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Objective: The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to assess cognition in patients with Parkinson's disease (PD). In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPACog (K-SCOPA-Cog)., Methods: We enrolled 129 PD patients with movement disorders from 31 clinics in South Korea. The original version of the SCOPA-Cog was translated into Korean using the translation-retranslation method. The test-retest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. Spearman's rank correlation analysis with the Montreal Cognitive Assessment-Korean version (MOCA-K) and the Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity., Results: The Cronbach's alpha coefficient was 0.797, and the ICC was 0.887. Spearman's rank correlation analysis revealed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively)., Conclusion: Our., Results: demonstrate that the K-SCOPA-Cog has good reliability and validity.

There has been an increasing demand for robotic coil positioning during repetitive transcranial magnetic stimulation (rTMS) treatment. Accurate coil positioning is crucial because rTMS generally targets specific brain regions for both research and clinical application with other reasons such as safety, consistency and reliability and individual variablity. Some previous studies have employed industrial robots or co-robots and showed they can more precisely stimulate the target cortical regions than traditional manual methods. In this study, we not only developed a custom-TMS robot for better TMS coil placement but also analyzed the therapeutic effects on depression. Treatment effects were evaluated by measuring regional cerebral blood flow (rCBF) using single-photon emission computed tomography and depression severity before and after rTMS for the two positioning methods. The rTMS preparation time with our robotic coil placement was reduced by 53% compared with that of the manual method. The position and orientation errors were also significantly reduced from 11.17 mm and 4.06° to 0.94 mm and 0.11°, respectively, confirming the superiority of robotic positioning. The results from clinical and neuroimaging assessments indicated comparable improvements in depression severity and rCBF in the left dorsolateral prefrontal cortex between the robotic and manual rTMS groups. A questionnaire was used to determine the patients' feelings about the robotic system, including the safety and preparation time. A high safety score indicated good acceptability of robotic rTMS at the clinical site., (© 2023. Springer Nature Limited.)

Purpose: We evaluated the associations between serum complement levels and tuberculous meningitis (TBM), bacterial meningitis (BM), and viral meningitis (VM), as well as the association between serum complement levels and mortality in TBM., Methods: Background information and blood/cerebrospinal fluid analysis results were collected from 2009 to 2019. Patients who had serum complement level data collected at admission and who were diagnosed with TBM (n = 97), BM (n = 31), or VM (n = 557) were enrolled., Results: Initial serum complement levels were significantly lower in the TBM group than the VM group in both the total population and the propensity score-matched population. In the TBM and VM groups, compared to patients with initial highest-quartile C4 level, patients in the lowest quartile (C4 < 24.3 mg/dL) had significantly greater odds of TBM diagnosis (odds ratio, 2.2; 95% confidence interval, 1.0-4.5; p = 0.038). In the TBM group, patients with the lowest-quartile C3 level (<96.9 mg/dL) experienced a significantly higher 90-day mortality rate compared to other TBM patients (hazard ratio, 19.0; 95% confidence interval, 2.1-167.4.5; p = 0.008)., Conclusion: Both serum C3 and C4 levels were significantly lower in the TBM group than in the VM group. TBM patients with lower serum C3 level had a significantly higher mortality rate than those with higher C3 level., Competing Interests: Conflicts of Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2023 Korean Encephalitis and Neuroinflammation Society.)

Introduction: Cervical dystonia is considered as a network disorder affecting various brain regions in recent days. Presumably, deep brain stimulation (DBS) of the internal segment of globus pallidus (GPi) may exert therapeutic effects for cervical dystonia through modulation of the aberrant brain networks. In the present study, we investigated postoperative regional cerebral blood flow (rCBF) changes after GPi DBS using single-photon emission computed tomography (SPECT) to identify significant activity changes in several relevant brain areas of cervical dystonia patients., Methods: A total of 9 patients with idiopathic cervical dystonia were recruited, and SPECT scans were conducted at baseline and 3 months after the bilateral GPi DBS. Voxel-wise changes of rCBF were analyzed using Statistical Parametric Mapping. Symptom severity of dystonia was measured using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) at the baseline, and 1 week, and 3 months after GPi DBS., Results: At the 3-month follow-up after DBS, rCBF was increased in the left pons and right postcentral gyrus and decreased in the left middle frontal gyrus, left cerebellum, right putamen and pallidum, and left thalamus (p < 0.001). Severity of cervical dystonia assessed by TWSTRS was significantly decreased at 1-week and 3-month follow-up (p = 0.004)., Conclusions: Clinical improvement of cervical dystonia after GPi DBS may be accompanied by rCBF changes in several brain areas of the cortico-basal ganglia-cerebellar network which are important for sensorimotor integration., (© 2022. The Author(s).)

Although various neuropsychiatric symptoms are frequently accompanied with Alzheimer's disease (AD) and pose a substantial burden to both patients and caregivers, their neurobiological underpinnings remain unclear. This study investigated associations between regional cerebral blood flow (rCBF) and neuropsychiatric symptom domains in early AD. A total of 59 patients with early AD underwent brain technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) scans. Neuropsychiatric symptoms were assessed by the Neuropsychiatric Inventory and clustered into the affective, apathy, hyperactivity, and psychotic domains. A voxel-wise multiple regression analysis was performed with four domain scores as independent variables and age, sex, and Mini-Mental State Examination scores as covariates. The affective domain score was negatively correlated with rCBF in the prefrontal cortex, thalamus, and caudate. The apathy domain score showed inverse correlations with rCBF in the prefrontal and pre/postcentral gyri and midbrain. Patients with higher hyperactivity domain scores had increased rCBF in the prefrontal and temporal lobes. The psychotic symptom domain was positively correlated with rCBF in the cuneus and negatively associated with rCBF in the prefrontal, cingulate, and occipital regions and putamen. The score of each neuropsychiatric symptom domain showed the differential correlates of brain perfusion, while altered rCBF in the prefrontal cortex was found in all domains. Although preliminary, our results may suggest common and distinct patterns of rCBF underlying neuropsychiatric symptoms in early AD. Further studies with larger samples and control participants are warranted to confirm these findings.

Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer's disease (AD) by opening the blood-brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), 18 F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall ( p = 0.03) and recognition memory ( p = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus ( p = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman's ρ = 0.77, p = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD.

Objective: Clinical and radiological findings on neurosyphilis are fairly non-specific and there is a paucity of functional neuroimaging studies on neurosyphilis other than case reports and case series. The purpose of this study was to investigate brain perfusion abnormalities in patients with neurosyphilis. Methods: Four HIV-negative neurosyphilis patients and 4 healthy controls underwent clinical evaluation, brain technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission computed tomography (SPECT) imaging, and neuropsychological assessments which included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating-Sum of Boxes (CDR-SOB), and Global Deterioration Scale (GDS). Voxel-wise differences in regional cerebral blood flow were compared between the two groups. Results: Neuropsychological test results indicated cognitive impairment in all patients. SPECT analysis revealed multifocal hypoperfusion predominantly in the frontal, insular, and posterior cingulate regions in neurosyphilis patients compared with healthy controls (family-wise error corrected p < 0.05). Conclusions: Together with previous findings, our results suggest that the hypoperfusion in the frontal, insular, and posterior cingulate regions may reflect cognitive impairments observed in neurosyphilis patients. Further studies with larger samples are needed to confirm our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Im, Jeong, Kim, Jang, Song and Chung.)

Purpose: Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD., Methods: After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS., Results: The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported., Conclusion: These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.

We evaluated the association between hyponatremia and tuberculous meningitis (TBM) with the aim of providing additional information for differential diagnosis from other types of infectious meningitis, especially viral meningitis (VM). Cross-sectional and longitudinal data involving 5026 participants older than 18 years were analyzed in the total population and a propensity-matched population. The initial and lowest sodium levels and longitudinal changes in TBM, bacterial meningitis (BM), and VM patients were compared. Participants in the TBM group were enrolled when they were diagnosed as possible, probable, or definite TBM according to the Marais' criteria. The initial serum sodium level was significantly lower in TBM patients than in BM and VM patients (136.9 ± 5.9 vs. 138.3 ± 4.7 mmol/L, p < 0.001 for TBM vs. BM, and 139.0 ± 3.1, p < 0.001 for TBM vs. VM), and it decreased significantly more steeply to lower levels in both the TBM and BM patients compared with VM patients. The lowest serum sodium level was in the order of TBM < BM < VM patients, and the change was statistically significant in all subgroups (131.8 ± 6.4, 133.1 ± 5.1, 137.4 ± 3.7, respectively, p < 0.001). Participants with lower serum sodium level were more likely to have a diagnosis of TBM rather than VM, and this association was more pronounced for the lowest sodium level than the initial sodium level [OR 4.6 (95% CI 2.4-8.8, p < 0.001)]. These findings indicate that baseline and longitudinal evaluation of serum sodium level can provide information for differential diagnosis of TBM from BM or VM.

Background and Aims: Some online gamers may encounter difficulties in controlling their gaming behavior. Previous studies have demonstrated beneficial effects of transcranial direct current stimulation (tDCS) on various kinds of addiction. This study investigated the effects of tDCS on addictive behavior and regional cerebral metabolic rate of glucose (rCMRglu) in problematic online gamers., Methods: Problematic online gamers were randomized and received 12 sessions of either active (n = 13) or sham tDCS (n = 13) to the dorsolateral prefrontal cortex over 4 weeks (anode F3/cathode F4, 2 mA for 30 min, 3 sessions per week). Participants underwent brain 18F-fluoro-2-deoxyglucose positron emission tomography scans and completed questionnaires including the Internet Addiction Test (IAT), Brief Self-Control Scale (BSCS), and Behavioral Inhibition System/Behavioral Activation System scales (BIS/BAS) at the baseline and 4-week follow-up., Results: Significant decreases in time spent on gaming (P = 0.005), BIS (P = 0.03), BAS-fun seeking (P = 0.04), and BAS-reward responsiveness (P = 0.01), and increases in BSCS (P = 0.03) were found in the active tDCS group, while decreases in IAT were shown in both groups (P < 0.001). Group-by-time interaction effects were not significant for these measures. Increases in BSCS scores were correlated with decreases in IAT scores in the active group (β = -0.85, P < 0.001). rCMRglu in the left putamen, pallidum, and insula was increased in the active group compared to the sham group (P for interaction < 0.001)., Discussion and Conclusions: tDCS may be beneficial for problematic online gaming potentially through changes in self-control, motivation, and striatal/insular metabolism. Further larger studies with longer follow-up period are warranted to confirm our findings.

The Ritchey-Common test is a widely used method for testing flat mirrors with a larger reference spherical mirror. However, with the increase in the size of the flat mirror, the fabrication of the spherical mirror becomes more time consuming and expensive. In this study, we developed a novel technique to test a large flat mirror with a smaller reference sphere using a dual subaperture stitching (DSS) method. One part of the DSS technique is a modified Ritchey-Common test, which uses a reference sphere smaller than the flat mirror. The other part involves scanning along the centerline of the flat mirror. The former can be used to determine the surface form error (SFE), except for rotationally symmetric components, such as power and spherical aberrations, which can be measured by the latter. To perform the stitching process using a smaller reference sphere, the flat mirror was repeatedly rotated by a fixed angular step. One of the advantages of the rotation of the flat mirror is that it can be used to identify the errors resulting from the reference sphere, which do not vary during the rotation of the flat mirror. We verified the DSS method using a 152 mm diameter optical flat mirror and determined the root-mean-square (rms) measurement error to be only 0.2 nm, which was comparable to the error of the full-aperture interferometric measurement. In addition, we tested a 1.2 m diameter flat mirror with a reference sphere with an aperture of 0.8 m and measured its SFE to be 11.9±0.5 n m rms.

Dizziness is a common symptom among the general population, especially in the elderly. Previous studies have reported that dizziness may be associated with various cognitive functions including memory impairment. However, few studies have investigated the neural correlates of dizziness in patients with cognitive impairment. The aim of this study was to examine regional cerebral blood flow (rCBF) in mild cognitive impairment (MCI) patients with or without dizziness using single photon emission computed tomography (SPECT). A total of 50 patients with MCI were recruited. All participants underwent technetium-99m ethyl cysteinate dimer brain SPECT and a neuropsychological battery and completed the Dizziness Handicap Inventory (DHI). Participants were divided into a dizziness group (DHI ≥ 1, n = 18) and a non-dizziness group (DHI = 0, n = 32). Voxel wise differences in rCBF between the groups were estimated. SPECT analysis revealed decreased rCBF in the left superior temporal gyrus, left lateral orbital gyrus, and right middle frontal gyrus in the dizziness group compared with the non-dizziness group ( p < 0.005). No significant clusters of increased rCBF were observed in the dizziness group compared with the non-dizziness group. Results of the neuropsychological tests showed a significant difference in Controlled Oral Word Association Test performance between MCI patients with and without dizziness. In conclusion, MCI patients with dizziness showed multifocal frontal and left temporal hypoperfusion compared with patients without dizziness. Our results suggest that hypoperfusion in the frontal and temporal cortices might be reflecting the negative impact of dizziness in MCI patients.

The neuropathology of Parkinson's disease dementia (PDD) is heterogenous, and the impacts of each pathophysiology and their synergistic effects are not fully understood. The aim of this study was to evaluate the frequency and impacts of co-existence with Alzheimer's disease in patients with PDD by using 18F-florbetaben PET imaging. A total of 23 patients with PDD participated in the study. All participants underwent 18F-florbetaben PET and completed a standardized neuropsychological battery and assessment of motor symptoms. The results of cognitive tests, neuropsychiatric symptoms, and motor symptoms were analyzed between the positive and negative 18F-florbetaben PET groups. Four patients (17.4%) showed significant amyloid burden. Patients with amyloid-beta showed poorer performance in executive function and more severe neuropsychiatric symptoms than those without amyloid-beta. Motor symptoms assessed by UPDRS part III and the modified H&Y Scale were not different between the two groups. The amyloid PET scan of a patient with PDD can effectively reflect a co-existing Alzheimer's disease pathology. Amyloid PET scans might be able to help physicians of PDD patients showing rapid progression or severe cognitive/behavioral features.

Background and Purpose: Impulse-control disorder is an important nonmotor symptom of Parkinson's disease (PD) that can lead to financial and social problems, and be related to a poor quality of life. A nationwide multicenter prospective study was performed with the aim of validating the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (K-QUIP-RS)., Methods: The K-QUIP-RS was constructed using forward and backward translation, and pretesting of the prefinal version. PD patients on stable medical condition were recruited from 27 movement-disorder clinics. Participants were assessed using the K-QUIP-RS and evaluated for parkinsonian motor and nonmotor statuses and for PD-related quality of life using a predefined evaluation battery. The test-retest reliability of the K-QUIP-RS was assessed over an interval of 10-14 days, and correlations between the KQUIP-RS and other clinical scales were analyzed., Results: This study enrolled 136 patients. The internal consistency of the K-QUIP-RS was indicated by a Cronbach's α coefficient of 0.846, as was the test-retest reliability by a Guttman split-half coefficient of 0.808. The total K-QUIP-RS score was positively correlated with the scores for depression and motivation items on the Unified PD Rating Scale (UPDRS), Montgomery-Asberg Depression Scale, and Rapid-Eye-Movement Sleep-Behavior-Disorders Questionnaire. The total K-QUIP-RS score was also correlated with the scores on part II of the UPDRS and the PD Quality of Life-39 questionnaire, and the dopaminergic medication dose., Conclusions: The K-QUIP-RS appears to be a reliable assessment tool for impulse-control and related behavioral disturbances in the Korean PD population., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 Korean Neurological Association.)

Background and Purpose: This study aimed to determine the clinimetric properties of the Korean version of Parkinson's Disease Sleep Scale-2 (K-PDSS-2) and whether distinct subtypes of sleep disturbance can be empirically identified in patients with Parkinson's disease (PD) using the cross-culturally validated K-PDSS-2., Methods: The internal consistency, test-retest reliability, scale precision, and convergent validity of K-PDSS-2 were assessed in a nationwide, multicenter study of 122 patients with PD. Latent class analysis (LCA) was used to derive subgroups of patients who experienced similar patterns of sleep-related problems and nocturnal disabilities., Results: The total K-PDSS-2 score was 11.67±9.87 (mean±standard deviation) at baseline and 12.61±11.17 at the retest. Cronbach's α coefficients of the total K-PDSS-2 scores at baseline and follow-up were 0.851 and 0.880, respectively. The intraclass correlation coefficients over the 2-week study period ranged from 0.672 to 0.848. The total K-PDSS-2 score was strongly correlated with health-related quality of life measures and other corresponding nonmotor scales. LCA revealed three distinct subtypes of sleep disturbance in the study patients: "less-troubled sleepers," "PD-related nocturnal difficulties," and "disturbed sleepers.", Conclusions: K-PDSS-2 showed good clinimetric attributes in accordance with previous studies that employed the original version of the PDSS-2, therefore confirming the cross-cultural usefulness of the scale. This study has further documented the first application of an LCA approach for identifying subtypes of sleep disturbance in patients with PD., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 Korean Neurological Association.)

Background: Amnestic mild cognitive impairment (aMCI) is highly likely to progress to dementia of the Alzheimer type (DAT). One of the most frequently reported symptoms in aMCI and DAT patients is memory impairment. This study compared the levels of beliefs about memory efficacy and control, cognitive activity, and depression among healthy older adults (OA), patients with aMCI, and patients with DAT., Methods: This study included 21 OA (11 males, 10 females), 16 aMCI patients (6 males, 10 females), and 18 DAT patients (10 males, 8 females). The memory efficacy questionnaire, memory control questionnaire, cognitive activity questionnaire, depression questionnaire, and Seoul Verbal Learning Test were administered to all subjects., Results: DAT patients showed significantly lower scores on the recognition test than did the OA and aMCI patients, and no difference in these scores was observed between the OA and aMCI patients. Regarding the memory efficacy, memory control, and cognitive activity questionnaires, DAT and aMCI patients showed significantly lower scores than did OA. However, there were no differences in these scores between aMCI and DAT patients., Conclusion: The results of this study suggest that aMCI patients experienced impairment in memory beliefs and memory control in the same way as DAT patients did. These results suggest that the early application of cognitive rehabilitation therapy for patients with aMCI may be effective in preventing or alleviating memory deterioration., Competing Interests: The researchers claim no conflicts of interest., (Copyright © 2019 by The Korean Geriatric Society.)

Aim: Excessive use of online games can have negative influences on mental health and daily functioning. Although the effects of transcranial direct current stimulation (tDCS) have been investigated for the treatment of addiction, it has not been evaluated for excessive online game use. This study aimed to investigate the feasibility and tolerability of tDCS over the dorsolateral prefrontal cortex (DLPFC) in online gamers., Methods: A total of 15 online gamers received 12 active tDCS sessions over the DLPFC (anodal left/cathodal right, 2 mA for 30 min, 3 times per week for 4 weeks). Before and after tDCS sessions, all participants underwent 18 F-fluoro-2-deoxyglucose positron emission tomography scans and completed the Internet Addiction Test (IAT), Brief Self Control Scale (BSCS), and Beck Depression Inventory-II (BDI-II)., Results: After tDCS sessions, weekly hours spent on games (p = .02) and scores of IAT (p < .001) and BDI-II (p = .01) were decreased, whereas BSCS score was increased (p = .01). Increases in self-control were associated with decreases in both addiction severity (p = .002) and time spent on games (p = .02). Moreover, abnormal right-greater-than-left asymmetry of regional cerebral glucose metabolism in the DLPFC was partially alleviated (p = .04)., Conclusions: Our preliminary results suggest that tDCS may be useful for reducing online game use by improving interhemispheric balance of glucose metabolism in the DLPFC and enhancing self-control. Larger sham-controlled studies with longer follow-up period are warranted to validate the efficacy of tDCS in gamers.

Background and Purpose: Apathy is one of the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD). It may have adverse impacts on the progression of AD. However, its neurobiological underpinnings remain unclear. The objective of this study was to investigate differences in regional cerebral blood flow (rCBF) between AD patients with apathy and those without apathy., Methods: Sixty-six apathetic AD patients and 66 AD patients without apathy completed Neuropsychiatric Inventory (NPI) and underwent technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) scans. Voxel-wise differences in rCBF between the 2 groups were examined. Association between rCBF and levels of apathy in the apathetic group was also assessed., Results: AD patients with apathy showed lower rCBF in the bilateral orbitofrontal cortex, left putamen, left nucleus accumbens, left thalamus, and bilateral insula than those without (all p <0.005). Mean perfusion across all significant clusters showed a negative linear correlation with NPI apathy score in AD patients with apathy (β=-0.25; p =0.04)., Conclusions: Hypoperfusion in the prefrontal, striatal, and insular areas may be neural correlates of apathy in AD patients., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Background: Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD., Methods: In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10-14 days., Results: The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ., Conclusion: The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2018 The Korean Academy of Medical Sciences.)

Background and Purpose: Nicergoline is an ergoline derivative that is used to treat cognitive deficits in cerebrovascular disease and various forms of dementia. Although therapeutic effects of nicergoline have been established, little is known about its effects on cerebral perfusion in Alzheimer's disease (AD). The aim of this study was to examine the role of nicergoline in regional cerebral blood flow (rCBF) of AD patients using technetium-99m hexa-methyl-propylene-amine-oxime single photon emission computed tomography (SPECT)., Methods: Sixteen patients with early AD underwent a comprehensive clinical assessment including cognitive testing and SPECT scans before and after nicergoline treatment. Nicergoline (30 mg twice daily) was administered for an average duration of 1.5 years. Clinical and cognitive functioning was assessed using the Mini-Mental State Examination, Clinical Dementia Rating (CDR), CDR-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living Index, Instrumental Activities of Daily Living, and Geriatric Depression Scale., Results: Nicergoline treatment induced changes in the severity of dementia, cognitive function, activities of daily living, and depressive symptoms, which were not statistically significant. During the follow-up, the patients showed significant increases in their relative rCBF in the superior frontal gyrus, precentral gyrus, and postcentral gyrus., Conclusions: Nicergoline treatment improves perfusion of the frontal and parietal regions in early AD patients. It is possible that the increased perfusion in the superior frontal gyrus may be related to the mechanisms that delay or prevent progressive deterioration of cognitive functions in AD., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Background and Purpose: Although sleep disturbances are common and considered a major burden for patients with Alzheimer's disease (AD), the fundamental mechanisms underlying the development and maintenance of sleep disturbance in AD patients have yet to be elucidated. The aim of this study was to examine the correlation between regional cerebral blood flow (rCBF) and sleep disturbance in AD patients using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT)., Methods: A total of 140 AD patients were included in this cross-sectional study. Seventy patients were assigned to the AD with sleep loss (SL) group and the rest were assigned to the AD without SL group. SL was measured using the sleep subscale of the Neuropsychiatric Inventory. A whole-brain voxel-wise analysis of brain SPECT data was conducted to compare the rCBF between the two groups., Results: The two groups did not differ in demographic characteristics, severity of dementia, general cognitive function, and neuropsychiatric symptoms, with the exception of sleep disturbances. The SPECT imaging analysis displayed decreased perfusion in the bilateral inferior frontal gyrus, bilateral temporal pole, and right precentral gyrus in the AD patients with SL group compared with the AD patients without SL group. It also revealed increased perfusion in the right precuneus, right occipital pole, and left middle occipital gyrus in the AD with SL group compared with the AD without SL group., Conclusions: The AD patients who experienced sleep disturbance had notably decreased perfusion in the frontal and temporal lobes and increased rCBF in the parietal and occipital regions. The findings of this study suggest that functional alterations in these brain areas may be the underlying neural correlates of sleep disturbance in AD patients., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. Cerebrovascular diseases such as cerebral ischemic lesion (CIL) also commonly occur in elderly adults. However, previous studies on the relationship between PD and cerebrovascular disease have not found consistent results. Therefore, we conducted this study to evaluate whether or not PD is related to an increased prevalence of ischemic cerebrovascular lesions., Methods: This study recruited 241 patients with PD and 112 healthy controls (HCs). All subjects underwent brain magnetic resonance imaging and general neuropsychological tests. The motor severity of PD was evaluated according to the Hoehn and Yahr stage (HY stage), and the severity of CIL in all subjects was classified according to Fazekas grade. The PD patients were classified into two subgroups according to HY stage (Group 1 - HY 1, 2; Group 2 - HY 3 to 5)., Results: Among all PD patients, 76% had small vessel disease, while 44% of all HCs had small vessel disease (p<0.001). Regarding the difference between the two subgroups according to motor severity, group 2 showed significantly higher Fazekas scale score and more severe CIL, indicating a higher prevalence of small vessel disease compared to group 1., Conclusion: This study demonstrates that PD patients have a significantly higher prevalence of CIL compared to HCs. Therefore, although the present study is not a large-scale study, we cautiously suggest that PD can play an important role as a risk factor in the occurrence of ischemic cerebrovascular disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background and Purpose: Although acetyl-L-carnitine (ALC) treatment may have beneficial effects on Alzheimer's disease (AD), its underlying neural correlates remain unclear. The purpose of this study was to investigate cerebral perfusion changes after ALC treatment in AD patients using technetium- 99 m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT)., Methods: A total of 18 patients with early AD were prospectively recruited and treated with ALC at 1.5 g/day for 1.4±0.3 years. At baseline and follow-up, brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI) were used to assess participants. After ALC administration, changes in brain perfusion, severity of dementia, cognitive performance, and neuropsychiatric disturbances were examined., Results: After ALC administration, changes in scores of MMSE, CDR, GDS, and NPI were not statistically significant ( p >0.05). Voxel-wise whole-brain image analysis revealed that perfusion was significantly ( p <0.001) increased in the right precuneus whereas perfusion was reduced in the left inferior temporal gyrus ( p <0.001), the right middle frontal gyrus ( p <0.001), and the right insular cortex ( p =0.001) at follow-up., Conclusions: Although previous studies have suggested that AD patients generally demonstrate progressive deterioration in brain perfusion and clinical symptoms, this study reveals that the perfusion of the precuneus is increased in AD patients after ALC administration and their cognitive and neuropsychiatric symptoms are not aggravated. Further studies are warranted to determine the potential association between perfusion increase in the precuneus and clinical symptoms after ALC treatment in AD patients., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Objective: Autonomic symptoms are commonly observed in patients with Parkinson's disease (PD) and often limit the activities of daily living. The Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT) was developed to evaluate and quantify autonomic symptoms in PD. The goal of this study was to translate the original SCOPA-AUT, which was written in English, into Korean and to evaluate its reliability and validity for Korean PD patients., Methods: For the translation, the following processes were performed: forward translation, backward translation, expert review, pretest of the pre-final version and development of the final Korean version of SCOPA-AUT (K-SCOPA-AUT). In total, 127 patients with PD from 31 movement disorder clinics of university-affiliated hospitals in Korea were enrolled in this study. All patients were assessed using the K-SCOPA-AUT and other motor, non-motor, and quality of life scores. Test-retest reliability for the K-SCOPA-AUT was assessed over a time interval of 10-14 days., Results: The internal consistency and reliability of the K-SCOPA-AUT was 0.727 as measured by the mean Cronbach's α-coefficient. The test-retest correlation reliability was 0.859 by the Guttman split-half coefficient. The total K-SCOPA-AUT score showed a positive correlation with other non-motor symptoms [the Korean version of non-motor symptom scale (K-NMSS)], activities of daily living (Unified Parkinson's Disease Rating Scale part II) and quality of life [the Korean version of Parkinson's Disease Quality of Life 39 (K-PDQ39)]., Conclusion: The K-SCOPA-AUT had good reliability and validity for the assessment of autonomic dysfunction in Korean PD patients. Autonomic symptom severities were associated with many other motor and non-motor impairments and influenced quality of life., Competing Interests: The authors have no financial conflicts of interest.

Objective: Although Parkinson's disease (PD) is frequently accompanied by depression, brain perfusion deficits in PD with depression remain unclear. This study aimed to assess alterations in regional cerebral blood flow (rCBF) in depressed PD patients using 99m Tc hexamethyl-propylene-amine-oxime single-photon emission computed tomography (SPECT)., Methods: Among 78 patients with PD, 35 patients were classified into the depressed PD group, while the rest (43 patients) was assigned to the nondepressed PD group based on the scores of the Geriatric Depressive Scale (GDS). All participants underwent brain SPECT imaging. The voxel-wise whole-brain analysis and region-of-interest (ROI) analysis of the limbic areas were conducted to compare rCBF between the depressed and nondepressed PD groups., Results: The depressed PD patients demonstrated higher GDS scores than nondepressed patients, whereas between-group differences in the PD severity and cognitive function were not significant. Perfusion in the left cuneus was increased, while that in the right superior temporal gyrus and right medial orbitofrontal cortex was reduced in the depressed PD patients as compared with nondepressed PD patients. In addition, the ROI analysis demonstrated rCBF decreases in the amygdala, anterior cingulate cortex, hippocampus, and parahippocampal gyrus in the depressed PD group. A positive correlation was found between the GDS scores and rCBF in the left cuneus cluster in the depressed PD patients., Conclusion: This study identified the regional pattern of brain perfusion that distinguished depressed from nondepressed PD patients. Hyperperfusion in the occipital areas and hypoperfusion in the fronto-temporo-limbic regions may be potential imaging biomarkers for depression in PD.

Background: Mild cognitive impairment (MCI) is a syndrome that disrupts an individual's cognitive function but preserves activities of daily living. MCI is thought to be a prodromal stage of dementia, which disrupts patients' daily lives and causes severe cognitive dysfunction. Although extensive clinical trials have attempted to slow or stop the MCI to dementia conversion, the results have been largely unsuccessful. The purpose of this study was to determine whether noninvasive electrical stimulation of MCI changes glucose metabolism., Methods: Sixteen MCI patients participated in this study. We used transcranial direct current stimulation (tDCS) (2 mA/day, three times per week for 3 weeks) and assessed positron emission tomography (18 F-FDG) before and after 3 weeks of stimulation., Results: We showed that regular and relatively long-term use of tDCS significantly increased regional cerebral metabolism in MCI patients. Furthermore, subjective memory satisfaction and improvement of the memory strategies of participants were observed only in the real tDCS group after 3 weeks of stimulation., Conclusion: Our findings suggest that neurophysiological intervention of MCI could improve glucose metabolism and transient memory function in MCI patients.

Background and Purpose: Although subjective cognitive impairment (SCI) is often accompanied by Parkinson's disease (PD) and may predict the development of mild cognitive impairment or dementia, longitudinal brain perfusion changes in PD patients with SCI remain to be elucidated. The current prospective study examined cerebral perfusion changes in PD patients with SCI using technetium-99m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT)., Methods: Among 53 PD patients at baseline, 30 patients were classified into the PD with SCI group and 23 patients were assigned to the PD without SCI group. The mean follow-up interval was 2.3±0.9 years. The Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale were used to assess impairments in cognitive function. Brain SPECT images were acquired at baseline and follow-up., Results: Significant differences between the two groups were not found for demographic variables, PD severity, or cognitive function at either baseline or follow-up. At baseline, the PD with SCI group showed decreased perfusion in the left angular gyrus compared to the PD without SCI group. Longitudinal analysis revealed widespread perfusion reductions primarily in the bilateral temporo-parieto-occipital areas and cerebellum in the PD with SCI group. Relative to the PD without SCI group, an excessive decrease of perfusion was found in the left middle frontal gyrus of the PD with SCI patients., Conclusions: Our findings suggest that perfusion deficits in the middle frontal area may play an important role in the pathophysiology of SCI in PD., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Background: Transcranial focused ultrasound (FUS) is gaining momentum as a novel non-invasive brain stimulation method, with promising potential for superior spatial resolution and depth penetration compared to transcranial magnetic stimulation or transcranial direct current stimulation. We examined the presence of tactile sensations elicited by FUS stimulation of two separate brain regions in humans-the primary (SI) and secondary (SII) somatosensory areas of the hand, as guided by individual-specific functional magnetic resonance imaging data., Results: Under image-guidance, acoustic stimulations were delivered to the SI and SII areas either separately or simultaneously. The SII areas were divided into sub-regions that are activated by four types of external tactile sensations to the palmar side of the right hand-vibrotactile, pressure, warmth, and coolness. Across the stimulation conditions (SI only, SII only, SI and SII simultaneously), participants reported various types of tactile sensations that arose from the hand contralateral to the stimulation, such as the palm/back of the hand or as single/neighboring fingers. The type of tactile sensations did not match the sensations that are associated with specific sub-regions in the SII. The neuro-stimulatory effects of FUS were transient and reversible, and the procedure did not cause any adverse changes or discomforts in the subject's mental/physical status., Conclusions: The use of multiple FUS transducers allowed for simultaneous stimulation of the SI/SII in the same hemisphere and elicited various tactile sensations in the absence of any external sensory stimuli. Stimulation of the SII area alone could also induce perception of tactile sensations. The ability to stimulate multiple brain areas in a spatially restricted fashion can be used to study causal relationships between regional brain activities and their cognitive/behavioral outcomes.

Background and Purpose: Nonmotor symptoms (NMS) in Parkinson's disease (PD) have multisystem origins with heterogeneous manifestations that develop throughout the course of PD. NMS are increasingly recognized as having a significant impact on the health-related quality of life (HrQoL). We aimed to determine the NMS presentation according to PD status, and the associations of NMS with other clinical variables and the HrQoL of Korean PD patients., Methods: We surveyed patients in 37 movement-disorders clinics throughout Korea. In total, 323 PD patients were recruited for assessment of disease severity and duration, NMS, HrQoL, and other clinical variables including demographics, cognition, sleep scale, fatigability, and symptoms., Results: In total, 98.1% of enrolled PD subjects suffered from various kinds of NMS. The prevalence of NMS and scores in each NMS domain were significantly higher in the PD group, and the NMS worsened as the disease progressed. Among clinical variables, disease duration and depressive mood showed significant correlations with all NMS domains (p<0.001). NMS status impacted HrQoL in PD (rS=0.329, p<0.01), and the association patterns differed with the disease stage., Conclusions: The results of our survey suggest that NMS in PD are not simply isolated symptoms of degenerative disease, but rather exert significant influences throughout the disease course. A novel clinical approach focused on NMS to develop tailored management strategies is warranted to improve the HrQoL in PD patients., Competing Interests: The authors have no financial conflicts of interest.

Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

Despite the clinical impact of non-motor symptoms (NMS) in Parkinson's disease (PD), the characteristic NMS in relation to the motor subtypes of PD is not well elucidated. In this study, we enrolled drug-naïve PD patients and compared NMS between PD subtypes. We enrolled 136 drug-naïve, early PD patients and 50 normal controls. All the enrolled PD patients were divided into tremor dominant (TD) and non-tremor dominant (NTD) subtypes. The Non-Motor Symptom Scale and scales for each NMS were completed. We compared NMS and the relationship of NMS with quality of life between normal controls and PD patients, and between the PD subtypes. Comparing with normal controls, PD patients complained of more NMS, especially mood/cognitive symptoms, gastrointestinal symptoms, unexplained pain, weight change, and change in taste or smell. Between the PD subtypes, the NTD subtype showed higher total NMS scale score and sub-score about weight change. Weight change was the characteristic NMS related to NTD subtype even after controlled other variables with logistic regression analysis. Even from the early stage, PD patients suffer from various NMS regardless of dopaminergic medication. Among the various NMS, weight change is the characteristic NMS associated with NTD subtype in PD patients., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Although the treatment efficacy of memantine in Parkinson's disease dementia (PDD) has been reported after several weeks of administration, the long-term effects on brain perfusion and clinical symptoms remain unclear. The current study aimed to follow-up PDD patients after 18 months of memantine treatment using 99m Tc hexamethylpropylene amine oxime single photon emission computed tomography (SPECT)., Methods: A total of 15 patients with PDD and 11 healthy participants were recruited into this study and they were assessed with brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI). Differences in regional cerebral blood flow (rCBF) between the two groups were evaluated at baseline. After 18 months of memantine administration, changes in brain perfusion, severity of dementia, cognition, and neuropsychiatric disturbances were examined in the patients with PDD., Results: The PDD group showed hypoperfusion in most of the cortical, subcortical, and cerebellar areas compared to healthy controls at baseline. At the follow-up, changes in rCBF, CDR ( p =0.32), sum of box of CDR ( p =0.49), MMSE ( p =0.61), GDS ( p =0.79), and NPI ( p =0.23) were not significant in the PDD patients., Conclusions: Our findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Objective Left atrial enlargement (LAE) may predispose individuals to blood stasis in atrial fibrillation (AF), and thus play a crucial role in thrombogenesis. The D-dimer level is one of the surrogate markers for a hypercoagulable state and reflects thrombus formation in AF. Since the D-dimer level reflects hypercoagulability as well as thrombus and fibrin burdens, LAE could be associated with a D-dimer elevation. However, no studies have explored this association or which factors contribute to increases in the D-dimer levels in patients with AF. Therefore, we assessed whether the serum D-dimer levels are related to the left atrial volume index (LAVI) or other vascular risk factors and also evaluated the association between the D-dimer levels and the initial stroke severity. Methods Ninety-eight consecutive patients with an acute ischemic stroke and non-valvular AF (NVAF) who were anticoagulation-naïve were enrolled, and all patients were stratified into moderate-to-severe and mild neurologic deficit groups using the National Institutes of Health Stroke Scale on admission. The association between the initial serum D-dimer levels and the LAVI was evaluated in all enrolled patients, and the serum D-dimer levels were compared between the two groups. Results The patients were classified into two groups according to the severity of the neurologic deficit. In a partial correlation coefficient analysis adjusted for confounding factors, an increase in the initial serum D-dimer levels was significantly associated with LAVI (r=0.286; p=0.027). A linear regression analysis showed that a history of peripheral artery disease was the factor most strongly associated with the serum D-dimer level (t=3.90, p<0.001), followed by LAVI (t=2.37, p=0.021) and a history of congestive heart failure (t=2.16, p=0.035). The D-dimer levels were higher in the moderate-to-severe neurologic deficit group than in the mild deficit group, but this difference was not statistically significant (4.5±7.1 vs. 1.6±2.6 mg/L, p=0.068). Conclusion The serum D-dimer levels were significantly associated with LAE in anticoagulation-naïve patients with an acute ischemic stroke and NVAF.

Objective: In this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta-blockers, by evaluating regional changes in cerebral glucose metabolism., Materials and Methods: Seventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F-18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program., Results: The mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls., Conclusion: Essential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy.

Background: Microglia are involved in immune surveillance in intact brains and become activated in response to inflammation and neurodegeneration. Microglia have different functions, neuroprotective or neurotoxic, according to aging in patients with PD. The clinical effect of microglia in patients with Alzheimer's disease (AD) is poorly defined. This prospective study was conducted to investigate the clinical effects of microglia according to the aging process in newly diagnosed AD., Methods: We examined 532 patients with newly diagnosed AD and 119 healthy controls, and the differences in hs-CRP between these groups were investigated. The patients with AD were classified into 3 subgroups according to age of newly diagnosed AD to investigate the relationship between hs-CRP and the aging process in newly diagnosed AD., Results: There was significantly higher serum high-sensitivity C-reactive protein (hs-CRP), levels in patients with AD compared with healthy controls. A post-hoc analysis of the 3 AD subgroups showed no significant differences in serum hs-CRP level between each group., Conclusion: We assumed that neuroinflammation play a role in the pathogenesis of AD, but found no clinical evidence that microglia senescence underlies the microglia switch from neuroprotective in young brains to neurotoxic in aged brains. To clarify the role of microglia and aging in the pathogenesis of AD, future longitudinal studies involving a large cohort are required.

Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.

Objective: Haptoglobin (Hpg) is known to have several functional properties, including antioxidant and anti-inflammatory activities. In addition, it has been shown that the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD), involves inflammation as well as oxidative stress. However, evidence suggesting an association between the serum Hpg level and AD is lacking. Therefore, we conducted this study in order to investigate whether serum Hpg is associated with AD., Methods: We compared the serum Hpg levels of 121 patients with newly diagnosed AD, 58 patients with Parkinson's disease (PD) and 43 healthy controls. We also evaluated the relationship between the severity of cognitive impairment in patients with AD and the serum Hpg level., Results: The mean serum Hpg level of the patients with AD was significantly higher than that of the healthy controls (p=0.042), although it was not significant different from that observed in the PD group (p=0.613). We also found a significant positive association between the serum Hpg level and the severity of cognitive impairment, as measured using several neuropsychological tests, in the patients with AD. The odds ratio (95% confidence interval) of the patients with AD grouped according to the Hpg level was 2.417 (95% confidence interval=1.134-5.149)., Conclusion: We observed a significantly higher mean serum Hpg level among the patients with AD compared to the healthy controls. These results support the hypothesis that oxidative stress and neuroinflammatory reactions play a role in the pathogenesis of AD.

A 34-year-old female had experienced head and hand tremors with a dystonic component for 8 months. Brain MRI showed T2 high signal intensity in the periaqueductal region, dorsal midbrain and dorsal upper pons. No abnormal uptake was noted on Tc-99m HMPAO SPECT or F-18 FP-CIT PET/CT. Wilson disease was diagnosed according to the 2008 consensus guideline from the American Association for the Study of Liver Disease and 2012 guideline from the European Association for the Study of the Liver. This case demonstrates T2 signal change in the basal ganglia, excluding the putamen, in a Wilson disease patient with relatively severe clinical findings, but normal Tc-99m HMPAO SPECT and F-18 FP-CIT PET/CT.

Objectives: This study was conducted to describe the demographic characteristics, and clinical signs and symptoms of patients who visited a general hospital because of the release of chemically hazardous hydrogen fluoride that occurred on September 27, 2012 in Gumi City, Korea., Methods: The medical records at 1 general hospital 9 km from the accident site were reviewed using a standardized survey format. There were 1,890 non-hospitalized and 12 hospitalized patients exposed to hydrogen fluoride between September 27 and October 13 2012., Results: Among the 12 hospitalized patients, 11 were discharged within 1 week and the other was hospitalized for 10 days. The chief complaints were respiratory symptoms such as hemoptysis and shortness of breath, gastrointestinal symptoms, neurologic symptoms, sore throat, and lip burn.The number of non-hospitalized patients exhibited a bimodal distribution, peaking on the first and twelfth days after the accident. Their chief complaints were sore throat (24.1%), headache (19.1%), cough (13.1%), and eye irritation (9.2%); some patients were asymptomatic (6.2%). Patients who visited the hospital within 3 days (early patients) of the spill more often had shortness of breath (27.0%) and nausea (6.3%) as the chief complaints than patients who visited after 3 days (late patients) (3.5% and 2.6%, respectively). However, cough and rhinorrhea were more common in the late patients (14.0% and 3.3%, respectively) than in the early patients (5.0% and 0.0%, respectively). Patients who were closer to the accident site more often had shortness of breath and sputum as the chief complaints than patients who were farther away. The mean serum calcium concentration was 9.37 mg/dL (range: 8.4-11.0 mg/dL); none of the patients had a decreased serum calcium level. Among 48 pulmonary function test results, 4 showed decreased lung function. None of the patients had abnormal urine fluoride levels on the eighth day after exposure., Conclusions: Patients hospitalized due to chemical hazard release of hydrogen fluoride had acute respiratory, gastrointestinal, and neurologic health problems. Non-hospitalized patients have acute symptoms mainly related to upper respiratory irritation.

Objective: High-sensitivity C-reactive protein (hs-CRP) is an extremely sensitive systemic marker of inflammation and tissue damage, and increased levels of hs-CRP are strongly associated with inflammatory reactions. Microglia-mediated neuroinflammation has been hypothesized to play an important role in the pathogenesis of idiopathic Parkinson's disease (PD). However, the clinical value of the hs-CRP level in patients with PD is poorly defined. Therefore, we conducted this study to analyze the differences in the hs-CRP levels in PD patients with and without dementia., Methods: We examined 72 PD patients without dementia (PDwoD) and 45 PD patients with dementia (PDD), as well as 84 control subjects. We investigated the differences in the hs-CRP and fibrinogen levels between these three groups., Results: The mean hs-CRP and fibrinogen values were not significantly different between the PDwoD and PDD groups; however, these two groups had significantly higher mean hs-CRP and fibrinogen values than the control group., Conclusion: It is known that inflammation plays a role in the pathogenesis of PD and dementia. However, based on the results of this study, we cautiously speculate that although neuroinflammation plays a role in the development of neurodegenerative diseases, including PD and dementia, it may be unrelated to the pathogenesis of dementia in patients with PD.

Purpose: The purpose of this study was to investigate the diagnostic value of dual time point F-18 FP-CIT PET imaging in idiopathic Parkinson's disease (PD)., Materials and Methods: Twenty-four patients with PD (mean age 69.6) and 18 healthy people (mean age 70.26) underwent two sequential PET/CT scans (dual time point imaging) at 90 and 210 min after F-18 FP-CIT injection. Tracer activity of region of interest was measured in the caudate, putamen and a reference region in the brain from both time points. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were obtained in the control group. The percent change in tracer activity between 90- and 210-min images was calculated. The SOR values and the percent change in tracer activity were compared between the patients and healthy control group., Results: The SOR values for the caudate, anterior and posterior putamen at both 90- and 210-min images were significantly reduced in the patients with PD. The lowest P value was obtained for the anterior and posterior putamen (p < 0.001) at both time points. There were significant differences of the percent change in tracer activity for the anterior and posterior putamen in the two groups (p = 0.01)., Conclusions: F-18 FP-CIT PET scans at 90 and 210 min after injection are both able to diagnose PD. Therefore, the 90-min image by itself is sufficient for diagnosing PD.

Background and Purpose: Alzheimer's disease (AD) is associated with structural alterations in the medial temporal lobe (MTL) and functional alterations in the posterior cortical region, especially in the early stages. However, it is unclear what mechanisms underlie these regional discrepancies or whether the posterior cortical hypometabolism reflects disconnection from the MTL lesion or is the result of local pathology. The precuneus, an area of the posteromedial cortex that is involved in the early stages of AD, has recently received a great deal of attention in functional neuroimaging studies. To assess the relationship between the precuneus and hippocampus in AD, we investigated the volumes of these two areas using a magnetic resonance volumetric method., Methods: Twenty-three subjects with AD and 14 healthy age-matched controls underwent T1-weighted three-dimensional volumetric brain magnetic resonance imaging. Volumetric measurements were performed in the precuneus and hippocampus., Results: Compared to controls, AD patients exhibited a significant reduction in total precuneal volume, which was more prominent on the right side, and significant bilateral reductions in hippocampal volume. No correlation was found between the total volumes of the precuneus and hippocampus in the AD group., Conclusions: These results suggest that volumetric measurements of both the precuneus and hippocampus are useful radiological indices for the diagnosis of AD. Furthermore, the lack of correlation is attributable to local pathology rather than being a secondary consequence of MTL pathology.

A decreased cardiac (123)I-metaiodobenzylguanidine ((123)I-MIBG) uptake has been used as a powerful tool to identify Lewy body disease, such as idiopathic parkinson's disease (IPD). We performed cardiac (123)I-MIBG scintigraphy in patient with autosomal recessive juvenile parkinsonism (ARJP) with parkin gene mutation (PARK2). The findings showed normal cardiac (123)I-MIBG uptake. Therefore, although the clinical features of ARJP are sometimes quite similar to those of late-onset IPD, cardiac (123)I-MIBG scintigraphy may be used as a valuable tool to identify patients with IPD and to distinguish them from patients with other parkinsonian syndromes.

Delayed encephalopathy after carbon monoxide (CO) intoxication involves a triad of characteristic symptoms consisting of mental deterioration, urinary incontinence, and gait disturbance. Additionally, while it is not normally associated with involuntary movement, delayed encephalopathy after CO intoxication can also, in extremely rare cases, lead to chorea. We report a patient with delayed encephalopathy due to CO intoxication, suffering from chorea involving a unilateral lower limb, and subsequent cognitive impairment and other extrapyramidal symptoms.

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are osmotic demyelination syndrome. A 45-year-old man with a history of alcoholism visited the ER with dysarthria and dysphagia for 2 days. These symptoms occurred 3 days after he had stopped drinking alcohol. The neurological symptoms progressed to anarthria, pseudobulbar palsy and gait disturbance. During admission, the electrolyte studies were within the normal range. Diffusion-weighted images revealed high signal intensities in the pons, thalamus and basal ganglia. Apparent diffusion coefficient image showed low signal intensities in the pontine lesion, but isosignal intensities in the extrapontine lesion. The symptoms gradually improved after 1 month with only conservative treatment. The 1 month-follow-up MRI showed significant reduction of the previous extrapontine lesions. These findings suggest that cytotoxic edema is central to the pathogenesis of CPM, but vasogenic edema plays an important role in the pathogenesis of EPM occurring during alcohol withdrawal.