Mesial temporal lobe epilepsy (MTLE), the most common form of partial epilepsy, affects the majority of patients with uncontrolled seizures. Seizures do not strike randomly but occur in daily patterns. Studies have shown that seizures can cluster at sleep-wake transitions or occur in diurnal or nocturnal patterns. Possible influences on the timing of seizures include the sleep-wake state, exogenous cycles such as the light- dark cycle, or endogenous rhythms of the biological clock. Because of the difficulty in testing these influences in humans, possible mechanisms have not been compared under rigorous conditions. The distinctions among these cycles is important because of their different physiology and potential effects on the timing of seizures. Understanding the temporal influences on seizure occurrences is a critical step in determining the factors that permit expression of seizures. This proposal examines the temporal distribution of spontaneous, limbic seizures in an animal model of partial epilepsy that shares clinical, electrographic, and histological similarities with human MTLE. Preliminary results show that limbic seizures occur non-randomly in a daily rhythm similar to that found in MTLE. In this study we will examine the role of endogenous circadian rhythms, measured by markers of motor activity and body temperature, on seizure timing. We will test these hypothesis. 1) Limbic seizures and the epileptic state alter circadian rhythms. 2) The distribution of limbic seizures is tied to phases of the sleep-wake state. 3) Limbic seizure occurrence is influenced occurrence is influenced by endogenous, circadian rhythms. In summary, the results will determine the chronobiological factors that facilitate partial seizure expression and may provide new perspectives into treatments for poorly controlled epilepsy.
