Seong-il Oh

Spectrum of cognitive impairment in Korean ALS patients without known genetic mutations.

Background Cognitive impairment is associated with a negative prognosis in amyotrophic lateral sclerosis (ALS), as well as with clinical specificity. We investigate neuropsychological function in ALS patients without known genetic mutations in a Korean tertiary clinic. Methods Three hundred and eighteen patients were enrolled in a prospective longitudinal cohort from September 2008 to February 2012. At the time of diagnosis of sporadic ALS, we carried out genetic and comprehensive neuropsychological tests on all patients, and collected demographic and clinical characteristics. Six cognitive domains, namely executive function, attention, language, calculation, visuospatial function and memory were evaluated. ANOVA and t-tests were used to assess differences in clinical characteristics and neuropsychological parameters between sporadic ALS patients. The Kaplan-Meier method and Cox proportional hazard model were used for survival analysis. Results One hundred and sixty-six patients were categorized into five subtypes: normal cognition (ALS pure), cognitive impairment (ALSci), behavioral impairment (ALSbi), frontotemporal dementia (ALS-FTD), and other types of dementia. Seventy patients (70/166, 42.2%) were cognitively or behaviorally impaired. Among the impaired patients, eight (8/166, 4.8%) had FTD-type dementia and one (1/166, 0.6%) was Alzheimers disease-type. The ALS patients with cognitive impairment (ALSci) and with FTD (ALS-FTD) were more severely impaired in executive function, attention, language and memory than the cognitively intact ALS patients (ALS pure). In a survival analysis, ALSci (β = 1.925, p = 0.025) and ALS-FTD groups (β = 4.150, p = 0.019) tended to have shorter survival than the ALS pure group. Conclusions About half of ALS patients without known genetic variation have cognitive or behavioral impairment. ALS patients with cognitive abnormalities, especially FTD, have a poorer prognosis than those without cognitive impairment. In neuropsychological profiling, executive tasks were effective in identifying cognitive impairment in the ALS patients. It would be useful for clinicians to classify ALS according to neuropsychological profiles, and screen for subtle cognitive impairment.

Socioeconomic costs of amyotrophic lateral sclerosis according to staging system

Abstract The objective of this study was to compare the cost of illness of amyotrophic lateral sclerosis (ALS) in the Korean population based on the staging system for ALS from the perspective of both patients and the government. Direct medical costs, care-related costs, and loss of productivity in patients with ALS were measured based on medical records and face-to-face interviews. The patients were divided into groups according to the staging system for ALS, and the cost of illness was analysed. A total of 151 patients with ALS were enrolled in the study. The mean monthly cost of ALS was US

Identification of mutations in Korean patients with amyotrophic lateral sclerosis using multigene panel testing.

7902 per patient and increased according to the disease stage (stage 2, US

De novo FUS mutations in 2 Korean patients with sporadic amyotrophic lateral sclerosis

5181; stage 3, US

Depression and Caregiving Burden in Families of Patients with Amyotrophic Lateral Sclerosis

7089; stage 4, US

Dietary intake of fruits and beta-carotene is negatively associated with amyotrophic lateral sclerosis risk in Koreans: A case-control study

10,557). Of direct medical costs (US

Acute bulbar palsy as a variant of Guillain-Barré syndrome

3436), 44.8% of the cost burden was carried by patients, and the remaining costs were paid by the government. In conclusion, although the current coverage rate of the National Health Insurance (NHI) system for rare and intractable diseases including ALS is 90%, the rate of direct medical costs paid by patients and out-of-pocket costs remain high. Moreover, coverage rates and cost of illness are closely related with disease severity.

Vitamin D levels are not predictors of survival in a clinic population of patients with ALS

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease involving motor neurons. Because a growing number of genes have been identified as the genetic etiology of ALS, simultaneous screening of mutations in multiple genes is likely to be more efficient than gene-by-gene testing. In this study, we performed a multigene panel testing by using targeted capture of 18 ALS-related genes followed by next-generation sequencing. Using this technique, we tried to identify mutations in 4 index patients with familial ALS and 148 sporadic ALS in Korean population and identified 4 known mutations in SOD1, ALS2, MAPT, and SQSTM1 genes, respectively, and 28 variants of uncertain significance in 9 genes. Among the 28 variants of uncertain significance, 6 missense variants were found in highly conserved residues and were consistently predicted to be deleterious by in silico analyses. These results suggest that multigene panel testing is an effective approach for mutation screening in ALS-related genes. Moreover, the relatively low frequency of mutations in known ALS genes implies marked genetic heterogeneity at least in Korean patients with ALS.

Effectiveness of a community‐based multidomain cognitive intervention program in patients with Alzheimer's disease

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder. Approximately 5% of ALS patients are familial (fALS) cases, and the remaining 95% are apparently sporadic (sALS) cases. To date, a number of genes have been discovered as associated with ALS, but the genetic background of sALS is not yet fully understood. The occurrence of de novo mutations in ALS genes might be an explanation for sALS, but reduced penetrance could be an alternative theory. Previously, we screened mutations in 5 ALS genes including SOD1 and FUS in 9 fALS and 249 sALS patients and found a total of 15 patients with either SOD1 (7 fALS and 3 sALS) or FUS (1 fALS and 4 sALS) mutations. Interestingly, only 1 fALS patient had the FUS mutation, whereas 4 sALS patients had mutations in this gene. To determine if the FUS mutations in sALS were de novo, we performed genetic analysis on 2 sALS patients with living parents. Genetic analysis confirmed that 2 FUS mutations, including the c.1483C>T (p.Arg495*) and the c.1509_1510delAG (p.Gly504Trpfs*12) mutations, were found only in the patients and not in their parents, confirming the de novo occurrence of these mutations. These findings support the notion that de novo mutations are responsible for a certain proportion of sALS.

Recombinant Human Erythropoietin in Amyotrophic Lateral Sclerosis: A Pilot Study of Safety and Feasibility

PURPOSE The purpose of this study was to describe depression, caregiving burden and the correlation of the two variables in the families of patients with amyotrophic lateral sclerosis (ALS) and to clarify factors predicting caregiving burden. METHODS A descriptive and cross-sectional study was conducted with 139 family members who provided care to patients with ALS. The characteristics of patients and families, Korean-Beck Depression Inventory (K-BDI), Korean version of Zarit Burden Interview (K-ZBI) and Korean-Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (K-ALSFRS-R) were used as study measures. RESULTS The mean score for K-BDI was 19.39 out of 63 suggesting sub-clinical depression and 38.2% of the family members exhibited depression. The mean score for K-ZBI was 66.03 out of 88. The predictors for K-ZBI were K-BDI, age of family member, length of time spent per day in caring, relationship to patient and K-ALSFRS-R. CONCLUSION The results of this study suggest that levels of depression and caregiving burden are high among family members caring for patients with ALS. As depression is associated with caregiving burden, screening and emotional supports should be provided to reduce the burden of care for these family. Support programs to alleviate the care burden are also needed, considering family demographics, time per day in caring giving and K-ALSFRS-R.