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.

Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

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.

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.
Brain Abscess* ; Brain Neoplasms* ; Brain* ; Diagnosis ; Diagnosis, Differential ; Exanthema ; Fever ; Headache ; Humans ; Korea ; Rickettsia* ; Typhus, Endemic Flea-Borne

BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.
Acyl-CoA Dehydrogenase ; Biomarkers ; Blotting, Western ; Carcinoma, Hepatocellular ; Humans ; Immunoblotting ; Liver ; Liver Cirrhosis ; Mass Spectrometry ; Methionine Adenosyltransferase ; Methionine ; Proteomics ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Two-Dimensional Difference Gel Electrophoresis

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.
Autoimmunity ; Cohort Studies ; Cranial Nerve Diseases ; Headache ; Humans ; Magnetic Resonance Imaging ; Meningitis* ; Neurologic Manifestations ; Paresthesia ; Rare Diseases ; Recurrence ; Rituximab* ; Seizures ; Steroids

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.
Aged ; Aging ; Animals ; Chromatography, Liquid ; Diet, High-Fat* ; Exercise* ; Humans ; Infant ; Kynurenic Acid ; Kynurenine* ; Mice ; Physiological Processes ; Tryptophan*

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.
Animals ; Cell Line ; Exosomes ; Huntington Disease* ; Methods ; Mice ; MicroRNAs ; Neurodegenerative Diseases ; Transcription Factors

PURPOSE: This study was to develop evidence-based clinical practice guideline in order to prevent contrast-induced nephropathy (CIN) for patients undergoing percutaneous coronary intervention (PCI). METHODS: The guideline was developed based on the “Scottish Intercollegiate Guidelines Network (SIGN)”. The first draft of guideline was developed through 5 stages and evaluated by 10 experts.(1) Clinical questions were ensured in PICO format.(2) Two researchers conducted a systematic search through electronic database, identifying 170 studies. We selected 27 full text articles including 16 randomized clinical trials, 7 systematic reviews, and 4 guidelines. Quality of each studies were evaluated by the Cochran's Risk of Bias, AMSTAR, K-AGREEII. Among the studies, 11 studies were excluded.(3) The strength of recommendations were classified and quality of recommendations were ranked.(4) Guideline draft was finalized.(5) Content-validation was conducted by an expert group. All contents were ranked above 0.8 in CVI. RESULTS: Evidence-based clinical practice guideline to prevent CIN was dveloped.(1) The guideline for preventing CIN recommends using 0.9% saline.(2) Standardized rate of fluid therapy is 1 to 1.5ml/kg/hr.(3) Execute hydration for 6~12hrs before PCI and after PCI. CONCLUSION: This study suggests evidence-based clinical practice guideline for preventing CIN which can be more efficiently used in clinical practice.
Acute Kidney Injury ; Bias (Epidemiology) ; Contrast Media ; Evidence-Based Practice ; Fluid Therapy ; Humans ; Percutaneous Coronary Intervention

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.
Acyclovir ; Cerebrospinal Fluid ; Consensus ; Electroencephalography* ; Encephalitis ; Encephalitis, Herpes Simplex* ; Epilepsy ; Herpes Simplex* ; Humans ; Magnetic Resonance Imaging* ; Male ; Multivariate Analysis ; Polymerase Chain Reaction ; Retrospective Studies ; Seizures ; Simplexvirus