Publications by authors named "Matthias J 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: 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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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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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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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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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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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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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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The idiopathic generalized epilepsies (IGE) make up a fifth of all epilepsies, but <1% of epilepsy research. This skew reflects misperceptions: diagnosis is straightforward, pathophysiology is understood, seizures are easily controlled, epilepsy is outgrown, morbidity and mortality are low, and surgical interventions are impossible. Emerging evidence reveals that patients with IGE may go undiagnosed or misdiagnosed with focal epilepsy if EEG or semiology have asymmetric or focal features.

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Artificial intelligence (AI)-based tools are widely employed, but their use for diagnosis and prognosis of neurological disorders is still evolving. Here we analyse a cross-sectional multicentre structural MRI dataset of 696 people with epilepsy and 118 control subjects. We use an innovative machine-learning algorithm, Subtype and Stage Inference, to develop a novel data-driven disease taxonomy, whereby epilepsy subtypes correspond to distinct patterns of spatiotemporal progression of brain atrophy.

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Objective: The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics.

Methods: We investigated 123 participants-23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME-who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function.

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Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk.

Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures.

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Aims: Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC).

Methods And Results: We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004.

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There is currently no evidence to support the use of antiseizure medications to prevent unprovoked seizures following stroke. Experimental animal models suggested a potential antiepileptogenic effect for eslicarbazepine acetate (ESL), and a Phase II, multicenter, randomized, double-blind, placebo-controlled study was designed to test this hypothesis and assess whether ESL treatment for 1 month can prevent unprovoked seizures following stroke. We outline the design and status of this antiepileptogenesis study, and discuss the challenges encountered in its execution to date.

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Perampanel, a noncompetitive antagonist of the postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic-clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping-derived measures of activation and task-modulated functional connectivity (psychophysiologic interaction), we investigated 14 people with focal epilepsy who had verbal fluency functional magnetic resonance imaging (fMRI) twice, before and after the add-on treatment of perampanel. For comparison, we included 28 people with epilepsy, propensity-matched for clinical characteristics, who had two scans but no change in anti-seizure medication (ASM) regimen in-between.

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Objective: Affective disorders are frequent comorbidities of temporal lobe epilepsy (TLE). The endogenous opioid system has been implicated in both epilepsy and affective disorders, and may play a significant role in their bidirectional relationship. In this cross-sectional study, we investigated the association between μ-opioid receptor binding and affective disorders in patients with TLE.

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Article Synopsis
  • Neurotransmitter receptors play a key role in signal transmission in the brain, but their organization and impact on brain function are not well understood.
  • Researchers created a comprehensive 3D normative atlas of 19 neurotransmitter receptors and transporters in the brains of over 1,200 healthy individuals using advanced imaging techniques.
  • The study revealed how these receptor profiles relate to brain structure, function, and even abnormalities linked with various mental disorders, paving the way for new research into brain organization and disorders.
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Introduction: Brivaracetam (BRV) is licensed as an adjunctive treatment for focal epilepsy. We describe our clinical experience with BRV at a large UK tertiary center.

Methods: Adults initiated on BRV between July 2015 and July 2020 were followed up until they discontinued BRV or September 2021.

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