Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Several medications are approved to treat coronavirus disease 2019 (COVID-19) in Korea including nirmatrelvir/ritonavir, remdesivir, and regdanvimab. There is potential drug-drug interaction between antiepileptic drugs (AEDs) and the medications used to treat COVID-19. Several AEDs such as phenytoin, carbamazepine, phenobarbital, and primidone are strong cytochrome P450 inducers and can inhibit the drugs used for COVID-19. Particularly, these drugs are contraindicated with nirmatrelvir/ritonavir (Paxlovid®). There is a weaker drug-drug interaction between the AEDs and remdesivir. No significant interaction has been reported between the AEDs and molnupiravir. Pharmacokinetic interactions of the AEDs are important in effective management of COVID-19 in patients with epilepsy.

One third of the overall epilepsy population are estimated to be a drug refractory epilepsy (DRE), defined as the patients who failed to control seizure reduction, even tried two or more appropriate antiepileptic drugs (AEDs) trials. Those people need additional AEDs trials or other treatment options (resective surgery, neuromoulation, etc.). Here, we, clinical guideline committee of the Korean Neurological Association (KNA) introduce the recommendations of AEDs treatments including not only old and new AEDs currently available in Korea but also AEDs planned to be launched in the new future for DRE patients with literature review to help efficient decision of the clinician. The authors reviewed literatures and assessed efficacy and tolerability on 12 currently available and four newly introduced/or planned AEDs applied to DRE patients, published from November 2015 to July 2021. Brivaracetam, eslicarbazepine, canabidiol and cenobamate are the four AEDs that are newly introduced or planned to be launched soon. The reviewed articles are publications after November 2015, 2018 American Association of Neurology guideline, new AEDs which were introduced or planned to be launched as of 2021. All AEDs are classified based on the therapeutic rating scheme, generating recommendations. Overall 173 papers have been reviewed and analyzed for recommendation rationales. KNA introduce additional add-on treatment or conversional monotherapy guidelines on the drug refractory focal and generalized epilepsy. We hope these guidelines or recommendations to help clinical decision for the treatment of drug refractory epilepsy patients

Background: and Purpose The aim of this study was to survey the expert opinions on treatments for convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) in adults. Methods: Forty-two South Korean epileptologists participated in this survey. They completed an online questionnaire regarding various patient scenarios and evaluated the appropriateness of medications used to treat CSE and NCSE. Results: Initial treatment with a benzodiazepine (BZD) followed by either a second BZD or an antiepileptic drug (AED) monotherapy was the preferred treatment strategy. More than two-thirds of the experts used a second BZD when the first one failed, and consensus was reached for 84.8% of the survey items. The preferred BZD was intravenous (IV) lorazepam for the initial treatment of status epilepticus. IV fosphenytoin and IV levetiracetam were chosen for AED monotherapy after the failure of BZD. The treatments for NCSE were similar to those for CSE. Continuous IV midazolam infusion was the treatment of choice for iatrogenic coma in refractory CSE, but other AEDs were preferred over iatrogenic coma in refractory NCSE. Conclusions The results of this survey are consistent with previous guidelines, and can be cautiously applied in clinical practice when treating patients with CSE or NCSE.

Status epilepticus (SE) is one of the most serious neurologic emergencies. SE is a condition that encompasses a broad range of semiologic subtypes and heterogeneous etiologies. The treatment of SE primarily involves the management of the underlying etiology and the use of antiepileptic drug therapy to rapidly terminate seizure activities. The Drug Committee of the Korean Epilepsy Society performed a review of existing guidelines and literature with the aim of providing practical recommendations for antiepileptic drug therapy. This article is one of a series of review articles by the Drug Committee and it summarizes staged antiepileptic drug therapy for SE. While evidence of good quality supports the use of benzodiazepines as the first-line treatment of SE, such evidence informing the administration of second- or third-line treatments is lacking; hence, the recommendations presented herein concerning the treatment of established and refractory SE are based on case series and expert opinions. The choice of antiepileptic drugs in each stage should consider the characteristics and circumstances of each patient, as well as their estimated benefit and risk to them. In tandem with the antiepileptic drug therapy, careful searching for and treatment of the underlying etiology are required.

Objectives: The aim of this study is to evaluate relationship of health-related quality of life (HRQoL) with chronotype along with quality and quantity of sleep in Korean middle adults. Methods: Data was derived from the nationwide, cross-sectional study on sleep surveyed 2,501 representative adult Koreans. We collected data from 1,435 participants aged ≥35 years and <65 years to represent Korean middle adults. The Chronotype Questionnaire was used to assess phase and distinctiveness of the circadian rhythm. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Quantity of sleep was investigated by questions regarding sleep habits during workdays and free days. EuroQol-5D 3-level version was used to measure HRQoL. Results: On univariable analyses, eveningness is associated with younger age (47.7±8.2 vs. 51.3±8.1 years, p<0.001), and higher PSQI total score (4.3±2.7 vs. 3.6±2.2, p<0.001) compared with morningness. Strong distinctiveness also associated with higher PSQI total score (4.2±2.3 vs. 3.6±2.5, p< 0.001) compared with weak distinctiveness. Age was not different between the two groups of distinctiveness. On multivariable analyses, strong distinctiveness is an independent factor predicting impairment of pain/discomfort [odd ratio (OR) 1.589, 95% confidence interval (CI) 1.182–2.130] and depression/anxiety (OR 1.412, 95% CI 1.003–1.987). Poor sleep quality was the most powerful independent factor predicting impairments in all five domains of the HRQoL. Conclusions Sleep quality is an important factor independently related to the HRQoL. Among chronotype variables, only distinctiveness has an independent relation with the HRQoL.

Antiepileptic drugs (AEDs) are the primary treatment strategy for epilepsy. As the use of AEDs has become more widespread and diverse over the past century, it has become necessary to refine the associated prescription strategies. This prompted the Drug Committee of the Korean Epilepsy Society to perform a systemic review of both international and domestic guidelines as well as literature related to medical treatment of epilepsy, and prepared a series of reviews to provide practical guidelines for clinicians to follow. This article is the first in a series on AED treatments for epilepsy in South Korea.

The incidence and prevalence of epilepsy are highest in elderly people, and the etiologies of epilepsy in the elderly differ from those in other age groups. Moreover, diagnosing and treating epilepsy in elderly people may be challenging due to differences in clinical characteristics and physiological changes associated with aging. This review focuses on the pharmacological treatment of epilepsy in elderly patients.

Epilepsy is a common neurological disorder that is mainly treated using antiepileptic drugs.Several antiepileptic drugs such as phenobarbital, phenytoin, primidone, and ethosuximide were developed in the early 20th century. More than 10 types of antiepileptic drugs have been developed since the 1990s, and there are now more than 20 antiepileptic drugs in active clinical use. The choice of antiepileptic drugs is based on the clinical features of the seizure types, electroencephalogram findings, epileptic syndrome, and drug stability. Currently there are 19 antiepileptic drugs approved by the Korean Food and Drug Administration, 18 of which (with the exclusion of brivaracetam) are covered by the National Health Insurance Service in Korea. We reviewed the selection of antiepileptic drugs according to the classification of epileptic seizures.

Autoimmune epilepsy is a newly emerging area of epilepsy. The concept of “autoimmune” as an etiology has recently been revisited thanks to advances in autoimmune encephalitis and precision medicine with immunotherapies. Autoimmune epilepsy presents with specific clinical manifestations, and various diagnostic approaches including cerebrospinal fluid analysis, neuroimaging, and autoantibody tests are essential for its differential diagnosis. The diagnosis is often indeterminate despite performing a thorough evaluation, and therefore empirical immunotherapy may be applied according to the judgment of the clinician. Autoimmune epilepsy often manifests as new-onset refractory status epilepticus (NORSE). A patient classified as NORSE should receive empirical immunotherapy as soon as possible. On the other hand, a morecautious, stepwise approach is recommended for autoimmune epilepsy that presents with episodic events. The type of autoimmune epilepsy is also an important factor to consider when choosing from among various immunotherapy options. Clinicians should additionally take the characteristics of antiepileptic drugs into account when using them as an adjuvant therapy. This expert opinion discusses the diagnostic and treatment approaches for autoimmune epilepsy from a practical point of view.