Epilepsy, a neurological disease characterized by recurrent seizures, is often associated with a history of previous lesions in the nervous system. Impaired regulation of the activation and resolution of inflammatory cells and molecules in the injured neuronal tissue is a critical factor to the development of epilepsy. However, it is still unclear as to how that unbalanced regulation of inflammation contributes to epilepsy. Therefore, one of the goals in epilepsy research is to identify and elucidate the interconnected inflammatory pathways in systemic and neurological disorders that may further develop epilepsy progression. In this paper, inflammatory molecules, in neurological and systemic disorders (rheumatoid arthritis, Crohn’s, Type I Diabetes, etc.) that could contribute to epilepsy development, are reviewed. Understanding the neurobiology of inflammation in epileptogenesis will contribute to the development of new biomarkers for better screening of patients at risk for epilepsy and new therapeutic targets for both prophylaxis and treatment of epilepsy.

Immune-inflammatory conditions in the central nervous system (CNS) rely on molecular and cellular interactions which are homeostatically maintained to protect neural tissue from harm. The CD40–CD40L interaction upregulates key proinflammatory molecules, a function best understood in the context of infection, during which B-cells are activated via CD40 signaling to produce antibodies. However, the role of CD40 in neurological disease of non-infectious etiology is unclear. We review the role of CD40–CD40L in traumatic brain injury, Alzheimer’s Disease, Parkinson’s Disease, stroke, epilepsy, nerve injury, multiple sclerosis, ALS, myasthenia gravis and brain tumors. We also highlight therapeutic advancements targeting the CD40 system to either attenuate the neuroinflammatory response or leverage the downstream effects of CD40 signaling for direct tumor cell lysis.

Epilepsy is a chronic central nervous system (CNS) disease associated with high morbidity. To date, there is no known disease-modifying therapy for epilepsy. A leading hypothesis for a mechanism of epileptogenesis is the generation of aberrant neuronal networks. Although the underlying biological mechanism is not clear, scientific evidence indicates that it is associated with a hyperexcitable synchronous neuronal network and active dendritic spine plasticity. Changes in dendritic spine morphology are related to altered expression of synaptic cytoskeletal proteins, inflammatory molecules, neurotrophic factors, and extracellular matrix signaling. However, it remains to be determined if these aberrant dendritic spine formations lead to neuronal hyperexcitability and abnormal synaptic connections or whether they constitute an underlying mechanism of seizure susceptibility. Focusing on dendritic spine machinery as a potential target for medications could limit or reverse the development of epilepsy.

Status epilepticus (SE) is a medical emergency characterized by uncontrolled, prolonged seizures with rapid and widespread neuronal damage. Patients that suffer from longer episodes of SE are more likely to have poorer clinical outcomes and a higher cost of healthcare. Understanding novel molecular mechanisms that regulate inhibitory and excitatory neurotransmission that initiate SE and the necessary medical infrastructure to stop SE could help identify targets for early intervention. Intranasal administration of benzodiazepines may shorten the time between initiation and cessation of seizures when compared to other routes of administration. Current pharmaceutical administration guidelines are appropriate for sporadic incidences of SE, but exploring other approaches is necessary to prepare for situations involving multiple patients outside of a hospital, such as a massive chemical weapons attack. Intranasal drug delivery helps to circumvent the blood–brain barrier and offers a noninvasive way to quickly administer drugs in settings that require an immediate response, such as nerve agent exposure. In addition, examining the intranasal delivery of new drugs, such as nanotherapeutics, may lead to more effective, noninvasive, scalable, and portable methods of treating SE.

Cutis verticis gyrata (CVG) is a neurocutaneous syndrome characterized by the formation of folds in the scalp that resembles the cerebral cortex. We present two cases of CVG and intellectual disability with drug‐resistant epilepsy. Recognizing CVG is necessary to provide interdisciplinary support for the treatment of comorbidities associated with this entity.

Epilepsy is among the most prevalent neurological disorders characterized by recurring spontaneous seizures. Seizures represent a clinical manifestation of uncontrolled, excessively synchronized neural cell activity. The extent of brain damage from seizures depends on their duration and intensity. Regrettably, there is no effective remedy for epilepsy. The aim of this investigation is to assess whether the planaria worm Dugesia dorotocephala could serve as a model to aid in identifying and developing treatments for epilepsy that can target acute seizures. Currently, various models, such as marine models, are used to evaluate antiseizure medications (ASM). However, they are very expensive, and there are ethical concerns. Alternatively, invertebrate models offer a cost-effective research opportunity in the drug discovery process for ASM. Planaria belong to the flatworm family and inhabit marine freshwater and terrestrial environments. Dugesia dorotocephala is the dominant species of aquatic planaria across North America. D. dorotocephala presents as a viable invertebrate model for epilepsy studies due to its cost-effectiveness, vertebrate-like neurons, and quantifiable behaviors, unlike other invertebrates or larger animals. They have been used in various pharmacology and environmental toxicology studies related to age, memory, and regeneration. In this study, planaria were exposed to different concentrations of pilocarpine, a common chemoconvulsant to study their behavior upon exposure. Following the observation, planaria were euthanized and preserved in either formaldehyde or Golgi solution for neurohistological assessment. Six distinct behavioral phenotypes were observed in planaria: dorsal oscillations, head oscillations, tail dorsal expansion, C-shape, head flick, and tail flick. Dorsal oscillation frequencies were significantly increased among experimental groups compared to the control and exhibited dose dependence. Additionally, pilocarpine disrupted the motility of the planaria. Pilocarpine-induced seizures in planaria can serve as a model to evaluate acute seizures and antiseizure medication, which is essential in developing therapeutic interventions for human patients suffering from epilepsy.