Objective Putaminal iron deposition is an important feature that helps differentiate multiple system atrophy with predominant parkinsonism (MSA-p) from Parkinson’s disease (PD). Most previous studies used visual inspection or quantitative methods with manual manipulation to perform this differentiation. We investigated the value of a new semiautomated diagnostic algorithm using 3T-MR susceptibility-weighted imaging for MSA-p.
Methods This study included 26 MSA-p, 68 PD, and 41 normal control (NC) subjects. The algorithm was developed in 2 steps: 1) determine the image containing the remarkable putaminal margin and 2) calculate the phase-shift values, which reflect the iron concentration. The next step was to identify the best differentiating conditions among several combinations. The highest phaseshift value of each subject was used to assess the most effective diagnostic set.
Results The raw phase-shift values were present along the lateral margin of the putamen in each group. It demonstrates an anterior- to-posterior gradient that was identified most frequently in MSA-p. The average of anterior 5 phase shift values were used for normalization. The highest area under the receiver operating characteristic curve (0.874, 80.8% sensitivity, and 86.7% specificity) of MSA-p versus PD was obtained under the combination of 3 or 4 vertical pixels and one dominant side when the normalization methods were applied. In the subanalysis for the MSA-p patients with a longer disease duration, the performance of the algorithm improved.
Conclusion This algorithm detected the putaminal lateral margin well, provided insight into the iron distribution of the putaminal rim of MSA-p, and demonstrated good performance in differentiating MSA-p from PD.
Objective The Montreal Cognitive Assessment (MoCA) is recommended for assessing general cognition in Parkinson’s disease (PD). Several cutoffs of MoCA scores for diagnosing PD with cognitive impairment (PD-CI) have been proposed, with varying sensitivity and specificity. This study investigated the utility of machine learning algorithms using MoCA cognitive domain scores for improving diagnostic performance for PD-CI.
Methods In total, 2,069 MoCA results were obtained from 397 patients with PD enrolled in the Parkinson’s Progression Markers Initiative database with a diagnosis of cognitive status based on comprehensive neuropsychological assessments. Using the same number of MoCA results randomly sampled from patients with PD with normal cognition or PD-CI, discriminant validity was compared between machine learning (logistic regression, support vector machine, or random forest) with domain scores and a cutoff method.
Results Based on cognitive status classification using a dataset that permitted sampling of MoCA results from the same individual (n = 221 per group), no difference was observed in accuracy between the cutoff value method (0.74 ± 0.03) and machine learning (0.78 ± 0.03). Using a more stringent dataset that excluded MoCA results (n = 101 per group) from the same patients, the accuracy of the cutoff method (0.66 ± 0.05), but not that of machine learning (0.74 ± 0.07), was significantly reduced. Inclusion of cognitive complaints as an additional variable improved the accuracy of classification using the machine learning method (0.87–0.89).
Conclusion Machine learning analysis using MoCA domain scores is a valid method for screening cognitive impairment in PD.
Objective This study aims to validate the Thai translation of the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS).
Methods The English version was translated into Thai and then back-translated into English. The translated version underwent 2 rounds of cognitive pretesting to assess the ease of comprehension, ease of use and comfort with the scale. Then, it underwent large clinimetric testing.
Results The Thai version was validated in 354 PD patients. The comparative fit index (CFI) for all four parts of the Thai version of the MDS-UPDRS was 0.93 or greater. Exploratory factor analysis identified isolated item differences in factor structure between the Thai and English versions.
Conclusion The overall factor structure of the Thai version was consistent with that of the English version based on the high CFIs (all CFI ≥ 0.90). Hence, it can be designated the official Thai version of the MDS-UPDRS.
Objective This study aims to develop an automated and objective tool to evaluate postural abnormalities in Parkinson’s disease (PD) patients.
Methods We applied a deep learning-based pose-estimation algorithm to lateral photos of prospectively enrolled PD patients (n = 28). We automatically measured the anterior flexion angle (AFA) and dropped head angle (DHA), which were validated with conventional manual labeling methods.
Results The automatically measured DHA and AFA were in excellent agreement with manual labeling methods (intraclass correlation coefficient > 0.95) with mean bias equal to or less than 3 degrees.
Conclusion The deep learning-based pose-estimation algorithm objectively measured postural abnormalities in PD patients.
Objective Using telemedicine is a way to improve the accessibility of specialists for patients with Parkinson’s disease (PD); however, it is not widely used in Japan. We investigated the efficacy of telemedicine in PD by using a single-center cross-sectional questionnaire survey.
Methods We sent a questionnaire to patients who agreed to participate from among 52 patients with PD who had used telemedicine services at Juntendo University Hospital from October 2017 to November 2018. Caregivers were asked to respond to one question separately.
Results A total of 38 patients responded to the questionnaire. Most patients were satisfied with the telemedicine consultation (7.8 ± 1.9), reporting that it was effective in reducing their travel burden. Twenty-one patients attended a telemedicine consultation with their caregivers, and their satisfaction was high (8.4 ± 1.8).
Conclusion In a specific cohort in Japan, patients with PD and their caregivers were mostly satisfied with the telemedicine service.
Jia Wei Hor, Shen-Yang Lim, Eng Soon Khor, Kah Kian Chong, Sze Looi Song, Norlinah Mohamed Ibrahim, Cindy Shuan Ju Teh, Chun Wie Chong, Ida Normiha Hilmi, Ai Huey Tan
J Mov Disord. 2022;15(2):106-114. Published online December 24, 2021
Objective Converging evidence suggests that intestinal inflammation is involved in the pathogenesis of neurodegenerative diseases. Previous studies on fecal calprotectin in Parkinson’s disease (PD) were limited by small sample sizes, and literature regarding intestinal inflammation in multiple system atrophy (MSA) is very scarce. We investigated the levels of fecal calprotectin, a marker of intestinal inflammation, in PD and MSA.
Methods We recruited 169 subjects (71 PD, 38 MSA, and 60 age-similar nonneurological controls). Clinico-demographic data were collected. PD and MSA were subtyped and the severity assessed using the MDS-UPDRS and UMSARS, respectively. Fecal calprotectin and blood immune markers were analyzed.
Results Compared to controls (median: 35.7 [IQR: 114.2] μg/g), fecal calprotectin was significantly elevated in PD (median: 95.6 [IQR: 162.1] μg/g, p = 0.003) and even higher in MSA (median: 129.5 [IQR: 373.8] μg/g, p = 0.002). A significant interaction effect with age was observed; between-group differences were significant only in older subjects (i.e., ≥ 61 years) and became more apparent with increasing age. A total of 28.9% of MSA and 18.3% of PD patients had highly abnormal fecal calprotectin levels (≥ 250 μg/g); however, this difference was only significant for MSA compared to controls. Fecal calprotectin correlated moderately with selected blood immune markers in PD, but not with clinical features of PD or MSA.
Conclusions Elevated fecal calprotectin suggests a role for intestinal inflammation in PD and MSA. A more complete understanding of gut immune alterations could open up new avenues of research and treatment for these debilitating diseases.
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by both motor and nonmotor symptoms. Although the basal ganglia is traditionally the primary brain region implicated in this disease process, this limited view ignores the roles of the cortex and cerebellum that are networked with the basal ganglia to support motor and cognitive functions. In particular, recent research has highlighted dysfunction in the supplementary motor complex (SMC) in patients with PD. Using the PubMed and Google Scholar search engines, we identified research articles using keywords pertaining to the involvement of the SMC in action sequencing impairments, temporal processing disturbances, and gait impairment in patients with PD. A review of abstracts and full-text articles was used to identify relevant articles. In this review of 63 articles, we focus on the role of the SMC in PD, highlighting anatomical and functional data to create new perspectives in understanding clinical symptoms and, potentially, new therapeutic targets. The SMC has a nuanced role in the pathophysiology of PD, with both hypo- and hyperactivation associated with various symptoms. Further studies using more standardized patient populations and functional tasks are needed to more clearly elucidate the role of this region in the pathophysiology and treatment of PD.
Objective The association between gastrointestinal (GI) symptoms and cognitive profile in patients with Parkinson’s disease (PD) at diagnosis remains unclear, although GI symptoms and cognitive impairment are highly prevalent in patients with PD. We investigated the relationship between constipation and cognitive status. We also aimed to identify the correlation between constipation and each neuropsychological dysfunction.
Methods A total of 427 patients with de novo Parkinson’s disease with normal cognition (PD-NC, n = 170) and Parkinson’s disease with mild cognitive impairment (PD-MCI, n = 257) at Korea University Guro Hospital in Seoul, Korea were included. All patients underwent comprehensive neuropsychological tests and completed the Non-Motor Symptoms Scale (NMSS). The frequency and severity of constipation were assessed using the NMSS GI symptoms scale, we used logistic regression analysis and partial correlation analysis to determine the associations between constipation score, MCI, and each neuropsychological dysfunction.
Results Frequent and severe constipation was associated with MCI in patients with PD at diagnosis regardless of disease severity. Specifically, constipation was related to poor performance in frontal-executive and visuospatial functions after controlling for age and sex.
Conclusion Our findings may provide an understanding of constipation as a marker associated with cognitive impairment in individuals with PD. Therefore, the evaluation of cognitive function is warranted in PD patients with constipation, while further studies are necessary to investigate the detailed mechanism of our results.
Objective A meta-analysis of locus-based genome-wide association studies recently identified a relationship between AXIN1 and Parkinson’s disease (PD). Few studies of Asian populations, however, have reported such a genetic association. The influences of rs13337493, rs758033, and rs2361988, three PD-associated genetic variants of AXIN1, were investigated in the present study because AXIN1 is related to Wnt/β-catenin signaling.
Methods A total of 2,418 individuals were enrolled in our Taiwanese cohort for analysis of the genotypic and allelic frequency. Polymerase chain reaction–restriction fragment length polymorphism analysis was employed for rs13337493 genotyping, and the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA) was used for rs758033 and rs2361988 genotyping in 672 patients with PD and 392 controls. Taiwan Biobank data of another 1,354 healthy controls were subjected to whole-genome sequencing performed using Illumina platforms at approximately 30× average depth.
Results Our results revealed that rs758033 {odds ratios [OR] (95% confidence interval [CI]) = 0.267 [0.064, 0.795], p = 0.014} was associated with the risk of PD, and there was a trend toward a protective effect of rs2361988 (OR [95% CI] = 0.296 [0.071, 0.884], p = 0.026) under the recessive model. The TT genotype of rs758033 (OR [95% CI] = 0.271 [0.065, 0.805], p = 0.015) and the CC genotype of rs2361988 (OR [95% CI] = 0.305 [0.073, 0.913], p = 0.031) were less common in the PD group than in the non-PD group.
Conclusion Our findings indicate that the rs758033 and rs2361988 polymorphisms of AXIN1 may affect the risk of PD in the Taiwanese population.
Objective The aim of this study was to assess the effects of dancing (using the Feldenkrais method) on motor and non-motor symptoms, quality of life (QoL), and objective parameters of gait at the time of intervention and at the end of the 1-year study period.
Methods This was a single-arm study in which 12 subjects with Parkinson’s disease (PD) received dance intervention during a 6-month period. Objective motor scales, gait analysis, and questionnaires on non-motor symptoms were evaluated at baseline and at 3, 6, and 12 months.
Results Dance intervention decreased motor scale (Unified Parkinson’s Disease Rating Scale and Tinetti scale) scores and improved gait disturbance (gait velocity and step length) without increasing levodopa equivalent dose. Furthermore, dancing decreased non-motor scale (Non-Motor Symptoms Scale and Montgomery-Asberg Depression Rating Scale) scores and improved QoL.
Conclusion Our findings suggest that dance intervention can be a complementary management method for PD patients.
Accumulation of alpha-synuclein (αSyn) protein in neurons is a renowned pathological hallmark of Parkinson’s disease (PD). In addition, accumulating evidence indicates that activated inflammatory responses are involved in the pathogenesis of PD. Thus, achieving a better understanding of the interaction between inflammation and synucleinopathy in relation to the PD process will facilitate the development of promising disease-modifying therapies. In this review, the evidence of inflammation in PD is discussed, and human, animal, and laboratory studies relevant to the relationship between inflammation and αSyn are explored as well as new therapeutic targets associated with this relationship.
Freezing of gait (FOG) is a common occurrence in patients with Parkinson’s disease (PD) that leads to significant limitations in mobility and increases risk of falls. Focused vibrotactile stimulation and cueing are two methods used to alleviate motor symptoms, including FOG, in patients with PD. While effective on their own, the effect of combining both focused vibrotactile stimulation and cueing has yet to be investigated. Two patients, both with a history of PD, suffered from frequent FOG episodes that failed to respond adequately to medication. A novel vibrotactile stimulation device that delivered rhythmic kinesthetic stimuli onto the sternum successfully reduced FOG episodes in both patients and drastically improved their mobility as measured by the Timed Up and Go test. We found that a combination of focused vibrotactile stimulation and cueing was effective in reducing FOG episodes in two patients with PD. Further well-designed prospective studies are needed to confirm our observations.
Parkinson’s disease (PD) is a severe neurodegenerative disease characterized by classic motor features associated with the loss of dopaminergic neurons and appearance of Lewy bodies in the substantia nigra. Due to the complexity of PD, a definitive diagnosis in the early stages and effective management of symptoms in later stages are difficult to achieve in clinical practice. Previous research has shown that colocalization of A2A receptors (A2AR) and dopamine D2 receptors (D2R) may induce an antagonistic interaction between adenosine and dopamine. Clinical trials have found that the A2AR antagonist istradefylline decreases dyskinesia in PD and could be used as an adjuvant to levodopa treatment. Meanwhile, the incretin hormone glucagon-like peptide 1 (GLP1) mainly facilitates glucose homeostasis and insulin signaling. Preclinical experiments and clinical trials of GLP1 receptor (GLP1R) agonists show that they may be effective in alleviating neuroinflammation and sustaining cellular functions in the central nervous system of patients with PD. In this review, we summarize up-to-date findings on the usefulness of A2AR antagonists and GLP1R agonists in PD management. We explain the molecular mechanisms of these medications and their interactions with other neurotransmitter receptors. Furthermore, we discuss the efficacy and limitations of A2AR antagonists and GLP1R agonists in clinical practice.
There is an extensive debate on the neurological consequences of 2019 novel coronavirus disease (COVID-19) and its impact on Parkinson’s disease (PD) patients, which seems to puzzle neurologists. Links between viral infections and PD have long been suspected and studied, but the exact relationship remains elusive. Since severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) enters the brain through multiple routes and has a direct impact on the brain, cumulative damage occurs due to the activation of proinflammatory cytokines and chemokines. SARS-CoV-2 seems to aggravate PD due to its effects on α-synuclein, mitochondrial dysfunction, and dopamine depletion. A few studies have even highlighted the higher vulnerability of PD patients to COVID-19. The sudden dramatic change in lifestyle caused by the pandemic and the widespread lockdowns that were implemented have added to the hidden sorrows of PD patients, as they already have a compromised mechanism for coping with stress. This review summarizes insights from basic science and the clinical effect of SARS-CoV-2 infection on the human brain, with a specific focus on PD.
The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) has led to a serious global health crisis. Increasing evidence suggests that elderly individuals with underlying chronic diseases, including Parkinson’s disease (PD), are particularly vulnerable to this infection. Changes in the routine care of PD patients should be implemented carefully without affecting the quality provided. The utilization of telemedicine for clinical consultation, assessment and rehabilitation has also been widely recommended. Therefore, the aim of this review is to provide recommendations in the management of PD during the pandemic as well as in the early phase of vaccination programs to highlight the potential sequelae and future perspectives of vaccination and further research in PD. Even though a year has passed since COVID- 19 emerged, most of us are still facing great challenges in providing a continuum of care to patients with chronic neurological disorders. However, we should regard this health crisis as an opportunity to change our routine approach in managing PD patients and learn more about the impact of SARS-CoV-2. Hopefully, PD patients can be vaccinated promptly, and more detailed research related to PD in COVID-19 can still be carried out.