Sujithra Srinivas

Circadian rhythm is a 24 hour or a day’s rhythmic oscillations with physiological and behavioural changes that is internally governed by the brain. This activity is generally anticipated by the internal and external cues from the environment. In circadian rhythm of our body is regulated by a transcriptional –translational Auto-regulatory loop which leads to the molecular oscillations of our “core clock genes” at a specific cellular level. In the many mammalian and animal models, the master pacemaker is in the hypothalamus at the suprachiasmatic nucleus (SCN) that can regulate downstream oscillations in the peripheral tissues of the brain. The core clock genes are self- sustained and cell autonomous not only on the pace maker but also on the other dissociated cultured cells and peripheral tissues. Here we can review the general mechanisms involved in the clock genes that is responsible for the circadian rhythmicity in epileptic syndromes and these findings can elucidate the cell specific expression of the clock genes in different syndromes. In the recent past there has been considerable amount of progress in elucidating the molecular and cellular mechanisms that is involved in understand the core clock gene expression and the circadian rhythms effects on epileptic syndromes. However, there is very little understanding on how these two mechanisms interact to cause a core clock genes disruptions plays an important role. Recent studies in several animal models have shown the effects of time of the day on the neurophysiology and path-physiology in the epileptic syndrome. Together, these evidences from the past suggest that there can be a common mechanism underlying the circadian rhythmicity and epileptogenesis mechanism.   Keywords: Circadian rhythm, Sleep, Epilepsy, Core clock gene expression

Sleep and epilepsy are known to have a bidirectional interaction. Although sleep is differentiated into Rapid eye movement and Non Rapid eye movement sleep, Further gets classified into different stages based on the electroencephalogram EEG traces. Sleep is popularly studied using a Polysomnogram (PSG) which is the golden standard in measuring sleep metrics. In 1929 using an intervention with electroencephalography (EEG) made better contributions to objective investigations and clinical observations for unravelling further reasoning. Although there is an increasing evidences of sleep disturbance in most cases of epileptic syndromes the sleep interaction methods are very poorly reasoned out. Using invasive intracranial EEG the evidences obtained on cortical activities of the deep and superficial brain structures are given evidences on the interaction mechanisms of sleep and epilepsy. The sleep spindles are phasic events seen in non –rapid eye movement sleep in mammals. The sleep spindle is relevant in many aspects of brain activities such as sleep quality, memory consolidation, aging and mental health. In the last decade one of the most important understanding the interplay between how spike wake discharge is modulated by the slow sleep waves underlining the role of epileptic activity to sleep .These studies helped to demonstrate how different seizure types affected by sleep and how epileptogenic zone can be better identified for epilepsy surgery. This article will review the influence of sleep in epileptic brain and its significances using an EEG.   Keywords: Sleep, Epilepsy, Sleep spindles, Epileptic Discharge, EEG

Every cell in the human body is said to produce a cell specific rhythmicity, these rhythms are governed by the brains internal core clock. These rhythms are essential for maintaining day to day function of our body. These rhythms play a greater role in therapeutics as the drug perfusion in our body is time dependent. In neurology, a 24 hour rhythmic activity of epileptic seizure is a topic of greater interest. The rhythmic activity in epilepsy and seizure occurrence is related to the circadian variation in excitatory and inhibitory balance in neurons. There are two core circadian genes BMAL1 and CLOCK, that code for transcription factors, tend to influence the excitability and threshold of the seizure. Although there is uncertainties about the circadian rhythmicity that includes rhythm related factors such as time of the day seizure responses, frequency of occurrences of the seizures. In other cases the time of occurrences of the seizure is consequential to the severity of the seizures. However an improved seizure prediction can open new possibilities of research by understanding the efficacy of the treatment and the drugs used to control seizure. Better clarity on the severity and rhythmicity of the seizure can bring about newer and novel therapeutic options which can be beneficial in treatment of epilepsy. Lastly future studies in these area can clarify the seizure pathways involved in generating the rhythmic patterns in disease manifestation. Keywords: Circadian Rhythm, Core Clock Gene, Sleep, Epilepsy, Epileptic Syndromes

Epilepsy is a neurological condition that affects approximately more than 50 million people around the globe, out of which the prevalence of this disease is also seen in developed countries. Epilepsy can be clinical defined by two or more non triggered seizures. A seizure can be characterized as a paroxysmal event which is caused due to hyper–synchronization in the neurons that many have various reasons of manifestation. The neuronal discharge maybe focal spreading in specific brain cortex or widespread throughout the cortex. An Electroencephalogram (EEG) is used to in diagnosis and management of epilepsy and can be used for routine examinations, it also considered to be the golden standard investigation of epileptic syndrome. While using EEG the distribution, presence and frequency of interictal epileptiform discharges IEDs are suggestive diagnosis of epilepsy. In other words the presence of IEDs in an individual’s EEG is a diagnosis of epilepsy. IEDs are predominantly found in EEG that is performed during sleep which can give basic diagnosis and prognosis of sleep related epilepsies in patients. During sleep latent interictal discharge are activated. Sleep IEDs are said to greatly affect the epilepsy management. These interaction mechanisms of sleep and epilepsies tends to bring about changes in behaviour of the seizure. Keywords: Sleep, Epilepsy, Circadian Rhythmicity, Ictal­Interictal Discharges, Circadian Rhythm

Infantile spasm (IS) comprises of both an age dependent epileptic seizure and distinctive seizure Onset in infants. In the recent past the key observation in classification and standardization of infantile spasm has culminated many recommendations in distinguishing and recognizing the seizure type and the epileptic syndrome or the West syndrome. The Infantile spasm is an early onset epileptic encephalopathy which presents unique electrographic and clinical features, these features are found in children in the middle of the first year of their birth .However the pathophysiology and the heterogeneity of the infantile spasm remains partially or incompletely understood. In the neurobiological basis there are multiple aetiologies converge to form similar clinical interpretations. The description of the electroencephalographic features of the spasm and its hypsarrthythmia plays a pivot role in early diagnosis. The treatment options for infantile spasm are very limited and it is also called a “catastrophic” due to the poor developmental, cognitive and epileptic progress. In the recent past more detailed information about the electrographic and clinical features of the spasms and hypsarrhythmia in EEG has emerged. The advances in the neuro imaging techniques have revealed about the aetiology and the pathophysiology of infantile spasm to yield a prognosis in patients with infantile spasms. The pathophysiology of infantile spasm needs to be better clarified for any kind of novel treatments and a wide range of preclinical animal studies are essential for advancing the knowledge. Here, in this review paper we focus on the preclinical models of Infantile spasm, with information’s regarding the existing models and research findings, elaborate on some novel models and discuss on new data that can help in advancing the understanding of the cellular mechanisms underlying the specific EEG changes such as ictal electrodecrement and interictal hypsarrhythmia presented in Infantile spasm IS.   Keywords: Infantile spasm (IS), Neurobiology, Hypsarrhythmia, Pathophysiology, Electro Encephalo graph (EEG