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Background: Interictal epileptiform discharges (IEDs) are an electrographic biomarker of epilepsy. Despite their crucial role in diagnosing epilepsy, heterogeneous findings exist on the mechanisms underlying their occurrence and the effects of anti-seizure medications (ASMs) on IEDs. Methods: We conducted a study to investigate the association between IED frequency and the serum concentration of two commonly used ASMs, levetiracetam (LEV) and lamotrigine (LTG). We included 56 patients undergoing a continuous video EEG monitoring in our center with tapering of ASM. IED frequency was analyzed using automated and semiautomated methods and serum samples were collected sequentially throughout the stay. Results: The cohort consisted of 41 patients (23 female, 18 male), between 19 and 64 years (mean 37.42 years), most of which were diagnosed with focal epilepsy (93%). IED frequency increased after ASM reduction revealing a negative correlation similarly with LEV and LTG serum concentrations (p = 0.0057 and p = 0.0426, respectively). Discussion: Notably, we observed a significant increase in IED frequency following dose reduction or discontinuation of both medications. This effect was reversed after ASM were re-dosed. This may indicate the suppressive properties of LEV and LTG against epileptic seizures. Furthermore, our study highlights the importance of ASM discontinuation, which may be required for capturing IEDs during diagnostic continuous EEG monitoring, and not be fully explained by circadian or ultradian rhythms alone. Conclusion: Our findings contribute to the understanding of ASM effects on IED frequency dynamics and suggest seizure suppressive properties of LEV and LTG. [ABSTRACT FROM AUTHOR]

Circadian rhythms are inherent to living organisms from single cells to humans and operate on a genetically determined cycle of approximately 24 hours. These endogenous rhythms are aligned with the external light/dark cycle of the Earth's rotation and offer the advantage of anticipating environmental changes. Circadian rhythms act directly on human cognition and indirectly through their fundamental influence on sleep/wake cycles. The strength of the circadian regulation of performance depends on the accumulated sleep debt and the cognitive domain, and it has been suggested to involve the activation of ascending arousal systems and their interaction with attention and other cognitive processes. In addition, attention-related cortical responses show extensive circadian rhythms, the phases of which vary across brain regions. This review discusses the impact of the circadian system on sleep/wake regulation and cognitive performance. It further addresses the health implications of circadian disruption, particularly in relation to mental and neurological disorders. [ABSTRACT FROM AUTHOR]

Epilepsy, characterized by recurrent seizures, is influenced by biological rhythms, such as circadian, seasonal, and menstrual cycles. These rhythms affect the frequency, severity, and timing of seizures, although the precise mechanisms underlying these associations remain unclear. This review examines the role of biological clocks, particularly the core circadian genes Bmal1, Clock, Per, and Cry, in regulating neuronal excitability and epilepsy susceptibility. We explore how the sleep-wake cycle, particularly non-rapid eye movement sleep, increases the risk of seizures, and discuss the circadian modulation of neurotransmitters like gamma-aminobutyric acid and glutamate. We explore clinical implications, including chronotherapy which refers to the practice of timing medical treatments to align with the body's natural biological rhythms, such as the circadian rhythm. Chronotherapy aligns anti-seizure medication administration with biological rhythms. We also discuss rhythm-based neuromodulation strategies, such as adaptive deep brain stimulation, which may dynamically change stimulation in response to predicted seizures in patients, provide additional therapeutic options. This review emphasizes the potential of integrating biological rhythm analysis into personalized epilepsy management, offering novel approaches to optimize treatment and improve patient outcomes. Future research should focus on understanding individual variability in seizure rhythms and harnessing technological innovations to enhance seizure prediction, precision treatment, and long-term management. [ABSTRACT FROM AUTHOR]