Jinyoung Youn

Safety and efficacy of recombinant human erythropoietin treatment of non-motor symptoms in Parkinson's disease.

BACKGROUND Numerous animal studies and clinical trials have demonstrated that erythropoietin (EPO) has therapeutic effects in ischemic and degenerative diseases. However, few clinical trials have investigated the effect of EPO in Parkinsons disease (PD) patients. This study was an exploratory pilot study to investigate the effects of recombinant human EPO (rhEPO) on motor and non-motor symptoms (NMS) in PD patients. METHODS A total of 26 PD patients at the Hanyang University Hospital were enrolled in the study. The participants were randomly assigned to rhEPO and placebo groups. The rhEPO group was infused intravenously (40,000 IU each) twice a week for 5 weeks. Clinical improvement was estimated using the Unified Parkinsons Disease Rating Scale-III (UPDRS-III), the NMS Scale (NMSS) and the 39-Item Parkinsons Disease Questionnaire (PDQ-39). [(18)F] N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) photon emission tomography (PET) scanning was performed on each participant at baseline and again after 12 months. RESULTS The rhEPO administration significantly improved the NMSS and PDQ-39 scores at 12 months. The UPDRS-III, which reflects motor function, did not change significantly after the rhEPO treatment. With the NMSS, the domains of cardiovascular autonomic function, sleep/fatigue, mood/cognition and attention/memory showed significant changes. None of the participants experienced any serious adverse effects. DISCUSSION We found that rhEPO had beneficial effects on NMS but not on motor function. Dopaminergic refractory NMS, such as cardiovascular autonomic dysfunction and cognition, showed improvement after the administration of rhEPO. Our results suggest that rhEPO might be a good candidate for the treatment of NMS in PD patients.

Efficacy of cumulative high-frequency rTMS on freezing of gait in Parkinson’s disease

Abstract Purpose: Freezing of gait (FOG) affects mobility and balance seriously. Few reports have investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on FOG in Parkinson’s disease (PD). We investigated the efficacy of high-frequency rTMS for the treatment of FOG in PD. Methods: Seventeen patients diagnosed with PD were recruited in a randomized, double-blinded, cross-over study. We applied high frequency rTMS (90% of resting motor threshold, 10 Hz, 1,000 pulses) over the lower leg primary motor cortex of the dominant hemisphere (M1-LL) for five sessions in a week. We also administered alternative sham stimulation with a two-week wash out period. The primary outcomes were measured before, immediately after, and one week after the intervention using the Standing Start 180° Turn Test (SS-180) with video analysis and the Freezing of Gait Questionnaire (FOG-Q). The secondary outcome measurements consisted of Timed Up and Go (TUG) tasks and the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Motor cortical excitability was also evaluated. Results: There were significant improvements in the step required to complete the SS-180 and FOG-Q in the rTMS condition compared to the sham condition, and the effects continued for a week. The TUG and UPDRS-III also showed significant ameliorations over time in the rTMS condition. The MEP amplitude at 120% resting motor threshold and intracortical facilitation also increased after real rTMS condition. Conclusions: High frequency rTMS over the M1-LL may serve as an add-on therapy for improving FOG in PD.

Effects of repetitive transcranial magnetic stimulation on freezing of gait in patients with Parkinsonism.

PURPOSE The aim of this study was to investigate the site-specific effects of repetitive transcranial magnetic stimulation (rTMS) on freezing of gait (FOG) in patients with parkinsonism. METHODS Twenty patients with parkinsonism and FOG were included. A single session of 10 Hz rTMS was applied over three different cortical regions of the dominant hemisphere: the primary motor cortex of the lower leg (M1-LL), the supplementary motor area (SMA), and the dorsolateral prefrontal cortex (DLPFC). We also performed sham stimulation as a control. The Timed Up and Go (TUG) test, Turn Steps and Turn Time in 180° turning, Unified Parkinsons Disease Rating Scale (UPDRS) part III, FOG Questionnaire (FOG-Q), and motor evoked potential (MEP) studies were performed before and after each intervention. RESULTS There were significant improvements in TUG test times after rTMS over the M1-LL and the DLPFC. Improvement was significantly greater after the M1-LL stimulation than sham condition. The M1-LL and DLPFC stimulation also resulted in significant improvements in both the number of Turn Steps and Turn Time. UPDRS-III scores were significantly decreased after the M1-LL and DLPFC stimulation. CONCLUSIONS Use of 10 Hz rTMS on the M1-LL and DLPFC is therapeutically effective for FOG in patients with parkinsonism.

Alterations of mean diffusivity of pedunculopontine nucleus pathway in Parkinson's disease patients with freezing of gait

BACKGROUND Although freezing of gait (FOG) is a common and disabling symptom in Parkinsons disease (PD), the underlying mechanism of FOG has not been clearly elucidated. Using analysis of diffusion tensor imaging (DTI), we investigated anatomic structures associated with FOG in PD patients. METHODS We enrolled 33 controls and 42 PD patients (19 patients with FOG and 23 without FOG). DTI data were compared between PD patients and controls, and also between PD patients with and without FOG. Whole brain voxel-based analysis and regions of interest analysis in the pedunculopontine nucleus were used for DTI analysis. RESULTS Compared with normal controls, PD patients showed microstructural changes in various subcortical structures (substantia nigra, globus pallidum and thalamus), frontal and insula cortex. PD patients with FOG demonstrated altered mean diffusivities in subcortical structures connected with pedunculopontine nucleus, such as basal ganglia, thalamus and cerebellum in voxel-based analysis. Using region of interest analysis of pedunculopontine nucleus, fractional anisotropy values were reduced and mean diffusivity values were increased bilaterally in PD patients with FOG. In correlation analysis, the fractional anisotropy value of the right pedunculopontine nucleus was moderately correlated with the severity of FOG. CONCLUSIONS Based on our results, microstructural changes of pedunculopontine nucleus and connected subcortical structures are closely related with FOG in PD patients.

Restless legs syndrome in Korean patients with drug-naïve Parkinson's disease: A nation-wide study

BACKGROUND Restless legs syndrome is a common neurologic disorder, and there is increasing evidence for a dopaminergic link between Parkinsons disease and restless legs syndrome. However, most previous studies did not take into account the effects of dopaminergic medication. We conducted a nation-wide, cross-sectional study to determine the prevalence and clinical characteristics of restless legs syndrome in Korean drug-naïve Parkinsons disease patients. METHODS One hundred and fifty-one drug-naïve patients with Parkinsons disease were enrolled from 18 centers in South Korea over the course of one year. Clinical profiles of parkinsonism, restless legs syndrome, psychiatric symptoms, and laboratory data were collected. The findings of subjects with and without restless legs syndrome were compared. RESULTS The prevalence of restless legs syndrome in drug-naïve patients with Parkinsons disease was 16.5%. Subjects with restless legs syndrome had a higher mean Hoehn and Yahr stage and more severe limb parkinsonism, especially tremor. There was, however, no difference in iron metabolism between patients with and without restless legs syndrome. Analysis demonstrated that Becks depression inventory score was associated with the severity of restless legs syndrome. CONCLUSION Our study demonstrated an increased prevalence of restless leg syndrome in drug-naïve patients with Parkinsons disease than in the general population. Based on the association between parkinsonism and restless legs syndrome, and the unique characteristics of restless legs syndrome in patients with Parkinsons disease, we suggest that the pathophysiology of restless legs syndrome in Parkinsons disease differs from that in patients without Parkinsons disease.

Caregiver Burden in Parkinson Disease With Dementia Compared to Alzheimer Disease in Korea

We compared caregiver burden in Parkinson disease with dementia (PDD) to that in Alzheimer disease (AD) and examined the factors contributing to the burden in PDD. Totally, 42 patients with PDD and 109 patients with AD and their caregivers participated in this study. The caregiver burden was measured using the Burden Interview (BI). Scores of Barthel activities of daily living (BADLs), Mini-Mental State Examination, Clinical Dementia Rating of patients, and score of Center for Epidemiologic Studies Depression scale, and Euro-quality of life of the caregivers were examined. The Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr stage of the patients were administered to assess burden relating to parkinsonism on PDD. We used multiple linear regression to assess the predictors. The BI of caregivers was higher in PDD (47.9, Standard deviation [SD]: 3.8) than in AD (36.3, SD:2.1). In the AD group, the BI was predicted by cognitive function ((β ± SE: −0.8 ± 0.4, P value =.04) and basic ADL status of patients (β ± SE: −1.3 ± 0.1, P < .001), depressive symptoms (β ± SE: 1.1 ± 0.1, P < .001), and poor quality of life (β ± SE: −0.2 ± 0.1, P = .017) in caregivers. In PDD group, BI was predicted only by scores of Part 1 on the UPDRS (β ± SE: 2.9 ± 1.3, P = .03) of patients and depressive symptoms (β ± SE: 1.1 ± 0.2, P < .001) of the caregivers. We concluded the caregiver burden is higher in PDD than in AD and factors predicting burden are different in AD and PDD. In patients with PDD, the neuropsychiatric problems are the major contributor to caregiver burden.

Factors Contributing to Spousal and Offspring Caregiver Burden in Parkinson’s Disease

Background/Aims: Parkinson’s disease (PD) is a common neurodegenerative disease with a chronic disease course. The increase in life expectancy of humans worldwide is expected to increase the prevalence and duration of PD; therefore, it is important to determine factors that contribute to the caregiver burden for both clinical and social reasons. Methods: We surveyed 91 main caregivers of patients, and compared factors contributing to caregiver burden between 50 spouses and 41 offspring of patients. We determined Burden Interview, Depression Scale, Health-Related Quality of Life, and Obligation Scale scores, as well as the degree of functional social support of caregivers. Results: Interestingly, the burden scores of the two groups were not significantly different. Correlation analysis revealed that depression, health-related quality of life, social support, subdivided parts of the Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr Scale, score of Mini-Mental State Examination, and Barthel index were correlated with burden in both spouses and offspring. However, in multiple regression, depression score and part 1 of the UPDRS were more significant predictors of burden in the spousal group, whereas social support of community and part 3 of the UPDRS were more important correlated factors in the offspring group. Conclusions: The caregiver burden of spousal and offspring caregivers of PD patients was not significantly different. However, different factors contributed to caregiver burden according to the caregiver’s relationship with the patient.

Cognitive Impairment and Its Structural Correlates in the Parkinsonian Subtype of Multiple System Atrophy

Background/Aims: Previous studies indicate that patients with the parkinsonian subtype of multiple system atrophy (MSA-P) experience cognitive impairment. This study aimed to identify the existence of cognitive impairments and the different topographic patterns of morphological changes in MSA-P by means of imaging analysis, and also whether these morphological changes could be associated with cognitive dysfunctions in MSA-P. Methods: We recruited 15 nondemented probable MSA-P patients and 32 normal controls (NC) for neuropsychological testing and MRI. We analyzed morphological changes using cortical thickness analysis, voxel-based morphometry (VBM) and cerebellar volumetry. Multiple linear regression analysis was performed to evaluate the correlation of each cognitive score with the mean thickness of significant cortical-thinning clusters, mean gray-matter density of VBM clusters and cerebellar volume. Results: The scores on the Digit Span Test, the Seoul Verbal Learning Test (immediate and delayed), the phonemic Controlled Oral Word Association Test and the Stroop color test were significantly lower in the MSA-P group than in the NC group. We found two clusters exhibiting significant cortical thinning in the right paracentral lobule and parahippocampal gyrus. VBM analysis revealed significant gray-matter atrophy in the MSA-P group in the bilateral basal ganglia, cerebellum and temporal and frontal cortical areas. Multiple linear regression analysis demonstrated that cognitive dysfunction correlated significantly with thinning in the neocortex, cerebellum and striatum. Conclusions: Our data demonstrate that cortical and cerebellar atrophy and striatal degeneration are associated with cognitive impairment in patients with MSA-P.

Ocular motor characteristics of different subtypes of spinocerebellar ataxia: Distinguishing features

Because of frequent involvement of the cerebellum and brainstem, ocular motor abnormalities are key features of spinocerebellar ataxias and may aid in differential diagnosis. Our objective for this study was to distinguish the subtypes by ophthalmologic features after head‐shaking and positional maneuvers, which are not yet recognized as differential diagnostic tools in most common forms of spinocerebellar ataxias. Of the 302 patients with a diagnosis of cerebellar ataxia in 3 Korean University Hospitals from June 2011 to June 2012, 48 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, or 8 or with undetermined spinocerebellar ataxias were enrolled. All patients underwent a video‐oculographic recording of fixation abnormalities, gaze‐evoked nystagmus, positional and head‐shaking nystagmus, and dysmetric saccades. Logistic regression analysis controlling for disease duration revealed that spontaneous and positional downbeat nystagmus and perverted head‐shaking nystagmus were strong predictors for spinocerebellar ataxia 6, whereas saccadic intrusions and oscillations were identified as positive indicators of spinocerebellar ataxia 3. In contrast, the presence of gaze‐evoked nystagmus and dysmetric saccades was a negative predictor of spinocerebellar ataxia 2. Positional maneuvers and horizontal head shaking occasionally induced or augmented saccadic intrusions/oscillations in patients with spinocerebellar ataxia types 1, 2, and 3 and undetermined spinocerebellar ataxia. The results indicated that perverted head‐shaking nystagmus may be the most sensitive parameter for SCA6, whereas saccadic intrusions/oscillations are the most sensitive for spinocerebellar ataxia 3. In contrast, a paucity of gaze‐evoked nystagmus and dysmetric saccades is more indicative of spinocerebellar ataxia 2. Head‐shaking and positional maneuvers aid in defining ocular motor characteristics in spinocerebellar ataxias.

Diffusion tensor imaging of freezing of gait in patients with white matter changes.

Freezing of gait is a common and disabling symptom of parkinsonism. However, the corresponding anatomic structures have yet to be clearly elucidated.