Dynamics of ideas about the concept of epileptic psychosis

Introduction: psychosis in epilepsy is more common than in the general population. The frequency of psychotic mental disorders varies from 0,5% to 10%. The article presents the dynamics of the development of the concept of epileptic psychosis, depending on the evolutionary approaches to the study of the problem of mental disorders in epilepsy. Materials and methods: the analysis of Russian—and English language articles in scientific databases on keywords from 1971 to 2011 was carried out. Results: the first systematic descriptions of mental disorders occurring in epilepsy date back to the 19th century. The contribution of foreign and domestic authors to the study of the problem is described. There are six main periods of the concept formation, including the definitions of the concept of epileptic psychosis, the dynamics of clinical manifestations, the role of the influence of biological, personal and social factors in the genesis and development of psychotic disorders in epilepsy. The following risk factors for the development of psychosis are considered: the form of epilepsy; age of onset of seizures, lateralization of the epileptic focus, gender, and drug therapy. Variants of classification approaches to the problem are presented. The article discusses the differences in the systematization of «endoform» syndromes, as well as the parallels between schizophrenia and psychoses in epilepsy. The dynamics of scientific views on the interest in the formation of epileptic psychoses in various parts of the brain: the temporal lobe (amygdala, hippocampus, paralimbic zones and parahippocampal bend), as well as GABA-ergic neurons of the upper tubercles of the quadriplegic, posterior hypothalamus and serotonergic neurons of the dorsal suture and noradrenergic neurons of the blue spot are reflected. The association of psychopathological manifestations with neurophysiological, biochemical, genetic and morphofunctional correlates is noted. The authors‘ interest in psychoses associated with the use of antiepileptic drugs is emphasized. Conclusion: despite all attempts to systematize these conditions, the factors that provoke the development of psychoses in patients with epilepsy, their structure and prognosis remain poorly predictable and require further in-depth study.

Transcriptomic Alterations Related to Epilepsy and Tumor Suppression in the Peritumoral Area of a Rat Glioma Model

Patients with glioma often demonstrate epilepsy. We previously found burst discharges in the peritumoral area in patents with malignant brain tumors during biopsy. Therefore, we hypothesized that the peritumoral area may possess an epileptic focus and that biological alterations in the peritumoral area may cause epileptic symptoms in patients with glioma. To test our hypothesis, we developed a rat model of glioma and characterized it at the cellular and molecular levels. We first labeled rat C6 glioma cells with tdTomato, a red fluorescent protein (C6-tdTomato) and implanted them into the somatosensory cortex of VGAT-Venus rats, which specifically expressed Venus, a yellow fluorescent protein in GABAergic neurons. We observed that the density of GABAergic neurons was significantly decreased in the peritumoral area of rats with glioma compared with the contralateral healthy side. By using a combination technique of laser capture microdissection and RNA sequencing(LCM-seq) of paraformaldehyde-fixed brain sections, we demonstrated that 19 genes were differentially expressed in the peritumoral area and that five of them were associated with epilepsy and neurodevelopmental disorders. In addition, the canonical pathways actively altered in the peritumoral area were predicted to cause a reduction in GABAergic neurons. These results suggest that biological alterations in the peritumoral area may be a cause of glioma-related epilepsy.

Phase–Amplitude Coupling and Epileptogenic Zone Localization of Frontal Epilepsy Based on Intracranial EEG

Objective: This study aimed to explore the characteristics of phase-amplitude coupling in patients with frontal epilepsy based on their electrocorticography data, in order to identify the localization of epileptic regions and further guide clinical resection surgery.Methods: We adopted the modulation index based on the Kullback-Leibler distance, phase-amplitude coupling co-modulogram, and time-varying phase-amplitude modulogram to explore the temporal-spatial patterns and characterization of PAC strength during the period from inter- seizure to post-seizure. Taking the resected area as the gold standard, the epileptogenic zone was located based on MI values of 7 different seizure periods, and the accuracy of localization was measured by the area under the receiver operating curve.Results: (1) The PAC in the inter- and pre-seizure periods was weak and paroxysmal, but strong PAC channels were confined more to the seizure-onset zone and resection region. PAC during the seizure period was intense and persistent, but gradually deviated from the seizure-onset zone. (2) The characteristics of coupling strength of the inter- and pre-seizure EEG can be used to accurately locate the epileptogenic zone, which is better than that in periods after the beginning of a seizure. (3) In an epileptic seizure, the preferred phases of coupling were usually in the rising branches at the pre- and early-seizure stages, while those in the middle- and terminal-seizure were usually in the falling branch. We thus speculate that the coupling occurred in the rising branch can promote the recruitment of abnormal discharge, while the coupling occurred in the falling branch can inhibit the abnormal discharge.Conclusion: The findings suggest that the phase-amplitude coupling during inter- and pre-seizure is a promising marker of epileptic focus location. The preferred phase of coupling changed regularly with the time of epileptic seizure, suggesting that the surge and suppression of abnormal discharges are related to different phases.

Certain risk factors for the development of cognitive impairment in persons with epilepsy and new therapeutic options

Epilepsy is a common chronic neurological disease. The problems of people with epilepsy go well beyond epileptic seizures. Comorbidities in epilepsy are very common and often cause more problems to the patients than the seizures themselves. Although seizures are the most prominent clinical presentation of epilepsy, people with epilepsy are exposed to risk of not only seizures, but also of many health problems. Both children and adults with epilepsy often complain of memory impairment. It is commonly believed that cognitive dysfunction in epilepsy is multifactorial. The components that deteriorate cognitive functions include active seizures and especially generalized tonic-clonic seizures, traumatic brain injuries, structural epilepsy, and drug therapy. Cognitive dysfunction is very often present as far back as during the onset of epilepsy. The cognitive dysfunction detected in patients with epilepsy depend on the localization of the epileptic focus, the frequency and type of epileptic seizures, and changes in the interictal electroencephalogram. Seizures can be controlled with antiepileptic drugs in most patients with epilepsy. Therapy of cognitive dysfunction in patients with epilepsy presents significant difficulties, as there is no evidence of the efficacy of various drugs in cognitive disorders. The article presents a new Russian antiepileptic drug based on phenosanic acid as part of combination therapy in patients with partial epileptic seizures with or without secondary generalization, which can improve cognitive functions in patients with epilepsy.

Mesoscopic Mapping of Ictal Neurovascular Coupling in Awake Behaving Mice Using Optical Spectroscopy and Genetically Encoded Calcium Indicators

Unambiguously identifying an epileptic focus with high spatial resolution is a challenge, especially when no anatomic abnormality can be detected. Neurovascular coupling (NVC)-based brain mapping techniques are often applied in the clinic despite a poor understanding of ictal NVC mechanisms, derived primarily from recordings in anesthetized animals with limited spatial sampling of the ictal core. In this study, we used simultaneous wide-field mesoscopic imaging of GCamp6f and intrinsic optical signals (IOS) to record the neuronal and hemodynamic changes during acute ictal events in awake, behaving mice. Similar signals in isoflurane-anesthetized mice were compared to highlight the unique characteristics of the awake condition. In awake animals, seizures were more focal at the onset but more likely to propagate to the contralateral hemisphere. The HbT signal, derived from an increase in cerebral blood volume (CBV), was more intense in awake mice. As a result, the “epileptic dip” in hemoglobin oxygenation became inconsistent and unreliable as a mapping signal. Our data indicate that CBV-based imaging techniques should be more accurate than blood oxygen level dependent (BOLD)-based imaging techniques for seizure mapping in awake behaving animals.

Neurophysiological phenotypes of pharmacoresistant temporal lobe epilepsy

Patients with a drug-resistant form of epilepsy can be treated by neurosurgery through the destruction or separation of the epileptic focus. If the results of clinical, neuro-imaging and neurophysiological methods are discordant, then the localization of the epileptogenic zone is performed based on the results of long-term invasive monitoring of the bioelectrical activity of the cortex and deep structures of the brain. The aim of this work was the retrospective analysis of the results of invasive monitoring of the bioelectrical activity of the brain to clarify the mechanisms of the formation of patterns of interictal and ictal activity in structural epilepsy. The study included 35 patients (18 men, 17 women) with drug-resistant temporal lobe epilepsy, who were treated at the Polenov Neurosurgical Institute. The examination included video-EEG monitoring, long-term invasive monitoring of bioelectrical activity of the cortex, and deep brain structures. The patients were divided into two groups according to the type of surgical treatment: 1) micro-surgical resection of the epileptic focus, including the zone of structural changes (24 patients); 2) stereotactic destruction of the amygdala-hippocampal complex (6 patients). The follow-up of the outcomes of the surgical treatment took place over 2-3 years. Depending on the results of the surgical treatment, the patients were divided into two groups: 1) patients with a favorable outcome (Engel 1–2) — 15 patients and 2) patients with no positive dynamics and a relatively poor outcome (Engel 3–4) — 15 patients. The results obtained showed that the patterns of interictal and ictal activity in their totality determine the neurophysiology, i.e the phenotype of temporal lobe epilepsy, reflecting the interference of pathogenetic and sanogenetic mechanisms. The localization of the epileptogenic zone should be based on the cumulative assessment of interictal and ictal activity. The presence of more than one focus of interictal activity, the secondary spread of epileptiform activity from the primary focus, are prognostically unfavorable factors.