Antiepileptic Drug Therapy for Status Epilepticus.

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.

Treatments for Convulsive and Nonconvulsive Status Epilepticus in Adults: An Expert Opinion Survey in South Korea.

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.

Gender differences in factors associated with resilience for health-related quality of life in persons with epilepsy.

PURPOSE: We determined whether resilience factors such as self-efficacy, stress coping styles, and social support were differentially associated with health-related quality of life (HRQoL) in men and women with epilepsy after controlling for depression, anxiety, and daily-life stress. METHODS: This was a cross-sectional study of 129 adults with epilepsy. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31), Epilepsy Self-Efficacy Scale, Way of Stress Coping Checklist, Social Support Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory, and Daily Hassles Scale were used. Stepwise linear regression analyses were performed. RESULTS: Except for medication effects, there were no gender differences in the QOLIE-31 and its subscales. The medication effects score was higher in men than in women after controlling for BDI scores. The BDI scores were independently associated with the QOLIE-31 score in men and women. Epilepsy self-efficacy was associated with the QOLIE-31 in men, whereas social support was associated with the QOLIE-31 in women. Coping strategies were associated with the QOLIE-31 in neither men nor women. Seizure frequency, daily-life stress, and anxiety were also negatively associated with the QOLIE-31, but only in men. The coefficients of determination were 0.637 and 0.587 in the men's and women's models, respectively. CONCLUSIONS: The influence of self-efficacy and social support on HRQoL differed between men and women with epilepsy even after controlling for psychological distress. These findings could contribute to the development of successful gender-specific psychosocial interventions to improve HRQoL in men and women with epilepsy.

Clinical Approach to Autoimmune Epilepsy.

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.

Antiepileptic Drug Selection According to Seizure Type in Adult Patients with Epilepsy.

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.

Pharmacological Treatment of Epilepsy in Elderly Patients.

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.

Refining General Principles of Antiepileptic Drug Treatments for Epilepsy.

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.

Treatment of epilepsy in adults: Expert opinion in South Korea.

OBJECTIVE: The aim of this study was to gather the expert opinions of Korean epileptologists regarding the treatment of adult patients with epilepsy. METHODS: A total of 42 neurologists who specialized in epilepsy were surveyed. They completed an online questionnaire describing multiple patient scenarios. Using these scenarios, they evaluated treatment strategies and gave their preference for specific antiepileptic drugs (AEDs) used to treat genetically mediated generalized epilepsy and focal epilepsy. RESULTS: Initial AED monotherapy, followed by a second form of alternative monotherapy or an add-on combination therapy, was the preferred treatment strategy. The experts reached consensus for 87.2% of the items. The most commonly selected AEDs for the initial monotherapy for patients with generalized epilepsy were levetiracetam or valproate. For those with focal epilepsy, levetiracetam, oxcarbazepine, or lamotrigine were the most popular selections. Ethosuximide was the treatment of choice only for patients with generalized epilepsy with prominent absence seizures. Levetiracetam was preferred as an add-on therapy for both generalized and focal epilepsy. For special populations of patients, such as elderly adults or those with comorbid diseases, levetiracetam or lamotrigine was selected as the treatment of choice. CONCLUSION: Most of the survey results were in accordance with the US expert opinion survey published in 2016. This survey can assist clinicians in making clinical decisions when treating individual adult patients with epilepsy.

Factors contributing to excessive daytime sleepiness in Korean adults with epilepsy: A sleep questionnaire-based study.

OBJECTIVES: We determined factors contributing to excessive daytime sleepiness (EDS) in Korean adults with epilepsy (AWE). METHODS: A total of 147 AWE who had been treated for >1 year were included. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Subjective sleep disturbances were assessed with the Sleep Apnea of Sleep Disorder Questionnaire (SA-SDQ) and questionnaires about insomnia and restless legs syndrome (RLS). The Hospital Anxiety and Depression Scale (HADS) was also used. An ESS score >10 was considered indicative of EDS. Multivariate logistic regression analyses using the backward elimination method were performed for variables with a p < 0.10 on univariate analysis. RESULTS: The mean ESS score was 6.8 (standard deviation [SD]: 4.4). Among the 147 subjects, 36 (24.5%) had EDS. Multivariate logistic regression analysis showed that being employed (odds ratio [OR]: 4.469, p < 0.01), the presence of at least one sleep disturbance (OR: 3.626, p < 0.01), and antiepileptic drug (AED) polytherapy (OR: 2.663, p < 0.05) were independently associated with EDS in the overall group of AWE. In contrast, being employed (p < 0.05) and higher Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) scores (p < 0.05) in a model for men with epilepsy, as well as having at least one sleep disturbance (p < 0.05) in a model for women with epilepsy, were identified as independent factors for EDS. CONCLUSIONS: Excessive daytime sleepiness in AWE may have a multifactorial origin. Being employed, subjective sleep disturbances, and AED polytherapy are independent predictors of EDS. There may be sex differences in factors associated with EDS.

Medial temporal lobe epilepsy associated with hippocampal sclerosis is a distinctive syndrome.

Epileptic syndromes are distinctive disorders with specific features, which when taken together, permit a specific diagnosis. There is actually a debate on that medial temporal lobe epilepsy with hippocampal sclerosis is an epileptic syndrome. To address this issue, we searched for discriminative semiological features between temporal lobe epilepsy patients with hippocampal sclerosis (TLE-HS patients or group 1), TLE patients with medial structural lesion other than hippocampal sclerosis or in MRI-negative cases with medial onset on further investigations (group 2) and lateral TLE patients (LTLE or group 3). We retrospectively collected data from medical and EEG-video records of 523 TLE patients, referred for surgery to the Pitié-Salpêtrière Epileptology Unit between 1991 and 2014. We identified 389 patients belonging to group 1, 61 patients belonging to group 2, and 73 patients belonging to group 3 and performed a comparative analysis of their clinical data and surgical outcomes. TLE-HS patients (group 1): (1) began epilepsy earlier (11 ± 9 vs. 20 ± 10 vs. 15 ± 9 years); (2) exhibited more frequently early febrile convulsions (FC) (59 vs 7 vs 5%); (3) presented more: ictal gestural automatisms (90 vs 54 vs 67%), dystonic posturing (47 vs 20 vs 23%), and secondary generalized tonic-clonic seizures (GTCS) (70 vs 44% vs 48%) as compared to both groups 2 and 3 patients (all p < 0.001). With respect to auras, abdominal visceral auras were more reported by TLE-HS than by LTLE patients (49 vs 16%). Three cardinal criteria correctly classified 94% of patients into TLE-HS group: history of FC, dystonic posturing, and secondary GTCS. Postoperative outcome was significantly better in TLE-HS group than in the two other groups (p = 0.03 and 0.003). Our study demonstrates that cardinal criteria are reliably helpful to distinguish patients with TLE-HS from those with other TLE and may allow considering TLE-HS as a distinctive syndrome.

Sleep hygiene and its association with mood and quality of life in people with epilepsy.

OBJECTIVES: We determined whether sleep hygiene is directly related to mood and quality of life (QoL) in people with epilepsy and, if not, documented the indirect effects of sleep hygiene through sleep quality. METHODS: Data were collected from 150 adults with epilepsy. The Sleep Hygiene Index (SHI), Quality of Life in Epilepsy-10 (QOLIE-10), Hospital Anxiety and Depression Scale (HADS), Sleep Problems Index-2 (SPI-2) of the Medical Outcomes Study-Sleep Scale, and Epworth Sleepiness Scale (ESS) were used. To determine the direct and indirect associations between SHI, mood, and QoL, multiple linear regression analyses and the Sobel test were performed. RESULTS: Inadequate sleep hygiene behaviors were answered affirmatively by ≥15% of the participants represented by 6 out of 13 items of the SHI. A younger age was independently related to higher SHI scores (p=0.013). The higher SHI scores were directly related to lower QoL independent of sleep quality, anxiety, and depressive symptoms (p<0.05) but not independently related to anxiety and depressive symptoms. The Sobel test confirmed that the SHI scores were associated with anxiety and depressive symptoms through sleep quality (p<0.001). CONCLUSIONS: Inadequate sleep hygiene is independently related to low QoL but indirectly related to anxiety and depressive symptoms through sleep quality. Patients of a younger age are at risk of poorer sleep hygiene.

Factors contributing to driving by people with uncontrolled seizures.

People with epilepsy (PWE) are restricted from driving because of the concern over seizure-related car accidents. We investigated the characteristics of driving in these people and aimed to identify factors associated with driving in those with uncontrolled seizures. Of 290 epilepsy patients, 58% had a driver's license, 40% had driven during the last year. Of 179 persons with uncontrolled seizures, 65 (36%) had driven a car in the previous year. About 9% of PWE with driver's license experienced seizure-related accidents in the previous 5 years, but it was significantly more reported by those with uncontrolled seizures. Being male, married, and employed, and taking fewer antiepileptic drugs were the factors independently associated with increased likelihood of driving in patients with uncontrolled seizures.

Factors contributing to concerns of persons living with epilepsy.

PURPOSE: To describe the concerns of Korean adults living with epilepsy and to compare the concerns of individuals with controlled and uncontrolled seizures. METHODS: Outpatients filled out questionnaires, including the Hospital Anxiety and Depression Scale, the Quality of Life in Epilepsy-10 questionnaire, the stigma scale, and a questionnaire on episodes of discrimination. Patients were asked to fill out the Epilepsy Foundation of America (EFA) Concerns Index and to list their concerns on a blank sheet of paper. RESULTS: Of the 178 participants, 152 described a total of 470 concerns, which could be assorted into 25 distinct concerns. Worrying about the hereditability of their condition was the only concern that differed significantly between individuals with controlled and uncontrolled seizures. Three significant factors were identified on the total EFA Concerns Index score: level of anxiety/depression (34.4%), age (6.3%), and degree of social discrimination (4.3%), resulting in a total explained variance of 45.0%. CONCLUSIONS: Korean adults with epilepsy had various concerns, with some differing from those in Western populations. Anxiety/depression, age and degree of discrimination were significantly associated with the degree of concern in Korean patients with epilepsy.

Factors contributing to depression in patients with epilepsy.

We investigated factors contributing to depression in patients with epilepsy. Data were collected from 150 adult patients. Beck Depression Inventory (BDI), Beck Anxiety Inventory, Daily Hassles Scale, Epilepsy Self-Efficacy Scale, Social Support Scale, Stress Coping Style Checklist, and Quality of Life in Epilepsy Inventory 31 (QOLIE-31) were used. The mean BDI score was 13.4 [standard deviation (SD) 9.0]. Abnormal BDI scores were recorded in 93 patients. Six significant predictors of BDI were identified in a stepwise linear regression analysis: level of stress (p < 0.001), social support (p = 0.037), anxiety (p = 0.001), self-efficacy (p < 0.001), employment status (p = 0.021), and age (p = 0.042). Stress accounted for 38.8% of the variance in BDI score, social support accounted for 6.8%, anxiety accounted for 3.9%, and the remaining three variables accounted for an additional 5.2% of the variance (total explained variance = 54.7%).

Relationship between hypometabolic patterns and ictal scalp EEG patterns in patients with unilateral hippocampal sclerosis: An FDG-PET study.

This study was to explore the relationship between scalp ictal EEG patterns and interictal hypometabolic patterns in hippocampal sclerosis-associated mesial temporal lobe epilepsy (HS-MTLE) and determine the clinical significance of interictal hypometabolic patterns. Twenty-five patients were classified into 2 groups based on initial ictal discharge (IID) frequency on scalp EEG: (a) those with a sustained regular 5- to 9-Hz rhythm with a restricted temporal or subtemporal distribution (group 1, N=9); and (b) those with an irregular 2- to 5-Hz rhythm with a widespread distribution (group 2, N=16). Using statistical parametric mapping, the PET results of each group were compared with age- and sex-matched controls to identify regions of significant hypometabolism, and the clinical characteristics were compared. Group 1 showed focal hypometabolism confined to the ipsilateral temporal lobe, whereas group 2 showed widespread hypometabolism in the ipsilateral temporal lobe, insular cortex and anterior part of the putamen. The two groups showed no significant differences in clinical characteristics. Among semiologic features, dystonic limb posturing was more frequently observed in group 2 (p=0.03). In summary, scalp EEG IID patterns in HS-MTLE can be important in determining hypometabolic patterns on interictal PET. Differences in hypometabolic patterns may reflect preferential pathways of ictal propagation rather than intrinsic epileptogenic regions.

The lateralizing value of IQ in mesiotemporal epilepsy: differences between patients with unitemporal and bitemporal epileptiform discharges.

PURPOSE: We investigated the lateralizing ability of intelligence scores in mesial temporal lobe epilepsy (MTLE) patients according to the distribution of interictal epileptiform discharges (IEDs). METHODS: This study enrolled 82 MTLE patients. All patients had preoperative neuropsychological evaluations, including Korean Wechsler Adult Intelligence Scale. Patients were categorized as having uni- or bitemporal IEDs based on IEDs distribution (cutoff point, 90%). RESULTS: In patients with unitemporal IEDs, performance IQ (PIQ) was significantly lower in the right than in the left subgroup (89.6 vs. 99.4, p<0.05). Verbal IQ (VIQ)-PIQ discrepancy scores differed significantly between the left and right subgroups, being negative in the left and positive in the right subgroup. Based on multivariate analyses, two variables, right MTLE (p=0.042) and the unitemporal distribution of IEDs (p=0.030), were independently related to the VIQ-PIQ discrepancy of more than 10 points. About 47.4% of those with unitemporal IEDs had VIQ-PIQ discrepancies of greater than 10 points and the rate for correct lateralization was 77.8%. In patients with bitemporal IEDs, however, none of the intelligence scores showed evidence of correct lateralization. In patients with bitemporal IEDs, Full-scale IQ and PIQ were significantly lower in the left subgroup, and there was a significant difference in VIQ-PIQ discrepancy scores with the wrong direction. CONCLUSIONS: We found that intelligence scores had some lateralizing ability, but only in MTLE patients with unitemporal IEDs.

Two novel mutations of the NOTCH3 gene in Korean patients with CADASIL.

Mutations in the NOTCH3 gene (NOTCH3) are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an adult-onset hereditary angiopathy leading to ischemic episodes, vascular dementia and other neurologic deficits. All mutations of NOTCH3 described so far are strictly stereotyped, leading to the gain or loss of a cysteine residue in a given epidermal growth factor (EGF)-like repeat of NOTCH3. We report two novel mutations of NOTCH3, R587C and C988Y, each resulting in an odd number of cysteine residues in an EGF-like repeat of NOTCH3. We identified these mutations in two unrelated Korean families with CADASIL, who presented with magnetic resonance imaging (MRI) abnormalities typical of CADASIL. These findings confirm that mutations in NOTCH3 are associated with the pathogenesis of CADASIL across different ethnic backgrounds.

Recurrent Cerebral Venous Thrombosis Associated with Elevated Factor VIII.

Cerebral venous thrombosis (CVT) rarely recurs, and the factors associated with a recurrence remain unclear. Recently, however, elevated plasma coagulation factor VIII has been considered a factor related to recurrent venous thromboembolism. Here we report a patient who had recurrent CVT associated with significantly elevated levels of factor VIII despite the chronic use of an antiplatelet agent. Factor IX was also elevated in this patient. These findings suggest that elevated factor VIII is a factor underlying the recurrence of CVT, and that prolonged anticoagulation therapy may have to be considered in patients with elevated coagulation factor levels.

Perceived self-control of seizures in patients with uncontrolled partial epilepsy.

Many patients with epilepsy have warning symptoms prior to seizure onset, and some of these individuals report the ability to abort or prevent these seizures. We investigated the clinical characteristics of perceived self-control of seizures in 174 patients with uncontrolled partial epilepsy. The warning symptoms were categorized as premonitory (prodrome) and as initial symptoms of simple partial seizure onset, depending on the relationship between the warning events and the ensuing seizures. About 50% of the patients with simple partial seizure onset and about 70% of those with prodrome or premonitory symptoms reported that they could abort or prevent their seizures by various self-developed techniques. Patients who attempted to abort or prevent their seizures reported success rates as high as 80%. The proportion of patients with secondary generalized seizures was significantly lower in patients who tried to abort their seizures than in those who did not (p<0.05). The ability to prevent seizures was significantly higher in patients with brain lesions on MRI than in those without lesions (p<0.05). These results suggest that spontaneously developed methods are helpful in controlling seizures in some patients with uncontrolled partial epilepsy and that the potential success of self-control methods may be influenced by structural abnormalities on brain MRI.