Seok Woo Yong

A comparison of cerebral glucose metabolism in Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies

Parkinsons disease dementia (PDD) and dementia with Lewy bodies (DLB) share many similar aspects, and making a clinical diagnosis of one disorder over the other relies heavily on an arbitrary criterion, so‐called 1‐year rule. This study was designed to search for any difference of metabolic patterns in these two disorders using F‐18 fluorodeoxyglucose (FDG) positron emission tomography (PET) images.

Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease

Mutations in five PARK genes (SNCA, PARKIN, DJ-1, PINK1, and LRRK2) are well-established genetic causes of Parkinson disease (PD). Recently, G2385R substitution in LRRK2 has been determined as a susceptibility allele in Asian PD. The objective of this study is to determine the frequency of mutations in these PARK genes in a Korean early-onset Parkinson disease (EOPD) cohort. The authors sequenced 35 exons in SNCA, PARKIN, DJ-1, PINK1, and LRRK2 in 72 unrelated EOPD (age-at-onset ≤50) recruited from ten movement disorders clinics in South Korea. Gene dosage change of the aforementioned genes was studied using multiple ligation-dependent probe amplification. We found four patients with PARKIN mutations, which were homozygous deletion of exon 4, compound heterozygous deletion of exon 2 and exon 4, heterozygous deletion of exon 4, and heterozygous nonsense mutation (Q40X). Four patients had PINK1 mutations; a compound heterozygous mutation (N367S and K520RfsX522) and three heterozygous mutations (G32R, R279H, and F385L). A missense mutation of SNCA (A53T) was found in a familial PD with autosomal dominant inheritance. Nine patients (12.5%) had heterozygous G2385R polymorphism of LRRK2, whereas none had G2019S mutation. However, no mutations were detected in DJ-1 and UCHL1 in our series. We identified genetic variants in PARKIN, PINK1, LRRK2, and SNCA as a cause or genetic risk factors for PD in 25% of Korean EOPD, and mutation of PARKIN was the most common genetic cause.

Internal and Cortical Border-Zone Infarction Clinical and Diffusion-Weighted Imaging Features

Background and Purpose— The pathogenesis of internal border-zone (IBZ) and cortical border-zone (CBZ) infarcts is unclear. Both types of infarct have been combined into a single group in most previous reports, which has produced conflicting results. We hypothesized that different pathogenic mechanisms underlie IBZ and CBZ infarcts. Methods— We reviewed 946 consecutive patients with ischemic stroke within the middle cerebral artery territory. IBZ and CBZ infarcts were selected based on diffusion-weighted imaging templates to identify vascular territories. Baseline patient characteristics, clinical courses, and neuroradiological features were compared between patients with IBZ and CBZ infarcts. Results— We identified 45 IBZ and 75 CBZ infarct patients. Compared with the CBZ infarct patients, IBZ infarct patients had a higher degree of stenosis or occlusion in either the middle cerebral or internal carotid artery (P=0.008) and exhibited a rosary-like pattern of infarction more frequently (P<0.001). In contrast, concomitant small cortical infarcts were observed more frequently in CBZ infarct patients (P<0.001). Clinical deterioration during the first 7 days of admission and poor outcome after 3 months after stroke was more prevalent in IBZ infarct patients than in CBZ infarct patients (P=0.002 and P=0.003, respectively). Conclusions— IBZ infarcts are caused mainly by hemodynamic compromise, whereas embolic pathogenesis appears to contribute greatly to the genesis of CBZ infarcts. Patients with IBZ infarcts showed poor early and late clinical courses. Our findings suggest that different therapeutic approaches may be required to prevent early clinical deterioration in patients with different types of border-zone infarcts.

Vertebral artery dominance contributes to basilar artery curvature and peri-vertebrobasilar junctional infarcts

Objectives: The diameters of the vertebral arteries (VAs) are very often unequal. Therefore, this study investigated if unequal VA flow contributes to the development of basilar artery (BA) curvature and if it is a link to the laterality of pontine or cerebellar infarcts occurring around the vertebrobasilar junction. Methods: Radiological factors were analysed (infarct laterality, VA dominance, BA curvature and their directional relationships) in 91 patients with acute unilateral pontine or posterior inferior cerebellar artery (PICA) territory infarcts. The “dominant” VA side was defined as either that the VA was larger in diameter or the VA was connected with the BA in more of a straight line, if both VAs looked similar in diameter on CT angiography. Multiple regression analysis was performed to predict moderate to severe BA curvature. Results: The dominant VA was more frequent on the left side (p<0.01). Most patients had an opposite directional relationship between the dominant VA and BA curvature (p<0.01). Pontine infarcts were opposite to the side of BA curvature (p<0.01) and PICA infarcts were on the same side as the non-dominant VA side (p<0.01). The difference in VA diameters was the single independent predictor for moderate to severe BA curvature (OR per 1 mm, 2.70; 95% CI 1.22 to 5.98). Conclusions: Unequal VA flow is an important haemodynamic contributor of BA curvature and development of peri-vertebrobasilar junctional infarcts.

Odour identification test and its relation to cardiac 123I‐metaiodobenzylguanidine in patients with drug induced parkinsonism

We investigated olfactory function and its relation to cardiac 123I-metaiodobenzylguanidine (MIBG) uptake in 15 patients with drug induced parkinsonism (DIP). The mean Cross Cultural Smell Identification (CCSI) score was significantly greater in patients with DIP than in those with Parkinson’s disease (PD: 6.9 (1.6) vs 4.4 (2.2); p<0.001); however, the mean CCSI score in patients with DIP was not significantly different from controls. One patient with DIP, whose CCSI score was significantly reduced, also exhibited decreased cardiac MIBG uptake. DIP patients with CCSI scores within the normal range had normal cardiac MIBG uptake. Our study suggests that an olfactory function test may be a useful tool for detecting DIP unrelated to PD and for identifying patients with DIP who have subclinical PD.

Olfactory function and neuropsychological profile to differentiate dementia with Lewy bodies from Alzheimer's disease in patients with mild cognitive impairment: A 5-year follow-up study

BACKGROUND Mild cognitive impairment (MCI) is a well-known precursor of Alzheimers disease (AD) but often also precedes dementia with Lewy bodies (DLB). The early differentiation of DLB from AD is important to delay disease progression. Olfactory dysfunction is a well-known early sign of both AD and Lewy body disorders, including Parkinsons disease (PD) and DLB. Thus, the aim of the present study was to determine whether olfactory and neuropsychological tests can aid in the differentiation of DLB from AD at the MCI stage. METHODS The present study included 122 MCI patients who were monitored until they developed dementia or until their condition stabilized; the follow-up period averaged 4.9 years (range: 3.9-6.2 years). Baseline olfactory function as measured with the Cross-Cultural Smell Identification (CCSI) test and neuropsychological data were compared. RESULTS During the follow-up period, 32 subjects developed probable AD (MCI-AD), 18 had probable DLB (MCI-DLB), 45 did not convert to dementia (MCI-stable), and eight developed a non-AD/DLB dementia. The mean CCSI score (95% confidence interval [CI]) in patients with MCI-DLB (4.6; 95% CI: 4.0-5.3) was significantly lower than that of MCI-AD patients (6.4; 95% CI: 6.0-6.7, p<0.001) and MCI-stable patients (7.3; 95% CI: 6.9-7.8, p<0.001). The area under the curve of the receiver operating characteristic to discriminate MCI-DLB from MCI-AD using CCSI scores was (0.84; 95% CI: 0.72-0.97). Frontal-executive function and visuospatial ability was worse in patients with MCI-DLB, while verbal recognition memory impairment was greater in those with MCI-AD. CONCLUSION Olfactory and neuropsychological tests can help predict conversion to DLB or AD in patients with MCI.

Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): a multicenter, randomized, double-blind, placebo-controlled trial.

Background: This study is intended to evaluate the propensities of cilostazol to reduce the pulsatility index (PI) in patients with acute lacunar infarction using the serial transcranial Doppler (TCD) examinations. Methods: In a multicenter, randomized, double-blind, placebo-controlled trial, patients were randomly assigned to receive either placebo or 100 mg cilostazol twice a day as well as aspirin 100 mg a day. The primary outcomes were the changes of middle cerebral artery (MCA) and basilar artery (BA) PIs at 14 and 90 days from the baseline TCD study. This study is registered with ClinicalTrials.gov (NCT00741286). Results: Trial medication was given to 203 patients, with 100 receiving cilostazol and 103 receiving placebo, and 164 were included in the per-protocol analysis of the primary outcome. Results from the linear mixed model showed that significant effects were obtained for time-by-group interactions (p = 0.008 in right MCA, p = 0.015 in left MCA, p = 0.002 in BA), suggesting that changes of PIs from the baseline to the 90-day study were different across the groups. Conclusions: Cilostazol further decreased TCD PIs at 90 days from baseline compared to placebo in acute lacunar infarction. This result may be related to pleiotropic effects, such as vasodilation, beyond its antiplatelet activity.

A Case-Control Study of Multiple System Atrophy in Korean Patients

A few case–control studies of multiple system atrophy (MSA) have been reported in Western populations. In this study, we included various epidemiological factors to evaluate whether the risk factors for MSA differed in Korean and Western populations. A total of 100 consecutive MSA patients and 104 controls at two referral hospitals participated. Information was obtained through face‐to‐face interviews using a structured questionnaire: history of living area, occupational history, food habits, alcohol and tobacco consumption, and use of drugs. Odds ratios and 95% confident intervals (OR [95% CI]) were computed using logistic regression. The multivariate logistic regression analysis revealed that use of antihypertensive medication (OR = 0.30 [0.12–0.78]) and vitamins (OR = 0.30 [0.14–0.64]) and consumption of meat and poultry (OR = 0.27 [0.13–0.56]) were associated with decreasing risk for MSA, whereas use of herbal medications (OR = 3.17 [1.28–7.84]) was associated with increasing risk for MSA. In univariate analysis adjusted for age, sex, education level, and recruitment center, use of aspirin (OR = 0.21 [0.07–0.61]) and coffee consumption (OR = 0.44 [0.23–0.84]) were significantly less frequent in MSA patients than in controls, whereas heavy smoking (≥40 pack‐years) was significantly more prevalent in MSA patients than in controls (OR = 3.44 [1.05–11.23]). There was no difference in living area, participation in farming, or exposure to agrichemicals and solvents between groups. This study showed that MSA in Korea is characterized by risk factors that are both similar to and different from those affecting Western populations and that herbal medicines constitute a new MSA risk factor for the Korean population.

Changes in Cerebral Glucose Metabolism in Patients with Parkinson Disease with Dementia After Cholinesterase Inhibitor Therapy

We investigated changes in cerebral glucose metabolism after cholinesterase inhibitor (ChEI) therapy in patients with Parkinson disease dementia (PDD) to determine whether cognitive improvements would be reflected in changes of cerebral metabolic patterns, thus offering insight into the neural substrate of cognitive dysfunction in patients with PDD. Methods: We performed a serial PET study before (baseline) and after ChEI therapy on 10 patients with PDD, using statistical parametric mapping. Additionally, covariance analysis was performed to extract regions in which increased change in regional cerebral metabolism correlated significantly with increased Mini-Mental State Examination scores. Results: The statistical parametric mapping analysis indicated that significantly increased cerebral metabolism after ChEI therapy, compared with at baseline, was most evident in the left angular gyrus extending to the supramarginal area and left superior and middle frontal gyri. Additionally, cerebral metabolism was significantly increased in the right superior frontal and left middle orbitofrontal gyri. In contrast, the right fusiform gyrus showed significantly decreased metabolism after ChEI, compared with at baseline. In the correlation analysis, improvements in Mini-Mental State Examination scores after ChEI treatment were significantly associated with increased cerebral metabolism in the left supramarginal, orbitofrontal, and cingulate areas. Conclusion: Our data suggest that prefrontal and parietal association areas may be relevant structures for the pharmacologic response to ChEI in patients with PDD.

Serum cholesterol levels and the risk of multiple system atrophy: A case-control study†

Cholesterol in brain membranes may modulate the conformational state and accumulation of α‐synuclein in α‐synucleinopathies.We examined the association between serum cholesterol and the risk of multiple system atrophy (MSA), one of the α‐synucleinopathies. We enrolled 142 patients with probable MSA from two tertiary referral hospitals and 155 age‐ and gender‐matched healthy people with no neurological disease. The levels of total cholesterol, low‐density lipoprotein cholesterol (LDL‐C), and high‐density lipoprotein cholesterol (HDL‐C) were significantly lower in MSA patients than in controls (total cholesterol: 172.7 vs. 196.3 mg/dL, P < 0.001; LDL‐C: 104.0 vs. 115.3 mg/dL, P = 0.001; HDL‐C: 47.3 vs. 54.2 mg/dL, P < 0.001). After adjusting for age, gender, use of cholesterol‐lowering drugs, and histories of hypertension, diabetes mellitus, and smoking, the odds ratios was 5.9 (95% CI = 2.3–11.5, P < 0.001) for MSA patients in the lowest quartile of total cholesterol and 2.6 (95% CI = 1.2–5.5, P = 0.016) for those in the lowest quartile of HDL‐C, compared with the highest quartiles. Levels of serum cholesterol did not significantly correlate with disease duration or severity. Our data suggest that lower levels of total cholesterol and HDL may be associated with an increased risk of MSA.