TDCs to Treat Drug-resistant Epilepsy

Spanish Foundation for Neurometrics Development150 enrolled

Overview

Epilepsy is the fourth overall neurologic disorder, regardless of age and gender, affecting more than 50 million people worldwide. Modern epidemiological studies indicate that the global annualized cumulative incidence ranges between 42.8 and 67.8 new cases per 100,000 people each year, with figures scaling up to 139 per 100,000 in low- and middle-income regions. A community-based study conducted in France concluded that up to 22.5% of patients could be classified as presenting drug-resistant epilepsy. This group presents significant hazards such as an increased risk of death, injuries, psychosocial dysfunction, and a reduced quality of life.

The International League Against Epilepsy (ILAE) defines drug-resistant epilepsy as follows: A failure of adequate trials of two (or more) tolerated, appropriately chosen, appropriately used antiepileptic drugs (whether administered as monotherapies or in a combination) to achieve freedom from seizures. This significant amount of patients is the drive to develop different approaches in order to offer alternatives for control.In this regard, non-invasive brain stimulation protocols lead the way, since the pathophysiological substrate of epilepsy is an enhanced cortical excitability, leading to paroxysmal depolarization shifts, an enhanced probability of high-frequency and hypersynchronous activity of small neuronal networks, and the abnormal spreading of this pathological activity along cortico-cortical and cortico-subcortical neuronal connections.Transcranial direct current stimulation (tDCS) consists of short-lasting electric stimulus delivered to specific brain regions. When delivered repeatedly, it generates long-lasting cortical excitability shifts through mechanisms resembling long-term depression (LTD). In this study, cathodal tDCS (c-tDCS) is utilized to apply a hyperpolarizing current directly over the primary epileptogenic focus, aiming to suppress pathological network activity and reduce seizure frequency in pediatric patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Eligibility

Sex: ALLMin age: 18 MonthsMax age: 120 MonthsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Pediatric patients aged between 4 and 6 years at the time of screening. * Formally diagnosed with drug-resistant focal epilepsy according to the International League Against Epilepsy (ILAE) criteria (failure of adequate trials of two or more tolerated, appropriately chosen, and appropriately used antiepileptic drug regimens). * Experiencing a baseline frequency of at least 3 clinical seizures per week, documented via a reliable prospective seizure diary kept by parents or caregivers. * Patients whose legal guardians are willing and able to provide written informed consent, and patients who can provide assent when age-appropriate. Exclusion Criteria: * Presence of metallic implants in the brain or skull (e.g., surgical clips, cochlear implants) near the site of electrode placement. * History of severe cardiac arrhythmias, unstable cardiovascular disease, or baseline pacemaker dependent, which may compromise safety during Heart Rate Variability (HRV) monitoring. * Progressive neurological disorders, neurodegenerative diseases, or active brain tumors. * Recent changes in antiepileptic drug (AED) dosages or types within the 4 weeks prior to baseline screening. * Any active skin lesions, inflammation, or structural cranial abnormalities at the target electrode site that prevent safe application of the tDCS pads. * Current participation in another clinical trial involving investigational drugs or neurostimulation devices.

Outcomes

Primary Outcomes

Weekly Seizure Frequency

Assessment of patient-reported quality of life. The total score ranges from 0 to 100 points, where higher scores indicate a better quality of life. This scale will be evaluated as a single independent outcome measure. BaselineF LIFE IN EPILEPSY - QOLIE-31.