Managing Agitated Delirium With Neuroleptics and Anti-Epileptics as a Neuroleptic Sparing Strategy...
DeliriumEpileptics1 moreTo examine the effects of haloperidol, chlorpromazine, valproic acid and placebo, in conjunction with standardized non-pharmacologic interventions, in the first line treatment of agitated delirium in hospitalized patients with cancer. This double-blind, randomized clinical trial aims to provide evidence on various therapeutic options for palliating delirium, thereby reducing delirium-related distress and ultimately alleviating suffering.
Navigation and Free Recall in Chronically Implanted Humans
EpilepsyThis study is designed to identify brain activity associated with good memory in subjects with a chronically implanted RNS® device and to study the effects of therapeutic stimulation for epilepsy on memory. This will be accomplished through analysis of ECoG data collected during memory encoding for short and long-term free recall as well as during navigation tasks.
Epileptic Hippocampus in Alzheimer's Disease
Alzheimer DiseaseMild Cognitive ImpairmentThe major goals of the study are to 1) characterize hippocampal activity in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and AD who have suspected hippocampal epileptic activity based on scalp EEG recordings from IRB # 21-001603; 2) study the efficacy of brivaracetam to suppress epileptic activity and pathological high frequency oscilations (pHFOs) during hippocampal depth electrode and scalp EEG in patients with MCI and AD; and 3) investigate the effects of brivaracetam on cognition in an open-label pilot study.
Bridging Gaps in the Neuroimaging Puzzle: New Ways to Image Brain Anatomy and Function in Health...
HealthyEpilepsy2 moreThe human brain presents outstanding challenges to science and medicine. Brain function and structure span broad spatial scales (from single neurons to brain-wide networks) as well as temporal scales (from milliseconds to years). Currently, none of the tools available for studying the brain can fully capture its structure and function across these diverse scales - "the neuroimaging puzzle". This poses crucial limitations to understanding how the brain works, and how it is affected by numerous diseases. The central goal of this project is to expand currently available tools for non-invasive human brain imaging, to bridge critical gaps in the neuroimaging puzzle. New methodologies will be developed, focused on ultra-high field magnetic resonance imaging (UHF MRI) and its combination with electroencephalography (EEG). New contrast mechanisms and technological advances enabled by UHF MRI and EEG will be explored to allow unprecedented views into the microstructure of brain regions like the thalamus, and to capture the activity of large-scale neuronal networks in the brain with high sensitivity, temporal and spatial specificity. These advances will be directly applied to address open questions in the diagnosis and treatment of essential tremor, and psychosis. In general, improved brain imaging techniques are critical for a deeper understanding of how the brain works, and to detect and characterize diseases more effectively, thereby improving clinical management and leading to a healthier population. The non-invasive characterization and treatment of neurodegenerative diseases like tremor is particularly relevant to aging modern societies.
Neurodevelopmental Impact of Epilepsy on Autonomic Function in Dravet Syndrome
Dravet SyndromeEpilepsyDravet Syndrome (DS) is a severe epileptic encephalopathy, which main cause is mutations of SCN1A, the gene coding for the Nav1.1 voltage-gated sodium channel. DS is characterized by childhood onset, severe cognitive deficit and drug-resistant seizures, including several generalized convulsive seizures per day, frequent status epilepticus and high seizure-related mortality rate. Sudden and unexpected death in epilepsy (SUDEP) represents the major cause of premature deaths. The risk of SUDEP is thus about 9/1000-person-year in comparison with about 5/1000-person-year in the whole population of patients with drug-resistant epilepsies. Experimental and clinical data suggest that SUDEP primarily result from a postictal central respiratory dysfunction. SUDEP in DS, might be the result of a seizure-induced fatal apnea in a patient who had developed epilepsy-related vulnerability to central autonomic and/or respiratory dysfunction. However, a key clinical issue which remains to be addressed is the temporal dynamics of the onset and evolution of the autonomic vulnerability in these patients. The main clinical risk factor of SUDEP is the frequency of convulsive seizures and the SUDEP risk can vary along the evolution of epilepsy. Although non-fatal seizure-induced ataxic breathing can be observed in patients with DS, whether or not repetition of seizures results in long-term alterations of breathing remains unclear. In the AUTONOMIC project, it will be investigate in a homogenous population of patients with DS the exact interplay between epilepsy-related cardiac and respiratory alterations on the one hand and the relation between the underlying neurodevelopmental disease, the repetition of seizure per se and these epilepsy-related autonomic alterations on the other hand. Autonomic functions will be investigated in the inter-ictal period (i.e. in the absence of immediate seizures, Work Package 1 (WP1)) and in the peri-ictal period, i.e. in the immediate time before, during (if possible) and after seizures (WP2). A multicenter cohort will be constituted, allowing to collect the inter-ictal and ictal cardio-respiratory data required in the 2 WP. The study will be sponsored by the Lyon's University Hospital. Patients will be recruited over a period of 24 months in one of the three participating clinical center. All patients will first enter in a prospective baseline period of 3 to 6 months duration in order to collect seizure frequency. After this period, all patients will then undergo a 24-48 hours video-EEG recordings as part of the routine clinical care. The monitoring will also include a full-night polysomnography. This patients will be eligible for inclusion in an extension follow-up study will monitor vital status every year in order to investigate long-term mortality, including SUDEP. The AUTONOMIC project will provide important results which will pave the way to develop and eventually validate therapeutic intervention to prevent SUDEP. By deciphering the exact interplay between epilepsy-related cardiac and respiratory alterations on the one hand and the relation between the underlying neurodevelopmental disease, the repetition of seizure per se and these epilepsy-related autonomic alterations on the other hand, the project will primarily deliver clinically relevant biomarkers.
Human Intracranial Electrophysiology
EpilepsyThis study will enroll patients with epilepsy who are being evaluated for epilepsy surgery and have electrodes implanted in the brain and/or have electrodes on the scalp. Additionally, this study will recruit normal and online controls (participants who do not have epilepsy). Participants will be asked to participate in 1 to 2 (30-90 minutes) daily sessions designed to test aspects of human cognition such as memory, speech, language, feeling, movement, attention, sound perception, and emotions. Generally, this will involve working on a computer, looking at pictures or watching videos, and answering questions. Additionally, participants may be asked to be hooked up to additional equipment such as eye tracker, electrical stimulator, heart rate monitor, sweat monitor or other non-invasive equipment. The overall aim of this study is to use human intracranial electrophysiology (the recording of the electrical activity of the human brain) to study localization and function of the human brain.
Precision Medicine in the Treatment of Epilepsy
EpilepsyPrimary objectives: The purpose of this study is to identify single and composite biomarkers (from neuroimaging, electrophysiological, and non-imaging biological measures), clinical measures (from cognitive, psychometric, and behavioral test scores), and risk/protective factors (e.g., from medical history, socioeconomic status, coping, lifestyle) that can: Predict antiseizure medication (ASM) treatment outcome, psychiatric, cognitive, or behavioral comorbidities, and quality of life in newly diagnosed epilepsy patients (Cohort II-III). Predict a second epileptic seizure/epilepsy diagnosis and behavioral, cognitive, psychiatric dysfunction and quality of life in patients after a first epileptic seizure (Cohort I).
Flexible Representation of Speech
EpilepsyThe overarching goal of this exploratory research is to understand the dynamic and flexible nature of speech processing in the human supratemporal plane. The temporal lobe has long been established as a region of interest in the speech perception and processing literature because it contains the auditory cortex. More recently, research has localized the supratemporal plane as an area that exhibits response specificity to acoustic properties of complex auditory signals like speech. The supratemporal plane, comprised of Heschl's gyrus, the planum polare, and the planum temporale, is capable of the rapid spectrotemporal analysis required to map acoustic information to linguistic representation. Neural activity in this area, however, is rarely studied directly because it is difficult to access with non-invasive measures like scalp electroencephalography (EEG). Capitalizing on the unique opportunity to access these areas via routine clinical stereoelectroencephalography (sEEG) in a patient population, this study seeks to understand how cortical responses reflect the diagnosticity of two acoustic-phonetic dimensions of interest and how responses rapidly and flexibly adapt to changes in listening demands. Examining how neural response to voice onset time (VOT) and fundamental frequency (F0) modulates as a function of perceptual weight carried in signaling phoneme categories, and identifying how changes in listening context shift perceptual weight, will provide invaluable data that indicates how speech processing flexibly adapts to short-term acoustic patterns.
Impact of Epileptic Discharge on the Structural Connectivity of the Developing Brain
EpilepsiesFocal2 moreFocal epilepsy is associated with widespread alterations in structural brain connectivity, often present at the disease onset and related to learning disabilities. Whether ongoing seizure activity contributes to network pathology is a matter of debate. This study intends to measure the impact of seizures on structural connectivity on a local and on a global level. In children examined with intracerebral electrodes to evaluate whether a surgical cure can be proposed, we combine intracerebral stereotactic electroencephalography (EEG) recordings with diffusion weighted imaging of white matter fibers. On the local level, the study will quantify the number of deficient connections in the seizure onset zone. On a global level, the study will compare the white matter fibers of the left and right hemisphere to probe whether physiological language lateralization is preserved.
The Becoming of Children With Doose Syndrome
Doose SyndromeEpileptic Syndromes1 moreDoose syndrome is a rare epileptic syndrome that can lead to learning difficulties and a poor quality of life. The goal of this study is to evaluate the evolution of epilepsy and its consequences on cognitive development and learning issues in children with Doose syndrome.