Lesion Detection Through MRI Postprocessing in Pathology-Proven Focal Cortical Dysplasia:Experience at a Single Institution in the Republic of Korea

Background@#and Purpose Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy, and necessitates a multimodal evaluation to ensure optimal surgical treatment. This study aimed to determine the supportive value of the morphometric analysis program (MAP) in detecting FCD using data from a single institution in Korea. @*Methods@#To develop a standard reference for the MAP, normal-looking MRIs by two scanners that are frequently used in this center were chosen. Patients with drug-resistant epilepsy and FCD after surgery were candidates for the analysis. The three-dimensional T1-weighted MRI scans of the patients were analyzed as test cases using the MAP. @*Results@#The MRI scans of 87 patients were included in the analysis. The radiologist detected abnormal findings correlated with FCD (RAD positive [RAD(+)]) in 34 cases (39.1%), while the MAP could detect FCD in 25.3% of cases. A combination of the MAP (MAP[+] cases) with interpretations by the radiologist increased the detection to 42.5% (37 cases). The lesion detection rate was not different according to the type of reference scanners except in one case. MAP(+)/RAD(-) presented in three cases, all of which had FCD type IIa. The detection rate was slightly higher using the same kind of scanner as a reference, but not significantly (35.0% vs. 22.4% p=0.26). @*Conclusions@#The results of postprocessing in the MAP for detecting FCD did not depend on the type of reference scanner, and the MAP was the strongest in detecting FCD IIa. We suggested that the MAP could be widely utilized without developing institutional standards and could become an effective tool for detecting FCD lesions.

Five-Year Retention of Perampanel and Polytherapy Patterns:328 Patients From a Single Center in South Korea

Background@#and Purpose Perampanel (PER) is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist used to treat focal and generalized epilepsy. Comprehensive data from real-world settings with long-term follow-ups are still scarce. This study aimed to determine the factors related to PER retention and the polytherapy pattern with PER. @*Methods@#We reviewed all patients with epilepsy with a history of PER prescription during 2008–2017 and over a follow-up of >3 years. PER usage patterns and associated factors were analyzed. @*Results@#Among the 2,655 patients in the cohort, 328 (150 females, 178 males) were enrolled.The ages at onset and diagnosis were 21.1±14.7 years and 25.6±16.1 years (mean±standard deviation), respectively. The age at the first visit to our center was 31.8±13.8 years. Seizure types were focal, generalized, and unknown onset in 83.8%, 15.9%, and 0.3% of patients, respectively. The most common etiology was structural (n=109, 33.2%). The maintenance duration of PER was 22.6±19.2 months (range=1–66 months). The initial number of concomitant antiseizure medications was 2.4±1.4 (range=0–9). The most common regimen was PER plus levetiracetam (n=41, 12.5%). The median number of 1-year seizures before PER usage was 8 (range=0–1,400). A seizure reduction of >50% was recorded in 34.7% of patients (52.0% and 29.2% in generalized and focal seizures, respectively). The 1-, 2-, 3-, 4-, and 5-year retention rates for PER were 65.3%, 50.4%, 40.4%, 35.3%, and 21.5%, respectively. A multivariate analysis indicated that lower age at onset was associated with longer retention (p=0.01). @*Conclusions@#PER was safely used in patients with diverse characteristics and was maintained for a long time in a real-world setting, especially in patients with a lower age at onset.

Association of Zolpidem With Increased Mortality in Patients With Brain Cancer: A Retrospective Cohort Study Based on the National Health Insurance Service Database

Background@#and Purpose Zolpidem is one of the most common hypnotics prescribed to treat insomnia worldwide. However, there are numerous reports of a positive association between zolpidem and mortality, including an association with increased cancer-specific mortality found in a Taiwanese cohort study. This study aimed to determine the association between zolpidem use and brain-cancer-specific mortality in patients with brain cancer. @*Methods@#This population-based, retrospective cohort study analyzed data in the National Health Insurance Service database. All incident cases of brain cancer at an age of ≥18 years at the time of brain cancer diagnosis over a 15-year period (2003–2017) were included. A multivariate Cox regression analysis after adjustment for covariables was performed to evaluate the associations of zolpidem exposure with brain-cancer-specific and all-cause mortality. @*Results@#This study identified 38,037 incident cases of brain cancer, among whom 11,823 (31.1%) patients were exposed to zolpidem. In the multivariate Cox regression model, the brain-cancer-specific mortality rate was significantly higher in patients who were prescribed zolpidem than in those with no zolpidem prescription (adjusted hazard ratio [HR]=1.14, 95% confidence interval [CI]=1.08–1.21, p<0.001). Zolpidem exposure was significantly associated with increased brain-cancer-specific mortality after adjustment in younger adults (age 18– 64 years; adjusted HR=1.37, 95% CI=1.27–1.49) but not in older adults (age ≥65 years; adjusted HR=0.94, 95% CI=0.86–1.02). @*Conclusions@#Zolpidem exposure was significantly associated with increased brain-cancerspecific mortality in patients with brain cancer aged 18–64 years. Further prospective studies are warranted to understand the mechanism underlying the effect of zolpidem on mortality in patients with brain cancer.

Clinical Outcomes of Japanese Encephalitis after Combination Treatment of Immunoglobulin, Ribavirin, and Interferon-α2b

Background@#and Purpose Japanese encephalitis (JE) is caused by the JE virus of the Flaviviridae family and is spread by mosquito bites, and no specific antiviral treatment for it exists. Here we describe the clinical presentations, laboratory findings, clinical outcomes, and adverse events after combination treatment of immunoglobulin, ribavirin, and interferon-α2b administered to patients with JE. @*Methods@#Data were collected and reviewed from a prospective cohort of encephalitis patients admitted to Seoul National University Hospital between August 1, 2010 and October 31, 2019.We reviewed the medical records of the patients diagnosed with JE and treated either with supportive care only or with combination treatment of intravenous immunoglobulin, oral ribavirin, and subcutaneous interferon-α2b. @*Results@#Eleven patients were diagnosed with laboratory-confirmed JE based on the diagnosis criteria of JE. The median age was 61 years, and five patients were male. Eight patients were treated with the combination therapy, while three patients received supportive management only. Four of the eight patients (50%) treated with the combination therapy showed partial recovery, while one patient (12.5%) showed complete recovery. Two patients experienced hemolytic anemia related to ribavirin and febrile reaction to immunoglobulin, respectively. Among the three patients who received supportive management only, one (33.3%) showed partial recovery and the other two (67.7%) did not show improvement. @*Conclusions@#Combination treatment of immunoglobulin, ribavirin, and interferon-α2b was found to be tolerable in JE in this study. Further studies of appropriate designs and involving larger numbers of patients are warranted to explore the efficacy of this combination therapy.

Clinical Outcomes of Japanese Encephalitis after Combination Treatment of Immunoglobulin, Ribavirin, and Interferon-α2b

Background@#and Purpose Japanese encephalitis (JE) is caused by the JE virus of the Flaviviridae family and is spread by mosquito bites, and no specific antiviral treatment for it exists. Here we describe the clinical presentations, laboratory findings, clinical outcomes, and adverse events after combination treatment of immunoglobulin, ribavirin, and interferon-α2b administered to patients with JE. @*Methods@#Data were collected and reviewed from a prospective cohort of encephalitis patients admitted to Seoul National University Hospital between August 1, 2010 and October 31, 2019.We reviewed the medical records of the patients diagnosed with JE and treated either with supportive care only or with combination treatment of intravenous immunoglobulin, oral ribavirin, and subcutaneous interferon-α2b. @*Results@#Eleven patients were diagnosed with laboratory-confirmed JE based on the diagnosis criteria of JE. The median age was 61 years, and five patients were male. Eight patients were treated with the combination therapy, while three patients received supportive management only. Four of the eight patients (50%) treated with the combination therapy showed partial recovery, while one patient (12.5%) showed complete recovery. Two patients experienced hemolytic anemia related to ribavirin and febrile reaction to immunoglobulin, respectively. Among the three patients who received supportive management only, one (33.3%) showed partial recovery and the other two (67.7%) did not show improvement. @*Conclusions@#Combination treatment of immunoglobulin, ribavirin, and interferon-α2b was found to be tolerable in JE in this study. Further studies of appropriate designs and involving larger numbers of patients are warranted to explore the efficacy of this combination therapy.

Comorbid Depression Is Associated with a Negative Treatment Response in Idiopathic REM Sleep Behavior Disorder

Background@#and PurposeThe first-line medications for the symptomatic treatment of rapid eye movement sleep behavior disorder (RBD) are clonazepam and melatonin taken at bedtime. We aimed to identify the association between depression and treatment response in patients with idiopathic RBD (iRBD). @*Methods@#We reviewed the medical records of 123 consecutive patients (76 males; age, 66.0±7.7 years; and symptom duration, 4.1±4.0 years) with iRBD who were treated with clonazepam and/or melatonin. Clonazepam and melatonin were initially administered at 0.25–0.50 and 2 mg/day, respectively, at bedtime, and the doses were subsequently titrated according to the response of individual patients. Treatment response was defined according to the presence or absence of any improvement in dream-enacting behaviors or unpleasant dreams after treatment. @*Results@#Forty (32.5%) patients were treated with clonazepam, 56 (45.5%) with melatonin, and 27 (22.0%) with combination therapy. The doses of clonazepam and melatonin at followup were 0.5±0.3 and 2.3±0.7 mg, respectively. Ninety-six (78.0%) patients reported improvement in their RBD symptoms during a mean follow-up period of 17.7 months. After adjusting for potential confounders, depression was significantly associated with a negative treatment response (odds ratio=3.76, 95% confidence interval=1.15–12.32, p=0.029). @*Conclusions@#We found that comorbid depression is significantly associated with a negative response to clonazepam and/or melatonin in patients with iRBD. Further research with larger numbers of patients is needed to verify our observations and to determine the clinical implications of comorbid depression in the pathophysiology of iRBD.

Delayed Diagnosis of Chromosome 22q11.2 Deletion Syndrome Due to Late-Onset Generalized Epilepsy

No abstract available.

A Psychiatric Side Effect of Levetiracetam Can Mimic a Relapse of Anti-Leucine-Rich Glioma Inactivated 1 Encephalitis

No abstract available.

Case of Rickettsia typhi-induced Brain Abscess Mimicking Brain Tumor

Murine typhus is one of the most prevalent rickettsial infections in the world, caused by the bacterial genus Rickettsia. Though the disease manifests a relatively benign clinical course with fever, rash, and headache being the 3 classic symptoms, neurological complications may arise in patients that could become permanent. In this case study, a patient with a brain abscess caused by R typhi infection is described. Based upon the recent reemergence of arthropod-borne disease, the findings in this case are significant; R typhi can cause a brain abscess that mimics a brain tumor, which delays the diagnosis and appropriate management of the disease. Murine typhus should always be considered when performing the differential diagnosis of brain abscesses in South Korea.

High-Fat Diet and Voluntary Chronic Aerobic Exercise Recover Altered Levels of Aging-Related Tryptophan Metabolites along the Kynurenine Pathway

Tryptophan metabolites regulate a variety of physiological processes, and their downstream metabolites enter the kynurenine pathway. Age-related changes of metabolites and activities of associated enzymes in this pathway are suggestable and would be potential intervention targets. Blood levels of serum tryptophan metabolites in C57BL/6 mice of different ages, ranging from 6 weeks to 10 months, were assessed using high-performance liquid chromatography, and the enzyme activities for each metabolic step were estimated using the ratio of appropriate metabolite levels. Mice were subjected to voluntary chronic aerobic exercise or high-fat diet to assess their ability to rescue age-related alterations in the kynurenine pathway. The ratio of serum kynurenic acid (KYNA) to 3-hydroxylkynurenine (3-HK) decreased with advancing age. Voluntary chronic aerobic exercise and high-fat diet rescued the decreased KYNA/3-HK ratio in the 6-month-old and 8-month-old mice groups. Tryptophan metabolites and their associated enzyme activities were significantly altered during aging, and the KYNA/3-HK ratio was a meaningful indicator of aging. Exercise and high-fat diet could potentially recover the reduction of the KYNA/3-HK ratio in the elderly.

Evaluation of Perioperative Antithrombotic Management in Patients Undergoing Moderate to High Risk Surgery

OBJECTIVE: The perioperative management of antithrombotic therapy is often challenging and it requires a fine balance between the risk of hemorrhage and thrombosis. We aimed to evaluate the antithrombotic management for moderate to high risk patients in real world setting. METHODS: Among the patients who were consulted to the neurologist for the evaluation of perioperative risk from 2010 to 2012, patients undergoing moderate to high risk surgery and taking antithrombotics within 30 days were identified. We analyzed the timing of discontinuation and reinitiation of antithrombotic drugs before or after surgery as well as the status of bridging therapy. In addition, the conformity with the guideline suggested by American College of Chest Physicians was assessed. The rate of thromboembolic event and major hemorrhage were also investigated. RESULTS: A total of 329 patients were included. The concordance rate of warfarin stop and restart time with guideline was 23.4% and 10.3%, respectively. Continuing aspirin in patients undergoing coronary artery bypass surgery or non-cardiac surgery in patients with high risk for cardiovascular events were 59.2% and 2.6%, respectively. Bridging therapy was adopted in 92.9% and 81.2% in patients who had received anticoagulant before surgery and who were at high and low risk thromboembolism, respectively. In entire cohorts, 30-day incidence of major bleeding and thromboembolic event were 31.9% and 3.0%. Co-morbid renal disease were shown as independent predictor for major bleeding (adjusted OR 2.65. 95% CI 1.33-5.28). CONCLUSION: The concordance rate with guideline regarding perioperative antithrombotic use was low and bridging therapy was prevalent in patients undergoing moderate to high risk surgery.

Rituximab Treatment for Idiopathic Hypertrophic Pachymeningitis

BACKGROUND AND PURPOSE: Hypertrophic pachymeningitis (HP) is a rare disease caused by autoimmunity in the meninx that causes various neurologic symptoms, including headache, seizures, weakness, paresthesia, and cranial nerve palsies. Although the first-line therapy for HP is steroids, many HP cases are refractory to steroids or recur when the steroids are tapered. Here we report three HP cases that were successfully treated with rituximab (RTX). METHODS: From an institutional cohort recruited from April 2012 to July 2016, three HP cases that were identified to be steroid-refractory were treated with RTX (four weekly doses of 375 mg/m²). Clinical improvement was assessed by the number of relapses of any neurologic symptom and the largest dural thickness in MRI. RESULTS: All three patients were recurrence-free of neurologic symptoms and exhibited prominent decreases in the dural thickness after RTX treatment. No adverse events were observed in the patients. CONCLUSIONS: We suggest RTX as a second-line therapy for steroid-refractory HP. Further studies are warranted to confirm this observation in a larger population and to consider RTX as a first-line therapy.

Exosome-Based Delivery of miR-124 in a Huntington's Disease Model

OBJECTIVE: Huntington's disease (HD) is a genetic neurodegenerative disease that is caused by abnormal CAG expansion. Altered microRNA (miRNA) expression also causes abnormal gene regulation in this neurodegenerative disease. The delivery of abnormally downregulated miRNAs might restore normal gene regulation and have a therapeutic effect. METHODS: We developed an exosome-based delivery method to treat this neurodegenerative disease. miR-124, one of the key miRNAs that is repressed in HD, was stably overexpressed in a stable cell line. Exosomes were then harvested from these cells using an optimized protocol. The exosomes (Exo-124) exhibited a high level of miR-124 expression and were taken up by recipient cells. RESULTS: When Exo-124 was injected into the striatum of R6/2 transgenic HD mice, expression of the target gene, RE1-Silencing Transcription Factor, was reduced. However, Exo-124 treatment did not produce significant behavioral improvement. CONCLUSION: This study serves as a proof of concept for exosome-based delivery of miRNA in neurodegenerative diseases.

Prognostic Value of Initial Standard EEG and MRI in Patients with Herpes Simplex Encephalitis

BACKGROUND AND PURPOSE: Herpes simplex encephalitis (HSE) is the most common type of sporadic encephalitis worldwide, and it remains fatal even when optimal antiviral therapy is applied. There is only a weak consensus on the clinical outcomes and prognostic factors in patients with HSE. This study examined whether the radiological and electrophysiological findings have a prognostic value in patients with HSE. METHODS: We retrospectively analyzed patients who were diagnosed with HSE by applying the polymerase chain reaction to cerebrospinal fluid and who received intravenous acyclovir at our hospital from 2000 to 2014. We evaluated the clinical outcomes at 6 months after onset and their correlations with initial and clinical findings, including the volume of lesions on MRI, the severity of EEG findings, and the presence of epileptic seizures at the initial presentation. RESULTS: Twenty-nine patients were enrolled (18 men and 11 women). Univariate analysis revealed that the presence of severe EEG abnormality and epileptic seizures at the initial presentation were significant correlated with a poor clinical outcome at 6 months (p=0.005 and p=0.009, respectively). In multivariate analysis, the presence of severe EEG abnormality was the only independent predictor of a poor outcome at 6 months (p=0.006). CONCLUSIONS: In cases of HSE, the initial EEG severity and seizure presentation may be useful predictive factors for the outcome at 6 months after acyclovir treatment.

Fractionated Stereotactic Gamma Knife Radiosurgery for Medial Temporal Lobe Epilepsy: A Case Report

An 18-year-old left-handed male harbored intractable medial temporal lobe epilepsy (MTLE) underwent fractionated gamma knife surgery (GKS) instead of open surgery, considering the mental retardation and diffuse cerebral dysfunction. GKS treatment parameters were: target volume, 8.8 cm3; total marginal dose, 24 Gy in 3 fractionations at the 50% isodose line. The patient has been free from seizures since 9 months after GKS, with notable improvement in cognitive outcome. Fractionated GKS could be considered as a safe tool for seizure control and neuropsychological improvement in patients with MTLE.

Fractionated Stereotactic Gamma Knife Radiosurgery for Medial Temporal Lobe Epilepsy: A Case Report

An 18-year-old left-handed male harbored intractable medial temporal lobe epilepsy (MTLE) underwent fractionated gamma knife surgery (GKS) instead of open surgery, considering the mental retardation and diffuse cerebral dysfunction. GKS treatment parameters were: target volume, 8.8 cm3; total marginal dose, 24 Gy in 3 fractionations at the 50% isodose line. The patient has been free from seizures since 9 months after GKS, with notable improvement in cognitive outcome. Fractionated GKS could be considered as a safe tool for seizure control and neuropsychological improvement in patients with MTLE.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis in Korea: Clinical Features, Treatment, and Outcome

BACKGROUND AND PURPOSE: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune synaptic encephalitis and it often responds to treatment. We analyzed the clinical characteristics of anti-NMDAR encephalitis in Korea. METHODS: Serum and/or cerebrospinal fluid (CSF) of adult patients (aged > or =18 years) with encephalitis of undetermined cause were screened for anti-NMDAR antibodies using a cell-based indirect immunofluorescence assay. The patients came from 41 university hospitals. RESULTS: Of the 721 patients screened, 40 were identified with anti-NMDAR antibodies and clinical details of 32 patients were obtained (median age, 41.5 years; 15 females). Twenty-two patients (68.8%) presented with psychiatric symptoms, 16 (50%) with seizures, 13 (40.6%) with movement disorders, 15 (46.9%) with dysautonomia, 11 (34.4%) with memory disturbance, and 11 (34.4%) with speech disturbance. Magnetic resonance imaging, electroencephalography, and CSF examinations yielded nonspecific findings. Tumor information was only available for 22 patients: 5 patients had tumors, and 2 of these patients had ovarian teratomas. Twenty-two patients received immunotherapy and/or surgery, and therapeutic responses were analyzed in 21 patients, of which 14 (66.7%) achieved favorable functional outcomes (score on the modified Rankin Scale of 0-2). CONCLUSIONS: This study investigated the clinical characteristics of adult anti-NMDAR encephalitis in Korea. Currently, elderly patients who do not have tumors are commonly diagnosed with this condition. Understanding the detailed clinical characteristics of this disease will improve the early detection of anti-NMDAR encephalitis in patients both young and old.

Oxcarbazepine Induced Leukopenia / 대한간질학회지

Oxcarbazepine (OXC) is generally assumed to be safe with regard to the risk for adverse hematopoietic effects. Recently, pancytopenia and leukopenia associated with the treatment of OXC have been reported. However, that serious adverse effect has never been reported in Korea. We describe a case of 47-year-old woman with temporal lobe epilepsy who developed reversible leukopenia following OXC monotherapy. She stopped to take OXC and WBC count was normalized completely.

Oxcarbazepine Induced Leukopenia

Oxcarbazepine (OXC) is generally assumed to be safe with regard to the risk for adverse hematopoietic effects. Recently, pancytopenia and leukopenia associated with the treatment of OXC have been reported. However, that serious adverse effect has never been reported in Korea. We describe a case of 47-year-old woman with temporal lobe epilepsy who developed reversible leukopenia following OXC monotherapy. She stopped to take OXC and WBC count was normalized completely.

Anti-LGI1 Limbic Encephalitis Presented with Atypical Manifestations

Anti-leucine-rich glioma inactivated-1 (LGI1) limbic encephalitis (LE) is a rare neurological disorder that has a subacute course of progressive encephalopathy and fasciobrachial dystonic seizures. We report a patient with anti-LGI1 LE that presented with atypical manifestations that complicated the diagnosis. A 62-year-old woman presented with a chronic course of memory disturbance and a subsequent relapse with an altered mental status after 10 months. The patient reported frequent chest pain of squeezing and dull nature, typically lasting 10-30 seconds. The chest pain was related to partial seizures, which were confirmed by video-EEG monitoring. Anti-LGI1 antibody was identified in serum and CSF. The patient's symptoms improved by immune modulation treatment. Patients with anti-LGI1 LE can experience atypical partial seizures, and a chronic relapsing course. Clinical suspicions and video-EEG monitoring are helpful for the early diagnosis and effective immune modulation.