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Around 1% of the population worldwide suffer from epilepsy, a condition which is characterized by recurring seizures. The development of reliable biomarkers for both prediction and targeted treatment of seizures is critical, as they can pave the way towards personalized therapy in epilepsy. In addition, sensitive biomarkers can be utilized for the detection of epilepsy in its early stages and allow for early treatment intervention. Various types of biomarkers have been studied in relation to epilepsy, with blood markers emerging as major candidates. Blood biomarkers offer the benefit of being cost and time efficient, in addition to being less invasive to sample in contrast to cerebrospinal fluid markers. Importantly, they can enhance patient diagnosis and prognosis when supplemented with other diagnostic methods, such as EEG. In this pilot study, five blood biomarkers of brain injury are studied in epilepsy, post-stroke epilepsy and single seizure patients. The aim is to analyze whether S100B, NSE, GFAP, NfL and tau are promising indicators of epilepsy after a first seizure in adults. The results present S100B as the most promising biomarker, with potential to predict early epilepsy.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21664号 / 医博第4470号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 浅野 雅秀, 教授 影山 龍一郎 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Objective: to compare dietary treatments and their effectiveness in reducing seizures through a systematic review and meta-analysis of clinical trials Methods: Using the PRISMA Method, the Primo database was searched to find peer-reviewed articles where researchers compared one treatment against another. The treatments of choice present in all studies are the Ketogenic Diet and the Modified Atkins Diet. Due to the nature of the experiments, the Ketogenic Diet was considered the control, as it was coined first. Results: Of the 450 articles identified, 378 met the primary peer review threshold and 190 were classified as Open Access. Eight met eligibility and were included in this review. 443 patients across all studies were assigned either a Ketogenic Diet or a Modified Atkins Diet for a median period of 3 months. 48.17% of MAD patients had a significant decrease in seizure frequency, compared to 61.11% of patients under KD. As much as the ketogenic diet showed better results overall, there was no statistical difference in the odds of achieving a significant reduction in seizures using either diet. Significance: Trials suggest that while there was not a significant difference in this study between the ketogenic diet and the modified Atkins diet, there was a trend for ketogenic diets to be more effective than the more recent Modified Atkins diet for drug-resistant epileptics. However, the sample size needs to be increased before a more accurate determination can be made.

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Epilepsy is a disease affecting millions of people worldwide. Despite over 50 years of research, the mechanisms that generate and sustain ictal discharges, a key neural hallmark of seizures, remain unknown. While once thought to be caused by hypersynchronous neuronal firing, we now recognize that the activity underlying ictal discharges is much more complex. With the development of microelectrode arrays (MEAs) suitable for use in humans, it is possible to observe neural activity at fine spatiotemporal scales in human patients with epilepsy. However, the diversity of seizure characteristics and limited patient population has led to a number of conflicting observations and theories. The purpose of this work is to elucidate mechanisms underlying ictal discharges in humans by applying statistical analyses and computational modeling to MEA recordings from human patients with epilepsy. We approach this aim in two projects. In the first project, we unify two seemingly conflicting theories surrounding cortical sources of ictal discharges. According to the ictal wavefront theory, ictal discharges are seeded at an expanding narrow front of high neuronal firing that delineates the boundary between regions of cortex with compromised functionality, and surrounding territory where the seizure is observable in electrical recordings, but cortical function remains intact. A second theory posits that discharges are predominantly seeded from a stationary localized cortical source. The two theories are based on observations from MEA recordings of seizures in two different small cohorts of patients. In this project, we analyze and model the discharge propagation patterns in a combined dataset from both cohorts. We show that discharges are seeded at the ictal wavefront in addition to other–possibly stationary–locations. In the second project, we characterize spatiotemporal patterns in the secondary transients of complex ictal discharges. Electrographic recordings of ictal discharges often have complex waveforms. Existing analyses focus on the spatiotemporal dynamics of the first, high-amplitude transient. In this project, we establish that ictal discharges often comprise multiple transients separated by ≈60 ms. Surprisingly, and contrary to our initial hypothesis, we find that individual transients within a complex discharge may propagate with different speeds, suggesting that different mechanisms are involved in the propagation of different transients.

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