Survey of the Knowledge, Attitudes, and Practices of Neurologists Regarding Exercise in Parkinson's Disease.

BACKGROUND AND PURPOSE: Exercise and physiotherapy can exert potentially beneficial effects on the motor and nonmotor features of Parkinson's disease (PD). We conducted an e-mail survey to assess the knowledge, attitudes, and practices of neurologists regarding exercise among patients with PD. METHODS: A total of 222 neurologists from the Korean Movement Disorder Society and the Korean Society of Neurologists completed the survey and were classified into 4 clusters using the k-means clustering algorithm based on their institute types, the proportions of PD patients in their clinics, and the number of years working as neurologists. RESULTS: Specialists working at referral hospitals (Clusters 1 and 2) were more confident than general neurologists (Clusters 3 and 4) about exercise improving the general motor features of PD. Specialists recommended more-frequent intense exercise compared with physicians not working at referral hospitals. The specialists in Cluster 1, representing >50% of PD patients in the clinics at referral hospitals, recommended exercise regardless of the disease stage, whereas the general neurologists in Clusters 3 and 4 recommended low-intensity exercise at an early stage of disease. Although most of the respondents agreed with the need for PD patients to exercise, less than half had prescribed rehabilitation or physiotherapy. More than 90% of the respondents answered that developing an exercise/physiotherapy protocol for PD would be helpful. CONCLUSIONS: Specialists were more confident than general neurologists about the effect of exercise and recommended more-intense activities regardless of the disease stage. These results highlight the need to develop clinical practice guidelines and PD-specialized exercise protocols to provide optimal care for PD patients.

Comparison of Enlarged Perivascular Spaces in Early-Onset and Late-Onset Alzheimer Disease-related Cognitive Impairment: A Single Clinic-based Study in South Korea.

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy.

Trends in Physiotherapy Interventions and Medical Costs for Parkinson's Disease in South Korea, 2011-2020.

Objective: Physiotherapy (PT), an effective strategy for managing Parkinson's disease (PD), can influence healthcare utilization. We analyzed trends in healthcare utilization, PT interventions, and medical costs among patients with PD. Methods: Using data from the Korean National Health Insurance Service from 2011 to 2020, we analyzed the number of patients with PD and their healthcare utilization and assessed the odds ratio (OR) for receiving regular PTs. Results: Over 10 years, 169,613 patients with PD were present. The number of patients with PD increased annually from 49,417 in 2011 to 91,841 in 2020. Patients with PD receiving PT increased from 4,847 (9.81%) in 2011 to 13,163 (14.33%) in 2020, and PT prescriptions increased from 81,220 in 2011 to 377,651 in 2019. Medical costs per patient with PD have increased from 1,686 United States Dollars (USD) in 2011 to 3,201 USD in 2020. Medical expenses for each patient with PD receiving PT increased from 6,581 USD in 2011 to 13,476 USD in 2020. Moreover, Regular PTs were administered to 31,782 patients (18.74%) and conducted only through hospitalization. Those in their 50s with disabilities demonstrated a high OR for regular PTs, while those aged 80 years or older and residing outside Seoul had a low OR. Conclusions: The PD burden increased in South Korea between 2011 and 2020, including an increase in healthcare utilization and medical costs. The significant rise in medical expenses can be associated with increased PD prevalence and PT interventions. Regular PT applications remain restricted and have barriers to access.

Neuropsychological, neuroimaging and autopsy findings of butane encephalopathy.

BACKGROUND: Butane is an aliphatic hydrocarbon used in various commercial products. While numerous reports of sudden cardiac-related deaths from butane inhalation have been described, butane-associated acute encephalopathy has rarely been reported. CASE PRESENTATION: A 38-year-old man presented with cognitive dysfunction after butane gas inhalation. Neuropsychological test results showed impairments in verbal and visual memory, and frontal executive function. Diffusion weighted MRI revealed symmetric high-signal changes in the bilateral hippocampus and globus pallidus. FDG-PET demonstrated decreased glucose metabolism in the bilateral precuneus and occipital areas and the left temporal region. At the 8-month follow-up, he showed still significant deficits in memory and frontal functions. Diffuse cortical atrophy with white matter hyperintensities and extensive glucose hypometabolism were detected on follow-up MRI and FDG-PET, respectively. Brain autopsy demonstrated necrosis and cavitary lesions in the globus pallidus. CONCLUSIONS: Only a few cases of butane encephalopathy have been reported to date. Brain lesions associated with butane encephalopathy include lesions in the bilateral thalamus, insula, putamen, and cerebellum. To the best of our knowledge, this is the first report on bilateral hippocampal and globus pallidal involvement in acute butane encephalopathy. The pathophysiology of central nervous system complications induced by butane intoxication is not yet fully understood. However, the direct toxic effects of butane or anoxic injury secondary to cardiac arrest or respiratory depression have been suggested as possible mechanisms of edematous changes in the brain after butane intoxication.

Changes in Starburst Amacrine Cells in Mice with Diabetic Retinopathy.

BACKGROUND: Neurodegenerative diseases, such as diabetic retinopathy (DR) and glaucoma, induce retinal neuron loss. Acetylcholine-containing cholinergic neurons, known as starburst amacrine cells (SACs), play critical roles in the generation of precise neuronal activity in the retina and are located in the inner nuclear layer (INL, conventional) and ganglion cell layer (GCL, displaced). METHODS: This study investigated the loss of and morphological changes in SACs in the retinas of streptozotocin (STZ)-induced diabetic and insulin-deficient C57BL/6-Tg(pH1-siRNAinsulin/CMV-hIDE)/Korl (IDCK) mice. SACs were immunocytochemically localized with anti-choline acetyltransferase (ChAT) antibody, and ChAT-labeled cells in the INL and GCL in the control and experimental groups were counted along the central vertical meridian in the whole-mounted retina using conventional fluorescent or confocal microscopes. RESULTS: ChAT-immunoreactive (IR) neurons in STZ-induced diabetic mouse retina decreased by 8.34% at 4-6 weeks and by 14.89% at 42 weeks compared with the control group. Localized ChAT-IR neuron counts in the retinas of 20-week-old IDCK mice were 16.80% lower than those of age-matched control mice. Cell body deformation and aggregation were detected in the retinas of mice with DR. Single-cell injection experiments revealed the loss and deformation of dendritic branches in ChAT-IR neurons in DR. All ChAT-IR neurons expressed the calcium-binding protein calretinin, whereas no ChAT-IR neuron colocalized with calbindin-D28K or parvalbumin. CONCLUSIONS: Our results revealed that the neurodegenerative effects of the loss and deformation of ChAT-IR neurons can provide a reference for future study of this disease.

Comparison of Retinal Structural and Neurovascular Changes between Patients with and without Amyloid Pathology.

To evaluate whether an impaired anterior visual pathway (retinal structures with microvasculature) is associated with underlying beta-amyloid (Aß) pathologies in patients with Alzheimer's disease dementia (ADD) and mild cognitive impairment (MCI), we compared retinal structural and vascular factors in each subgroup with positive or negative amyloid biomarkers. Twenty-seven patients with dementia, thirty-five with MCI, and nine with cognitively unimpaired (CU) controls were consecutively recruited. All participants were divided into positive Aß (A+) or negative Aß (A-) pathology based on amyloid positron emission tomography or cerebrospinal fluid Aß. The retinal circumpapillary retinal nerve fiber layer thickness (cpRNFLT), macular ganglion cell/inner plexiform layer thickness (mGC/IPLT), and microcirculation of the macular superficial capillary plexus were measured using optical coherence tomography (OCT) and OCT angiography. One eye of each participant was included in the analysis. Retinal structural and vascular factors significantly decreased in the following order: dementia < MCI < CU controls. The A+ group had significantly lower microcirculation in the para- and peri-foveal temporal regions than did the A-. However, the structural and vascular parameters did not differ between the A+ and A- with dementia. The cpRNFLT was unexpectedly greater in the A+ than in the A- with MCI. mGC/IPLT was lower in the A+ CU than in the A- CU. Our findings suggest that retinal structural changes may occur in the preclinical and early stages of dementia but are not highly specific to AD pathophysiology. In contrast, decreased temporal macula microcirculation may be used as a biomarker for the underlying Aß pathology.

Dopamine receptor and dopamine transporter in obesity: A meta-analysis.

The brain plays a major role in controlling the desire to eat. This meta-analysis aimed to assess the association between dopamine receptor (DR) availability and dopamine transporter (DAT) availability, measured using positron emission tomography, and obesity. We performed a systematic search of MEDLINE (from inception to November 2020) and EMBASE (from inception to November 2020) for articles published in English using the keywords "dopamine receptor," "dopamine transporter," "obesity," and "neuroimaging." Body mass index (BMI) and the corresponding binding potential (BPND ) were extracted from figures in each study using Engauge Digitizer, version 12.1, and plotted for radiopharmaceuticals and regions of interest (ROIs). Five studies involving 119 subjects with DR and five studies including 421 subjects with DAT were eligible for inclusion in this study. In overweight or obese subjects with BMI of 25 kg/m2 or higher, DR availability from 11 C-Racloprie was negatively associated with BMI. However, DR availability from 11 C-PHNO was positively associated with BMI. DAT ratio was calculated after dividing DAT availabilities of overweight/obese BMI with mean DAT availabilities of normal BMI. The association between DAT ratio and BMI was not significant regardless of radiopharmaceuticals. In conclusion, dopamine plays a main role in the reward system with regard to obesity. Overweight and obese subjects had negative association between DR availability from 11 C-Raclopride and BMI. However, the association of DR availability with BMI was dependent on radiopharmaceuticals. DAT availability did not show the significant relationship with BMI regardless of radiopharmaceuticals.

Temporal trajectory model for dopaminergic input to the striatal subregions in Parkinson's disease.

INTRODUCTION: Almost half of the nigral neurons are already lost during the preclinical period of Parkinson's disease (PD), and then the speed of neuronal loss is slowly attenuated during the subsequent progression. We sought to establish long-term temporal trajectory models for the dopaminergic input to the striatal subregions and a 4D-temporal trajectory model for the dopamine transporter positron emission tomography (PET). METHODS: We selected 83 patients in PD spectrum who underwent dopamine transporter PET scan twice and 71 age-matched healthy controls. We created temporal trajectories of specific binding ratios of the striatal subregions by integrating function between baseline values and their annual change rates and also created 4D-temporal trajectory model by applying the same method for each striatal voxel. Using the PET data of additional 100 PD patients, we estimated an individual time point in the 4D-temporal trajectory model for the validation. RESULTS: Degenerative loss of striatal dopaminergic input first appeared in the posterior dorsal putamen in the more affected side at 14.4 years before the clinical onset, and subsequently in the posterior ventral and anterior putamen, and finally in the caudate. The time delay between the initiation of dopaminergic loss in the more and less affected posterior dorsal putamen was 6.1 years. The estimated individual time points within the entire disease course were correlated with the motor severity. CONCLUSION: Our temporal trajectory model demonstrated a sequential loss of dopaminergic input in the striatal subregions in PD and may be beneficial for the evaluation of individual status of disease progression.

Efficacy and Safety of Opicapone for Motor Fluctuations as an Adjuvant to Levodopa Therapy in Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy. OBJECTIVE: We provide pooled scientific evidence highlighting the efficacy and safety of opicapone, a newly approved COMT inhibitor, as an adjuvant to levodopa. METHODS: We searched Ovid Medline, Embase, and Cochrane databases for relevant reports. Efficacy and safety were evaluated as off-time reduction and risk ratio (RR) of dyskinesia, respectively. Data were independently extracted using predefined criteria. Selected placebo-controlled trials were divided into double-blind and open-label periods. Using a random-effects model, the mean difference (MD) of the off-time reduction (efficacy), RR for the occurrence of dyskinesia, and on-time without/with troublesome dyskinesia (TD; safety assessment) were compared between opicapone and placebo groups. RESULTS: Five studies from three randomized controlled trials were included, and a meta-analysis was performed with 407 patients receiving opicapone 50 mg and 402 patients receiving placebo. Compared with the placebo, opicapone (50 mg) reduced off-time by 49.91 min during the double-blind period (95% confidence intervals [CIs] = -71.39, -28.43; I2 = 0%). The RR of dyskinesia was 3.43 times greater in the opicapone 50 mg group than in the placebo group (95% CI = 2.14, 5.51; I = 0%). Compared with the placebo, opicapone increased the on-time without TD by 44.62 min (95% CI = 22.60, 66.64; I2 = 0%); the on-time increase with TD did not differ between treatments. CONCLUSION: Opicapone can play a positive role as an adjuvant to levodopa in patients with PD by reducing off-time and prolonging on-time without PD.