Study for the Diagnosis and Treatment of Drug-resistant Focal Epilepsies (EpiBesta)

Multimodal Study for the Diagnosis and Treatment of Drug-resistant Focal Epilepsies

Epilepsy is a clinical condition that affects about fifty million people worldwide, with an estimated occurrence of 16-51 new cases per 100,000 people each year. In 60% of these patients, the origin of seizures is due to a localized (focal) alteration of the brain. In about 25 percent of patients with focal epilepsy, drug treatment is ineffective, a condition defined by the International League Against Epilepsy (ILAE) as drug-resistant epilepsy ; this condition results in a drastic reduction in quality of life associated with psychosocial dysfunction and an increased risk of sudden death. A possible treatment alternative for drug-resistant patients is ablation of the epileptogenic zone through surgical methods that are effective and safe when patients are carefully selected. The percentage of patients with epilepsy who are completely cured after surgery is about 70% for temporal lobe epilepsies, and can be as high as 90% in the case of some brain malformations.

Pre-surgical screening and therapeutic intervention (particularly surgery) have health care costs that are amortized over 2-6 years depending on the procedures required before surgery. In the last decade, moreover, the refinement of noninvasive/mini-invasive methods such as radiosurgery, Magnetic Resonance-guided Focused Ultrasound (MRgFUS) and laser interstitial thermal therapy (LiTT) have allowed us to hypothesize a possible specific treatment of drug-resistant patients with epileptogenic areas that are difficult to reach with traditional surgery and patients with complex comorbidities for whom the risks of standard resective surgery would outweigh the possible benefits. Finally, there is a subgroup of patients with drug-resistant epilepsy who cannot undergo ablative surgery. In these patients, seizures originate from multiple areas of the brain (multifocal epilepsy) or the epileptogenic area affects functionally eloquent areas. In these cases, alternative functional treatments are proposed, which aim to decrease the frequency and intensity of seizures and the need for medication, such as: i) application of a vagal stimulator, a pulse generator that is implanted in the chest and connected to the vagus nerve, ii) implantation of deep brain stimulation devices, iii) neuromodulation. Therefore, careful selection of patients during the diagnostic/pre-surgical process is crucial. The multimodal assessments under study, proposed in support of clinical practice, aim to improve such selection by analyzing the causative factors of seizures, the location of the epileptogenic zone, and the clinical-epileptological course of patients who are candidates for surgical or functional treatment of epilepsies.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy

• Study Type: Observational
• Enrollment (Estimated): 337

Contacts and Locations

• Study Contact: Name: Marco De Curtis, M.D.; Phone Number: 2242 02.2394.2242; Email: marco.decurtis@istituto-besta.it
• Study Contact Backup: Name: Roberta Di Giacomo, M.D.; Phone Number: 2242 02.2394.2242; Email: roberta.digiacomo@istituto-besta.it

Study Locations

• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Foundation IRCCS Carlo Besta Neurological Institute
    • Contact: Marco De Curtis, MD; Phone Number: 2242 + 39 02.2394; Email: marco.decurtis@istituto-besta.it
    • Contact: Roberta Di Giacomo, MD; Phone Number: 2242 +39 02 2394; Email: roberta.digiacomo@istituto-besta.it
    • Principal Investigator: Marco De Curtis, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with focal epilepsy, long history of drug-resistant seizures, on mono- or polypharmacy antiepileptic therapy affected by known epileptogenic lesion or without lesions evident on neuroimaging investigations (cryptogenic). - - Patients with recent onset of focal seizures, in mono- or polypharmacy, with controlled or rare seizures, or still in the absence of antiepileptic therapy affected by neoplastic lesion.

Description

Inclusion Criteria:

• Adult patients with focal epilepsy, long history of drug-resistant seizures, on mono- or polypharmacy antiepileptic therapy affected by known epileptogenic lesion or without lesions evident on neuroimaging investigations (cryptogenic). - - - Patients with recent onset of focal seizures, in mono- or polypharmacy, with controlled or rare seizures, or still in the absence of antiepileptic therapy affected by neoplastic lesion.

Exclusion Criteria:

• Patients in whom the diagnosis of epilepsy is doubtful. Patients with cognitive or psychiatric disorders that prevent participation in an interview, proper understanding of informed consent, or completion of questionnaires.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Treatment	To assess the clinical-epileptological course of patients with focal epilepsy who are candidates for surgical treatment of epilepsies	10 years
Alternative to resective surgery	To assess the clinical-epileptological course of patients with focal epilepsy who are candidates for diagnostic and therapeutic interventions as an alternative to conventional resective surgery.	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate the factors	To investigate the factors (environmental/molecular/genetic) leading to the development of epilepsies, in particular the forms resistant to pharmacological treatment	10 years
Identify new approaches	To identify new and more effective non-invasive approaches in order to precisely identify the surgical target (epileptogenic zone) reducing the use of invasive monitoring and treatment techniques	10 years
Improving clinical outcomes	Improving clinical outcomes by reducing costs and risks associated with diagnostic and therapeutic procedures in epilepsy surgery	10 years
Database	Structuring a database of patients with drug-resistant focal epilepsy for future treatment	10 years

Collaborators and Investigators

• Sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2021
• Primary Completion (Estimated): March 1, 2041
• Study Completion (Estimated): March 1, 2041

Study Registration Dates

• First Submitted: December 6, 2024
• First Submitted That Met QC Criteria: January 21, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Epilepsy surgery; drugs resistant focal epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: EpiBesta

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No