Machine learning-based lateralization and localization of seizure onset in focal cortical dysplasia patients using ictal scalp EEG.

Glioblastoma multiforme (GB) remains the most aggressive and fatal primary tumor of the central nervous system in adults []. It is characterized by rapid growth, high invasiveness and significant resistance to available treatment methods. Despite the use of multimodal therapeutic strategies, including maximally safe surgical resection, radiotherapy and chemotherapy with temozolomide, the median survival of patients with GB rarely exceeds 15–18 months [,]. Such an unfavorable prognosis results from the unique biological complexity of this cancer, including genetic and phenotypic heterogeneity, the presence of subpopulations of cells with stem cell characteristics, and the ability to dynamically adapt metabolically []. In recent years, there has been increasing attention to the metabolic reprogramming of GB cells as one of the key elements of their pathophysiology, which opens up new therapeutic possibilities beyond classical pharmacological approaches [,]. One of the most promising avenues of research is the use of nutritional interventions, particularly the ketogenic diet (KD), as a strategy to support the treatment of GB. The KD, characterized by a very low supply of carbohydrates, moderate amounts of protein and high fat content, leads to the induction of ketosis—a metabolic state in which ketone bodies become the main source of energy. This mechanism may be of particular importance in the context of GB, as glioma cells exhibit a strong dependence on glucose and a limited ability to efficiently use ketone bodies as an energy substrate [,]. Therefore, KD can limit the availability of glucose for cancer cells, while providing an alternative source of energy for healthy neurons and astrocytes []. In addition to influencing the availability of energy substrates, the KD can modulate numerous biological processes relevant to GB progression. Preclinical studies suggest that KD may reduce the activity of insulin and IGF-1-dependent signaling pathways, reduce oxidative stress, affect mitochondrial function, and modulate inflammatory and immune responses []. In addition, it is observed that KD can increase the sensitivity of GB cells to radiation therapy and chemotherapy, making it a potential tool to enhance the effectiveness of standard therapies. In the clinical context, the KD is also considered as a way to improve the quality of life of patients by stabilizing energy levels, reducing fatigue, and possible neuroprotective effects [,]. Despite the growing interest in the KD as an adjunctive therapy in GB, the available evidence remains scattered and highly heterogeneous. The differences concern, m.in, the type of nutritional intervention used (classic KD, MCT-KD, low glycemic index diet), the degree of carbohydrate restriction, the duration of therapy, the methods of monitoring ketosis, and the endpoints used []. In addition, many studies focus on individual metabolic aspects, ignoring the broader clinical context, such as the patient’s nutritional status, dietary tolerance, comorbidities or concomitant oncological treatment. The lack of standardization of protocols and a limited number of randomized trials make it difficult to interpret the results and limit the possibility of formulating unambiguous clinical recommendations [,]. It is also worth noting that the use of a KD in patients with GB is associated with a number of practical challenges. Maintaining strict ketosis requires high nutritional discipline, dietary support and regular monitoring of metabolic parameters. Patients with GB often struggle with appetite disorders, weight loss, nausea or difficulty swallowing, which can make it difficult to follow restrictive dietary recommendations [].