Aryun Kim

Presynaptic striatal dopaminergic depletion predicts the later development of freezing of gait in de novo Parkinson's disease: An analysis of the PPMI cohort

INTRODUCTIONnThe current study was designed to determine whether the degree of presynaptic striatal dopamine depletion can predict the later development of freezing of gait (FOG) in Parkinsons disease (PD).nnnMETHODSnThis retrospective cohort study included 390 de novo patients with PD without FOG at baseline. The participants were divided into tertiles according to the baseline dopamine transporter (DAT) uptake of each striatal subregion, and the cumulative risk of FOG was compared using the Kaplan-Meier method. Cox proportional hazard models were used to assess the predictive power of DAT uptake of striatal subregions for the development of FOG.nnnRESULTSnDuring a median follow-up period of 4.0 years, 143 patients with PD (36.7%) developed FOG. The severe reduction group of DAT uptake in the caudate nucleus and putamen had a significantly higher incidence of FOG than that of the mild and moderate reduction groups. Multivariate Cox regression analyses showed that DAT uptakes in the caudate nucleus (hazard ratio [HR] 0.551; 95% confidence interval [CI] 0.392-0.773; pu202f=u202f0.001) and putamen (HR 0.441; 95% CI 0.214-0.911; pu202f=u202f0.027) predicted the development of FOG. In addition, male sex, higher postural instability and gait difficulty score, and a lower Montreal Cognitive Assessment score were also significant predictors of FOG.nnnCONCLUSIONnOur finding suggests that presynaptic striatal dopaminergic denervation predicts the later development of FOG in de novo patients with PD, which may provide reliable insight into the mechanism of FOG in terms of nigrostriatal involvement.

Depression may negatively affect the change in freezing of gait following subthalamic nucleus stimulation in Parkinson's disease

OBJECTIVEnTo assess the influence of preoperative depression on the change in freezing of gait (FOG) following subthalamic nucleus stimulation (STN-DBS) in patients with Parkinsons disease (PD).nnnMETHODSnOne hundred and twelve PD patients were included who received bilateral STN-DBS. Of these, 33 had no preoperative depression (PD-ND) and the other 79 had preoperative depression (PD-D). Each PD-ND patient was matched with one PD-D patient by the propensity score for which sex, age at PD onset, disease duration, UPDRS-III score during off-medication state, levodopa-equivalent daily dose, and mini mental state examination were the independent variables. We compared both a FOG-questionnaire (FOG-Q) and the axial score from UPDRS-III between the two groups over 12-month follow-up.nnnRESULTSnDuring the off-medication state, FOG-Q at 12-month was decreased with STN-DBS in both PD-ND (-52.9%, pxa0<xa00.001) and PD-D (-24.2%, pxa0<xa00.001) with a significant difference in the change of FOG in favor of PD-ND (pxa0=xa00.001). Similarly, there was an improvement in the axial score for both PD-ND (-66.1%, pxa0<xa00.001) and PD-D (-45.3%, pxa0<xa00.001) at 12-month with a significant difference between the groups. (pxa0=xa00.005). During the on-medication state, both the FOG-Q and axial score at 12-month were not improved with STN-DBS in the PD-ND and PD-D with no difference between the groups.nnnCONCLUSIONSnOur findings suggest that preoperative depression negatively affects the outcome of FOG following STN-DBS in the off-medication state but not in the on-medication state.

Dry facts are not always inviting: a content analysis of Korean videos regarding Parkinson’s disease on YouTube

This study aimed to evaluate the accuracy of Korean videos regarding Parkinsons disease (PD) on YouTube and viewers responses to them. YouTube search was performed using the search term Parkinson disease in Korean language on March 28, 2017. Two independent neurologists categorized the videos into reliable, misleading or patient experiences. The number of views, days since upload, video length, number of likes and dislikes, and upload source were collected for each video. A total of 138 videos were included in this study. Of these, 91 videos (65.9%) were reliable; 31 (22.5%) were misleading, and 16 (11.6%) were of patient experiences. The videos with patient experiences had the highest number of mean views with 9710.4±3686.9, followed by misleading videos with 5075.0±1198.6, and reliable videos with 2146.8±353.4 (ANOVA, p<0.001). The number of mean views per day was 4.0±0.6 for the reliable videos, which was significantly lower than the misleading videos (9.7±3.4, p=0.020) and the videos of patient experiences (11.3±4.6, p=0.023). The reliable videos were mostly uploaded by university hospitals (46.2%) and misleading videos by health-related commercial entities (74.2%). The misleading videos as well as the videos of patient experiences advocated diet asa treatment of PD. The current study found that only two-thirds of the Korean videos regarding PD on YouTube provide reliable information. More importantly, the videos with reliable contents were less popular than videos with misleading contents. Further efforts are warranted to effectively increase the dissemination of accurate and scientifically proven PD information to YouTube users.

Characteristics of Early Oropharyngeal Dysphagia in Patients with Multiple System Atrophy

Background/Aims: Dysphagia, a symptom of multiple system atrophy (MSA), is a major clinical concern. In this study, we investigate the characteristics of early oropharyngeal dysphagia (OD) in patients with MSA, and the differences between MSA subtypes. Methods: Patients enrolled in the study had previously been diagnosed with MSA at the clinic of the Department of Neurology, and had been referred for a videofluoroscopic swallowing study (VFSS), between 2005 and 2014, to check for dysphagia. The clinical characteristics and VFSS findings were analyzed and compared between the MSA subtypes. Results: This study enrolled 59 patients with MSA (24 men; 31 with MSA-P, 21 with MSA-C, and 7 with MSA-PC). Dysphagia symptoms were mostly limited to aspiration symptoms (90.48%) in patients with MSA-C, while difficulty in swallowing, increased mealtime, and drooling were frequent in those with MSA-P. The most common VFSS finding amongst patients was vallecular residue (n = 53, 89.8%), followed by penetration/aspiration (n = 40, 67.8%), and coating of the pharyngeal wall (n = 39, 66.1%). Comparison analysis between subtypes showed that apraxia and vallecular residue were more frequent and severe in MSA-P than in MSA-C (p = 0.033 and p = 0.010, respectively). Conclusion: Understanding early OD characteristics in patients with MSA and the differences between MSA subtypes could be helpful in managing dysphagia in patients with MSA. Several dysphagia symptoms similar to those of Parkinson disease were frequently observed in MSA-P, but not in MSA-C. A follow-up study is needed to elucidate the natural course of OD in MSA patients and the difference between MSA subtypes.

Amantadine and the Risk of Dyskinesia in Patients with Early Parkinson’s Disease: An Open-Label, Pragmatic Trial

Objective We examined whether amantadine can prevent the development of dyskinesia. Methods Patients with drug-naïve Parkinson’s disease (PD), younger than 70 years of age and in the early stage of PD (Hoehn and Yahr scale < 3), were recruited from April 2011 to December 2014. The exclusion criteria included the previous use of antiparkinsonian medication, the presence of dyskinesia, significant psychological disorders, and previous history of a hypersensitivity reaction. Patients were consecutively assigned to one of 3 treatment groups in an open label fashion: Group A-1, amantadine first and then levodopa when needed; Group A-2, amantadine first, dopamine agonist when needed, and then levodopa; and Group B, dopamine agonist first and then levodopa when needed. The primary endpoint was the development of dyskinesia, which was analyzed by the Kaplan-Meier survival rate. Results A total of 80 patients were enrolled: Group A-1 (n = 27), Group A-2 (n = 27), and Group B (n = 26). Twenty-four patients were excluded from the analysis due to the following: withdrawal of amantadine or dopamine agonist (n = 9), alternative diagnosis (n = 2), withdrawal of consent (n = 1), and breach in the protocol (n = 12). After exclusion, 5 of the 56 (8.93%) patients developed dyskinesia. Patients in Group A-1 and A-2 tended to develop dyskinesia less often than those in Group B (cumulative survival rates of 0.933, 0.929, and 0.700 for A-1, A-2, and B, respectively; p = 0.453). Conclusion Amantadine as an initial treatment may decrease the incidence of dyskinesia in patients with drug-naïve PD.

Validation of the Conversion between the Mini-Mental State Examination and Montreal Cognitive assessment in Korean Patients with Parkinson’s Disease

Objective Two conversion tables between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) have recently been established for Parkinson’s disease (PD). This study aimed to validate them in Korean patients with PD and to evaluate whether they could be influenced by educational level. Methods A total of 391 patients with PD who undertook both the Korean MMSE and the Korean MoCA during the same session were retrospectively assessed. The mean, median, and root mean squared error (RMSE) of the difference between the true and converted MMSE scores and the intraclass correlation coefficient (ICC) were calculated according to educational level (6 or fewer years, 7–12 years, or 13 or more years). Results Both conversions had a median value of 0, with a small mean and RMSE of differences, and a high correlation between the true and converted MMSE scores. In the classification according to educational level, all groups had roughly similar values of the median, mean, RMSE, and ICC both within and between the conversions. Conclusion Our findings suggest that both MMSE-MoCA conversion tables are useful instruments for transforming MoCA scores into converted MMSE scores in Korean patients with PD, regardless of educational level. These will greatly enhance the utility of the existing cognitive data from the Korean PD population in clinical and research settings.

Wrist sensor-based tremor severity quantification in Parkinson's disease using convolutional neural network

Tremor is a commonly observed symptom in patients of Parkinsons disease (PD), and accurate measurement of tremor severity is essential in prescribing appropriate treatment to relieve its symptoms. We propose a tremor assessment system based on the use of a convolutional neural network (CNN) to differentiate the severity of symptoms as measured in data collected from a wearable device. Tremor signals were recorded from 92 PD patients using a custom-developed device (SNUMAP) equipped with an accelerometer and gyroscope mounted on a wrist module. Neurologists assessed the tremor symptoms on the Unified Parkinsons Disease Rating Scale (UPDRS) from simultaneously recorded video footages. The measured data were transformed into the frequency domain and used to construct a two-dimensional image for training the network, and the CNN model was trained by convolving tremor signal images with kernels. The proposed CNN architecture was compared to previously studied machine learning algorithms and found to outperform them (accuracyu202f=u202f0.85, linear weighted kappau202f=u202f0.85). More precise monitoring of PD tremor symptoms in daily life could be possible using our proposed method.

Liquid levodopa-carbidopa in advanced Parkinson's disease with motor complications

While levodopa, carbidopa, ascorbic acid solution (LCAS) therapy has been used in patients with advanced Parkinsons disease (PD) for many years, long-term follow-up data is scarce. The present study aimed to determine the long-term retention rate for LCAS therapy, and to identify the causes of LCAS therapy withdrawal. Our study included a series of 38 patients with PD (14 men and 24 women) who underwent LCAS treatment between 2011 and 2013 to alleviate motor complications that were not satisfactorily controlled by optimized conventional anti-parkinsonian treatment at the Seoul National University Hospital. All patients were admitted to educate them about and initiate LCAS treatment for 2-5days, and were then followed up as outpatients. The mean follow-up duration was 12.8months, and three main reasons for LCAS treatment discontinuation were worsening of wearing-off symptoms (8 patients), persistent dyskinesia (4 patients), and poor drug adherence (4 patients). Fourteen patients (36.8%) maintained the LCAS treatment after 12months, and were categorized as the treatment-retention group. The mean percentage of on time without dyskinesia significantly increased from 33.6±17.6% to 57.0±27.7% after LCAS initiation (p=0.016) in the treatment-retention group. Twelve patients (31.6%) were still receiving LCAS treatment after 30months. LCAS treatment can be a non-device assisted therapeutic option for patients who have no access to advanced therapies such as deep brain stimulation and infusional treatments.

A 7-year observation of the effect of subthalamic deep brain stimulation on impulse control disorder in patients with Parkinson's disease

INTRODUCTIONnPrevious studies have reported improvement of impulse control disorders (ICDs) after subthalamic nucleus (STN) deep brain stimulation (DBS) as well as some de novo ICDs. However, it is not clear how STN DBS changes ICDs in the long-term.nnnMETHODS MATERIALSnEighty-nine patients with Parkinsons disease (PD) who had received a bilateral STN DBS from 2005 to 2009 and were included in our previous study were followed for 7 years with the modified Minnesota Impulsive Disorders Interview (mMIDI). Their mMIDI scores, medication, and frontal function tests measured preoperatively and at 1 and 7 years postoperatively were compared.nnnRESULTSnA total of 61 patients were analyzed after excluding 10 and 18 patients due to death and lost to follow-up, respectively. The numbers of the patients with an ICD at each point were 8, 10, and 7, respectively. All preoperative ICDs disappeared after DBS. De novo ICDs within 1 year after DBS disappeared except for 1 patient. Six of the seven patients, who reported ICDs 7 years after the DBS developed that ICD between 1 and 7 years. Their total levodopa equivalent daily dose (LEDD) and dopamine agonist dose were not higher compared to the other 54 patients without ICDs. There was no correlation with the frontal lobe dysfunction and the electrode position in the subthalamus.nnnCONCLUSIONnSTN DBS improves baseline ICDs and results in the development of transient de novo ICDs in the short-term. In addition, there is a unique group of the patients who develop ICDs a long time after DBS.

Emergence of non-motor fluctuations with reference to motor fluctuations in Parkinson's disease

INTRODUCTIONnNon-motor fluctuations (NMF) and motor fluctuations (MF) are frequent in patients with Parkinsons disease (PD) with long-term medical treatment. We aimed to examine the timing of the emergence of NMF with reference to MF in a prospective cohort of patients with PD without symptom fluctuations.nnnMETHODSnA total of 334 patients with PD who had neither MF nor NMF were recruited. The exclusion criteria included a Mini-Mental State Examination score of less than 26 points at baseline and an alternative diagnosis or significant comorbidity during follow-up. The SNUH-Fluctuation Questionnaire consisting of 29 items (9 on MF and 20 on NMF) was administered on a semi-annually basis for 3 years.nnnRESULTSnThree hundred seven out of 334 patients were analyzed for symptom fluctuations with the Kaplan-Meier survival analysis. MF were observed in more patients and developed earlier than NMF (cumulative survival of 0.572 for MF and 0.619 for NMF at 36 months of follow-up). In 212 patients who finished the follow-up for 36 months, MF and NMF developed simultaneously in 58 (27.4%), MF developed first in 45 (21.2%), and NMF developed first in only 3 (1.4%). The remaining 106 patients (50.0%) did not develop either MF or NMF.nnnCONCLUSIONnNMF developed simultaneously with or later than MF. From these data, we hypothesize that NMF develop in the disease state where the pathology in the brain has been severe enough to develop MF. Hence, pharmacologic management should consider targeting both dopaminergic and non-dopaminergic systems to treat NMF.