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2022 ◽  
Author(s):  
Sule Tinaz ◽  
Serageldin Kamel ◽  
Sai S Aravala ◽  
Mohamed Elfil ◽  
Ahmed Bayoumi ◽  
...  

Background: Parkinson's disease (PD) causes difficulty with maintaining the speed, size, and vigor of movements, especially when they are internally generated. We previously proposed that the insula is important in motivating intentional movement via its connections with the dorsomedial frontal cortex (dmFC). We demonstrated that subjects with PD can increase the right insula-dmFC functional connectivity using fMRI-based neurofeedback (NF) combined with kinesthetic motor imagery (MI). The current study is a randomized clinical trial testing whether NF-guided kinesthetic MI training can improve motor performance and increase task-based and resting-state right insula-dmFC functional connectivity in subjects with PD. Methods: We assigned nondemented subjects with mild PD (Hoehn & Yahr stage ≤ 3) to the experimental kinesthetic MI with NF (MI-NF, n=22) and active control visual imagery (VI, n=22) groups. Only the MI-NF group received NF-guided MI training (10-12 runs). The NF signal was based on the right insula-dmFC functional connectivity strength. All subjects also practiced their respective imagery tasks at home daily for 4 weeks. Post-training changes in 1) task-based and resting-state right insula-dmFC functional connectivity were the imaging outcomes, and 2) MDS-UPDRS motor exam and motor function scores were the clinical outcomes. Results: The MI-NF group did not show significant NF regulation and was not significantly different from the VI group in any of the imaging or clinical outcome measures. The MI-NF group reported subjective improvement in kinesthetic body awareness. There was significant and comparable improvement only in motor function scores in both groups. This improvement correlated with NF regulation of the right insula-dmFC functional connectivity only in the MI-NF group. Both groups showed specific training effects in whole-brain functional connectivity with distinct neural circuits supporting kinesthetic motor and visual imagery (exploratory outcome). Conclusions: The functional connectivity-based NF regulation was unsuccessful in our cohort with mild PD. However, kinesthetic MI practice by itself or in combination with other imagery techniques is a promising tool in motor rehabilitation in PD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tian Xu ◽  
Lanxiao Cao ◽  
Wenying Long ◽  
Guohua Zhao

Background: Impulse control and related disorders (ICRDs) have gained recognition as a severe complication of Parkinson's disease (PD) and are connected to poor quality of life and devastating financial and social problems. This study aimed to evaluate the usefulness of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) and estimate the risk factors for ICRDs in Chinese patients with PD.Methods: 207 PD patients were assessed using the QUIP and evaluated for PD motor and nonmotor symptoms. ICRDs were diagnosed via interviews of patients or their caregivers, and the clinical characteristics of patients with and without ICRDs were compared.Results: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the C-QUIP were 95.0, 83.4, 38.0, 99.4, and 84.5%. The prevalence of each disorder among participants diagnosed via interview was pathological gambling (0.5%), hypersexuality (1.9%), compulsive shopping (1.0%), binge eating (3.9%), hobbyism (1.9%), punding (0.5%), walkabout (0.5%), and dopamine dysregulation syndrome (2.9%). PD patients with ICRDs had longer PD duration, higher Hoehn and Yahr stage, Non-Motor Symptoms Scale (NMSS), and Hamilton-Depression Rating Scale (HAMD). Also, they received a larger total daily levodopa equivalent dose (LED), levodopa dosage, and dopamine agonist only LED (DA-LED) than did PD patients without ICRDs.Conclusions: Given its psychometric properties, the C-QUIP is a valid and rapid screening instrument for assessing of ICRDs in PD patients. Higher Hoehn and Yahr staging, NMSS and HAMD scores, a larger mean LED and levodopa dosage are risk factors for ICRDs.


2021 ◽  
pp. 1-10
Author(s):  
Ines Chendo ◽  
Carlos Silva ◽  
Gonçalo S. Duarte ◽  
Luisa Prada ◽  
Valerie Voon ◽  
...  

Background: Psychotic symptoms are highly frequent in Parkinson’s disease (PD) patients and are associated with poor prognosis. They include hallucinations, delusions, and minor psychotic phenomena, including sense of presence, passage hallucinations, and illusions. Objective: To evaluate the frequency of psychosis in PD patients. Methods: A systematic review and meta-analysis of clinical trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies reporting the frequency of psychosis, hallucinations, and delusions in PD. Results: Electronic database search wielded 3,536 articles, an additional 91 were identified through citation chaining. Of these, 163 were fully inspected, 57 removed, and 106 included as relevant for neuropsychiatric events frequency, with 32 meeting our inclusion criteria (psychosis and/or specific psychotic phenomena). The pooled frequency of psychosis was 20.7% (95% CI 14.5 to 28.6; I2 = 94%, 15 studies; combined n = 2919). None of the pre-defined meta-regressions or subgroup analyses were statistically significant or helped explain the statistical heterogeneity. The pooled frequency of any form of hallucination was 21.6% (95% CI 14.7 to 30.6; I2 = 95%; 18 studies; combined n = 3,161). Duration of PD at baseline and mean baseline Hoehn & Yahr stage helped explain the statistical heterogeneity in the meta-analysis of hallucinations. Conclusion: Based on the available evidence, around a fifth of PD patients experience psychosis or hallucinations. The risk of developing hallucinations is likely moderated by the disease duration, Hoehn & Yahr stage, and the cognitive status.


2021 ◽  
pp. 1-15
Author(s):  
Hannah Staunton ◽  
Kim Kelly ◽  
Louise Newton ◽  
Mathias Leddin ◽  
Raul Rodriguez-Esteban ◽  
...  

Background: Individuals with Parkinson’s disease (PD) develop a significant disease burden over time that contributes to a progressive decline in health-related quality of life (HRQoL). There is a paucity of qualitative research to understand symptoms and impacts in individuals with early-stage PD (i.e., Hoehn and Yahr stage 1–2 and ≤2 years since diagnosis). Objective: The collection of qualitative data to inform the selection of clinical outcome assessments for clinical trials is advocated by regulators. This patient-centered, multistage study sought to create a conceptual model of symptoms and their impact for individuals with early-stage PD. Methods: Symptoms and impacts of PD were gathered from a literature review of qualitative research, a quantitative social media listening analysis, and qualitative patient concept elicitation interviews (n = 35). Clinical experts provided input to validate and finalize the concepts. Results: The final conceptual model consisted of 27 symptoms categorized into ‘motor’ or ‘non-motor’ domains, and 39 impacts divided into five domains. Most frequently reported symptoms in early-stage PD were ‘tremors’ (89%), ‘stiffness and rigidity’, and ‘fatigue’ (69%, both). Most frequently reported impacts included ‘anxiety’ (74%), ‘eating and drinking’ (71%), followed by ‘exercise/sport’ and ‘relationship with family/family life’ (66%, both). Conclusion: This study provides initial insights relating to the symptom and impact burden of early-stage PD patients. The conceptual model can be used to help researchers to develop and select optimal patient-centered outcomes to measure treatment benefit in clinical trials. These findings could inform future qualitative research and the development of outcomes specifically for early-stage PD patients.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Corinne Quadalti ◽  
Giovanna Calandra-Buonaura ◽  
Simone Baiardi ◽  
Andrea Mastrangelo ◽  
Marcello Rossi ◽  
...  

AbstractNeurofilament light chain (NfL) and α-synuclein oligomeric seeds (α-syn-s) are promising biomarkers for patients with parkinsonism. We assessed their performance in discriminating Parkinson disease (PD) from atypical parkinsonisms (APDs) and evaluated the association between NfL levels and clinical measures of disease severity. We measured NfL in cerebrospinal fluid (CSF) and/or plasma by immunoassays and α-syn-s in CSF by real-time quaking-induced conversion (RT-QuIC) in patients with PD (n = 153), multiple system atrophy (MSA) (n = 80), progressive supranuclear palsy/cortico-basal syndrome (PSP/CBS) (n = 58), dementia with Lewy bodies (n = 64), isolated REM-sleep behaviour disorder (n = 19), and isolated autonomic failure (n = 30). Measures of disease severity included disease duration, UPDRS-III score, Hoehn and Yahr stage, orthostatic hypotension, MMSE score, and CSF amyloid-beta profile. Both CSF NfL (cNfL) and plasma NfL (pNfL) levels were markedly elevated in APDs, and allowed differentiation with PD (vs. APDs, cNfL AUC 0.96; pNfL AUC 0.95; vs. MSA cNfL AUC 0.99; pNfL AUC 0.97; vs. PSP/CBS cNfL AUC 0.94; pNfL AUC 0.94). RT-QuIC detected α-syn-s in 91.4% of PD, but only 2.5% of APDs (all MSA). In PD/PDD, motor scales significantly correlated with cNfL levels. Although pNfL and both cNfL and α-syn-s accurately distinguished PD from APDs, the combined assessment of CSF markers provided a higher diagnostic value (PD vs. APDs AUC 0.97; vs. MSA AUC 0.97; vs. PSP/CBS AUC 0.99) than RT-QuIC alone (p = 0.047 vs. APDs; p = 0.002 vs MSA; p = 0.007 vs PSP/CBS), or cNfL alone (p = 0.011 vs. APDs; p = 0.751 vs MSA; p = 0.0001 vs. PSP/CBS). The results support the use of these assays in specialised clinics.


2021 ◽  
Vol 11 (10) ◽  
pp. 1331
Author(s):  
Mei-Ling Chen ◽  
Chun-Hsiang Tan ◽  
Hui-Chen Su ◽  
Pi-Shan Sung ◽  
Chia-Yi Chien ◽  
...  

This study aimed to understand the impact of sex on the neurocognitive function of patients with Parkinson’s disease (PD). Ninety-four participants with idiopathic PD and 167 age-matched healthy individuals as normal controls (NCs) were recruited and underwent comprehensive neuropsychological assessments. Sex differences were found in NCs, but not in patients with PD. Among male participants, patients with PD showed worse performance on the Digit Symbol Substitution (DSS) (p < 0.001) test and Symbol Search (SS) (p < 0.001) than NCs. Among female participants, patients with PD showed worse performance on the category score of the Modified Wisconsin Card Sorting Test (p < 0.001), SS (p < 0.001), and pentagon copying (p < 0.001) than NCs. After controlling for the effects of age and years of education, Hoehn and Yahr stage was found to predict the performance of the Color Trails Test part A (βA = 0.241, pA = 0.036), Stroop Color and Word Test (β = −0.245, p = 0.036), and DSS (β = −0.258, p = 0.035) in men with PD. These results indicate the differential effect of sex on the neurocognitive function among healthy aging and PD populations. The disappearance of sex differences, which is present in healthy aging, in patients with PD suggests a gradual loss of the neuroprotective effect of estrogen after the initiation of the neurodegenerative process. This study also found mental flexibility and visuospatial function to be the susceptible cognitive domains in women with PD, while the disease severity could predict the working memory and processing speed in men with PD.


2021 ◽  
Vol 3 (3) ◽  
pp. 59-62
Author(s):  
Anna Misyail Abd Rashid ◽  
Mohamad Syafeeq Faeez Md Noh ◽  
Abdul Hanif Khan Yusof Khan ◽  
Mohd Naim Mohd Yaakob ◽  
Norafida Bahari ◽  
...  

A 66-year-old man with underlying hypertension and dyslipidemia presented with left hand tremor for one year. He also noticed difficulty in initiating movement and slowness in activities of daily living. On examination, he was noted to have mask-like facies with reduced blinking and monotonous speech. There was presence of resting pill-rolling tremor, bradykinesia, and cogwheel rigidity which was worst on the left upper limb. Gait assessment revealed difficulty in standing up, shuffling gait with reduced arm swing which was more prominent on the left side, and turning in numbers. No cerebellar signs and supranuclear palsy were present to suggest Parkinson-plus syndrome. Susceptibility weighted imaging (SWI) showed loss of the swallow tail sign on the right side [Figure 1]. The clinical presentation, supplemented by the imaging findings were concluded to be pathognomonic of idiopathic Parkinson’s disease (IPD), Hoehn & Yahr stage 1. He was started on levodopa and benserazide twice daily with improvement of symptoms.The nigrosomes are primary subregions of the substantia nigra where dopaminergic cells are lost in IPD. Within these nigrosomes, maximal cell loss occurs in nigrosome-1; the largest subgroup of nigrosomes. Normally, they appear as a SWI-hyperintense area surrounded by hypointensity within the dorsolateral substantia nigra, akin to a swallow’s tail. In one study, poor visualization of nigrosome-1 was significantly associated with higher motor asymmetry in the contralateral side (sensitivity 98.5%, specificity 93.6%, positive-predictive value 98.3%, negative-predictive value 98.3% and an accuracy of 96%) [1]. Noh et al [2] showed that abnormality involving nigrosome-1 can be detected at 3T MR imaging with an accuracy of 94.6%. Due to the difficulty in diagnosis of early stage IPD, a loss of the swallow tail sign serves as a useful imaging biomarker to supplement the clinical diagnosis, as seen in our patient.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeong-Ho Park ◽  
Suk Yun Kang

AbstractDizziness is common in Parkinson’s disease (PD) patients. It is known that orthostatic hypotension (OH) is the main cause of such dizziness, but even without OH, quite a few PD patients complain of dizziness in the clinic. It can be regarded as non-specific because most of these patients have no neurological abnormalities. We hypothesized that this type of dizziness would be associated with vestibular function, although included patients did not have clinically confirmed vestibulopathy. We studied 84 patients without OH among 121 PD patients. Their clinical features and function were compared between patients with and without dizziness. Hoehn and Yahr stage (H&Y stage), the Unified Parkinson's Disease Rating Scale (UPDRS) part III, the Korean version of the Mini-Mental State Examination (K-MMSE), education years, disease duration, total levodopa equivalent daily dose (LEDD), the presence of dizziness, the dizziness severity, and orthostatic hypotension were tested. Vestibular evoked myogenic potentials (VEMPs) were used to characterize vestibular function. Ocular (oVEMPs) and cervical (cVEMPs) were recorded. oVEMPs in the right side showed significantly reduced potentials (p = 0.016) in PD patients with dizziness, but cVEMPs did not (all ps > 0.2). Bilateral absent oVEMP responses were more common in PD patients with dizziness (p = 0.022), but the frequencies of bilateral absent cVEMP responses were not different between the dizzy and non-dizzy groups (p = 0.898). Dizziness in PD patients without orthostatic hypotension may be associated with vestibular hypofunction. Our results provide evidence that can aid clinicians when making a treatment plan for patients with dizziness. i.e., strategies to enhance reduced vestibular function may be helpful, but this suggestion remains to be evaluated.


2021 ◽  
pp. 1-12
Author(s):  
Klara Komici ◽  
Grazia Daniela Femminella ◽  
Leonardo Bencivenga ◽  
Giuseppe Rengo ◽  
Gennaro Pagano

Background: A link between diabetes mellitus (DM) and Parkinson’s disease (PD) have been proposed but evidence are sparse and inconsistent. Objective: Perform a systematic review of all evidence that link DM and PD characterising the prevalence of DM in PD patients, the risk of developing PD in DM patients and the influence of DM on PD severity and progression. Methods: MEDLINE, Scopus, and Cochrane Library from inception to June 30, 2021 were searched. Studies reporting prevalence, incidence, severity and disease progression of DM and PD were included. Prevalence of DM in PD and incidence of PD in DM patients, and characteristics of PD. Results: A total of 21 studies (n = 11,396) included data on DM prevalence in PD patients, 12 studies (n = 17,797,221) included data on incidence of PD in DM patients, and 10 studies (n = 2,482) included data on DM impact on PD severity and disease progression. The prevalence of DM in PD patients was 10.02 %, (95%C.I. 7.88 –12.16), DM patients showed a higher risk of developing PD (OR: 1.34 95%CI 1.26–1.43 p <  0.0001) compared to non-DM, and PD patients with DM showed a greater severity of motor symptoms, with higher Hoehn and Yahr stage (SMD: 0.36 95%CI 0.12–0.60; p <  0.001) and higher UPDRS (SMD 0.60 95%CI 0.28–0.92; p <  0.001) compared with PD patients without DM. Conclusion: Although the prevalence of DM in PD patients is similar to the general population, patients with DM have a higher risk of developing PD, and the presence of DM is associated with greater PD severity and faster progression, which suggests that DM may be a facilitating factor of neurodegeneration.


2021 ◽  
pp. 1-12
Author(s):  
Yohei Okada ◽  
Hiroyuki Ohtsuka ◽  
Noriyuki Kamata ◽  
Satoshi Yamamoto ◽  
Makoto Sawada ◽  
...  

Background: Long-term physiotherapy is acknowledged to be crucial to manage motor symptoms for Parkinson’s disease (PD) patients, but its effectiveness is not well understood. Objective: This systematic review and meta-analysis aimed to assess the evidence regarding the effectiveness of long-term physiotherapy to improve motor symptoms and reduce antiparkinsonian medication dose in PD patients. Methods: Pubmed, Cochrane, PEDro, and CINAHL were searched for randomized controlled trials before August 31, 2020 that investigated the effectiveness of physiotherapy for 6 months or longer on motor symptoms and levodopa-equivalent dose (LED) in PD patients with Hoehn and Yahr stage 1– 3. We performed random effects meta-analyses for long-term physiotherapy versus no/control intervention and estimated standard mean differences with 95% confidence intervals (CIs). Levels of evidence were rated by the Grading of Recommendation Assessment, Development and Evaluation approach. Results: From 2,940 studies, 10 studies involving 663 PD patients were assessed. Long-term physiotherapy had favorable effects on motor symptoms in off medication state [– 0.65, 95% CI – 1.04 to – 0.26, p = 0.001] and LED [– 0.49, 95% CI – 0.89 to – 0.09, p = 0.02]. Subgroup analyses demonstrated favorable effects on motor symptoms in off medication state by aerobic exercise [– 0.42, 95% CI – 0.64 to – 0.20, p <  0.001] and LED by multidisciplinary rehabilitation of primarily physiotherapy [– 1.00, 95% CI – 1.44 to – 0.56, p <  0.001]. Quality of evidence for aerobic exercise and multidisciplinary rehabilitation were low and very low. Conclusion: This review provided evidence that long-term physiotherapy has beneficial impact on motor symptoms and antiparkinsonian medication dose in PD patients and could motivate implementation of long-term physiotherapy.


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