Long-term motor learning in focal hand dystonia.

OBJECTIVE: Because focal hand dystonia usually occurs in the over-learned stage, it would be valuable to know long-term motor learning characteristics and underlying pathophysiological features that might predispose to dystonia. METHODS: We conducted a case-control exploratory study of 15 visits over 12 weeks in the non-affected hand of a 4-finger sequence of 8 key presses in eight patients with FHD compared with eight age- and sex-matched, healthy volunteers (HVs). We studied the behavioral data and the physiological changes of the brain, including motor cortical excitability and cortical oscillations. RESULTS: There was no significant difference in the time to reach 100 % accuracy between FHD and HV during the 80-day follow-up period. There was a statistically significant difference in the accuracy of sequential finger movement tasks between patients with FHD compared with HVs over 12 weeks, but post-hoc analysis with multiple comparion correction did not show difference. There were no significant differences in recruitment curve changes and task-related power changes of alpha and beta bands. CONCLUSION: Over 12 weeks, FHD have motor learning capacity comparable to HVs and do not show pathophysiological abnormalities. SIGNIFICANCE: Further studies would be valuable with more patients, more extended periods of practice, and more detailed electrophysiological explorations.

Urodynamic study and its correlation with cardiac meta-iodobenzylguanidine (MIBG) in body-first and brain-first subtypes of Parkinson's disease.

BACKGROUND AND PURPOSE: Lower urinary tract symptoms (LUTS) are frequently observed in patients with Parkinson's disease (PD), but the underlying mechanism remains elusive. The concept of "body-first" and "brain-first" subtypes in PD has been proposed, but the correlation of PD subtype with LUTS remains unclear. We aimed to investigate the disparities in urological dysfunctions between body-first and brain-first subtypes of PD using urodynamic studies (UDS). METHODS: We reviewed patients with PD (disease duration <3 years) who had undergone UDS and completed urological questionnaires (Overactive Bladder Symptom Score [OABSS] and International Prostate Symptom Score [IPSS]) and a voiding diary. Patients were categorized as having body-first or brain-first PD based on cardiac sympathetic denervation (CSD) using cardiac meta-iodobenzylguanidine (MIBG) uptake and the presence of rapid eye movement sleep behavior disorder (RBD), assessed using a questionnaire (PD with CSD and RBD indicating the body-first subtype). RESULTS: A total of 55 patients with PD were categorized into body-first PD (n = 37) and brain-first PD (n = 18) groups. The body-first PD group exhibited smaller voiding volume and first desire volume (FDV) than the brain-first PD group (p < 0.05 in both). Also, the body-first PD group had higher OABSS and IPSS scores, and higher prevalence of overactive bladder diagnosed by OABSS, compared to the brain-first PD group. In multiple linear regression, cardiac MIBG uptake was positively correlated with FDV and voiding volume and negatively correlated with OABSS and IPSS (p < 0.05 in all). CONCLUSIONS: Patients with the body-first PD subtype exhibited more pronounced overactive bladder symptoms and impaired storage function in the early stage of disease. Additionally, cardiac MIBG was significantly associated with urological dysfunction.

Fatigue in Parkinson's Disease Is Due to Decreased Efficiency of the Frontal Network: Quantitative EEG Analysis.

OBJECTIVE: Fatigue is a common, debilitating nonmotor symptom of Parkinson's disease (PD), but its mechanism is poorly understood. We aimed to determine whether electroencephalography (EEG) could objectively measure fatigue and to explore the pathophysiology of fatigue in PD. METHODS: We studied 32 de novo PD patients who underwent EEG. We compared brain activity between 19 PD patients without fatigue and 13 PD patients with fatigue via EEG power spectra and graphs, including the global efficiency, characteristic path length, clustering coefficient, small-worldness, local efficiency, degree centrality, closeness centrality, and betweenness centrality. RESULTS: No significant differences in absolute or relative power were detected between PD patients without or with fatigue (all p > 0.02, Bonferroni-corrected). According to our network analysis, brain network efficiency differed by frequency band. Generally, the brain network in the frontal area for theta and delta bands showed greater efficiency, and in the temporal area, the alpha1 band was less efficient in PD patients without fatigue (p < 0.0001, p = 0.0011, and p = 0.0007, respectively, Bonferroni-corrected). CONCLUSION: Our study suggests that PD patients with fatigue have less efficient networks in the frontal area than PD patients without fatigue. These findings may explain why fatigue is common in PD, a frontostriatal disorder. Increased efficiency in the temporal area in PD patients with fatigue is assumed to be compensatory. Brain network analysis using graph theory is more valuable than power spectrum analysis in revealing the brain mechanism related to fatigue.

Opicapone to Treat Early Wearing-off in Parkinson's Disease Patients: The Korean ADOPTION Trial.

BACKGROUND: Increasing levodopa (L-dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing-off symptoms in Parkinson's disease (PD) patients. OBJECTIVES: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing-off in PD patients. METHODS: ADOPTION was a randomized, parallel-group, open-label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L-dopa 100 mg (n = 81) (added to current L-dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society-Unified Parkinson's Disease Rating Scale and 8-item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. RESULTS: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L-dopa 100 mg (-62.1 vs. -16.7 minutes; P = 0.0015). Opicapone-treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L-dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. CONCLUSIONS: Opicapone 50 mg was more effective than an additional 100 mg L-dopa dose at decreasing off time in patients with PD and early wearing-off.

Comparative Olfactory Profiles in Parkinson's Disease and Drug-Induced Parkinsonism.

OBJECTIVE: Drug-induced parkinsonism (DIP) is a frequently encountered diagnostic possibility when considering Parkinson's disease (PD). While olfactory dysfunction is a common clinical feature in PD, the comparison of olfactory function between the two conditions remains insufficient. This study aimed to compare olfactory function, including threshold, discrimination, and identification (TDI) profiles, between PD and DIP. METHODS: Consecutive patients with drug-naïve PD (n = 78) or DIP (n = 31) confirmed through dopamine transporter imaging were enrolled in this study. The YSK olfactory function (YOF) test, composed of TDI domains culturally familiar odorants to Koreans, was administered to all patients. RESULTS: In the study population, patients with DIP were significantly older than patients with PD. Over 70% of patients in each group had hyposmia or anosmia, and there was no significant difference in the occurrence of olfactory dysfunction between the two groups. In addition, there were no differences in the total YOF score and threshold score between the two groups. Meanwhile, the PD group had a significantly lower discrimination and identification score than the DIP group after adjusting for age, sex, the existence of diabetes, disease duration, and cognitive function. CONCLUSION: This study demonstrated that detailed olfactory profiles are different in PD and DIP, even though olfactory dysfunction can be observed in both conditions.

What is the analgesic range of acupuncture stimulus for treating acute pain?

Introduction: Since the analgesic effect of acupuncture stimulation is derived from different mechanisms depending on the type of pain, it is important to know which acupuncture points to stimulate. In this study, to confirm the effect of acupuncture stimulation on acute pain from a neurological point of view, somatosensory evoked potential and sensory threshold changes were evaluated to identify the nerve range that is affected by acupuncture stimulation on LI4 (Hapgok acupuncture point, of the radial nerve) during acute pain. Methods: The subjects were 40 healthy men and women aged 19-35 years. The study was designed as a randomly controlled, crossover trial with acupuncture stimulation at LI4 as the intervention. The washout period for acupuncture stimulation was 2 weeks, and the subjects were divided into two groups, i.e., an acupuncture stimulation group and a nonstimulation group, with 10 men and 10 women in each group. Somatosensory evoked potential measurement was carried out for 5 min by alternately applying 2 HZ-pulse electrical stimulation to the thumb and the little finger of the hand acupunctured with a 64-channel electroencephalogram. The verbal rating scale was used before and after each acupuncture stimulation session. Result and discussion: The results of the study confirmed that the somatosensory evoked potential amplitude value of the thumb was significantly decreased and that the intensity of sensory stimulation corresponding to a verbal rating scale score of 6 was significantly increased only in the thumb after acupuncture stimulation. Therefore, the results show that acupuncture treatment for acute pain is more effective when direct acupuncture stimulation is applied to the painful area.

Scaling problem in Parkinson's disease patients with pain.

INTRODUCTION: Although pain is common in Parkinson's disease (PD), the underlying mechanism remains unknown. Scaling function and dopaminergic hypofunction may contribute to pain development because increased pain sensitivity is observed in PD and is normalized after levodopa administration. We aimed to determine whether spatial discrimination (SD) and striatal dopaminergic activity (DA) differed between PD patients with and without pain. METHODS: We divided 90 patients with drug-naïve PD into two groups based on the presence or absence of pain and compared the SD threshold (SDT). We evaluated the correlation of the SDT with pain severity in PD with pain. We also compared the DA of 48 patients and analyzed the correlation with pain severity in PD patients with pain. RESULTS: The SDTs did not differ between the two groups, but unmeasurable SDT was more frequent in PD with pain. There was a positive correlation of pain severity with the SDT of the more affected hand but no correlation with the SDT of the less affected hand. The DA did not differ between the groups. There was a negative trend of pain severity with the DA of the ventral striatum (VS) but no correlation with the other striatal subregions. CONCLUSIONS: Pain in PD may be associated with scaling dysfunction in the sensory system. The abnormal scaling function would render the PD patient hypersensitive to even mild pain. The dopamine in the VS appears to be associated with pain severity; however, the relationship of striatal dopaminergic deficits with pain occurrence requires further investigation.

Editorial: Chronic Inflammation and Related Diseases: From Mechanisms to Therapies.

The purpose of this Special Issue is to identify the exact mechanism underlying inflammation to direct more effective strategies for inflammation management and to provide basic data for the development of anti-inflammatory and analgesic treatment methods for patients with inflammatory pain [...].

Analgesic efficacy of median nerve stimulation in mice with chemotherapy-induced peripheral neuropathymodulation of brain-derived neurotrophic factor expression.

OBJECTIVE: Chemotherapeutic agents such as docetaxel (DTX) can trigger chemotherapy-induced peripheral neuropathy (CIPN), which is characterized by unbearable pain. This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation (LFMNS) on DTX-induced tactile hypersensitivity in mice. METHODS: To produce CIPN, DTX was administered intraperitoneally 4 times, once every 2 d, to male ICR mice. LFMNS was performed on the wrist area, and the pain response was measured using von Frey filaments on both hind paws. Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brain-derived neurotrophic factor (BDNF). RESULTS: Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area. CONCLUSIONS: LFMNS might be an effective non-pharmaceutical option for treating patients suffering from CIPN regulating the expression of peripheral and central BDNF.

Attenuation of immobilization stress-induced hypertension by temperature-controllable warm needle acupuncture in rats and the peripheral neural mechanisms.

Introduction: We and others have shown that electrical stimulation of the PC-6 acupoint over the wrist relieves hypertension by stimulating afferent sensory nerve fibers and activating the central endogenous opioid system. Warm needle acupuncture has long been utilized to treat various diseases in clinics. Methods: Here, we developed a temperature-controllable warm needle acupuncture instrument (WAI) and investigated the peripheral mechanism underlying the effect of warm needle acupuncture at PC-6 on hypertension in a rat model of immobilization stress-induced hypertension. Results: Stimulation with our newly developed WAI and traditional warm needle acupuncture attenuated hypertension development. Such effects were reproduced by capsaicin (a TRPV1 agonist) injection into PC-6 or WAI stimulation at 48°C. In contrast, PC-6 pretreatment with the TRPV1 antagonist capsazepine blocked the antihypertensive effect of WAI stimulation at PC-6. WAI stimulation at PC-6 increased the number of dorsal root ganglia double-stained with TRPV1 and CGRP. QX-314 and capsaicin perineural injection into the median nerve for chemical ablation of small afferent nerve fibers (C-fibers) prevented the antihypertensive effect of WAI stimulation at PC-6. Additionally, PC-6 pretreatment with RTX ablated the antihypertensive effect of WAI stimulation. Conclusion: These findings suggest that warm needle acupuncture at PC-6 activates C-fiber of median nerve and the peripheral TRPV1 receptors to attenuate the development of immobilization stress-induced hypertension in rats.

Cortical mean diffusivity is reliable in measuring brain abnormalities in drug-naïve essential tremor patients.

OBJECTIVE: Essential tremor (ET) is a common movement disorder, but the pathogenesis is poorly understood. Several associated brain areas were reported with inconsistent results due to heterogeneous populations. It is necessary to analyze a more homogeneous patient group. METHODS: We recruited 25 drug-naïve ET patients and 36 age- and sex-matched controls. All participants were right-handed. ET. ET was defined according to diagnostic criteria of the Consensus Statement of the Movement Disorder Society on Tremor. ET patients were divided into sporadic (SET) and familial ET (FET). We assessed tremor severity in ET. The cortical microstructural changes were compared between ET patients and controls using mean diffusivity (MD) of diffusion tensor imaging, and cortical thickness. The correlation of tremor severity with the cortical MD and thickness were respectively analyzed. RESULTS: MD values were increased in the insular, precuneus, medial orbitofrontal, posterior, and isthmus cingulate and temporo-occipital areas in ET. In comparison between SET and FET, MD values were higher in the superior and caudal middle frontal, postcentral, and temporo-occipital regions in FET. The cortical thickness of ET patients was more increased in the left lingual gyrus and lower in the right bankssts gyrus. We could not find any correlation of tremor severity with the MD values in ET patients. Still, there was a positive correlation with the cortical thickness of the frontal and parietal areas. CONCLUSIONS: Our results support the idea that ET is a disorder that disrupts widespread brain regions and indicates that cortical MD may be more sensitive to measure brain abnormalities than cortical thickness.

Retinal Thickness and Its Interocular Asymmetry Between Parkinson's Disease and Drug-Induced Parkinsonism.

BACKGROUND: Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging. Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson's disease (PD). METHODS: We investigated 97 de novo PD patients and 27 DIP patients using OCT and [18F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specific/non-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. RESULTS: No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all P values > 0.090). The mean SNBRAI was significantly higher in PD than in DIP (P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). CONCLUSION: Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.

Correlations with REM sleep behavior disorder severity in isolated rapid eye movement sleep behavior disorders patients.

OBJECTIVES: The pathogenesis of isolated rapid eye movement sleep behavior disorders (iRBD) is poorly understood. The severity of RBD may reflect its pathogenesis. METHODS: We compared motor function and non-motor symptoms (NMSs) between iRBD patients and healthy volunteers. We correlated motor function, NMSs, and striatal dopaminergic activity with RBD severity using video-polysomnography. RESULTS: Twenty-one iRBD patients and 17 controls participated. The Unified Parkinson's Disease Rating Scale part III scores were higher in patients compared to controls (p < 0.001). There was no difference in upper extremity function between patients and controls (right, p = 0.220; left, p = 0.209), but gait was slower in iRBD patients (walking time, p < 0.001; number of steps, p < 0.001). The mean value of the Korean version of the Mini-Mental State Exam and Clinical Dementia Rating were lower in patients (p = 0.006, p = 0.003, respectively). Patients with were also more depressed (p = 0.002), had decreased olfactory function (p < 0.001), reported more frequent sleep/fatigue episodes (p < 0.001), worse attention/memory capacity (p < 0.001), gastrointestinal problems (p = 0.009), urinary problems (p = 0.007), and pain (p = 0.083). Further, iRBD patients reported more frequent sleep-related disturbances (p = 0.004), but no difference in daytime sleepiness (p = 0.663). Disease severity was correlated with pain (r = 0.686, p = 0.002) and visuospatial function (r= -0.507, p = 0.038). There were no correlations between RBD severity and striatal dopaminergic activities (p > 0.09). CONCLUSIONS: iRBD is a multisystem neurodegenerative disorder, and gait abnormalities may be a disease characteristic, possibly related to the akinetic-rigid phenotype of Parkinson's disease. The correlation between pain/visuospatial dysfunction and RBD severity may be related to its pathogenesis.

Initial Vestibular Function May Be Associated with Future Postural Instability in Parkinson's Disease.

BACKGROUNDS: We aimed to understand the association between initial vestibular function examination and postural instability (PI) development in Parkinson's disease (PD). METHODS: After screening 51 PD patients, we divided 31 patients into 2 groups based on the presence of PI at the follow-up visit and compared the clinical features and vestibular-evoked myogenic potential (VEMP) variables. RESULTS: The mean values of Hoehn and Yahr stage, Unified Parkinson's Disease Rating Scale (UPDRS) part III, and item 30 (postural stability) of UPDRS were larger in patients with PI at a follow-up visit (p = 0.000, 0.006, 0.048, respectively). In VEMP analyses, the onset latencies of left and right cervical VEMPs were significantly reduced in patients with PI (p = 0.013, 0.040, respectively). CONCLUSION: We found that the initial VEMP test may be associated with later postural imbalance in PD, suggesting the baseline evaluation may help predict future PI occurrence. A more significant number of patients and more long-term follow-ups are likely to be required for confirmation.

Biopotential changes of acupuncture points by acupuncture stimulation.

Background: The energy flow at acupuncture point is important for understanding the mechanism of acupuncture treatment. However, there are few studies on energy at acupuncture point, and related studies have limitation in explaining the energy flow in all meridians. Thus, we aimed to understand the properties of electrical energy at acupuncture point in twelve meridians by measuring the biopotential at acupuncture and non-acupuncture points. Methods: For each meridian, twenty subjects were participated, and biopotential was measured at five transport points and their adjacent non-acupuncture points. In each subject, both 'non-stimulation' and 'stimulation' experiments were conducted in random order. The data were analyzed in two parts: biopotential variability and biopotential difference between acupuncture and non-acupuncture points. Results: The biopotential variability at acupuncture point was increased by acupuncture stimulation, and it was related to the activation of Qi flow by acupuncture stimulation. The biopotential difference between acupuncture and non-acupuncture points was formed in the direction related to the Qi flow theory, and this biopotential difference tended to decrease by acupuncture stimulation. Conclusion: The study on biopotential can provide a foundation for research on energy flow mechanism of acupuncture stimulation, and it is expected to overcome limitation of qualitative explanation in traditional medicine.

Pain in atypical parkinsonism, vascular parkinsonism, and Parkinson's disease.

BACKGROUND: Pain is a common symptom in Parkinson's disease (PD) and is considered a pre-motor symptom suggesting sensory involvement in the pre-motor stage. Pain in other parkinsonian disorders such as atypical parkinsonism and vascular parkinsonism (VP) has been investigated in only a few studies. The characteristics of pain in other parkinsonian disorders, including the temporal relationships between pain and motor symptoms, were investigated in the present study. METHODS: A total of 236 PD, 42 multiple system atrophy (MSA), 31 progressive supranuclear palsy (PSP), and 38 VP patients were screened for pain. After excluding patients with dementia and pain not related to PD, the presence of pain, severity, onset, type, and location were compared among the four patient groups. RESULTS: Difference was not observed in pain presence (χ2 = 3, p = 0.186), severity (F = 1.534, p = 0.207), or type (χ2 = 6, p = 0.400) among the four groups. However, the temporal relationship between pain and motor symptoms differed (H(3) = 8.764, p = 0.033). Pain predated motor symptoms in PD, MSA, and VP but often followed motor symptoms in PSP. The pain location in the body was different among the four patient groups (χ2 = 21, p = 0.018), and leg involvement was more common in PSP. CONCLUSION: The present study results suggest that pain can be a pre-motor symptom in PD, MSA, and VP but not in PSP, implying different pain pathogeneses in these disorders. Pain locations were other for each group, which requires further investigation with a more extensive study cohort.