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An understanding of mechanisms underlying seizure disorders depends critically on the insights provided by model systems. In particular with the development of cellular, molecular, and genetic investigative tools, there has been an explosion of basic epilepsy research. Models of Seizures and Epilepsy brings together, for the first time in 30 years, an overview of the most widely-used models of seizures and epilepsy. Chapters cover a broad range of experimental approaches (from in vitro to whole animal preparations), a variety of epileptiform phenomenology (including burst discharges and seizures), and suggestions for model characterization and validation, such as electrographic, morphologic, pharmacologic, and behavioral features. Experts in the field provide not only technical reviews of these models but also conceptual critiques - commenting on the strengths and limitations of these models, their relationship to clinical phenomenology, and their value in developing a better understanding and treatments. Models of Seizures and Epilepsy is a valuable, practical reference for investigators who are searching for the most appropriate laboratory models for addressing key questions in the field. It also provides an important background for physicians, fellows, and students, offering insight into the potential for advances in epilepsy research. · The first comprehensive description of animal models of epilepsy since the early 1970's· Comprehensive analysis of \"What the models model\" to guide the selection of each model, and what specific questions it will answer· Elegant examples of the use of novel technologies that can be applied in experimental epilepsy research· World expert opinions on the clinical relevance of each model

STXBP1 and SCN2A gene mutations are observed in patients with epilepsies, although the circuit basis remains elusive. Here, we show that mice with haplodeficiency for these genes exhibit absence seizures with spike-and-wave discharges (SWDs) initiated by reduced cortical excitatory transmission into the striatum. Mice deficient for Stxbp1 or Scn2a in cortico-striatal but not cortico-thalamic neurons reproduce SWDs. In Stxbp1 haplodeficient mice, there is a reduction in excitatory transmission from the neocortex to striatal fast-spiking interneurons (FSIs). FSI activity transiently decreases at SWD onset, and pharmacological potentiation of AMPA receptors in the striatum but not in the thalamus suppresses SWDs. Furthermore, in wild-type mice, pharmacological inhibition of cortico-striatal FSI excitatory transmission triggers absence and convulsive seizures in a dose-dependent manner. These findings suggest that impaired cortico-striatal excitatory transmission is a plausible mechanism that triggers epilepsy in Stxbp1 and Scn2a haplodeficient mice. Spike and wave discharge (SWD) activity is seen during absence seizures and is thought to be thalamocortical in origin. Here, the authors show that SWDs are initiated through the impaired corticostriatal excitatory transmissions onto striatal fast spiking interneurons.

During the summer of 1969, young soldier Dalton Joiner finds out that his girlfriend Jane back home has dumped him and vows to sneak out of Vietnam during his one-week leave to win her back. His best friend Mickey Wright will do anything to help his buddy out, as long as there might be a few girls along the way. In just seven days they must get to the States, change Jane's mind and make it back to the war without getting caught. But when they arrive they find Jane and her activist friend Candace at the heart of the anti-war movement. Now the young soldiers must make some life changing decisions as they spend the week learning the truth about love, honor and commitment.

Typical absence seizures represent a distinctive form of epileptic activity typically observed in pediatric populations, predominantly manifesting between the ages of 4 and 10, constituting Childhood Absence Epilepsy (CAE). However, a subset of patients presents with Early-onset Absence Epilepsy (EOAE), characterized by seizure onset before the fourth year of life, often displaying favorable outcomes with antiseizure medication. Conversely, atypical absence seizures exhibit prolonged duration and frequently entail tonic, atonic, or myoclonic motor elements, suggesting a more severe clinical course, commonly associated with epileptic encephalopathies of childhood onset. Recent genetic investigations have highlighted the involvement of specific genes, notably the SLC1A2 mutation, identified in 10 % of EOAE cases, underlying the GLUT1 deficiency syndrome. Timely recognition of such genetic anomalies facilitates tailored interventions, including ketogenic dietary regimes, shown to ameliorate epileptic symptomatology and neurocognitive sequelae. This retrospective study aimed to delineate the distinct features of EOAE and early-onset atypical absence seizures, facilitating prompt diagnosis, particularly emphasizing genetic aberrations, and initiating precision therapeutic approaches to optimize patient outcomes. Evaluation of 23 patients with absence epilepsy onset within the first four years of life, conducted at the Neuropediatrics Outpatient Clinic of the Policlinico of Modena, revealed that children with atypical absences often exhibit a complex clinical and electroencephalographic phenotype, frequently associated with genetic abnormalities. Notably, neurocognitive prognosis appears less favorable in this subgroup, with half of the patients displaying pharmacoresistance. In contrast, all EOAE cases demonstrated seizure freedom, corroborating previous literature suggesting a relatively benign clinical course in these individuals. •EOAE presents distinct clinical challenges, especially with atypical absence seizures.•Typical EOAE often shows better seizure control and neurocognitive outcomes.•Atypical absences are linked to pharmacoresistance and developmental delays.•Genetic testing is crucial for personalized diagnosis and treatment in EOAE.•Early recognition aids in optimizing therapy and improving patient quality of life.

Increased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. By comparison, at present, little is known about the role of this cytokine in childhood (non-convulsive) absence epilepsy. The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30 mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. It is known that lipopolysaccharide (LPS)-induced changes in inflammatory processes increase absence epileptic activity. In order to study the central effects of TCZ, we investigated whether administration of this anti-IL-6R antibody could modulate the lipopolysaccharide (LPS) or IL-6-evoked changes in absence epileptic activity in WAG/Rij rats. Our results demonstrate that TCZ, at both doses, significantly reduced the development of absence seizures in adult WAG/Rij rats at 6 months of age (1 month after treatment suspension) compared with untreated controls, thus showing disease-modifying effects. Decreased absence seizure development at 6 months of age was also accompanied by reduced comorbid depressive-like behavior, whereas no effects were observed on anxiety-related behavior. Acute treatment with TCZ, at 30 mg/kg, had anti-absence properties lasting ~25 h. The co-administration TCZ with i.c.v. LPS or IL-6 showed that TCZ inhibited the worsening of absence seizures induced by both proinflammatory agents in the WAG/Rij rats, supporting a central anti-inflammatory-like protective action. These results suggest the possible role of IL-6 and consequent neuroinflammation in the epileptogenic process underlying the development and maintenance of absence seizures in WAG/Rij rats. Accordingly, IL-6 signaling could be a promising pharmacological target in absence epilepsy and depressive-like comorbidity.

The neural underpinnings of impaired consciousness and of the variable severity of behavioural deficits from one absence seizure to the next are not well understood. We aimed to measure functional MRI (fMRI) and electroencephalography (EEG) changes in absence seizures with impaired task performance compared with seizures in which performance was spared. In this cross-sectional study done at the Yale School of Medicine, CT, USA, we recruited patients from 59 paediatric neurology practices in the USA. We did simultaneous EEG, fMRI, and behavioural testing in patients aged 6–19 years with childhood or juvenile absence epilepsy, and with an EEG with typical 3–4 Hz bilateral spike-wave discharges and normal background. The main outcomes were fMRI and EEG amplitudes in seizures with impaired versus spared behavioural responses analysed by t test. We also examined the timing of fMRI and EEG changes in seizures with impaired behavioural responses compared with seizures with spared responses. 93 patients were enrolled between Jan 1, 2005, and Sept 1, 2013; we recorded 1032 seizures in 39 patients. fMRI changes during seizures occurred sequentially in three functional brain networks. In the default mode network, fMRI amplitude was 0·57% (SD 0·26) for seizures with impaired and 0·40% (0·16) for seizures with spared behavioural responses (mean difference 0·17%, 95% CI 0·11–0·23; p<0·0001). In the task-positive network, fMRI amplitude was 0·53% (SD 0·29) for seizures with impaired and 0·39% (0·15) for seizures with spared behavioral responses (mean difference 0·14%, 95% CI 0·08–0·21; p<0·0001). In the sensorimotor-thalamic network, fMRI amplitude was 0·41% (0·25) for seizures with impaired and 0·34% (0·14) for seizures with spared behavioural responses (mean difference 0·07%, 95% CI 0·01–0·13; p=0·02). Mean fractional EEG power in the frontal leads was 50·4 (SD 15·2) for seizures with impaired and 24·8 (6·5) for seizures with spared behavioural responses (mean difference 25·6, 95% CI 21·0–30·3); middle leads 35·4 (6·5) for seizures with impaired, 13·3 (3·4) for seizures with spared behavioural responses (mean difference 22·1, 95% CI 20·0–24·1); posterior leads 41·6 (5·3) for seizures with impaired, 24·6 (8·6) for seizures with spared behavioural responses (mean difference 17·0, 95% CI 14·4–19·7); p<0·0001 for all comparisons. Mean seizure duration was longer for seizures with impaired behaviour at 7·9 s (SD 6·6), compared with 3·8 s (3·0) for seizures with spared behaviour (mean difference 4·1 s, 95% CI 3·0–5·3; p<0·0001). However, larger amplitude fMRI and EEG signals occurred at the outset or even preceding seizures with behavioural impairment. Impaired consciousness in absence seizures is related to the intensity of physiological changes in established networks affecting widespread regions of the brain. Increased EEG and fMRI amplitude occurs at the onset of seizures associated with behavioural impairment. These finding suggest that a vulnerable state might exist at the initiation of some absence seizures leading them to have more severe physiological changes and altered consciousness than other absence seizures. National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Science, the Loughridge Williams Foundation, and the Betsy and Jonathan Blattmachr Family.