Publications by authors named "Matthias Koepp"

The persistence of common, heritable conditions, like epilepsy, that are associated with reduced reproductive fitness is an evolutionary paradox. Endogenous analgesic, anti-depressant, and inflammatory mechanisms able to repair compromised functions can offer advantages in unexpected crises. Here, we challenge current thinking about the detrimental effects of seizures and epilepsy and suggest that (1) seizure-driven neuroplasticity might provide a protective mechanism, (2) seizure-induced neurotransmitter release not only helps to stop seizures but also increases resilience to pain, and (3) innate immune mechanisms triggered by recurrent seizures might neutralize novel viruses, like SARS-CoV-2, more rapidly, and so provided protection during the recent pandemic.

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Objective: Phosphorylated tau (pTau) has been reported in surgical resections in refractory epilepsy. It is unclear whether this is activity-driven physiological pTau or signifies the advent of neurodegenerative cascades, relevant to memory decline. To date, primarily hippocampal sclerosis and focal cortical dysplasia (FCD) type II have been studied.

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Objective: Hypothalamic hamartomas (HHs) are developmental malformations associated with focal epilepsy. We investigated the patterns of gray matter morphology and cerebral metabolism in individuals with HHs, with and without focal to bilateral tonic-clonic seizures (FBTCSs), aiming to clarify the accompanying network abnormalities.

Methods: We analyzed magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (PET) data from 59 patients with HHs (28 with FBTCSs, 31 without), as well as MRI data from 30 healthy controls (HCs) and PET data from 45 HCs.

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Background: Acute symptomatic seizures (ASyS) increase the risk of epilepsy and mortality after a stroke. The impact of the timing and type of ASyS remains unclear.

Methods: This multicenter cohort study included data from 9 centers between 2002 and 2018, with a final analysis in February 2024.

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Approximately 20% of epilepsy is caused by acute central nervous system insults such as traumatic brain injury (TBI), stroke, and infection. There is a latent period of weeks to years between the insult and epilepsy onset, which offers an opportunity to prevent epilepsy. No preventive treatments exist.

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Knowledge of the structural underpinnings of human verbal memory is scarce. Understanding the human verbal memory network at a finer anatomical scale will have important clinical implications for the management of patients with verbal memory impairment. In this cross-sectional study, we aimed to assess the contributions of cerebral cortex and hippocampal subfields to verbal memory encoding in temporal lobe epilepsy.

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Approximately 40% of individuals undergoing anterior temporal lobe resection for temporal lobe epilepsy experience episodic memory decline. There has been a focus on early memory network changes; longer-term plasticity and its impact on memory function are unclear. Our study investigates neural mechanisms of memory recovery and network plasticity over nearly a decade post-surgery.

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Background And Objectives: Mesial temporal lobe epilepsy (mTLE) is generally associated with focal brain atrophy, but little knowledge exists on possible disease-related hypertrophy of brain structures. We hypothesized that repeated seizures or adaptive plasticity may lead to focal brain hypertrophy and aimed to investigate associated clinical correlates.

Methods: In this cohort study, we included patients with mTLE undergoing detailed epilepsy evaluations and matched healthy volunteers (HVs) from 2 tertiary centers (discovery and validation cohorts).

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Objective: Blood-brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals.

Methods: We scanned 50 drug-resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE-MRI.

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Objective: Cortical atrophy close to medial temporal structures has been described consistently in patients with temporal lobe epilepsy (TLE). Successful TLE surgery may have a neuroprotective effect preventing further atrophy of temporal and extratemporal cortex. However, the effects of epilepsy surgery on subcortical structures demand additional enlightenment.

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Article Synopsis
  • White matter changes in temporal lobe epilepsy (TLE) are linked to cognitive impairments and possible neurodegenerative processes, with a study examining surgical resections from 44 patients.
  • The research found increased arteriolosclerosis and alterations in microvascular structure, including reduced vessel size and higher pericyte coverage, particularly in deeper white matter, independent of age and linked to epilepsy duration.
  • Additionally, there were significant changes in glial and myelin cell densities, with gene expression analysis indicating stronger myelination reductions in patients with hippocampal sclerosis, highlighting a relationship between imaging abnormalities and cognitive decline.
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Background And Objectives: Neuroimaging studies have so far identified structural changes in individuals with juvenile myoclonic epilepsy (JME) when compared with controls. However, the underlying mechanisms of drug-resistant JME remain unknown. In this study, we aimed at characterizing the structural underpinnings of drug-resistant JME using MRI-derived cortical morphologic markers.

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Article Synopsis
  • The 17th Eilat Conference on New Antiepileptic Drugs and Devices was held in Madrid from May 5-8, 2024, focusing on investigational drugs for epilepsy.
  • Presentations included advanced clinical compounds with available antiseizure activity data, such as azetukalner, bexicaserin, radiprodil, soticlestat, and STK-001.
  • The diversity in these compounds reflects various approaches to developing new treatments for seizures and epilepsy, with some already showing efficacy in clinical trials.
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Background: Juvenile myoclonic epilepsy (JME) is associated with cortical thinning of the motor areas. The relative contribution of antiseizure medication to cortical thickness is unknown. We aimed to investigate how valproate influences the cortical morphology of JME.

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Epilepsy is a common brain disorder, characterized by spontaneous recurrent seizures, with associated neuropsychiatric and cognitive comorbidities and increased mortality. Although people at risk can often be identified, interventions to prevent the development of the disorder are not available. Moreover, in at least 30% of patients, epilepsy cannot be controlled by current antiseizure medications (ASMs).

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Article Synopsis
  • - The Eilat Conference on New Antiepileptic Drugs and Devices, held in Madrid in May 2024, served as a platform for discussing recent advances in therapies for epilepsy and seizures involving scientists, clinicians, and health professionals.
  • - Key treatments showcased included AMT-260 (gene therapy for drug-resistant seizures), BHV-7000 (for focal epilepsy), and several others targeting conditions like Dravet syndrome and Lennox-Gastaut syndrome.
  • - The conference highlighted innovative drug candidates aimed at improving outcomes for patients with epilepsy, with a focus on drug-resistant cases and mechanisms like potassium channel activation and GABAergic neuron modulation.
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Introduction: About 25 % of new-onset epilepsies are diagnosed after age 65. Late-onset epilepsy (LOE) is predicted to become a major healthcare problem in the next 15 years as the global population increases and ages. Neurodegenerative disorders account for 10-20 % of LOE, while over 20 % of these patients have an unknown etiology.

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Objective: Anterior temporal lobe resection (ATLR) effectively controls seizures in medically refractory temporal lobe epilepsy but risks significant episodic memory decline. Beyond 1 year postoperatively, the influence of preoperative clinical factors on episodic memory and long-term network plasticity remain underexplored. Ten years post-ATLR, we aimed to determine biomarkers of successful memory network reorganization and establish presurgical features' lasting impact on memory function.

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Objective: Amygdala enlargement can occur in temporal lobe epilepsy, and increased amygdala volume is also reported in sudden unexpected death in epilepsy (SUDEP). Apnea can be induced by amygdala stimulation, and postconvulsive central apnea (PCCA) and generalized seizures are both known SUDEP risk factors. Neurite orientation dispersion and density imaging (NODDI) has recently provided additional information on altered amygdala microstructure in SUDEP.

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Purpose: P-glycoprotein (P-gp) has been hypothesized to be involved in drug-resistance of epilepsy by actively extruding antiseizure medications (ASMs) from the brain. The P-gp inhibitor tariquidar (TQD) has been shown to effectively inhibit P-gp at the human blood-brain barrier, improving brain entry of several ASMs. A potential strategy to overcome drug-resistance is the co-administration of P-gp inhibitors such as TQD to ASMs.

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Poststroke epilepsy (PSE) is associated with higher mortality and poor functional and cognitive outcomes in patients with stroke. With the remarkable development of acute stroke treatment, there is a growing number of survivors with PSE. Although approximately 10% of patients with stroke develop PSE, given the significant burden of stroke worldwide, PSE is a significant problem in stroke survivors.

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Article Synopsis
  • After having a stroke, some people might have seizures, which can affect their ability to drive safely.
  • Researchers studied over 4,400 stroke survivors to figure out their risk of having a seizure in the next year using the SeLECT model.
  • The results showed that people without seizures right after their stroke have a lower risk, while those with seizures have a much higher risk, and tools like apps can help decide if they can drive safely.
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Objective: To assess asymptomatic rates and severity of SARS-CoV-2 infection in people with epilepsy and their healthcare workers in a long-term care facility which had implemented weekly surveillance testing between April 2020 and June 2022.

Methods: Questionnaires focused on objective and subjective COVID-19 symptoms for people with epilepsy residing in and their healthcare workers at the Chalfont Centre for Epilepsy in June 2022. Demographic information, comorbidities, and seizure frequency were gathered from medical records.

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Article Synopsis
  • - This study investigates how using language fMRI-guided tractography can predict naming difficulties after surgery in patients with temporal lobe epilepsy (TLE).
  • - It involved 20 patients who underwent fMRI tasks to assess brain activation and track white matter language pathways; results indicated that larger volumes of these tracts were linked to greater naming decline post-surgery.
  • - The findings suggest that analyzing white matter tract volumes can help predict surgical outcomes and potentially reduce the risk of language deficits in TLE patients.
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