Mihee Jang

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.

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.

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.

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.

Myotonia Congenita Can Be Mistaken as Paroxysmal Kinesigenic Dyskinesia

Paroxysmal kinesigenic dyskinesia (PKD) is commonly thought to be first described by Kertez.1 However, the typical clinical features of PKD were previously described by Shuzo Kure in a Japanese medical journal in 1892, as reviewed by Kato et al.2 The case described a 23-year-old male who had involuntary movement attacks with onset at 10 years of age that gradually increased in frequency. The attacks were triggered by sudden movement and started in the legs, sometimes spread to the body, and were very brief. They were preceded by a sensory aura, and the patient learned how to inhibit or stunt the attacks. He never lost consciousness, and abnormal neurological signs were not observed.2 These descriptions are in perfect agreement with our current definition of PKD.3 However, Kure misdiagnosed the case as an “atypical case of Thomsen disease [myotonia congenita (MC)],” despite noting that there were no longlasting muscle contractions during the attacks and there was an absence of percussion myotonia.2 Herein, we describe a case of MC referred as PKD (Figure 1). MC and PKD are similar in that both are characterized by attacks of involuntary movement triggered by sudden movement and lasting only a brief duration. We will discuss the essentials for differential diagnosis between PKD and MC. The pediatrics department referred a 19-year-old man (III-2) with possible paroxysmal movement disorder. Since 12 years old, he noted difficulty with initiating movement and getting stiff at the start of voluntary movements. For example, when getting on the bus, he had difficulty with the first couple of steps because of his feet getting curled up and becoming stiff, which got better after several steps. His hand use was similarly impaired and would become stiff upon first grip. These problems worsened after a period of prolonged rest but did not occur in the middle of active exercise. The patient was conscripted to the military after 7 years of stable conditions. In the army, he was observed as having the same problems, which interfered with his military training, and he was asked to seek a medical opinion. At first, he went to the pediatrician treating his elder brother (III-1), who had been diagnosed with MC due to a difficulty relaxing his hand grip since the age of 13. The patient’s brother (III-1) had myotonia when gripping his hand and percussion myotonia in the thenar muscles and tongue. The presence of myotonic discharge was confirmed using electromyography (EMG), and a diagnosis of MC was made without genetic analysis. The pediatrician considered the patient’s clinical history to be different from his brother’s and referred the proband (III-2) to us, believing he might have a different disease. After a careful interview, it was determined that the involuntary movement attacks occurred simultaneously with immediate movement initiation, did not spread to other body parts, always consisted of stiffening without chorea, and were consistently triggered after a period of prolonged rest. Upon neurological examination, his cranial nerve, sensory, and motor systems were normal, apart from grip myotonia in both hands. He did not have percussion myotonia or muscular hypertrophy. In the clinic, a prolonged resting period was required before sudden standing and walking to induce muscle stiffening in the legs. This stiffening was localized to the legs and hindered his first several steps https://doi.org/10.14802/jmd.17056 / J Mov Disord 2018;11(1):49-51 pISSN 2005-940X / eISSN 2093-4939

Peripheral blood inflammatory markers in early Parkinson’s disease

The aim of this study was to characterize peripheral inflammatory markers in patients with early Parkinsons disease (PD) and to explore whether these markers contribute to motor and non-motor symptoms. We collected serum from patients with early PD (nu202f=u202f58) and from healthy control subjects (nu202f=u202f20). The following inflammatory markers were measured: interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-α, and high-sensitivity C-reactive protein. The Movement Disorders Society Unified Parkinsons Disease Rating Scale part 3 and Hoehn and Yahr stage were used to assess motor symptoms, and the Non-motor Symptoms Scale, the Cross-Cultural Smell Identification Test, the Montreal Cognitive Assessment, and the Composite Autonomic Symptom Score 31 (COMPASS-31) were used to assess non-motor symptoms. The levels of IL-1β, IL-2, and IL-6 were higher in the PD group than in the control group. However, only IL-1β among those markers remained significant after Bonferroni correction (Pu202f=u202f0.024). In the PD group, the anti-inflammatory cytokine IL-10 levels correlated positively with the COMPASS-31 score (ru202f=u202f0.277, Pu202f=u202f0.035), whereas no correlation was found between the other inflammatory marker levels and motor or non-motor symptoms. Among the domains of the COMPASS-31, the IL-10 levels correlated only with the gastrointestinal domain (ru202f=u202f0.358, Pu202f=u202f0.006). Our results suggest increased peripheral inflammation in the early stage of PD, but the role of inflammation in motor and non-motor symptoms is unclear. Although we found a correlation between IL-10 levels and gastrointestinal symptoms, this finding may simply reflect a protective response against inflammatory processes associated with the disease.

Need for Registration and Reporting of Acupuncture Trials in Parkinson’s Disease in Korea

Objective Many people dealing with Parkinson’s disease (PD) turn to complementary and alternative medicine when searching for a cure or relief from symptoms. Acupuncture is widely used in the Korean PD population to alleviate symptoms and in hopes of curing the illness. However, acupuncture use for PD patients has only recently begun to be studied scientifically and is still considered an unproven treatment for PD. Therefore, there is an urgent need for acupuncture to be studied, validated and used for PD. Thus, our study’s aim is to examine how many acupuncture studies in PD are registered and reported in Korea. Methods The registries Clinicaltrials.gov and the Clinical Research Information Service (CRIS) and the search engine PubMed were searched to find relevant human clinical studies involving acupuncture therapy in PD patients. We examined the registration of trials, the posting and publication of results, and whether published articles were registered. Results In Clinicaltrials.gov, one completed trial was found with published results. In CRIS, one completed trial was found with published results. A total of 6 publications were found in our study: 2 articles were registered, but only 1 had the registered trial number listed in the article. Conclusion Acupuncture is popular among the PD population in Korea regardless of its unproven safety and efficacy. Despite the pressing need for clinical trials, the number of studies listed in the registries was small, and only a few publications were registered. More effort and rigor are needed to validate the efficacy and safety of acupuncture for PD.