Sleepiness and Depression in Parkinson's Disease Patients Treated with Ropinirole and Levodopa

OBJECTIVE: We aimed to investigate the effect of ropinirole on excessive daytime sleepiness (EDS) and depression in Parkinson's disease (PD) with a large population. METHODS: We conducted a cross-sectional observational study at nine hospitals in Korea between April 24, 2013, and April 22, 2015. We analyzed the demographic and clinical features, other medical history, history of antiparkinsonian medication within 6 months, Hoehn and Yahr stage (HY stage), Unified Parkinson's Disease Rating Scale (UPDRS) part II and III, Epworth Sleepiness Scale (ESS), and 30-item Geriatric Depression Scale (GDS-30). RESULTS: Four-hundred-thirteen patients with PD (mean age: 65.2 ± 9.0 years; men: 227 patients) were analyzed. Multivariate logistic regression analysis showed that age at examination, UPDRS II, and GDS-30 were independent risk factors for EDS and that sex, UPDRS II, and ESS were independent risk factors for depression. CONCLUSION: Our large group study did not find any significant associations of ropinirole with EDS and depression in Korean PD patients.ope

Patterns of Neuropsychological Profile and Cortical Thinning in Parkinson's Disease with Punding

BACKGROUND: Punding, one of dopamine replacement treatment related complications, refers to aimless and stereotyped behaviors. To identify possible neural correlates of punding behavior in patients with Parkinson's disease (PD), we investigated the patterns of cognitive profiles and cortical thinning. METHODS: Of the 186 subjects with PD screened during the study period, we prospectively enrolled 10 PD patients with punding and 43 without punding on the basis of a structured interview. We performed comprehensive neuropsychological tests and voxel-based and regions-of-interest (ROIs)-based cortical thickness analysis between PD patients with and without punding. RESULTS: The prevalence of punding in patients with PD was 5.4%. Punding behaviors were closely related to previous occupations or hobbies and showed a temporal relationship to changes of levodopa-equivalent dose (LED). Significant predisposing factors were a long duration of PD and intake of medications of PD, high total daily LED, dyskinesia, and impulse control disorder. Punding severity was correlated with LED (p = 0.029). The neurocognitive assessment revealed that PD patients with punding showed more severe cognitive deficits in the color Stroop task than did those without punding (p = 0.022). Voxel-based analysis showed that PD-punders had significant cortical thinning in the dorsolateral prefrontal area relative to controls. Additionally, ROI-based analysis revealed that cortical thinning in PD-punders relative to PD-nonpunders was localized in the prefrontal cortices, extending into orbitofrontal area. CONCLUSIONS: We demonstrated that PD patients with punding performed poorly on cognitive tasks in frontal executive functions and showed severe cortical thinning in the dorsolateral prefrontal and orbitofrontal areas. These findings suggest that prefrontal modulation may be an essential component in the development of punding behavior in patients with PD.ope

Neuroanatomical Heterogeneity of Essential Tremor According to Propranolol Response

BACKGROUND: Recent studies have suggested that essential tremor (ET) is a more complex and heterogeneous clinical entity than initially thought. In the present study, we assessed the pattern of cortical thickness and diffusion tensor white matter (WM) changes in patients with ET according to the response to propranolol to explore the pathogenesis underlying the clinical heterogeneity of ET. METHODS: A total of 32 patients with drug naive ET were recruited prospectively from the Movement Disorders outpatient clinic. The patients were divided into a propranolol-responder group (n = 18) and a non-responder group (n = 14). We analyzed the pattern of cortical thickness and diffusion tensor WM changes between these two groups and performed correlation analysis between imaging and clinical parameters. RESULTS: There were no significant differences in demographic characteristics, general cognition, or results of detailed neuropsychological tests between the groups. The non-responder group showed more severe cortical atrophy in the left orbitofrontal cortex and right temporal cortex relative to responders. However, the responders exhibited significantly lower fractional anisotropy values in the bilateral frontal, corpus callosal, and right parietotemporal WM compared with the non-responder group. There were no significant clusters where the cortical thickness or WM alterations were significantly correlated with initial tremor severity or disease duration. CONCLUSIONS: The present data suggest that patients with ET have heterogeneous cortical thinning and WM alteration with respect to responsiveness to propranolol, suggesting that propranolol responsiveness may be a predictive factor to determine ET subtypes in terms of neuroanatomical heterogeneity.ope

Mesenchymal stem cells can modulate longitudinal changes in cortical thickness and its related cognitive decline in patients with multiple system atrophy

Multiple system atrophy (MSA) is an adult-onset, sporadic neurodegenerative disease. Because the prognosis of MSA is fatal, neuroprotective or regenerative strategies may be invaluable in MSA treatment. Previously, we obtained clinical and imaging evidence that mesenchymal stem cell (MSC) treatment could have a neuroprotective role in MSA patients. In the present study, we evaluated the effects of MSC therapy on longitudinal changes in subcortical deep gray matter volumes and cortical thickness and their association with cognitive performance. Clinical and imaging data were obtained from our previous randomized trial of autologous MSC in MSA patients. During 1-year follow-up, we assessed longitudinal differences in automatic segmentation-based subcortical deep gray matter volumes and vertex-wise cortical thickness between placebo (n = 15) and MSC groups (n = 11). Next, we performed correlation analysis between the changes in cortical thickness and changes in the Korean version of the Montreal Cognitive Assessment (MoCA) scores and cognitive performance of each cognitive subdomain using a multiple, comparison correction. There were no significant differences in age at baseline, age at disease onset, gender ratio, disease duration, clinical severity, MoCA score, or education level between the groups. The automated subcortical volumetric analysis revealed that the changes in subcortical deep gray matter volumes of the caudate, putamen, and thalamus did not differ significantly between the groups. The areas of cortical thinning over time in the placebo group were more extensive, including the frontal, temporal, and parietal areas, whereas these areas in the MSC group were less extensive. Correlation analysis indicated that declines in MoCA scores and phonemic fluency during the follow-up period were significantly correlated with cortical thinning of the frontal and posterior temporal areas and anterior temporal areas in MSA patients, respectively. In contrast, no significant correlations were observed in the MSC group. These results suggest that MSC treatment in patients with MSA may modulate cortical thinning over time and related cognitive performance, inferring a future therapeutic candidate for cognitive disorders.ope

Apathy and olfactory dysfunction in early Parkinson's disease

OBJECTIVE: Olfactory and emotional dysfunctions are very common in patients with Parkinson's disease (PD). Olfaction and emotions share common neuroanatomical substrates. Therefore, in this study, we evaluated the association between olfactory and emotional dysfunctions in patients with PD. METHODS: Parkinson's disease patients who had been assessed for their olfactory function and neuropsychiatric symptoms including emotional dysfunction were included. A logistic regression analysis was performed to evaluate the association between low olfaction and different neuropsychiatric symptoms. RESULTS: The patients with low olfaction (cross cultural smell identification test score ≤ 6) showed a higher prevalence of apathy when compared with those with high olfaction, whereas the frequencies of other neuropsychiatric symptoms were comparable between the two groups. A multivariate logistic regression analysis revealed that the presence of apathy/indifference [odds ratio (OR) = 2.859, p = 0.007], age 70 years or more (OR = 2.281, p = 0.009), and the male gender (OR = 1.916, p = 0.030) were significantly associated with low olfaction. CONCLUSIONS: Our results demonstrate that apathy/indifference is a unique emotional dysfunction associated with olfactory dysfunction in PD. The findings also suggest that PD patients with low olfaction have a high prevalence of apathy.ope

Clinical and electrophysiologic characteristics of MuSK MG in Koreans

의학과/석사전신형 혈청음성 중증근무력증 환자 중 40~70%에서 Muscle-specific tyrosine kinase (MuSK)에 대한 항체가 발견된다. MuSK 항체 양성환자 (MuSK MG) 는 AchR 항체 양성 환자 (AchR MG) 와 임상증상, 전기생리학적 검사 결과가 다를 뿐 아니라 치료 방법에서도 차이를 보이기 때문에 정확한 진단이 중요하다. 한국의 MuSK 항체 양성 환자에 대한 연구가 증례보고 이외에 거의 없기 때문에 이 환자들에 대한 임상적, 전기생리학적 특징을 알아보고자 하였다. MuSK MG 41명과 성별, 발병연령, 질병 중증도를 매칭시킨 AchR MG를 비교 분석하였다. 사회 인구학적 특성과 발병연령, 발병 첫 증상, 유병기간 동안의 임상 증상을 의학적 기록을 토대로 검토하였으며 신경생리학적 검사로 반복신경자극검사와 약물검사 결과를 후향적으로 조사하였다.본 연구에서 MuSK MG 의 특징적인 임상 소견으로 안검하수 보다는 복시가 흔하며 연수 증상 중 삼킴장애와 발음장애가 많았으며 호흡장애가 빈번하였다. 신경학적 진찰에서 관찰되는 경부 및 상지 위약에 비하여 반복신경학적 검사에서 관찰되는 팔근육의 복합근육활동전위의 감소반응이 미약했으며, 약물검사에서 뚜렷한 증상 호전이 뚜렷하지 않은 특징을 보였다.ope

Does education modify motor compensation in Parkinson's disease?

BACKGROUND: In Alzheimer's disease, higher educational attainment is associated with fewer cognitive deficits despite similar pathological lesions. In animal models of Parkinson's disease (PD), enhanced levels of cognitive and physical stimulation can reduce motor deficits due to dopaminergic neuronal loss. Therefore, in this study, we tested whether higher educational attainment has a beneficial influence on PD motor symptoms. METHODS: We included data from 182 patients with de novo PD without dementia, who underwent dopamine transporter (DAT) scans for an initial diagnostic work-up. Patients were divided into 2 groups according to their educational attainment; high education (HE-PD; ≥12years of education) and low education (LE-PD; <12years of education). RESULTS: The HE-PD group exhibited significantly higher mini-mental state exam scores, fewer motor deficits, and lower DAT binding to the posterior putamen than the LE-PD group, despite a similar duration of PD symptoms. A general linear model revealed that this difference in motor deficits remained statistically significant after controlling for potential confounding factors (p=0.032). CONCLUSION: These results suggest that higher educational attainment can lead to reduced motor deficits in PD despite greater reductions in dopamine levels.restrictio

Levodopa-induced dyskinesia in a patient who has normal presynaptic dopaminergic neurons

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α-Synuclein pathology is related to postoperative delirium in patients undergoing gastrectomy

Objective: The clinical characteristics of postoperative delirium are similar to core features of α-synuclein–related cognitive disorders, such as dementia with Lewy bodies or Parkinson disease dementia. We therefore investigated the α-synuclein pathology in patients who experienced postoperative delirium after gastrectomy for stomach cancer. Method: Patients with and without postoperative delirium were selected among patients undergoing total gastrectomy for primary gastric cancer from 2007 to 2011 (each n = 16) at the university hospital. Immunohistochemical staining for α-synuclein of both normal and phosphorylated form was performed in the myenteric plexus. A logistic regression analysis was applied to identify independent predictors of postoperative delirium. Results: No significant differences were observed for age, sex, operation time, or onset of delirium after total gastrectomy between patients with and without postoperative delirium. Patients with postoperative delirium had a higher frequency of intensive care unit admissions (43.8 vs 6.3%, p = 0.037) and α-synuclein–positive pathologies of normal (56.3 vs 12.5%, p = 0.023) and phosphorylated form (43.8 vs 6.3%, p = 0.037) compared with those without postoperative delirium. A logistic regression analysis revealed that immunoreactivity for normal α-synuclein (odds ratio [OR] 9.20) and intensive care unit admission (OR 11.97) were independently associated with postoperative delirium. Conclusion: These results suggest that underlying α-synuclein pathologies in the stomach are associated with postoperative delirium, implying that postoperative delirium represents a preclinical stage of α-synuclein related to cognitive disorders.ope

The perfusion pattern in a patient with lithium intoxication mimicking creutzfeldt-jakob disease

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