Activated N‐methyl‐D‐aspartate receptor ion channels detected in focal epilepsy with [18F]GE‐179 positron emission tomography
Epilepsia
Published On 2021/12
Objective Imaging activated glutamate N‐methyl‐D‐aspartate receptor ion channels (NMDAR‐ICs) using positron emission tomography (PET) has proved challenging due to low brain uptake, poor affinity and selectivity, and high metabolism and dissociation rates of candidate radioligands. The radioligand [18F]GE‐179 is a known use‐dependent marker of NMDAR‐ICs. We studied whether interictal [18F]GE‐179 PET would detect foci of abnormal NMDAR‐IC activation in patients with refractory focal epilepsy. Methods Ten patients with refractory focal epilepsy and 18 healthy controls had structural magnetic resonance imaging (MRI) followed by a 90‐min dynamic [18F]GE‐179 PET scan with simultaneous electroencephalography (EEG). PET and EEG findings were compared with MRI and previous EEGs. Standard uptake value (SUV) images of [18F]GE‐179 were generated and global gray matter uptake was …
Journal
Epilepsia
Published On
2021/12
Volume
62
Issue
12
Page
2899-2908
Authors
Arne Møller
Aarhus Universitet
Position
MD Associate Professor
H-Index(all)
50
H-Index(since 2020)
31
I-10 Index(all)
0
I-10 Index(since 2020)
0
Citation(all)
0
Citation(since 2020)
0
Cited By
0
Research Interests
Neuroscience
Neuroimaging
Gambling Disorder
University Profile Page
Andreas Højlund
Aarhus Universitet
Position
Postdoc
H-Index(all)
13
H-Index(since 2020)
11
I-10 Index(all)
0
I-10 Index(since 2020)
0
Citation(all)
0
Citation(since 2020)
0
Cited By
0
Research Interests
Neurolinguistics
Cognitive Neuroscience
Parkinson's disease
Deep brain stimulation
University Profile Page
Martin Dietz
Aarhus Universitet
Position
DK
H-Index(all)
13
H-Index(since 2020)
12
I-10 Index(all)
0
I-10 Index(since 2020)
0
Citation(all)
0
Citation(since 2020)
0
Cited By
0
Research Interests
Neuroscience
Computational psychiatry
University Profile Page
Other Articles from authors
Arne Møller
Aarhus Universitet
Movement Disorders
Microglial Activation and Progression of Nigrostriatal Dysfunction in Isolated REM Sleep Behavior Disorder
Background Using 11C‐(R)‐PK11195‐PET, we found increased microglia activation in isolated REM sleep behavior disorder (iRBD) patients. Their role remains to be clarified. Objectives The objective is to assess relationships between activated microglia and progression of nigrostriatal dysfunction in iRBD. Methods Fifteen iRBD patients previously scanned with 11C‐(R)‐PK11195 and 18F‐DOPA‐PET underwent repeat 18F‐DOPA‐PET after 3 years. 18F‐DOPA Ki changes from baseline were evaluated with volumes‐of‐interest and voxel‐based analyses. Results Significant 18F‐DOPA Ki reductions were found in putamen and caudate. Reductions were larger and more widespread in patients with increased nigral microglia activation at baseline. Left nigral 11C‐(R)‐PK11195 binding at baseline was a predictor of 18F‐DOPA Ki reduction in left caudate (coef = −0.0426, P = 0.016). Conclusions …
2024/3/13
Article DetailsArne Møller
Aarhus Universitet
European Journal of Neurology
Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder
Background Reduced cortical acetylcholinesterase activity, as measured by 11C‐donepezil positron emission tomography (PET), has been reported in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD). However, its progression and clinical implications have not been fully investigated. Here, we explored the relationship between longitudinal changes in brain acetylcholinesterase activity and cognitive function in iRBD. Methods Twelve iRBD patients underwent 11C‐donepezil PET at baseline and after 3 years. PET images were interrogated with statistical parametric mapping (SPM) and a regions of interest (ROI) approach. Clinical progression was assessed with the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale‐Part III (MDS‐UPDRS‐III). Cognitive function was rated using the Mini‐Mental State Examination (MMSE) and the Montreal Cognitive …
2024/1
Article DetailsAndreas Højlund
Aarhus Universitet
Authorea Preprints
Avoiding artifactual components in summary metrics in Deep Brain Stimulation corrupted MEG data
The surgical procedure or Deep Brain Stimulation (DBS) is an established technique aimed at neuromodulation and is most often used for treating neurological and neuropsychiatric disorders. In clinical studies, Magnetoencephalography (MEG) is a widely used technique for characterizing the effects of Deep Brain Stimulation (DBS). A significant limitation of DBS stimulation is the inability to distinguish stimulation artifacts from actual neuronal activity, especially in the lower frequencies, where it may obscure the biological response and be a confounding factor. This paper aims to understand how to circumvent the DBS artifactual component in the summary metrics of DBS-corrupted MEG data. To do the same, we used a watermelon as a phantom model of the head to deploy DBS electrodes. The spectral signature of the artifactual component of DBS and it's power in different clinically significant bands of interest …
2024/4/2
Article DetailsAndreas Højlund
Aarhus Universitet
European Journal of Neuroscience
Dopamine dysregulation in Parkinson's disease flattens the pleasurable urge to move to musical rhythms
The pleasurable urge to move to music (PLUMM) activates motor and reward areas of the brain and is thought to be driven by predictive processes. Dopamine in motor and limbic networks is implicated in beat‐based timing and music‐induced pleasure, suggesting a central role of basal ganglia (BG) dopaminergic systems in PLUMM. This study tested this hypothesis by comparing PLUMM in participants with Parkinson's disease (PD), age‐matched controls, and young controls. Participants listened to musical sequences with varying rhythmic and harmonic complexity (low, medium and high), and rated their experienced pleasure and urge to move to the rhythm. In line with previous results, healthy younger participants showed an inverted U‐shaped relationship between rhythmic complexity and ratings, with preference for medium complexity rhythms, while age‐matched controls showed a similar, but weaker …
2024/1
Article DetailsArne Møller
Aarhus Universitet
Cryo-TEM structure of β-glucocerebrosidase in complex with its transporter LIMP-2
Nearly all lysosomal enzymes reach the lysosome via the mannose-6-phosphate receptor pathway. One of the few known exceptions is the enzyme β-glucocerebrosidase (GCase) that requires the lysosomal integral membrane protein type-2 (LIMP-2) as a proprietary lysosomal transporter. Genetic variations in the GCase encoding gene GBA1 are the cause of Gaucher’s disease (GD) and the highest genetic risk factor for developing Parkinson’s disease (PD). Activators targeting GCase have emerged as a promising therapeutic approach for the treatment of both GD and PD, with pre-clinical and clinical trials ongoing. In this study, we resolved the complex of GCase and LIMP-2 to 3.6 Å using cryo-electron microscopy with the aid of an engineered LIMP-2 shuttle and two GCase-targeted pro-macrobodies. We identified helix 5 and helix 7 of LIMP-2 to interact with a binding pocket in GCase, forming a mostly hydrophobic interaction interface. Understanding the interplay of GCase and LIMP-2 on a structural level is crucial for identifying potential activation sites and conceptualizing novel therapeutic approaches targeting GCase. Here, we unveil the protein structure of a mannose-6-phosphate-independent lysosomal transporting complex and provide fundamental knowledge for translational clinical research to overcome GD and PD.
2024/4/29
Article DetailsArne Møller
Aarhus Universitet
Advanced Science
Activation and Purification of ß‐Glucocerebrosidase by Exploiting its Transporter LIMP‐2 – Implications for Novel Treatment Strategies in Gaucher's and Parkinson …
Genetic variants of GBA1 can cause the lysosomal storage disorder Gaucher disease and are among the highest genetic risk factors for Parkinson's disease (PD). GBA1 encodes the lysosomal enzyme beta‐glucocerebrosidase (GCase), which orchestrates the degradation of glucosylceramide (GluCer) in the lysosome. Recent studies have shown that GluCer accelerates α‐synuclein aggregation, exposing GCase deficiency as a major risk factor in PD pathology and as a promising target for treatment. This study investigates the interaction of GCase and three disease‐associated variants (p.E326K, p.N370S, p.L444P) with their transporter, the lysosomal integral membrane protein 2 (LIMP‐2). Overexpression of LIMP‐2 in HEK 293T cells boosts lysosomal abundance of wt, E326K, and N370S GCase and increases/rescues enzymatic activity of the wt and E326K variant. Using a novel purification approach, co …
2024/4/26
Article DetailsAndreas Højlund
Aarhus Universitet
Adapting to the Sound of Music—Development of Music Discrimination Skills in Recently Implanted CI Users
Cochlear implants (CIs) are optimized for speech perception but poor in conveying musical sound features such as pitch, melody, and timbre. Here, we investigated the early development of discrimination of musical sound features after cochlear implantation. Nine recently implanted CI users (CIre) were tested shortly after switch-on (T1) and approximately 3 months later (T2), using a musical multifeature mismatch negativity (MMN) paradigm, presenting four deviant features (intensity, pitch, timbre, and rhythm), and a three-alternative forced-choice behavioral test. For reference, groups of experienced CI users (CIex; n = 13) and normally hearing (NH) controls (n = 14) underwent the same tests once. We found significant improvement in CIre's neural discrimination of pitch and timbre as marked by increased MMN amplitudes. This was not reflected in the behavioral results. Behaviorally, CIre scored well above …
2023/2
Article DetailsArne Møller
Aarhus Universitet
Journal of Psychosomatic Research
Imbalanced brain connectome: A possible link behind functional somatic disorders, multiple chemical sensitivity, and long COVID patients
Background:Functional Somatic Disorders (FSDs) are characterized by persistent physical symptoms that cannot be explained by other somatic or psychiatric conditions. Multiple Chemical Sensitivity (MCS) is a non-allergic FSD characterized by odour intolerance and various somatic symptoms being attributed to the influence of toxic environmental chemicals in low, usually harmless doses. The pathophysiology of FSDs are still not clear. Smell and taste complaints were also among the notable symptoms characterizing the covid epidemic and the latest evidence suggests overlaps between long COVID and FSDs. Method (s) The study includes advanced analysis of MRI-derived functional and structural connectomes acquired on a 3 T MR scanner. Furthermore, it includes questionnaires and paraclinical tests, eg the Sniffin'Stick olfactory test, Mini-Mental State Examination, and Sino-Nasal Outcome test 22. The pilot part of the project included 6 MCS patients who were compared with 6 matched healthy participants. Later follow-up included analysis of 8 multiorgan FSD and 4 post-COVID patients. Result (s) The MCS group showed important brain structural connectivity differences in 34 tracts. Notably, for MCS patients, the olfactory cortex (especially in the right hemisphere) showed decreased connectivity with regions in the emotional system. Conclusion (s) We plan to extend these findings with whole-brain modelling of the functional connectivity in the patient groups. Long-term this could be used as a'fingerprint'which could help with diagnosis and treatment monitoring in FSDs as well as with new diagnoses such as long-COVID. Copyright© 2023
2023
Article DetailsAndreas Højlund
Aarhus Universitet
Topics in Cognitive Science
A Multivariate Method for Dynamic System Analysis: Multivariate Detrended Fluctuation Analysis Using Generalized Variance
Fractal fluctuations are a core concept for inquiries into human behavior and cognition from a dynamic systems perspective. Here, we present a generalized variance method for multivariate detrended fluctuation analysis (mvDFA). The advantage of this extension is that it can be applied to multivariate time series and considers intercorrelation between these time series when estimating fractal properties. First, we briefly describe how fractal fluctuations have advanced a dynamic system understanding of cognition. Then, we describe mvDFA in detail and highlight some of the advantages of the approach for simulated data. Furthermore, we show how mvDFA can be used to investigate empirical multivariate data using electroencephalographic recordings during a time‐estimation task. We discuss this methodological development within the framework of interaction‐dominant dynamics. Moreover, we outline how the …
2023/9/14
Article DetailsAndreas Højlund
Aarhus Universitet
Neuropsychologia
Speech comprehension across time, space, frequency, and age: MEG-MVPA classification of intertrial phase coherence
Language is a key part of human cognition, essential for our well-being at all stages of our lives. Whereas many neurocognitive abilities decline with age, for language the picture is much less clear, and how exactly speech comprehension changes with ageing is still unknown. To investigate this, we employed magnetoencephalography (MEG) and recorded neuromagnetic brain responses to auditory linguistic stimuli in healthy participants of younger and older age using a passive task-free paradigm and a range of different linguistic stimulus contrasts, which enabled us to assess neural processing of spoken language at multiple levels (lexical, semantic, morphosyntactic). Using machine learning-based classification algorithms to scrutinise intertrial phase coherence of MEG responses in cortical source space, we found that patterns of oscillatory neural activity diverged between younger and older participants across …
2023/9/9
Article DetailsAndreas Højlund
Aarhus Universitet
An fMRI study on the groove experience in Parkinson's disease
• Significant main effect of rhythm on urge to move and pleasure ratings, no significant main effect of group• Rhythm by group interaction observed for both ratings• Urge to move and pleasure ratings correlated across groups• Averaged PLUMM ratings show significant main effect of rhythm, no significant main effect of group, and a rhythm by group interaction
2023
Article DetailsAndreas Højlund
Aarhus Universitet
Rhythm perception and experience of groove in cochlear implant users
RESULTS Alberte B. Seeberg1, Tomas E. Matthews1, Andreas Højlund2, Peter Vuust1, Bjørn Petersen1 INTRODUCTION DISCUSSION METHO
2023/8/27
Article DetailsAndreas Højlund
Aarhus Universitet
Cortex; a journal devoted to the study of the nervous system and behavior
No selective action verb impairment in patients with Parkinson's disease: Evidence from Danish patients reading naturalistic texts, a commentary on García et al., 2018
No selective action verb impairment in patients with Parkinson's disease: Evidence from Danish patients reading naturalistic texts, a Commentary on García et al., 2018 No selective action verb impairment in patients with Parkinson's disease: Evidence from Danish patients reading naturalistic texts, a Commentary on García et al., 2018 Cortex. 2023 Jan:158:176-180. doi: 10.1016/j.cortex.2022.07.006. Epub 2022 Sep 10. Authors Marie Louise Holm Møller 1 , Sabine Hagen Høj 2 , Karen Østergaard 3 , Mikkel Wallentin 2 , Andreas Højlund 4 Affiliations 1 Center of Functionally Integrative Neuroscience (CFIN), Department of Clinical Medicine, Aarhus University, Denmark; Dept. of Linguistics, Cognitive Science and Semiotics, Aarhus University, Denmark. Electronic address: marielouise@cfin.au.dk. 2 Center of Functionally Integrative Neuroscience (CFIN), Department of Clinical Medicine, Aarhus University, Denmark; …
2023/1
Article DetailsArne Møller
Aarhus Universitet
Psychological Medicine
Anterior cingulate glutamate levels associate with functional activation and connectivity during sensory integration in schizophrenia: a multimodal 1H-MRS and fMRI study
BackgroundGlutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.MethodsFifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses …
2023/8
Article DetailsMartin Dietz
Aarhus Universitet
International Journal of Clinical and Health Psychology
Impaired social learning in patients with major depressive disorder revealed by a reinforcement learning model
Background/objectivePatients with major depressive disorder (MDD) have altered learning rates for rewards and losses in non-social learning paradigms. However, it is not well understood whether the ability to learn from social interactions is altered in MDD patients. Using reinforcement learning during the repeated Trust Game (rTG), we investigated how MDD patients learn to trust newly-met partners in MDD patients.MethodSixty-eight MDD patients and fifty-four controls each played as ‘investor’ and interacted with ten different partners. We manipulated both the level of trustworthiness by varying the chance of reciprocity (10, 30, 50, 70 and 90%) and reputation disclosure, where partners’ reputation was either pre-disclosed or hidden.ResultsOur reinforcement learning model revealed that MDD patients had significantly higher learning rates for losses than the controls in both the reputation disclosure and non …
2023/10/1
Article DetailsAndreas Højlund
Aarhus Universitet
Beyond syncopation: the importance of rhythmic streams for the experience of groove
Beyond syncopation: the importance of rhythmic streams for the experience of groove — Aarhus University Skip to main navigation Skip to search Skip to main content Aarhus University Home Aarhus University Logo Help & FAQ English Dansk Home Profiles Research units Projects Research output Prizes Activities Courses Press/Media Search by expertise, name or affiliation Beyond syncopation: the importance of rhythmic streams for the experience of groove Alberte Baggesgaard Seeberg, Tomas Matthews, Andreas Højlund, Bjørn Petersen, Peter Vuust Department of Clinical Medicine - Center for Music In the Brain School of Communication and Culture - Cognitive Science Research output: Contribution to conference › Poster › Research › peer-review Overview Original language English Publication date 27 Aug 2023 Publication status Published - 27 Aug 2023 Event 17th International Conference on Music …
2023/8/27
Article DetailsArne Møller
Aarhus Universitet
Psychiatry Research: Neuroimaging
Neural fingerprints of gambling disorder using diffusion tensor imaging
Gambling disorder (GD) is a behavioral addiction associated with personal, social and occupational consequences. Thus, examining GD's clinical relationship with its neural substrates is critical. We compared neural fingerprints using diffusion tensor imaging (DTI) in GD subjects undergoing treatment relative to healthy volunteers (HV). Fifty-three (25 GD, 28 age-matched HV) males were scanned with structural magnetic resonance imaging (MRI) and DTI. We applied probabilistic tractography based on DTI scanning data, preprocessed and analyzed using permutation testing of individual connectivity weights between regions for group comparison. Permutation-based comparisons between group-averaged connectomes highlighted significant structural differences. The GD group demonstrated increased connectivity, and striatal network reorganisation, contrasted by reduced connectivity within and to frontal lobe …
2023/8/1
Article DetailsMartin Dietz
Aarhus Universitet
Topics in Cognitive Science
A Multivariate Method for Dynamic System Analysis: Multivariate Detrended Fluctuation Analysis Using Generalized Variance
Fractal fluctuations are a core concept for inquiries into human behavior and cognition from a dynamic systems perspective. Here, we present a generalized variance method for multivariate detrended fluctuation analysis (mvDFA). The advantage of this extension is that it can be applied to multivariate time series and considers intercorrelation between these time series when estimating fractal properties. First, we briefly describe how fractal fluctuations have advanced a dynamic system understanding of cognition. Then, we describe mvDFA in detail and highlight some of the advantages of the approach for simulated data. Furthermore, we show how mvDFA can be used to investigate empirical multivariate data using electroencephalographic recordings during a time‐estimation task. We discuss this methodological development within the framework of interaction‐dominant dynamics. Moreover, we outline how the …
2023/9/14
Article DetailsAndreas Højlund
Aarhus Universitet
Structural and functional changes in the retina in Parkinson’s disease
Parkinson’s disease is caused by degeneration of dopaminergic neurons, originating in the substantia nigra pars compacta and characterised by bradykinesia, rest tremor and rigidity. In addition, visual disorders and retinal abnormalities are often present and can be identified by decreased visual acuity, abnormal spatial contrast sensitivity or even difficulty in complex visual task completion. Because of their early onset in patients with de novo Parkinson’s disease, the anatomical retinal changes and electrophysiological modification could be valuable markers even at early stages of the disease. However, due to the concomitant occurrence of normal ageing, the relevance and specificity of these predictive values can be difficult to interpret. This review examines retinal dysfunction arising in Parkinson’s disease. We highlight the electrophysiological delays and decreased amplitude in the electroretinography …
2023/6/1
Article DetailsArne Møller
Aarhus Universitet
Neurochemical Research
Dopamine D2/3 Receptor Availabilities in Striatal and Extrastriatal Regions of the Adult Human Brain: Comparison of Four Methods of Analysis
Values of binding potentials (BPND) of dopamine D2/3 receptors differ in different regions of the brain, but we do not know with certainty how much of this difference is due either to different receptor numbers, or to different affinities of tracers to the receptors, or to both. We tested the claim that both striatal and extrastriatal dopamine D2/3 receptor availabilities vary with age in vivo in humans by determining the values of BPND of the specific radioligand [11C]raclopride. We determined values of BPND in striatal and extrastriatal volumes-of-interest (VOI) with the same specific receptor radioligand. We estimated values of BPND in individual voxels of brains of healthy volunteers in vivo, and we obtained regional averages of VOI by dynamic positron emission tomography (PET). We calculated average values of BPND in caudate nucleus and putamen of striatum, and in frontal, occipital, parietal, and temporal cortices of …
2023/5
Article DetailsOther articles from Epilepsia journal
Ashley Akbari
Swansea University
Epilepsia
Health care utilization and mortality for people with epilepsy during COVID-19: A population study
Objective This study was undertaken to characterize changes in health care utilization and mortality for people with epilepsy (PWE) during the COVID‐19 pandemic. Methods We performed a retrospective study using linked, individual‐level, population‐scale anonymized health data from the Secure Anonymised Information Linkage databank. We identified PWE living in Wales during the study “pandemic period” (January 1, 2020–June 30, 2021) and during a “prepandemic” period (January 1, 2016–December 31, 2019). We compared prepandemic health care utilization, status epilepticus, and mortality rates with corresponding pandemic rates for PWE and people without epilepsy (PWOE). We performed subgroup analyses on children (<18 years old), older people (>65 years old), those with intellectual disability, and those living in the most deprived areas. We used Poisson models to calculate adjusted rate …
2024/3/5
Article DetailsPhilippe Ryvlin
Université de Lausanne
Epilepsia
Focal electroclinical features in generalized tonic–clonic seizures: Decision flowchart for a diagnostic challenge
Objective Bilateral tonic–clonic seizures with focal semiology or focal interictal electroencephalography (EEG) can occur in both focal and generalized epilepsy types, leading to diagnostic errors and inappropriate therapy. We investigated the prevalence and prognostic values of focal features in patients with idiopathic generalized epilepsy (IGE), and we propose a decision flowchart to distinguish between focal and generalized epilepsy in patients with bilateral tonic–clonic seizures and focal EEG or semiology. Methods We retrospectively analyzed video‐EEG recordings of 101 bilateral tonic–clonic seizures from 60 patients (18 with IGE, 42 with focal epilepsy). Diagnosis and therapeutic response were extracted after ≥1‐year follow‐up. The decision flowchart was based on previous observations and assessed concordance between interictal and ictal EEG. Results Focal semiology in IGE was observed in 75 …
2024/1/27
Article DetailsLawrence Hirsch
Yale University
Epilepsia
Immediate and long‐term management practices of acute symptomatic seizures and epileptiform abnormalities: A cross‐sectional international survey
Objectives Acute symptomatic seizures (ASyS) and epileptiform abnormalities (EAs) on electroencephalography (EEG) are commonly encountered following acute brain injury. Their immediate and long‐term management remains poorly investigated. We conducted an international survey to understand their current management. Methods The cross‐sectional web‐based survey of 21 fixed‐response questions was based on a common clinical encounter: convulsive or suspected ASyS following an acute brain injury. Respondents selected the option that best matched their real‐world practice. Respondents completing the survey were compared with those who accessed but did not complete it. Results A total of 783 individuals (44 countries) accessed the survey; 502 completed it. Almost everyone used anti‐seizure medications (ASMs) for secondary prophylaxis after convulsive or electrographic ASyS (95.4% and …
2024/2/15
Article DetailsSteven M Wolf
New York Medical College
Epilepsia
A multi‐center comparison of surgical techniques for corpus Callosotomy in pediatric drug‐resistant epilepsy
Objectives Corpus callosotomy (CC) is used to reduce seizures, primarily in patients with generalized drug‐resistant epilepsy (DRE). The invasive nature of the procedure contributes to underutilization despite its potential superiority to other palliative procedures. The goal of this study was to use a multi‐institutional epilepsy surgery database to characterize the use of CC across participating centers. Methods Data were acquired from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database, a prospective observational study collecting data on children 0–18 years referred for surgical evaluation of DRE across 22 U.S. pediatric epilepsy centers. Patient, epilepsy, and surgical characteristics were collected across multiple CC modalities. Outcomes and complications were recorded and analyzed statistically. Results Eighty‐three patients undergoing 85 CC procedures at 14 participating epilepsy …
2024/2
Article DetailsMaarten De Vos
Katholieke Universiteit Leuven
Epilepsia
Home recording of 3‐Hz spike–wave discharges in adults with absence epilepsy using the wearable Sensor Dot
Objective Home monitoring of 3‐Hz spike–wave discharges (SWDs) in patients with refractory absence epilepsy could improve clinical care by replacing the inaccurate seizure diary with objective counts. We investigated the use and performance of the Sensor Dot (Byteflies) wearable in persons with absence epilepsy in their home environment. Methods Thirteen participants (median age = 22 years, 11 female) were enrolled at the university hospitals of Leuven and Freiburg. At home, participants had to attach the Sensor Dot and behind‐the‐ear electrodes to record two‐channel electroencephalogram (EEG), accelerometry, and gyroscope data. Ground truth annotations were created during a visual review of the full Sensor Dot recording. Generalized SWDs were annotated if they were 3 Hz and at least 3 s on EEG. Potential 3‐Hz SWDs were flagged by an automated seizure detection algorithm, (1) using …
2024/2
Article DetailsSarah McKeown Ruggiero
University of Pennsylvania
Epilepsia
Early life seizures and epileptic spasms in STXBP1‐related disorders
Objective Individuals with disease‐causing variants in STXBP1 frequently have epilepsy onset in the first year of life with a variety of seizure types, including epileptic spasms. However, the impact of early onset seizures and antiseizure medication (ASM) on the risk of developing epileptic spasms and impact on their trajectory are poorly understood, limiting informed and anticipatory treatment, as well as trial design. Methods We retrospectively reconstructed seizure and medication histories in weekly intervals for individuals with STXBP1 developmental and epileptic encephalopathy (DEE) with epilepsy onset in the first year of life and quantitatively analyzed longitudinal seizure histories and medication response. Results We included 61 individuals with early onset seizures, 29 of whom had epileptic spasms. Individuals with neonatal seizures were likely to have continued seizures after the neonatal period (25/26 …
2024/1/27
Article DetailsMatthew R. Hudson
Monash University
Epilepsia
Epilepsy phenotype and its reproducibility after lateral fluid percussion‐induced traumatic brain injury in rats: Multicenter EpiBioS4Rx study project 1
Objective This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites. Methods A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion‐induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow‐up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post‐TBI month, rats were video‐EEG monitored for epilepsy diagnosis. Results A total of 245 rats were video‐EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats …
2024/2
Article DetailsAlfredo Lucas
University of Pennsylvania
Epilepsia
iEEG‐recon: a fast and scalable pipeline for accurate reconstruction of intracranial electrodes and implantable devices
Objective Clinicians use intracranial electroencephalography (iEEG) in conjunction with noninvasive brain imaging to identify epileptic networks and target therapy for drug‐resistant epilepsy cases. Our goal was to promote ongoing and future collaboration by automating the process of “electrode reconstruction,” which involves the labeling, registration, and assignment of iEEG electrode coordinates on neuroimaging. We developed a standalone, modular pipeline that performs electrode reconstruction. We demonstrate our tool's compatibility with clinical and research workflows and its scalability on cloud platforms. Methods We created iEEG‐recon, a scalable electrode reconstruction pipeline for semiautomatic iEEG annotation, rapid image registration, and electrode assignment on brain magnetic resonance imaging (MRI). Its modular architecture includes a clinical module for electrode labeling and localization …
2024/3
Article DetailsRuth Ottman
Columbia University in the City of New York
Epilepsia
The role of copy number variants in the genetic architecture of common familial epilepsies
Objective Copy number variants (CNVs) contribute to genetic risk and genetic etiology of both rare and common epilepsies. Whereas many studies have explored the role of CNVs in sporadic or severe cases, fewer have been done in familial generalized and focal epilepsies. Methods We analyzed exome sequence data from 267 multiplex families and 859 first‐degree relative pairs with a diagnosis of genetic generalized epilepsies or nonacquired focal epilepsies to predict CNVs. Validation and segregation studies were performed using an orthogonal method when possible. Results We identified CNVs likely to contribute to epilepsy risk or etiology in the probands of 43 of 1116 (3.9%) families, including known recurrent CNVs (16p13.11 deletion, 15q13.3 deletion, 15q11.2 deletion, 16p11.2 duplication, 1q21.1 duplication, and 5‐Mb duplication of 15q11q13). We also identified CNVs affecting monogenic …
2024/3
Article DetailsMichael J. Boland
Columbia University in the City of New York
Epilepsia
Early life seizures and epileptic spasms in STXBP1‐related disorders
Objective Individuals with disease‐causing variants in STXBP1 frequently have epilepsy onset in the first year of life with a variety of seizure types, including epileptic spasms. However, the impact of early onset seizures and antiseizure medication (ASM) on the risk of developing epileptic spasms and impact on their trajectory are poorly understood, limiting informed and anticipatory treatment, as well as trial design. Methods We retrospectively reconstructed seizure and medication histories in weekly intervals for individuals with STXBP1 developmental and epileptic encephalopathy (DEE) with epilepsy onset in the first year of life and quantitatively analyzed longitudinal seizure histories and medication response. Results We included 61 individuals with early onset seizures, 29 of whom had epileptic spasms. Individuals with neonatal seizures were likely to have continued seizures after the neonatal period (25/26 …
2024/1/27
Article DetailsFrank Provenzano
Columbia University in the City of New York
Epilepsia
Interaction of interictal epileptiform activity with sleep spindles is associated with cognitive deficits and adverse surgical outcome in pediatric focal epilepsy
Objective Temporal coordination between oscillations enables intercortical communication and is implicated in cognition. Focal epileptic activity can affect distributed neural networks and interfere with these interactions. Refractory pediatric epilepsies are often accompanied by substantial cognitive comorbidity, but mechanisms and predictors remain mostly unknown. Here, we investigate oscillatory coupling across large‐scale networks in the developing brain. Methods We analyzed large‐scale intracranial electroencephalographic recordings in children with medically refractory epilepsy undergoing presurgical workup (n = 25, aged 3–21 years). Interictal epileptiform discharges (IEDs), pathologic high‐frequency oscillations (HFOs), and sleep spindles were detected. Spatiotemporal metrics of oscillatory coupling were determined and correlated with age, cognitive function, and postsurgical outcome. Results …
2024/1
Article DetailsMarco Mula
St George's, University of London
Epilepsia
Effect of drug treatment changes and seizure outcomes on depression and suicidality in adults with drug‐resistant focal epilepsy
Objective To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug‐resistant focal epilepsy. Methods Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6‐month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment‐related variables were assessed by using a stepwise logistic regression model. Results At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was …
2024/2
Article DetailsStanislas Lagarde (MD, PhD, Associate Professor)
Aix-Marseille Université
Epilepsia
Stereo‐EEG–based ictal functional connectivity in patients with periventricular nodular heterotopia–related epilepsy
Nodular heterotopia (NH)–related drug‐resistant epilepsy is challenging due to the deep location of the NH and the complexity of the underlying epileptogenic network. Using ictal stereo‐electroencephalography (SEEG) and functional connectivity (FC) analyses in 14 patients with NH‐related drug‐resistant epilepsy, we aimed to determine the leading structure during seizures. For this purpose, we compared node IN and OUT strength between bipolar channels inside the heterotopia and inside gray matter, at the group level and at the individual level. At seizure onset, the channels within NH belonging to the epileptogenic and/or propagation network showed higher node OUT‐strength than the channels within the gray matter (p = .03), with higher node OUT‐strength than node IN‐strength (p = .03). These results are in favor of a “leading” role of NH during seizure onset when involved in the epileptogenic‐ or …
2024/2/12
Article DetailsLaura Mirandola
Università degli Studi di Modena e Reggio Emilia
Epilepsia
Effect of drug treatment changes and seizure outcomes on depression and suicidality in adults with drug‐resistant focal epilepsy
Objective To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug‐resistant focal epilepsy. Methods Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6‐month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment‐related variables were assessed by using a stepwise logistic regression model. Results At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was …
2024/2
Article DetailsEric Kossoff
Johns Hopkins University
Epilepsia
The role of copy number variants in the genetic architecture of common familial epilepsies
Objective Copy number variants (CNVs) contribute to genetic risk and genetic etiology of both rare and common epilepsies. Whereas many studies have explored the role of CNVs in sporadic or severe cases, fewer have been done in familial generalized and focal epilepsies. Methods We analyzed exome sequence data from 267 multiplex families and 859 first‐degree relative pairs with a diagnosis of genetic generalized epilepsies or nonacquired focal epilepsies to predict CNVs. Validation and segregation studies were performed using an orthogonal method when possible. Results We identified CNVs likely to contribute to epilepsy risk or etiology in the probands of 43 of 1116 (3.9%) families, including known recurrent CNVs (16p13.11 deletion, 15q13.3 deletion, 15q11.2 deletion, 16p11.2 duplication, 1q21.1 duplication, and 5‐Mb duplication of 15q11q13). We also identified CNVs affecting monogenic …
2024/3
Article DetailsAvantika Singh
Harvard University
Epilepsia
Timing the clinical onset of epileptic spasms in infantile epileptic spasms syndrome: A tertiary health center's experience
Objective Lead time to treatment (clinical onset of epileptic spasms [ES] to initiation of appropriate treatment) is known to predict outcomes in infantile epileptic spasms syndrome (IESS). Timing the clinical onset of ES is crucial to establish lead time. We investigated how often ES onset could be established to the nearest week. We aimed to (1) ascertain the exact date or estimate the nearest week of ES onset and (2) compare clinical/demographic factors between patients where date of ES onset was determined or estimated to the nearest week and patients whose date of ES onset could not be estimated to the nearest week. Reasons for difficulties in estimating date of ES onset were explored. Methods Retrospective chart review of new onset IESS patients (January 2019–May 2022) extracted the date or week of the clinical onset of ES. Predictors of difficulty in date of ES onset estimation to the nearest week were …
2024/2/5
Article DetailsElisa Bruno
King's College London
Epilepsia
Minimum clinical utility standards for wearable seizure detectors: A simulation study
Objective Epilepsy management employs self‐reported seizure diaries, despite evidence of seizure underreporting. Wearable and implantable seizure detection devices are now becoming more widely available. There are no clear guidelines about what levels of accuracy are sufficient. This study aimed to simulate clinical use cases and identify the necessary level of accuracy for each. Methods Using a realistic seizure simulator (CHOCOLATES), a ground truth was produced, which was then sampled to generate signals from simulated seizure detectors of various capabilities. Five use cases were evaluated: (1) randomized clinical trials (RCTs), (2) medication adjustment in clinic, (3) injury prevention, (4) sudden unexpected death in epilepsy (SUDEP) prevention, and (5) treatment of seizure clusters. We considered sensitivity (0%–100%), false alarm rate (FAR; 0–2/day), and device type (external wearable vs …
2024/2/17
Article DetailsEdward J Novotny
University of Washington
Epilepsia
The role of copy number variants in the genetic architecture of common familial epilepsies
Objective Copy number variants (CNVs) contribute to genetic risk and genetic etiology of both rare and common epilepsies. Whereas many studies have explored the role of CNVs in sporadic or severe cases, fewer have been done in familial generalized and focal epilepsies. Methods We analyzed exome sequence data from 267 multiplex families and 859 first‐degree relative pairs with a diagnosis of genetic generalized epilepsies or nonacquired focal epilepsies to predict CNVs. Validation and segregation studies were performed using an orthogonal method when possible. Results We identified CNVs likely to contribute to epilepsy risk or etiology in the probands of 43 of 1116 (3.9%) families, including known recurrent CNVs (16p13.11 deletion, 15q13.3 deletion, 15q11.2 deletion, 16p11.2 duplication, 1q21.1 duplication, and 5‐Mb duplication of 15q11q13). We also identified CNVs affecting monogenic …
2024/3
Article DetailsEvan Eichler
University of Washington
Epilepsia
The role of copy number variants in the genetic architecture of common familial epilepsies
Objective Copy number variants (CNVs) contribute to genetic risk and genetic etiology of both rare and common epilepsies. Whereas many studies have explored the role of CNVs in sporadic or severe cases, fewer have been done in familial generalized and focal epilepsies. Methods We analyzed exome sequence data from 267 multiplex families and 859 first‐degree relative pairs with a diagnosis of genetic generalized epilepsies or nonacquired focal epilepsies to predict CNVs. Validation and segregation studies were performed using an orthogonal method when possible. Results We identified CNVs likely to contribute to epilepsy risk or etiology in the probands of 43 of 1116 (3.9%) families, including known recurrent CNVs (16p13.11 deletion, 15q13.3 deletion, 15q11.2 deletion, 16p11.2 duplication, 1q21.1 duplication, and 5‐Mb duplication of 15q11q13). We also identified CNVs affecting monogenic …
2024/3
Article DetailsP Emanuela Voinescu
Harvard University
Epilepsia
Lacosamide and pregnancy: Data from spontaneous and solicited reports
Objective In pregnancy, it is important to balance the risks of uncontrolled epileptic seizures to the mother and fetus against the potential teratogenic effects of antiseizure medications. Data are limited on pregnancy outcomes among patients taking lacosamide (LCM), particularly when taken as monotherapy. The objective of this analysis was to evaluate the pregnancy outcomes of LCM‐exposed pregnancies. Methods This analysis included all reports in the UCB Pharma pharmacovigilance database of exposure to LCM during pregnancy from spontaneous sources (routine clinical settings) or solicited reports from interventional clinical studies and noninterventional postmarketing studies. Prospective and retrospective reports were analyzed separately. Results At the data cutoff (August 31, 2021), there were 202 prospective pregnancy cases with maternal exposure to LCM and known outcomes. Among these …
2024/2/27
Article Details