The latest medical research on Parkinson’s Disease
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Request AccessAssessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson's Disease with Sleep Disorders.
Journal Parkinsons DiseasePrevious studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS.
To evaluate the association between LC impairment and sleep disorders in ET and PD patients.
A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC) and free-water value of LC (FWLC) with PSQI scores in ET and PD groups.
CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients.
LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS.
Effects of Continuous Dopaminergic Stimulation on Parkinson's Disease Gait: A Longitudinal Prospective Study with Levodopa Intestinal Gel Infusion.
Journal Parkinsons DiseaseGait issues, including reduced speed, stride length and freezing of gait (FoG), are disabling in advanced phases of Parkinson's disease (PD), and their treatment is challenging. Levodopa/carbidopa intestinal gel (LCIG) can improve these symptoms in PD patients with suboptimal control of motor fluctuations, but it is unclear if continuous dopaminergic stimulation can further improve gait issues, independently from reducing Off-time.
To analyze before (T0) and after 3 (T1) and 6 (T2) months of LCIG initiation: a) the objective improvement of gait and balance; b) the improvement of FoG severity; c) the improvement of motor complications and their correlation with changes in gait parameters and FoG severity.
This prospective, longitudinal 6-months study analyzed quantitative gait parameters using wearable inertial sensors, FoG with the New Freezing of Gait Questionnaire (NFoG-Q), and motor complications, as per the MDS-UPDRS part IV scores.
Gait speed and stride length increased and duration of Timed up and Go and of sit-to-stand transition was significantly reduced comparing T0 with T2, but not between T0-T1. NFoG-Q score decreased significantly from 19.3±4.6 (T0) to 11.8±7.9 (T1) and 8.4±7.6 (T2) (T1-T0 p = 0.018; T2-T0 p < 0.001). Improvement of MDS-UPDRS-IV (T0-T2, p = 0.002, T0-T1 p = 0.024) was not correlated with improvement of gait parameters and NFoG-Q from T0 to T2. LEDD did not change significantly after LCIG initiation.
Continuous dopaminergic stimulation provided by LCIG infusion progressively ameliorates gait and alleviates FoG in PD patients over time, independently from improvement of motor fluctuations and without increase of daily dosage of dopaminergic therapy.
Ciita Regulates Local and Systemic Immune Responses in a Combined rAAV-α-synuclein and Preformed Fibril-Induced Rat Model for Parkinson's Disease.
Journal Parkinsons DiseaseParkinson's disease (PD) is characterized by alpha-synuclein (α-Syn) pathology, neurodegeneration and neuroinflammation. Human leukocyte antigen (HLA) variants associated with PD and α-Syn specific CD4+ T lymphocytes in PD patients highlight the importance of antigen presentation in PD etiology. The class II transactivator (CIITA) regulates major histocompatibility complex class II (MHCII) expression. Reduced Ciita levels significantly increase α-Syn pathology, nigrostriatal neurodegeneration and behavioral deficits in α-Syn-induced rat PD models.
Characterize immune profiles associated with enhanced PD-like pathology observed in rats expressing lower Ciita levels (DA.VRA4) compared to the background strain (DA).
To model PD, we combined rAAV-mediated α-Syn overexpression in the substantia nigra with striatal injection of α-Syn preformed fibrils. Immune profiles in brain and blood were analyzed by flow cytometry and multiplexed ELISA in naïve rats, 4- and 8 weeks post rAAV injection.
Flow cytometry showed Ciita-dependent regulation of MHCII on microglia, brain macrophages and circulating myeloid cells. The MHCII-dependent microglial response was highest at 4 weeks post rAAV injection, whereas the MHCII levels in circulating myeloid cells was highest at 8 weeks. There was no major infiltration of macrophages or T lymphocytes into the CNS in response to α-Syn and only subtle Ciita- and/or α-Syn-dependent changes in the T lymphocyte compartment. Lower Ciita levels were consistently associated with higher TNF levels in serum.
Ciita regulates susceptibility to PD-like pathology through minor but detectable changes in resident and peripheral immune cells and TNF levels, indicating that mild immunomodulatory therapies could have therapeutic effects in PD.
Atypical Presentations of Huntington Disease-like 2 in South African Individuals.
"Movement Disorders Clinical PracticeHuntington disease-like 2 (HDL2) is a neurodegenerative disorder, affecting only individuals of African ancestry. Full penetrance occurs in individuals with 40 repeats or more.
To describe the phenotypic variability of HDL2 in a group of mixed ancestry individuals from South Africa.
Eight patients were assessed with analysis of repeat size and magnetic resonance brain imaging. We applied the Unified Huntington's Disease Rating Scale (UHDRS), but in deceased patients (4), this was estimated from video material.
Cognitive domains were more severely affected than motor; UHDRS motor scores were notable for bradykinesia, and to a slightly lesser extent, for rigidity and dystonia; a single patient had marked chorea. Repeat lengths ranged from 45 to 63 (median, 52).
This South African group of mixed ancestry HDL2 individuals presented with severe cognitive and behavioral impairments, with lesser degrees or absence of chorea. This presentation is possibly related to large repeat sizes.
Long-Term Medication Profiles in Parkinson's Disease under Subthalamic Deep Brain Stimulation: A Controlled Study.
"Movement Disorders Clinical PracticeSubthalamic deep brain stimulation (STN-DBS) reduces antiparkinsonian medications in Parkinson's disease (PD) compared with the preoperative state. Longitudinal and comparative studies on this effect are lacking.
To compare longitudinal trajectories of antiparkinsonian medication in STN-DBS treated patients to non-surgically treated control patients.
We collected retrospective information on antiparkinsonian medication from PD patients that underwent subthalamic DBS between 1999 and 2010 and control PD patients similar in age at onset and baseline, sex-distribution, and comorbidities.
In 74 DBS patients levodopa-equivalent daily dose (LEDD) were reduced by 33.9-56.0% in relation to the preoperative baseline over the 14-year observational period. In 61 control patients LEDDs increased over approximately 10 years, causing a significant divergence between groups. The largest difference amongst single drug-classes was observed for dopamine agonists.
In PD patients, chronic STN-DBS was associated with a lower LEDD compared with control patients over 14 years.
The Quality in Quality of Life in Parkinson's Disease: A Qualitative Meta-Synthesis.
"Movement Disorders Clinical PracticeQuality of life (QoL) is known to be impaired in people with Parkinson's disease (PwPD). Not surprisingly, a considerable effort of health interventions is aimed at maintaining or improving QoL. Yet, little is known about its determinants from a PwPD perspective to inform person-centered health care interventions.
This systematic review aims to overcome this information gap by synthesizing existing evidence on factors associated with PwPD' self-perceived QoL.
We searched six electronic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science, Cochrane Library) from inception to January 2022 for eligible qualitative studies of QoL in PwPD, supplemented by citation tracking and hand searching. Study quality was assessed using the QualSyst tool. In order to characterize the determinants of QoL in PwPD, we conducted a qualitative meta-synthesis.
Our analysis revealed a wide range of facilitators and barriers to QoL relating to seven overarching themes: Illness experience, health care, everyday life, social life, identity, spirituality/religion, and environment.
Our systematic review reinforces the impact of symptom experience on PwPD's QoL. However, it also highlights the need to consider the non-physical dimensions of PD when assessing patients' QoL. It is therefore essential that health care professionals acknowledge the psychological, social and spiritual repercussions of PD and endeavor to respond to these concerns through a comprehensive and patient-centered strategy. Further research is needed to gain a deeper understanding of these facets of PD and to formulate successful interventions aimed at improving the QoL of PwPD.
The Priority Goals and Underlying Impairments Contributing to Goal-Related Problems of People with Parkinson's Disease Receiving a Community-Based Rehabilitation Program.
Parkinsons DiseaseGoal setting is a core rehabilitation practice in Parkinson's disease (PD). Targeting therapy towards specific goals leads to greater improvements in performance and psychosocial outcomes. Goal setting in PD is feasible, and although the nature of goals has been described in previous studies, the underlying impairments related to goals have not been described. Understanding the nature of goals ensures that interventions for people with PD are aligned with their needs and priorities. Understanding the underlying impairments highlights which symptoms have the biggest impact on daily life and is necessary for planning appropriate interventions to target them.
To describe the nature of the goals of people with PD; the underlying impairments related to goals; and to compare differences between high and low priority goals.
Deductive content analysis was used to map goal statements to the international classification of function (ICF) activity and participation category and to map therapist field notes detailing the primary underlying impairment to the ICF Body Functions category. These results were then compared across goal priority rankings.
88 goals of 22 people with PD were analysed. We found that people with PD set diverse goals across all chapters of the ICF Activity and Participation category, with "self-care" goals making up the highest proportion of goals. The primary underlying impairment related to the goals was predominantly related to impairments in "mental functions" under the Body Functions category. Regardless of goal priority, most goal-related underlying impairments were found to be in the "mental functions" category.
The goals of this sample of community-dwelling people with PD highlight their diverse needs and priorities. These findings indicate that nonmotor symptoms, namely, executive dysfunction and amotivation most commonly impact the performance of and participation in activities of greatest importance to people with PD. This trial is registered with ACTRN12621001483842.
Effects of Blood Flow Restriction Resistance Training on Autonomic and Endothelial Function in Persons with Parkinson's Disease.
Journal Parkinsons DiseaseAutonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to one's quality of life. While exercise interventions have proven helpful for motor symptoms of PD, improving associated non-motor symptoms is limited. Low-intensity resistance training with blood flow restriction (LIRT-BFR) improves autonomic dysfunction in non-PD patients and high-intensity resistance training (HIRT) is recommended for motor symptom improvements for people with PD (PwPD).
To determine the effects of LIRT-BFR and HIRT on homocysteine and autonomic and endothelial function in PwPD and to determine the hemodynamic loads during LIRT-BFR and HIRT in PwPD using a novel exercise protocol.
Thirty-eight PwPD were assigned LIRT-BFR, HIRT or to a control (CNTRL) group. The LIRT-BFR and HIRT groups exercised three days per week for four weeks. The LIRT-BFR protocol used 60% limb occlusion pressure (LOP) and performed three sets of 20 repetitions at 20% of the one-repetition maximum (1RM). The HIRT group performed three sets of eight repetitions at 80% 1RM. The CNTRL group was asked to continue their normal daily routines.
LIRT-BFR significantly improved orthostatic hypotension (p = 0.026), homocysteine levels (p < 0.001), peripheral circulation (p = 0.003), supine blood pressure (p = 0.028) and heart rate variability (p = 0.041); LIRT-BFR improved homocysteine levels (p < 0.018), peripheral circulation (p = 0.005), supine blood pressure (p = 0.007) and heart rate variability (p = 0.047) more than HIRT; and hemodynamic loads for LIRT-BFR and HIRT were similar.
LIRT-BFR may be more effective than HIRT for autonomic and endothelial function improvements in PwPD and hemodynamic loads may be lessened in LIRT-BFR protocols using single-joint exercises with intermittent blood flow restriction. Further research is needed to determine if non-motor symptoms improve over time and if results are sustainable.
Oculomotor Dysfunction in Idiopathic and LRRK2-Parkinson's Disease and At-Risk Individuals.
Journal Parkinsons DiseaseVideo-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson's disease (PD).
To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2 (L2PD), as well as to evaluate oculomotor function in asymptomatic carriers of the G2019S variant of LRRK2.
The study enrolled 129 subjects: 30 PD (16 iPD, 14 L2PD), 23 asymptomatic carriers, 13 non-carrier relatives of L2PD patients, and 63 unrelated HCs. The video-oculographic evaluation included fixation, prosaccade, antisaccade, and memory saccade tests.
We did not find significant differences between iPD and L2PD. Compared to controls, PD patients displayed widespread oculomotor deficits including larger microsaccades, hypometric vertical prosaccades, increased latencies in all tests, and lower percentages of successful antisaccades and memory saccades. Non-carrier relatives showed oculomotor changes with parkinsonian features, such as fixation instability and hypometric vertical saccades. Asymptomatic carriers shared multiple similarities with PD, including signs of unstable fixation and hypometric vertical prosaccades; however, they were able to reach percentages of successful antisaccade and memory saccades similar to controls, although at the expense of longer latencies. Classification accuracy of significant oculomotor parameters to differentiate asymptomatic carriers from HCs ranged from 0.68 to 0.74, with BCEA, a marker of global fixation instability, being the parameter with the greatest classification accuracy.
iPD and LRRK2-G2019S PD patients do not seem to display a differential oculomotor profile. Several oculomotor changes in asymptomatic carriers of LRRK2 mutations could be considered premotor biomarkers.
Patient and Public Involvement and Engagement in the Development of a Platform Clinical Trial for Parkinson's Disease: An Evaluation Protocol.
Journal Parkinsons DiseasePatient and public involvement and engagement (PPIE) in the design of trials is important, as participant experience critically impacts delivery. The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative is a UK consortium designing a platform trial for disease modifying therapies in PD.
The integration of PPIE in all aspects of trial design and its evaluation throughout the project.
PwP and care partners were recruited to a PPIE working group (WG) via UK Parkinson's charities, investigator patient groups and participants of a Delphi study on trial design. They are supported by charity representatives, trial delivery experts, researchers and core project team members. PPIE is fully embedded within the consortium's five other WGs and steering group. The group's terms of reference, processes for effective working and PPIE evaluation were co-developed with PPIE contributors.
11 PwP and 4 care partners have supported the PPIE WG and contributed to the development of processes for effective working. A mixed methods research-in-action study is ongoing to evaluate PPIE within the consortium. This includes the Patient Engagement in Research Scale -a quantitative PPIE quality measure; semi-structured interviews -identifying areas for improvement and overall impressions of involvement; process fidelity- recording adherence; project documentation review - identifying impact of PPIE on project outputs.
We provide a practical example of PPIE in complex projects. Evaluating feasibility, experiences and impact of PPIE involvement in EJS ACT-PD will inform similar programs on effective strategies. This will help enable future patient-centered research.
Oscillation-specific nodal differences in Parkinson's disease patients with anxiety.
Journal Parkinsons DiseaseParkinson's disease (PD) is a common neurodegenerative disorder that is predominantly known for its motor symptoms but is also accompanied by non-motor symptoms, including anxiety.
The underlying neurobiological substrates and brain network changes associated with comorbid anxiety in PD require further exploration.
An analysis of oscillation-specific nodal properties in patients with and without anxiety was conducted using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory. We used a band-pass filtering approach to differentiate oscillatory frequency bands for subsequent functional connectivity (FC) and graph analyses.
The study included 68 non-anxiety PD (naPD) patients, 62 anxiety PD (aPD) patients, and 64 healthy controls (NC). Analyses of nodal betweenness centrality (BC), degree centrality (DC), and efficiency were conducted across multiple frequency bands. The findings indicated no significant differences in BC among naPD, aPD, and NC within the 0.01-0.08 Hz frequency range. However, we observed a specific reduction in BC at narrower frequency ranges in aPD patients, as well as differing patterns of change in DC and efficiency, which are believed to reflect the neurophysiological bases of anxiety symptoms in PD.
Differential oscillation-specific nodal characteristics have been identified in PD patients with anxiety, suggesting potential dysregulations in brain network dynamics. These findings emphasize the complexity of brain network alterations in anxiety-associated PD and identify oscillatory frequencies as potential biomarkers. The study highlights the importance of considering oscillatory frequency bands in the analysis of brain network changes.
Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant.
"Movement Disorders Clinical PracticeGenetic syndromes of hyperkinetic movement disorders associated with epileptic encephalopathy and intellectual disability are becoming increasingly recognized. Recently, a de novo heterozygous NACC1 (nucleus accumbens-associated 1) missense variant was described in a patient cohort including one patient with a combined mitochondrial oxidative phosphorylation (OXPHOS) deficiency.
The objective is to characterize the movement disorder in affected patients with the recurrent c.892C>T NACC1 variant and study the NACC1 protein and mitochondrial function at the cellular level.
The movement disorder was analyzed on four patients with the NACC1 c.892C>T (p.Arg298Trp) variant. Studies on NACC1 protein and mitochondrial function were performed on patient-derived fibroblasts.
All patients had a generalized hyperkinetic movement disorder with chorea and dystonia, which occurred cyclically and during sleep. Complex I was found altered, whereas the other OXPHOS enzymes and the mitochondria network seemed intact in one patient.
The movement disorder is a prominent feature of NACC1-related disease.
