"Development of a Comprehensive Innovative Technology for Diagnostic Selection and Surgical Treatment of Drug-Resistant Focal Epilepsy"

Individual Registration Number (IRN): BR28512409

Implementation period: 2025–2026

Funding source – Ministry of Science and Higher Education of the Republic of Kazakhstan (Contract No. 129-PCF-25-26)

Head of the Temporary Research Team – Mukhit Abdimuratovich Dosov

Program Goal:

To introduce innovative diagnostic methods, develop modern treatment approaches for drug-resistant forms of epilepsy, and identify effective surgical treatment methods to improve treatment outcomes and patient adaptation in society.

Program Objectives:

1. Improving diagnostic, treatment, and social adaptation outcomes in patients with drug-resistant forms of epilepsy through the optimization and implementation of a justified system for presurgical diagnostics and surgical correction of the disease. Focused on early detection of focal epilepsy (FE), localization and preservation of the epileptogenic focus, optimized diagnostic methods will determine their significance in ensuring the accuracy of resective surgery and improving surgical outcomes (Engel class assessment) and patient social adaptation. A retrospective analysis (data from 100 patients from 2017–2024) and a prospective analysis (50 patients) of the complex, multifactorial integration of data will allow the formation of a pathogenetically justified system for managing FE through effective surgical intervention. A comprehensive technology based on this system for diagnosis, patient selection, and surgical treatment of drug-resistant FE will be piloted and implemented at the BMTC UDP.
2. Study of structural changes in the epileptogenic focus and neurological disorders through the comparison of dynamics in electrophysiological, molecular-genetic, pathomorphological, and clinical data. This analysis is crucial for understanding the structural basis of epileptic foci and identifying correlations with clinical outcomes. It will allow for the identification of the most accurate localization of the epileptogenic focus. Targeted gene sequencing will identify rare and common gene variants potentially involved in seizure recurrence or remission.
3. Investigation of the structure, severity, and dynamics of major cognitive impairments affecting quality of life and social adaptation in patients with drug-resistant epilepsy. A prospective analysis will assess the severity and changes in neuropsychological indicators of attention and executive functions before and one year after surgery using the Epitrack screening tool. Epitrack evaluates attention and cognitive functions through verbal and visuomotor mechanisms.
4. Development of algorithms for assessing structural and functional neuroimaging data aimed at creating a system for selecting patients with severe forms of drug-resistant epilepsy for surgical or alternative treatments. Evaluating the effectiveness of preoperative, surgical, and postoperative approaches will allow a comparison of domestic and international data and the development of a pathogenetically justified standard for selecting patients for surgical treatment of the most complex cases and alternative treatment of difficult-to-treat epilepsy.
5. Analysis of modern methods of presurgical preparation and surgical treatment organization, and comparison of their effectiveness. The selection and implementation of the optimal system into daily clinical practice. The results of this analysis, along with findings from this program, will enhance clinical protocols for surgical preparation and effective surgical treatment methods.
6. Development of a digital database of clinical, genetic, and neuroimaging data of patients. The architecture of the database will ensure timely data entry, effective storage, and search across various data types for analysis. The scientific data will serve as a basis for future scientific research directions.

The Technology Readiness Level (TRL) of the development at the beginning of the program corresponds to Level 7 of the Production Mastery Stage, in accordance with the Methodology for determining TRL of scientific organizations and research universities, and their developments (Appendix to the Order of the Chairman of the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan dated July 18, 2023).

As part of the pilot production, all steps will be completed for certification and obtaining the necessary production documentation, confirming the compliance of clinical results with international standards.

Thus, upon completion of the program, TRL Levels 7–8 will be achieved, and readiness for the production of a technology for diagnostic selection and surgical treatment of drug-resistant focal epilepsy at the clinical practice level will be ensured.

Here is the English translation of the section titled "Scientific Novelty and Significance of the Program", including the contact information at the end:

Scientific Novelty and Significance of the Program

Timely replacement at the level of clinical practice of ineffective symptomatic antiepileptic drug therapy for focal epilepsy (FE) with pathogenetically grounded resective surgical technologies will significantly reduce the cost of subsidized medication for drug-resistant forms of FE. The standards, clinical guidelines, and algorithms developed based on the obtained results—adapted for different levels of medical care within a unified clinical framework—will help address the issue of accessibility to an integrated innovative technology for diagnosis, selection, and surgical treatment of drug-resistant FE in Kazakhstan.

The competitiveness of the research results is ensured, on the one hand, by the assessment of structural changes in the epileptogenic focus and neurological disorders through the comparison of electrophysiological, molecular-genetic, pathomorphological, and clinical data dynamics. According to a preliminary national literature review, such studies have not yet been conducted in Kazakhstan. Thus, the national healthcare system may gain insights into new diagnostic opportunities. Furthermore, the assessment of the prognostic value of structural genomic variability in the Kazakh population will contribute to the understanding of general pathophysiological links and open new therapeutic avenues.

The main distinction of this project from previous ones lies in the formation of a pathogenetically grounded, stage-by-stage management system for FE based on complex, multifactorial integration of diagnostic data through effective surgical intervention. This approach expands the possibilities for scientific exploration and may uncover new insights into the pathogenesis of FE.

Additionally, the detailed description of a research cohort of 100 individuals, in which a large number of confounding factors will be accounted for, will provide new knowledge by examining the largest differences at the extremes of the quantitative distribution of phenotypic traits. The epidemiological landscape of FE among over 25,000 individuals of Kazakh ethnicity from the patient population of the BMTC UDP RK (Republic of Kazakhstan) will further enrich the study’s scope. No such research has been conducted in Kazakhstan to date.

Contact Information:

Dosov Mukhit Abdimuratovich – +7 705 294 27 17