Background: We aimed to evaluate long-term outcomes of gamma knife radiosurgery (GKS) for cerebral cavernous malformations (CCMs). Methods: Among the 233 CCM patients who underwent GKS, 79 adult patients (96 lesions) followed for over 10 years were included and analyzed retrospectively. Annual hemorrhage rate (AHR) was analyzed the entire cohort of 233 patients and the subset of 79 enrolled patients by dividing lesions into overall CCM lesions and brainstem lesions. AHR, neurologic outcome, adverse radiation effect (ARE), and changes of lesions in magnetic resonance imaging (MRI) were compared before and after GKS. Cox-regression analysis was performed to identify risk factors for hemorrhage following GKS. Results: Mean follow-up duration of 79 enrolled patients was 14 years (range, 10–23 years).The AHR of all CCMs for entire cohort at each time point was 17.8% (pre-GKS), 5.9% (≤ 2 years post-GKS), 1.8% (≤ 10 years post-GKS). The AHR of all CCM for 79 enrolled patients was 21.4% (pre-GKS), 3.8% (2 years post-GKS), 1.4% (10 years post-GKS), and 2.3% (> 10 years post-GKS). The AHR of brainstem cavernous malformation (CM) for entire cohort at each time point was 22.4% (pre-GKS), 10.1% (≤ 2 years post-GKS), 3.2% (≤ 10 years post-GKS). The AHR of brainstem CM for 79 enrolled patients was 27.2% (pre-GKS), 5.8% (2 years post-GKS), 3.4% (10 years post-GKS), and 3.5% (> 10 years post-GKS). Out of the 79 enrolled patients, 35 presented with focal neurologic deficits at the initial clinical visit. Among these patients, 74.3% showed recovery at the last follow-up. Symptomatic ARE occurred in five (6.4%) patients. No mortality occurred. Most lesions were decreased in size at the last follow-up MRI. Previous hemorrhage history (hazard ratio [HR], 8.38; 95% confidence interval [CI], 1.07–65.88; P = 0.043), and brainstem location (HR, 3.10; 95% CI, 1.26–7.64; P = 0.014) were significant risk factors for hemorrhage event. Conclusion GKS for CCM showed favorable long-term outcomes. GKS should be considered for CCM, especially when it has a previous hemorrhage history and brainstem location.

Background: Treatment for large (> 10 mL) arteriovenous malformations (AVMs) remains highly challenging. This study evaluated long-term effect of time-staged gamma knife radiosurgery (GKS) for large AVMs. Methods: For patients with large AVMs treated by time-staged GKS over 10 years, timestaged GKS was repeated every three years targeting the entire nidus if total obliteration was not achieved. Obliteration rate and post-GKS complications were assessed based on 10 mL volume interval of AVMs. Prognostic factors for these outcomes were evaluated using Cox regression analysis. Results: Ninety-six patients were analyzed. For AVMs in the 10–20 mL subgroup, a dose ≥ 13.5Gy yielded higher obliteration rate in the first GKS. In the 20–30 mL subgroup, a second GKS significantly boosted obliteration. AVMs > 30 mL did not achieve any obliteration with the first GKS. Among 35 (36.4%) cases lost to follow-up, 7 (7.2%) were lost due to GKS complications. Kaplan-Meier analysis showed that each subgroup needed different time for achieving 50% favorable obliteration outcome rate: 3.5, 6.5, and 8.2 years for 10–20 mL, 20–30 mL, and > 30 mL subgroup, respectively. Total obliteration rate calculated by intention-to-treat method: 73%, 51.7%, 35.7%, respectively, 61.5% overall. Post-GKS hemorrhage and chronic encapsulated expanding hematoma (CEEH) occurred in 13.5% and 8.3% of cases, respectively.Two patients died. Dose and volume were significant prognostic factors for obliteration. Initial AVM volume was a significant prognostic factor of post-GKS hemorrhage and CEEH. Conclusion Time-staged GKS for large AVMs less than 30 mL has highly favorable long-term outcome and a tolerable complication rate.

Recently, aducanumab, a beta amyloid targeted immunotherapy, has been approved by the US Food and Drug Administration for the treatment of Alzheimer’s dementia (AD). Although many questions need to be answered, this approval provides a promising hope for the development of AD drugs that could be supported by new biomarkers such as blood-based ones and composite neuropsychological tests that can confirm pathologic changes in early stages of AD. It is important to elucidate the complexity of AD which is known to be associated with other factors such as vascular etiologies and neuro-inflammation. Through the second international conference of the Korean Dementia Association (KDA), researchers from all over the world have participated in the exchange of opinions with KDA members on the most up-to-date topics. The Academic Committee of the KDA summarizes lectures to provide the depth of the conference as well as discussions. This will be an important milestone to widen the latest knowledge in the research of AD’s diagnosis, therapeutics, pathogenesis that can lead to the establishment of future directions.

Objective: : High-dose radiation is well known to induce and modulate the immune system. This study was performed to evaluate the correlation between clinical outcomes and changes in natural killer cell activity (NKA) after Gamma Knife Radiosurgery (GKS) in patients with brain cancer. Methods: : We performed an open-label, prospective, cross-sectional study of 38 patients who were treated with GKS for brain tumors, including metastatic and benign brain tumors. All of the patients underwent GKS, and blood samples were collected before and after GKS. NKA was measured using an enzyme-linked immunosorbent assay kit, to measure interferon-gamma (IFNγ) secreted by ex vivo-stimulated NK cells from whole blood. We explored the correlations between NK cell-produced IFNγ (NKA-IFNγ) levels and clinical parameters of patients who were treated with GKS for brain tumors. Results: : NKA-IFNγ levels were decreased in metastatic brain tumor patients compared to those with benign brain tumors (p<0.0001). All the patients who used steroid treatment to reduce brain swelling after GKS had an NKA-IFNγ level of zero except one patient. High NKA-IFNγ levels were not associated with a rapid decrease in brain metastasis and did not increase after GKS. Conclusion : The activity of NK cells in metastatic brain tumors decreased more than that in benign brain tumors after GKS.

Background/Aims: We investigated the distribution of serum uric acid (SUA) levels and estimated the prevalence of hyperuricemia and hypouricemia in the Korean population. Methods: This cross-sectional study used data from the Korean Genome and Epidemiology Study and included 172,970 participants (58,981 men and 113,989 women) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex. Results: The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall prevalence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prevalence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years. Conclusions The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.

Objective: Both hypouricemia and hyperuricemia are reportedly associated with reduced kidney function. This study investigated the association between uric acid levels and the risk of reduced renal function in men and women. Methods: We conducted a cross-sectional study using data from a government-funded health examinee cohort of a Korean genome and epidemiological study. A total of 172,970 participants (58,981 men, 113,989 women) aged 40∼79 years were included. A logistic regression test was performed, and the odds ratio (OR) and 95% confidence interval (CI) were calculated to examine the relationship between stratified uric acid levels and the frequency of chronic kidney disease. Results: As the uric acid level increased, the risk of reduced renal function increased. Moreover, for uric acid levels ≤2.0 mg/dL, the risk of reduced renal function was higher than that of the reference group. Among the total, man, and woman groups, a statistically significant association was observed in men (OR 1.71, 95% CI 0.945∼3.111, OR 5.003, 95% CI 1.405∼17.809, and OR 1.377, 95% CI 0.696∼2.724, respectively). Conclusion The OR of reduced renal function according to uric acid levels formed a J-shaped curve in both genders.

Objective: Both hypouricemia and hyperuricemia are reportedly associated with reduced kidney function. This study investigated the association between uric acid levels and the risk of reduced renal function in men and women. Methods: We conducted a cross-sectional study using data from a government-funded health examinee cohort of a Korean genome and epidemiological study. A total of 172,970 participants (58,981 men, 113,989 women) aged 40∼79 years were included. A logistic regression test was performed, and the odds ratio (OR) and 95% confidence interval (CI) were calculated to examine the relationship between stratified uric acid levels and the frequency of chronic kidney disease. Results: As the uric acid level increased, the risk of reduced renal function increased. Moreover, for uric acid levels ≤2.0 mg/dL, the risk of reduced renal function was higher than that of the reference group. Among the total, man, and woman groups, a statistically significant association was observed in men (OR 1.71, 95% CI 0.945∼3.111, OR 5.003, 95% CI 1.405∼17.809, and OR 1.377, 95% CI 0.696∼2.724, respectively). Conclusion The OR of reduced renal function according to uric acid levels formed a J-shaped curve in both genders.

Background: and PurposeMild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [18F]THK5351 in MCI subgroups. Methods: This study included 96 participants comprising 38 with amnestic MCI (aMCI), 21 with nonamnestic MCI (naMCI), and 37 with normal cognition (NC) who underwent 3.0-T MRI, [18F]THK5351 PET, and detailed neuropsychological tests. [18F]flutemetamol PET was also performed in 62 participants. The aMCI patients were further divided into three groups: 1) verbal-aMCI, only verbal memory impairment; 2) visual-aMCI, only visual memory impairment; and 3) both-aMCI, both visual and verbal memory impairment. Voxel-wise statistical analysis and region-of-interest -based analyses were performed to evaluate the retention of [18F]THK5351 in the MCI subgroups. Subgroup analysis of amyloid-positive and -negative MCI patients was also performed. Correlations between [18F]THK5351 retention and different neuropsychological tests were evaluated using statistical parametric mapping analyses. Results: [18F]THK5351 retention in the lateral temporal, mesial temporal, parietal, frontal, posterior cingulate cortices and precuneus was significantly greater in aMCI patients than in NC subjects, whereas it did not differ significantly between naMCI and NC participants. [18F] THK5351 retention was greater in the both-aMCI group than in the verbal-aMCI and visualaMCI groups, and greater in amyloid-positive than amyloid-negative MCI patients. The cognitive function scores were significantly correlated with cortical [18F]THK5351 retention. Conclusions [18F]THK5351 PET might be useful for identifying distinct topographic patterns of [18F]THK5351 retention in subgroups of MCI patients who are at greater risk of the progression to Alzheimer's dementia.

OBJECTIVE: This study aimed to evaluate the relationship between serum immunoglobulin G4 (IgG4) levels and the presence and disease activity of rheumatoid arthritis (RA). METHODS: The study enrolled 128 participants (RA, 96; healthy controls, 17; osteoarthritis, 11; and IgG4-related disease, 4) between March 2014 and July 2017. Blood samples were collected prior to the commencement of treatment, and serum IgG4 levels were determined using a nephelometric assay (levels ≥135 mg/dL were considered elevated). The levels of serum IgG4 and the ratio of IgG4/total IgG in patients with RA were compared with those in healthy controls, patients with osteoarthritis, and patients with IgG4-related disease. Furthermore, the relationship between serum IgG4 levels and RA disease activity was evaluated. RESULTS: Among the 96 patients with RA, the mean (±standard deviation) serum IgG4 level was 48.0±45.4 mg/dL; 6 (6.3%) patients had elevated serum IgG4 levels. However, none of the healthy controls or patients with osteoarthritis had elevated serum IgG4 levels. The mean serum IgG4/IgG ratio in patients with RA was 3.5%±2.8% (range, 0.2%~16.9%). Using Spearman's correlation coefficient analysis, a significant correlation was found between serum IgG4 levels and the Disease Activity Score-28 with erythrocyte sedimentation rate (r, 0.245; p=0.016). CONCLUSION There was an increased frequency of elevated serum IgG4 levels in patients with RA, and the levels were correlated with RA disease activity.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.
Acetaminophen ; Acetates ; Acetic Acid ; Anti-Inflammatory Agents, Non-Steroidal ; Cicatrix ; Classification ; Cyclooxygenase 2 Inhibitors ; Diethylpropion ; Drug Hypersensitivity ; Drug Hypersensitivity Syndrome ; Hospitals, University ; Incidence ; Korea ; Phenotype ; Propionates ; Prospective Studies ; Retrospective Studies ; Salicylates ; Salicylic Acid ; Stevens-Johnson Syndrome