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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.

Abstract The gut–brain axis is a hot topic in Parkinson's disease (PD). It has been postulated that gut pathogens and dysbiosis can contribute to peripheral inflammatory states or trigger downstream metabolic effects that exacerbate the neurodegenerative process in PD. Several preclinical and clinical studies have demonstrated disrupted intestinal permeability, intestinal inflammation, altered gut microbiome, and reduced fecal short‐chain fatty acids in PD. In this regard, microbial‐directed therapies such as probiotics are emerging as potential therapeutic options. Probiotic supplementation is postulated to confer a variety of health benefits due to the diverse functions of these live microorganisms, including inhibition of pathogen colonization, modulation/“normalization” of the microbiome and/or its function, immunomodulatory effects (e.g. reducing inflammation), and improved host epithelial barrier function. Interestingly, several PD animal model studies have demonstrated the potential neuroprotective effects of probiotics in reducing dopaminergic neuronal degeneration. Notably, two randomized placebo‐controlled trials have provided class I evidence for probiotics as a treatment for constipation in PD. However, the effects of probiotics on other PD aspects, such as motor disability and cognitive function, and its long‐term efficacy (including effects on PD drug absorption in the gut) have not been investigated adequately. Further targeted animal and human studies are also warranted to understand the mechanisms of actions of probiotics in PD and to tailor probiotic therapy based on individual host profiles to improve patient outcomes in this disabling disorder.

The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene in the Contursi kindred in 1997 indisputably confirmed a genetic cause in a subset of Parkinson's disease (PD) patients. Currently, pathogenic variants in one of the seven established PD genes or the strongest known risk factor gene, GBA1, are identified in ∼15% of PD patients unselected for age at onset and family history. In this Debate article, we highlight multiple avenues of research that suggest an important - and in some cases even predominant - role for genetics in PD aetiology, including familial clustering, high rates of monogenic PD in selected populations, and complete penetrance with certain forms. At first sight, the steep increase in PD prevalence exceeding that of other neurodegenerative diseases may argue against a predominant genetic etiology. Notably, the principal genetic contribution in PD is conferred by pathogenic variants in LRRK2 and GBA1 and, in both cases, characterized by an overall late age of onset and age-related penetrance. In addition, polygenic risk plays a considerable role in PD. However, it is likely that, in the majority of PD patients, a complex interplay of aging, genetic, environmental, and epigenetic factors leads to disease development. [ABSTRACT FROM AUTHOR]

Background: The thalamus is an important relay station for the motor circuit of human. Levodopa can reverse the clinical manifestations by modulating the function of motor circuits, but its detailed mechanisms are still not fully understood. We aimed to explore (1) the mechanism by which levodopa modulates the functional connectivity (FC) in the subregions of the thalamus; (2) the relationship between the changed FC and the improvement of motor symptoms in Parkinson's disease (PD) patients. Methods: Resting‐state functional MRI was used to scan 36 PD patients and 37 healthy controls. The FC between the subregions in the thalamus and the whole brain was measured and compared under different medication states of PD patients. The correlation between the improvement of motor symptoms and changes in FC in the thalamus subregions was examined. Results: The PD on state exhibited decreased FC between the right pre‐motor thalamus and the right postcentral gyrus, as well as the right lateral pre‐frontal thalamus and the right postcentral gyrus. These decreases were positively correlated with the improvement of resting tremor. The PD on state also exhibited decreased FC between the left lateral pre‐frontal thalamus and right paracentral lobule, which was positively correlated with the improvement of bradykinesia. Conclusions: This study demonstrates that levodopa treats PD by decreasing the FC between the thalamus subregions and pre/post‐central cortex. Our results provide a basis for further exploration of the functional activity of thalamic subregions and offer new insights into the precision treatment in PD patients [ABSTRACT FROM AUTHOR]

This article explores the challenges and opportunities surrounding genetic testing for Parkinson's disease and other movement disorders in low- and middle-income countries (LMICs). Limited availability and accessibility of genetic testing services, along with financial constraints and limited test options, pose significant barriers in these areas. The shortage of healthcare professionals specializing in neurology, movement disorders, clinical genetics, and genetic counseling further hampers access to genetic testing. Cultural factors, health literacy, and ethical considerations also influence the acceptability of genetic testing. The article proposes various strategies to overcome these barriers, including improving education and training programs for both patients and healthcare professionals, disseminating information through culturally appropriate channels, and advocating for equitable access to genetic testing in LMICs. [Extracted from the article]

Abstract Background The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K‐R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population. Methods Cases (523) which conformed to the United Kingdom PD Brain Bank Criteria for PD were recruited through trained neurologists and age‐ and ethnically matched controls (491) were individuals free of any neurological disorder. The N551K and R1398H mutations were genotyped using the Taqman SNP genotyping assay. Results A significant protective association for N551K was found in those of Malay ancestry, with a protective trend seen for R1398H. A meta‐analysis of Chinese individuals in this cohort with other published cohorts of Chinese ancestry indicated a significant protective role for N551K and R1398H. Conclusion This study reports that the N551K‐R1398H haplotype is also relevant to the Malaysian population, with a significant protective effect found in those of Malay and Chinese ancestries.

Purposeless groaning has been reported in advanced progressive supranuclear palsy. We present a case of purposeless groaning occurring as a primary complaint in a patient with advanced Parkinson’s disease. Purposeless groaning is thought to be a manifestation of disinhibition and perseveration due to frontal-subcortical dysfunction. Proper recognition of this phenomenon will help clinicians to avoid unnecessary investigations and treatment (e.g., prescription of opioid medications).

Background: Human genetics research lacks diversity; over 80% of genome‐wide association studies have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. Objective: This systematic review provides an overview of research involving Parkinson's disease (PD) genetics in underrepresented populations (URP) and sets a baseline to measure the future impact of current efforts in those populations. Methods: We searched PubMed and EMBASE until October 2021 using search strings for "PD," "genetics," the main "URP," and and the countries in Latin America, Caribbean, Africa, Asia, and Oceania (excluding Australia and New Zealand). Inclusion criteria were original studies, written in English, reporting genetic results on PD from non‐European populations. Two levels of independent reviewers identified and extracted information. Results: We observed imbalances in PD genetic studies among URPs. Asian participants from Greater China were described in the majority of the articles published (57%), but other populations were less well studied; for example, Blacks were represented in just 4.0% of the publications. Also, although idiopathic PD was more studied than monogenic forms of the disease, most studies analyzed a limited number of genetic variants. We identified just nine studies using a genome‐wide approach published up to 2021, including URPs. Conclusion: This review provides insight into the significant lack of population diversity in PD research highlighting the immediate need for better representation. The Global Parkinson's Genetics Program (GP2) and similar initiatives aim to impact research in URPs, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Screening for orthostatic hypotension (OH) is integral in Parkinson's disease (PD) management, yet evidence-based guidelines on best practice methods for diagnosing OH in PD are lacking. We investigated the frequency and correlates of OH, symptomatic OH, and neurogenic OH, in a large consecutively recruited PD cohort (n = 318), and compared the diagnostic performance of the sit-to-stand vs. the supine-to-stand blood pressure (BP) test. We evaluated the utility of continuous BP monitoring and tilt table testing in patients with postural symptoms or falls who were undetected to have OH with clinic-based BP measurements. Disease severity, fluid intake, orthostatic and overactive bladder symptoms, falls, comorbidities and medication history were evaluated. Patients' mean age was 66.1 ± 9.5years, with mean disease duration 7.8 ± 5.5years. OH frequency was 35.8 % based on the supine-to-stand test. OH in PD was significantly associated with older age, lower body mass index, longer disease duration, worse motor, cognitive and overactive bladder symptoms and functional disabilities, falls, and lower fluid intake. A similar profile was seen with asymptomatic OH. Three quarters of OH were neurogenic, with the majority also having supine hypertension. The sit-to-stand test had a sensitivity of only 0.39. One quarter of patients were additionally diagnosed with OH during continuous BP monitoring. The sit-to-stand test substantially underdiagnoses OH in PD, with the important practice implication that supine-to-stand measurements may be preferred. Screening for OH is warranted even in asymptomatic patients. Adequate fluid intake, treatment of urinary dysfunction and falls prevention are important strategies in managing PD patients with OH. • Orthostatic hypotension (OH) is prevalent in PD (35.8 %) and frequently asymptomatic. • PD patients with OH have reduced fluid intake and worse overactive bladder symptoms. • OH in PD is usually neurogenic, with the majority also having supine hypertension. • The sit-to-stand BP test substantially underdiagnoses OH in PD. • Continuous BP monitoring can be useful in cases undetected during bedside testing. [ABSTRACT FROM AUTHOR]

Background: Neuropalliative care is an emerging field for those with neurodegenerative illnesses, but access to neuropalliative care remains limited. Objective: We sought to determine Movement Disorder Society (MDS) members' attitudes and access to palliative care. Methods: A quantitative and qualitative survey instrument was developed by the MDS Palliative Care Task Force and e‐mailed to all members for completion. Descriptive statistics and qualitative analysis were triangulated. Results: Of 6442 members contacted, 652 completed the survey. Completed surveys indicating country of the respondent overwhelmingly represented middle‐ and high‐income countries. Government‐funded homecare was available to 54% of respondents based on patient need, 25% limited access, and 21% during hospitalization or an acute defined event. Eighty‐nine percent worked in multidisciplinary teams. The majority endorsed trigger‐based referrals to palliative care (75.5%), while 24.5% indicated any time after diagnosis was appropriate. Although 66% referred patients to palliative care, 34% did not refer patients. Barriers were identified by 68% of respondents, the most significant being available workforce, financial support for palliative care, and perceived knowledge of palliative care physicians specific to movement disorders. Of 499 respondents indicating their training in palliative care or desire to learn these skills, 55% indicated a desire to gain more skills. Conclusions: The majority of MDS member respondents endorsed a role for palliative care in movement disorders. Many members have palliative training or collaborate with palliative care physicians. Although significant barriers exist to access palliative care, the desire to gain more skills and education on palliative care is an opportunity for professional development within the MDS. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (MCCC1)/lysosome-associated membrane protein 3 (LAMP3) loci (rs10513789, rs12637471, rs12493050) reduce the risk of Parkinson's disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (DGKQ) gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry. Methods: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays. Results: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis. Conclusion: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population. [ABSTRACT FROM AUTHOR]

Background: Purposeless groaning is primarily encountered in patients with progressive supranuclear palsy and has also been reported to occur in advanced Parkinson's disease (PD).Objective: We describe a case of pronounced purposeless groaning occurring as a medication OFF-period nonmotor phenomenon in PD. To our knowledge, this has not been previously reported in the literature.Methods and Materials: We describe and provide video documentation of a patient with moderately advanced PD and motor fluctuations, in whom OFF-period groaning was reported by the family and observed during clinic consultations to be a prominent feature, occupying approximately 40% of his OFF periods as calculated from his PD diary.Results and: Conclusions: Although rare, OFF-period purposeless groaning in PD can be very disruptive and add significantly to caregiver burden. It is postulated to be a disinhibitory and perseverative behavior related to overactivation of the cingulo-periaqueductal circuit; further study is needed to delineate the underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Osteoporotic fractures are common in Parkinson's disease (PD). Standard dual-energy X-ray absorptiometry (DXA) measuring bone mineral density (BMD) at the femoral neck and lumbar spine (central sites) has suboptimal sensitivity in predicting fracture risk in the general population. An association between sarcopenia and osteoporosis in PD has not been studied. We compared BMD and osteoporosis prevalence in PD patients vs controls; determined the osteoporosis detection rates using central alone vs central plus distal radius DXA; and analyzed factors (in particular, sarcopenia) associated with osteoporosis. One hundred and fifty-six subjects (102 patients with PD, 54 spousal/sibling controls) underwent femoral neck-lumbar spine-distal radius DXA. Seventy-three patients and 46 controls were assessed for sarcopenia using whole-body DXA and handgrip strength. Patients underwent clinical and serum biochemical evaluations. PD patients had significantly lower body mass index compared to controls. After adjustment for possible confounders, distal radius BMD and T-scores were significantly lower in PD patients compared to controls, but not at the femoral neck/lumbar spine. With distal radius DXA, an additional 11.0% of patients were diagnosed with osteoporosis (32.0% to 43.0%), vs 3.7% in controls (33.3% to 37.0%) additionally diagnosed; this increase was largely driven by the markedly higher detection rate in female PD patients. Female gender (adjusted odds ratio [OR adjusted ] = 11.3, 95% confidence interval [CI]: 2.6–48.6) and sarcopenia (OR adjusted = 8.4, 95% CI: 1.1–64.9) were independent predictors for osteoporosis in PD. Distal radius DXA increased osteoporosis detection, especially in female PD patients, suggesting that diagnostic protocols for osteoporosis in PD could be optimized. A close association between osteoporosis and sarcopenia was documented for the first time in PD, which has important implications for clinical management and future research. [ABSTRACT FROM AUTHOR]

Introduction: Although in some countries, palliative care (PC) still remains poorly implemented, its importance throughout the course of Parkinson's disease (PD) is increasingly being acknowledged. With an emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, growing emphasis has been placed on the palliative needs of people with Parkinson's (PwP), particularly elderly, frail, and with comorbidities. Areas covered: The ongoing COVID-19 pandemic poses an enormous challenge on aspects of daily living in PwP and might interact negatively with a range of motor and non-motor symptoms (NMS), both directly and indirectly – as a consequence of pandemic-related social and health care restrictions. Here, the authors outline some of the motor and NMS relevant to PC, and propose a pragmatic and rapidly deployable, consensus-based PC approach for PwP during the ongoing COVID-19 pandemic, potentially relevant also for future pandemics. Expert opinion: The ongoing COVID-19 pandemic poses a considerable impact on PwP and their caregivers, ranging from mental health issues to worsening of physical symptoms – both in the short- and long-term, (Long-COVID) and calls for specific, personalized PC strategies relevant in a lockdown setting globally. Validated assessment tools should be applied remotely to flag up particular motor or NMS that require special attention, both in short- and long-term. [ABSTRACT FROM AUTHOR]

The gut–brain axis is a hot topic in Parkinson's disease (PD). It has been postulated that gut pathogens and dysbiosis can contribute to peripheral inflammatory states or trigger downstream metabolic effects that exacerbate the neurodegenerative process in PD. Several preclinical and clinical studies have demonstrated disrupted intestinal permeability, intestinal inflammation, altered gut microbiome, and reduced fecal short‐chain fatty acids in PD. In this regard, microbial‐directed therapies such as probiotics are emerging as potential therapeutic options. Probiotic supplementation is postulated to confer a variety of health benefits due to the diverse functions of these live microorganisms, including inhibition of pathogen colonization, modulation/"normalization" of the microbiome and/or its function, immunomodulatory effects (e.g. reducing inflammation), and improved host epithelial barrier function. Interestingly, several PD animal model studies have demonstrated the potential neuroprotective effects of probiotics in reducing dopaminergic neuronal degeneration. Notably, two randomized placebo‐controlled trials have provided class I evidence for probiotics as a treatment for constipation in PD. However, the effects of probiotics on other PD aspects, such as motor disability and cognitive function, and its long‐term efficacy (including effects on PD drug absorption in the gut) have not been investigated adequately. Further targeted animal and human studies are also warranted to understand the mechanisms of actions of probiotics in PD and to tailor probiotic therapy based on individual host profiles to improve patient outcomes in this disabling disorder. This review introduces readers to the gut–brain axis theory in Parkinson's disease (PD) and summarizes relevant literature regarding alterations of gut microbiome/physiology in PD. This is then followed by a focused review on the potential roles of probiotics in PD, with critical appraisals of published clinical and preclinical evidence. Importantly, current knowledge gaps and leads for future research are highlighted. [ABSTRACT FROM AUTHOR]

We describe the clinical features of two sisters with Parkinson's disease (PD) of Indian descent living in Malaysia. Both were homozygous for the known PINK1 mutation p.Leu489Pro (c.1466T>C). The proband, who has been followed up by us over a span of 35 years, had a fairly "classic" clinical presentation for PARK-PINK1, including young onset, a clear response to dopamine replacement therapy, and development of troublesome motor fluctuations and dyskinesias. Her dyskinesias improved substantially with clozapine treatment, which to our knowledge has not specifically been reported for PARK-PINK1; this treatment has been sustained for nearly a decade. The clinical phenotype of the older sister was more akin to later-onset "idiopathic" PD; however, her brain MRI showed abnormal signal in the posterior limb of the internal capsules and the hypothalamus. Our report contributes to the scarce literature on monogenic PD in the Malaysian / Indian population, and further supports the pathogenicity of the PINK1 p.Leu489Pro variant. [ABSTRACT FROM AUTHOR]

We describe the clinical features of a Malaysian woman with Parkinson's disease (PD) who carried the PRKN p.Cys441Arg mutation in the homozygous state. She had a fairly "classic" clinical presentation for PARK-Parkin, including juvenile onset and a clear response to dopaminergic medication complicated by motor fluctuations and dyskinesias. She had a substantial benefit with apomorphine infusion treatment, which to our knowledge has not been reported for PARK-Parkin. Our report contributes to the very scarce literature on monogenic causes of PD in the Malaysian population, and highlights an alternative treatment option to oral dopaminergic medication or deep brain stimulation surgery. [ABSTRACT FROM AUTHOR]

Objective: Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance. Methods: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry. Results: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR‐based metabolome. Microbiome and NMR‐based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N‐oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability–gait disorder scores. Interpretation: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut–brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546–559 [ABSTRACT FROM AUTHOR]

Objective: The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD).Background: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016.Methods: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported.Results: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful.Conclusions: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (HP) infection has been associated with worse motor function in Parkinson's disease (PD). Objective: We aimed to evaluate the effects of HP eradication on PD symptoms. Methods: In this parallel‐group, double‐blind, randomized placebo‐controlled, single‐center trial, patients with PD with positive HP urea breath test and serology were block randomized (1:1) to receive standard eradication triple therapy or identically appearing placebo capsules for 1 week. Prespecified motor (International Parkinson and Movement Disorder Society Unified PD Rating Scale [MDS‐UPDRS], timed tests, and home‐based wearable sensor measurements), nonmotor (Leeds Dyspepsia Questionnaire and Montreal Cognitive Assessment), and quality‐of‐life (Parkinson's Disease Questionnaire‐39) outcome measures were assessed at weeks 6, 12, 24, and 52. The primary outcome was the baseline‐to‐week 12 change in ON medication MDS‐UPDRS motor scores. Lactulose‐hydrogen breath testing for concomitant small intestinal bacterial overgrowth was performed at baseline and repeated at week 24, together with the urea breath test. Results: A total of 310 patients were screened for eligibility and 80 were randomly assigned, of whom 67 were included in the full‐analysis set (32 treatment group patients, 35 placebo patients). HP eradication did not improve MDS‐UPDRS motor scores at week 12 (mean difference 2.6 points in favor of placebo, 95% confidence interval: −0.4 to 5.6, P = 0.089). There was no significant improvement in any motor, nonmotor, or quality‐of‐life outcome at weeks 12 and 52. Both the full‐analysis and per‐protocol analyses (based on eradication status) supported these conclusions. Small intestinal bacterial overgrowth status did not influence treatment results. Conclusions: HP eradication does not improve clinical outcomes in PD, suggesting that there is no justification for routine HP screening or eradication with the goal of improving PD symptoms. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and Parkinson's disease (PD) and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of α-synuclein aggregates from the enteric nervous system to the brain. Here, we review evidence linking GM changes with PD, highlighting mechanisms supportive of pathological α-synuclein spread and intestinal inflammation in PD. We summarise existing patterns and correlations seen in clinical studies of the GM in PD, together with the impacts of non-motor symptoms, medications, lifestyle, diet and ageing on the GM. Roles of GM modulating therapies including probiotics and faecal microbiota transplantation are discussed. Encouragingly, alterations in the GM have repeatedly been observed in PD, supporting a biological link and highlighting it as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background: The primary motor cortex (M1) is a critical node in Parkinson's disease (PD)-related motor circuitry; however, the functional roles of its subregions are poorly understood. In this study, we investigated changes in the functional connectivity patterns of M1 subregions and their relationships to improved clinical symptoms following levodopa administration. Methods: Thirty-six PD patients and 37 healthy controls (HCs) were enrolled. A formal levodopa challenge test was conducted in the PD group, and the Unified Parkinson's Disease Rating Scale motor section (UPDRS-III) was assessed before (off state) and 1 h after administration of levodopa (on state). The PD group underwent resting-state functional magnetic resonance imaging in both off and on states, whereas the HC group was scanned once. We used the Human Brainnetome Atlas template to subdivide M1 into twelve regions of interest (ROIs). Functional connectivity (FC) was compared between PD on and off states [paired t -test, voxel-level p < 0.001, cluster-level p < 0.05, Gaussian random field (GRF) correction] and between patients and HC (two-sample t -test voxel-level p < 0.001, cluster-level p < 0.05). Correlations between ΔFC (differences in FC between PD off and on states) and clinical symptom improvements were examined. Results: There was decreased FC between the right caudal dorsolateral area 6 and the anterior cingulate gyrus (ACC), the right upper limb region and the left medial dorsal thalamus (mdTHA), as well as increased FC between the left tongue and larynx region and the left medial frontal gyrus. ΔFC between the right caudal dorsolateral area 6 and ACC was positively correlated with improvements in UPDRS-III total scores as well as the rigidity (item 22) and bradykinesia (items 23–26 and 31) subscores. ΔFC between the right upper limb region and left thalamus was positively correlated with improvements in the left upper limb tremor (items 20c and 21b) and postural tremor (item 21b) subscores. Conclusions: Our results reveal novel information regarding the underlying mechanisms in the motor circuits in the M1 and a promising way to explore the internal function of the M1 in PD patients. Notably, M1 is a potential therapeutic target in PD, and the exploration of its subregions provides a basis and a source of new insights for clinical intervention and precise drug treatment. [ABSTRACT FROM AUTHOR]