Drug-resistant epilepsy

There are over 30 million people with drug-resistant epilepsy worldwide. When neuroimaging and non-invasive neural recordings fail to localise seizure onset zones (SOZ), intracranial recordings become the best chance for localisation and seizure-freedom in those patients. However, intracranial neural activities remain hard to visually discriminate across recording channels, which limits the success of intracranial visual investigations. In this presentation, I present methods which quantify intracranial neural time series and combine them with explainable machine learning algorithms to localis

…cerebral cortex and a main cause of drug-resistant epilepsy in children. A loss of the excitation and inhibition (E/I) balance has emerged as a key feature for neuronal hyperexcitability, underlying the pathogenesis of seizures. However, it remains unclear how synaptic ultrastructure is altered in the human patients with FCD. Here we performed morphological analyses on the synaptic density, shape, and distribution of intrasynaptic organelles in the temporal cortical layer III of a FCD patient using 3D electron microscopy. Our qu

…In the current study 31 drug-resistant epilepsy patients undergoing stereo EEG surgery with depth electrode contacts implanted in various MLT regions. During continuous intracranial EEG recording, each participant was presented with a series of images of neutral objects. Across patients, we delivered a brief stimulation to the BLA (8 trains of 50-Hz pulses at 0.5 mA) before, during, or a

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. Despite the availability of many antiepileptic drugs (AEDs), 30% of the patients are resistant to standard therapies. GABAA receptor (GABAAR) expression and function are altered in the epileptic tissue, resulting in impaired inhibition and reduced sensitivity to GABAergic AEDs. Therefore, we are developing a gene therapy strategy for focal drug-resistant epilepsy based on the overexpression of specific GABAAR subunits in hippocampal excitatory neurons, aiming at increasing network inhibition and enhancing the effe

Poor patient outcomes in resective epilepsy surgery remain an area of clinical concern. Regardless of epilepsy type, a third or greater of drug-resistant epilepsy (DRE) patients who undergo resection do not report seizure freedom at a two-year follow-up. One of the likely causes is that current methods for identifying which tissue to resect are subjective and potentially inaccurate. Much of resective surgery planning is based on identification of initial ictogenic tissue--the seizure onset zone (SOZ). However, complete resection of the SOZ, as currently identified, is a poor prognosticator of

…memory performance in patients with drug-resistant epilepsy.Twenty-nine patients completed simple eye-tracking tasks, probing Smooth Pursuit (SP) and Anti-Pro-Saccade (AP) gaze movements, and were groupe

…approach for drug resistant epilepsy treatment. However, the optimaltiming of stimulation relative to the ongoing brain oscillations remains to be established foroptimizing efficiency.This study investigates the phase specificity of transcranial ISP stimulation in terminatingepileptic seizures, using both animal models and clinical data. By analyzing deep-brainactivity during seizures in rats and post-hoc analysis of clinical data from human patientsunderwent closed-loop ictal stimulation,

Temporal lobe epilepsy (TLE) is one of the most common forms of drug-resistant epilepsy and its precise etiology is still unknown making it imperative to understand the molecular pathways contributing to the disease. It is, therefore, crucial to study the therapeutic targets and signalling pathways involved in the treatment of this disease. Pyk2 has previously been shown to be activated in stress-mediated pathways in the brain. Consequently, we hypothesized that Pyk2 activation might contribute to the pathogenesis of the disease. A pilocarpine model of TLE was used to examine p-Pyk2Tyr402 prot

…(ASD), Down syndrome (DS), and drug-resistant epilepsy (DRE). Interestingly, NKCC1 inhibition rescues core symptoms of these brain conditions in rodent models and/or clinical trials. However, current NKCC1 inhibitors have diuretic effects by also inhibiting the kidney Cl transporter NKCC2. These diuretic effects pose critical health conc

…laminar neural recording in drug-resistant epilepsy patients. The 3D array comprises nine parallel shanks (3x3, lateral spacing: 1 mm) fixed on a 4.5x4.5 mm PEEK platform. An individual shank (185 μm OD) has a conical-shaped taper and contains 16 or 24 recording sites (15 μm OD microwires, Pt/Ir–90/10%; inter-site distances may vary between 50–200 μm). The microwires provide an uninterrupted connection between the recording sites and a PCB with Omnetics connectors for headstage input. The 3D array allows for easy and quick oper

The neurovascular unit (NVU) consists of cerebral blood vessels, neurons, astrocytes, microglia, and pericytes. It plays a vital role in regulating blood flow and ensuring the proper functioning of neural circuits. Among other, this is made possible by the blood-brain barrier (BBB), which acts as both a physical and functional barrier. Previous studies have shown that dysfunction of the BBB is common in most neurological disorders and is associated with neural dysfunction. Our studies have demonstrated that BBB dysfunction results in the transformation of astrocytes through transforming growth

Epilepsy surgery is a safe but underutilised treatment for drug-resistant focal epilepsy. One challenge in the presurgical evaluation of patients with drug-resistant epilepsy are patients considered “MRI negative”, i.e. where a structural brain abnormality has not been identified on MRI. A major pathology in “MRI negative” patients is focal cortical dysplasia (FCD), where lesions are often small or subtle and easily missed by visual inspection. In recent years, there has been an explosion in artificial intelligence (AI) research in the field of healthcare. Automated FCD detection is an area wh