Jin Whan Cho

Decreased Metabolism in the Cerebral Cortex in Early-Stage Huntington's Disease: A Possible Biomarker of Disease Progression?

Background and Purpose Huntingtons disease (HD) is an autosomal-dominant inherited neurodegenerative disorder. Genetic analysis of abnormal CAG expansion in the IT15 gene allows disease confirmation even in the preclinical stage. However, because there is no treatment to cure or delay the progression of this disease, monitoring of biological markers that predict progression is warranted. Methods FDG-PET was applied to 13 patients with genetically confirmed HD in the early stage of the disease. We recorded the initial and follow-up statuses of patients using the Independence Scale (IS) of the Unified Huntingtons Disease Rating Scale. The progression rate (PR) was calculated as the annual change in the IS. The patients were divided into two groups with faster and slower progression, using the median value of the PR as the cut-off. FDG-PET data were analyzed using regions of interest, and compared among the two patient groups and 11 age- and sex-matched controls. Results The mean CAG repeat size in patients was 44.7. The CAG repeat length was inversely correlated with the age at onset as reported previously, but was not correlated with the clinical PR. Compared with normal controls, hypometabolism was observed even at very early stages of the disease in the bilateral frontal, temporal, and parietal cortices on FDG-PET. The decreases in metabolism in the bilateral frontal, parietal, and right temporal cortices were much greater in the faster-progression group than in the slower-progression group. Conclusions A decrease in cortical glucose metabolism is suggested as a predictor for identifying a more rapid form of progression in patients with early-stage HD.

Validation of the Korean-Version of the Nonmotor Symptoms Scale for Parkinson's Disease

Background and Purpose Non-motor symptoms are common in Parkinsons disease (PD), and are the primary cause of disability in many PD patients. Our aim in this study was to translate the origin non-motor symptoms scale for PD (NMSS), which was written in English, into Korean (K-NMSS), and to evaluate its reliability and validity for use with Korean-speaking patients with PD. Methods In total, 102 patients with PD from 9 movement disorders sections of university teaching hospitals in Korea were enrolled in this study. They were assessed using the K-NMSS, the Unified Parkinsons Disease Rating Scale (UPDRS), the Korean version of the Mini-Mental Status Examination (K-MMSE), the Korean version of the Montgomery-Asberg Depression Rating Scale (K-MADS), the Epworth Sleepiness Scale (ESS), and Parkinsons Disease Questionnaire 39 (PDQ39). Test-retest reliability was assessed over a time interval of 10-14 days in all but one patient. Results The K-NMSS was administered to 102 patients with PD. The internal consistency and reliability of this tool was 0.742 (mean Cronbachs α-coefficient). The test-retest correlation reliability was 0.941 (Guttman split-half coefficient). There was a moderate correlation between the total K-NMSS score and the scores for UPDRS part I [Spearmans rank correlation coefficient, (rS)=0.521, p<0.001] and UPDRS part II (rS=0.464, p=0.001), but there was only a weak correlation between the total K-NMSS score and the UPDRS part III score (rS=0.288, p=0.003). The total K-NMSS score was significantly correlated with the K-MADS (rS=0.594, p<0.001), K-MMSE (rS=-0.291, p=0.003), and ESS (rS=0.348, p<0.001). The total K-NMSS score was also significantly and positively correlated with the PDQ39 score (rS=0.814, p<0.001). Conclusions The K-NMSS exhibited good reliability and validity for the assessment of non-motor symptoms in Korean PD patients.

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.

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.

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]

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.