Sooyeoun You

Longitudinal fMRI study for locomotor recovery in patients with stroke

The authors investigated bihemispheric motor network reorganization supporting locomotor recovery after stroke over time. They determined longitudinal changes in locomotor function and fMRI in 10 stroke patients at the subacute stage and the chronic stage. The results suggest that the bihemispheric reorganization mechanism underlying locomotor recovery evolved from the ipsilateral (contralesional) primary sensorimotor cortex (SM1) activation at the subacute stage to the contralateral (ipsilesional) SM1 activation at the chronic stage.

Alzheimer's disease and Parkinson's disease genome-wide association study top hits and risk of Parkinson's disease in Korean population

Alzheimers disease (AD) and Parkinsons disease (PD) have overlapping clinical and pathological features, suggesting a common pathway for these 2 neurodegenerative disorders. Here we investigated the association of both AD and PD GWAS top hits with PD susceptibility. We selected 25 single nucleotide polymorphisms (SNPs) in 9 genes (ABCA7, APOE, BST1, CLU, CR1, LRRK2, PARK16, PICALM, and SNCA) that were genotyped in 1036 PD case patients and 1208 controls. Case patients and controls were all ethnic Koreans. Logistic regression analysis was performed to calculate age- and sex-adjusted odds ratios. None of the AD-susceptibility loci (ABCA7, APOE, CLU, CR1, and PICALM) showed statistically significant association with PD susceptibility. In contrast, we replicated associations of SNCA, LRRK2, BST1, and PARK16 with PD susceptibility in Koreans. Of those, the SNCA SNP rs11931074 showed the most significant association with PD susceptibility (adjusted odds ratio = 1.48; 95% confidence interval = 1.31-1.67; p = 2.20E-10). In a logistic regression analysis with SNPs coded under an additive model, there was no significant genetic interaction between the LRRK2 and the PARK16 locus gene RAB7L1 in PD risk. Our results confirm the associations of SNCA, LRRK2, BST1, and PARK16 with PD susceptibility and fail to show significant associations of AD genome-wide association study (GWAS) top hits with PD susceptibility in a Korean population.

Dysport and Botox at a ratio of 2.5:1 units in cervical dystonia: A double‐blind, randomized study

We aimed to compare Dysport (abobotulinumtoxinA, Ipsen Biopharm, Slough, UK) and Botox (onabotulinumtoxinA, Allergan, Irvine, CA, USA) at a 2.5:1 ratio in the treatment of cervical dystonia (CD). A Dysport/Botox ratio of lower than 3:1 was suggested as a more appropriate conversion ratio, considering its higher efficacy and more frequent incidence of adverse effects not only in the treatment of CD but also in other focal movement disorders. A randomized, double‐blind, multicenter, non‐inferiority, two‐period crossover study was done in CD, with a duration of at least 18 months. Patients were randomly assigned to treatment for the first period with Dysport or Botox, and they were followed up for 16 weeks after the injection. After a 4‐week washout period, they were switched to the other formulation and then followed up for 16 weeks. The primary outcome was the changes in the Tsui scale between the baseline value and that at 1 month after each injection. A total of 103 patients were enrolled, and 94 completed the study. Mean changes in the Tsui scale between baseline and 4 weeks after each injection tended to favor Botox; however, this was not statistically significant (4.0 ± 3.9 points for the Dysport treatment vs. 4.8 ± 4.1 points for Botox; 95% confidence interval, −0.1‐1.7; P = 0.091). The mean change of the Toronto western spasmodic torticollis rating scale score, the proportion of improvement in clinical global impression and patient global impression, and the incidences of adverse events were not significantly different between the two treatments. With regard to safety and efficacy, Dysport was not inferior to Botox in patients with CD at a conversion factor of 2.5:1. [clinicaltrial.gov: NCT00950664]

Exome array study did not identify novel variants in Alzheimer's disease.

Genetic variants so far identified explain a small fraction of the overall inherited risk of Alzheimers disease (AD). We aimed to identify novel genetic variants in AD using exome array that contains comprehensive panel. We genotyped 295,988 variants in 1005 subjects (400 AD cases and 605 controls) using Axiom Exome Genotyping Array that contains a pool of variants discovered in over 16 major human exome sequencing initiatives. Logistic regression analysis and the sequence kernel association optimal test were performed. The APOE, APOC1, and TOMM40 showed significant associations with AD in the single variant analysis. However, no significant association of other variants with AD was observed. This exome array study failed to identify novel genetic variants in AD.

CR1, ABCA7, and APOE genes affect the features of cognitive impairment in Alzheimer's disease

BACKGROUND The genetic factors that determine the heterogeneity of cognitive impairment in Alzheimers disease (AD) patients have been rarely reported. We aimed to investigate the association between top hits of genome-wide association studies (GWAS) and specific cognitive domains in AD patients. METHODS We investigated 86 single nucleotide polymorphisms (SNPs) selected from 12 genes (ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, LRAT, MS4A6A, PCDH11X, and PICALM) based on results of the recent GWAS and genotyped in 211 AD cases. We also analyzed results of comprehensive neuropsychological evaluations in all cases. We performed multiple regression analyses. RESULTS There were four significant associations between genotypes and phenotypes of AD patients: CR1 SNP rs11803956 correlated with Mini-Mental State Examination (MMSE) score (β=1.718, Pcorrected=0.002); ABCA7 SNP rs3752232 correlated with Rey Complex Figure Test (RCFT) copy score (β=-6.861, Pcorrected=0.013); APOE SNP rs2075650 correlated with the percentile of RCFT copy score (β=14.005, Pcorrected=0.021) and the percentile of total score in phonemic fluency (β=11.052, Pcorrected=0.035). CONCLUSION Our results suggest that CR1, ABCA7, and APOE correlate with specific aspects of cognitive impairments in AD patients.

Clinical features of drug-induced parkinsonism based on [18F] FP-CIT positron emission tomography

Drug-induced parkinsonism (DIP) is the common cause of parkinsonism. It is difficult to make a differentiation between DIP and Parkinson’s disease (PD) because there are no notable differences in the clinical characteristics between the two entities. In this study, we examined the relationship between the characteristics of [18F] fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane (FP-CIT) positron emission tomography (PET) images and clinical features in DIP patients. We retrospectively studied 76 patients with DIP who underwent [18F] FP-CIT PET. We also enrolled 16 healthy controls who underwent it. We compared the clinical characteristics between the DIP patients with normal [18F] FP-CIT PET scans and those with abnormal ones. Symmetric parkinsonism was more frequent in the patients with normal [18F] FP-CIT PET scans as compared with those with abnormal ones. Interval from drug intake to onset of parkinsonism was longer in the patients with abnormal [18F] FP-CIT PET scans as compared with those with normal ones. A semi-quantitative analysis showed that specific to non-specific binding ratios in the putamen was lower in the patients with abnormal [18F] FP-CIT PET scans as compared with those with normal ones and the age-matched control group. Our results suggest that symmetric parkinsonism was more prevalent, and the duration of drug exposure before the onset of parkinsonism was shorter in the patients with normal [18F] FP-CIT PET scans as compared with those with abnormal ones.

Mortality of advanced Parkinson's disease patients treated with deep brain stimulation surgery

OBJECTIVE Despite the widespread use of deep brain stimulation (DBS) for patients with Parkinsons disease (PD), long-term outcomes remain unclear. We aimed to analyze the mortality of advanced PD patients who received DBS surgery. METHODS We assessed the survival rate of 158 consecutive advanced PD patients who underwent DBS surgery between April 2002 and May 2014. Kaplan-Meier survival curves were constructed using death as the endpoint. Cox proportional hazards regression models were used to assess the association of clinical risk factors with survival. RESULTS Twenty-seven (17.1%) PD patients (13 men and 14 women) died during the mean follow-up period of 5.3±3.1years. The survival rate was 97% at 3years and 85% at 5years after DBS surgery. Pneumonia (n=7) was the most common specific cause of death. Orthostatic hypotension was more frequent in deceased patients than in survivors (P=0.026). In a step-wise Cox regression analysis, male sex (hazard ratio (HR) = 2.58; 95% confidence interval (CI) = 1.19–5.60; P = 0.016), visual hallucination (HR = 9.53; 95% CI = 3.50–26.01; P < 0.001), and nursing home admission (HR = 6.76; 95% CI = 2.40–18.99; P < 0.001) predicted poor survival. CONCLUSION The poor survival of advanced PD patients who underwent DBS surgery was associated with male sex, orthostatic hypotension, visual hallucination, and nursing home admission.

Validation of the Korean Version of the Scale for Outcomes in Parkinson's Disease-Autonomic

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.

Teaching Video NeuroImages: Cephalic tetanus as a pseudodystonic emergency

A 58-year-old woman was admitted because of paroxysmal painful spasms of the cranio-cervical muscles (video 1 on the Neurology ® Web site at www.neurology.org). Electromyogram showed abnormal continuous activities in resting state and loss of silent period (figure). Two days after admission, she suddenly developed severe laryngospasm, requiring bedside emergency …

Validation of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Sleep

Background Sleep problems commonly occur in patients with Parkinsons 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 Parkinsons 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 Parkinsons Disease Rating Scale (UPDRS), Parkinsons Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinsons 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 (Cronbachs 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.