which is performed manually viscero-osteopathically on the abdomen (voVNS). We explore the impact of short-term voVNS on various local and global characteristics of EEG-derived, large-scale evolving functional brain networks from a group of 20 subjects with and without epilepsy. We observe differential voVNS-mediated alterations of these characteristics that can be interpreted as a reconfiguration and modification of networks and their stability and robustness properties. Clearly, future studies are necessary to assess the impact of such a non-pharmaceutical intervention on clinical decision-making in the treatment of epilepsy. However, our findings may add to the current discussion on the importance of the gut-brain axis in health and disease.
Language	English
Publishing date	2023-07-13
Publishing country	Switzerland
Document type	Journal Article
ISSN	2674-0109
ISSN (online)	2674-0109
DOI	10.3389/fnetp.2023.1205476
Database	MEDical Literature Analysis and Retrieval System OnLINE

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