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International Review of Neurobiology 2023Parkinsonism and dystonia co-occur across many movement disorders and are most encountered in the setting of Parkinson's disease. Here we aim to explore the shared...
Parkinsonism and dystonia co-occur across many movement disorders and are most encountered in the setting of Parkinson's disease. Here we aim to explore the shared neurobiological underpinnings of dystonia and parkinsonism through the clinical lens of the conditions in which these movement disorders can be seen together. Foregrounding the discussion, we briefly review the circuits of the motor system and the neuroanatomical and neurophysiological aspects of motor control and highlight their relevance to the proposed pathophysiology of parkinsonism and dystonia. Insight into shared biology is then sought from dystonia occurring in PD and other forms of parkinsonism including those disorders in which both can be co-expressed simultaneously. We organize these within a biological schema along with important questions to be addressed in this space.
Topics: Humans; Parkinson Disease; Dystonia; Dystonic Disorders; Parkinsonian Disorders; Biology
PubMed: 37482398
DOI: 10.1016/bs.irn.2023.05.001 -
Annals of Neurology Jun 2023Cerebral small vessel disease (SVD) is associated with motor impairments and parkinsonian signs cross-sectionally, however, there are little longitudinal data on whether...
OBJECTIVE
Cerebral small vessel disease (SVD) is associated with motor impairments and parkinsonian signs cross-sectionally, however, there are little longitudinal data on whether SVD increases risk of incident parkinsonism itself. We investigated the relation between baseline SVD severity as well as SVD progression, and incident parkinsonism over a follow-up of 14 years.
METHODS
This study included 503 participants with SVD, and without parkinsonism at baseline, from the RUN DMC prospective cohort study. Baseline inclusion was performed in 2006 and follow-up took place in 2011, 2015, and 2020, including magnetic resonance imaging (MRI) and motor assessments. Parkinsonism was diagnosed according to the UK Brain Bank criteria, and stratified into vascular parkinsonism (VaP) and idiopathic Parkinson's disease (IPD). Linear mixed-effect models were constructed to estimate individual rate changes of MRI-characteristics.
RESULTS
Follow-up for incident parkinsonism was near-complete (99%). In total, 51 (10.2%) participants developed parkinsonism (33 VaP, 17 IPD, and 1 progressive supranuclear palsy). Patients with incident VaP had higher SVD burden compared with patients with IPD. Higher baseline white matter hyperintensities (hazard ratio [HR] = 1.46 per 1-SD increase, 95% confidence interval [CI] = 1.21-1.78), peak width of skeletonized mean diffusivity (HR = 1.66 per 1-SD increase, 95% CI = 1.34-2.05), and presence of lacunes (HR = 1.84, 95% CI = 0.99-3.42) were associated with increased risk of all-cause parkinsonism. Incident lacunes were associated with incident VaP (HR = 4.64, 95% CI = 1.32-16.32).
INTERPRETATION
Both baseline SVD severity and SVD progression are independently associated with long-term parkinsonism. Our findings indicate a causal role of SVD in parkinsonism. Future studies are needed to examine the underlying pathophysiology of this relation. ANN NEUROL 2023;93:1130-1141.
Topics: Humans; Prospective Studies; Parkinsonian Disorders; Cerebral Small Vessel Diseases; Brain; Parkinson Disease; Magnetic Resonance Imaging; Disease Progression
PubMed: 36762437
DOI: 10.1002/ana.26615 -
Journal of Neural Transmission (Vienna,... Sep 2022To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is... (Review)
Review
To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is already advanced. However, disease modification or neuroprotection, is considered to be most effective before marked neurodegeneration has occurred. In recent years, early clinical or prodromal stages of Parkinson syndromes came into focus. Moreover, subtypes of distinct diseases will allow predictions of the individual course of the diseases more precisely. Thereby, patients will be enrolled into clinical trials with more specific disease entities and endpoints. Furthermore, novel fluid and imaging biomarkers that allow biochemical diagnoses are under development. These will lead to earlier diagnoses and earlier therapy in the future as consequence. Furthermore, therapeutic approaches will take the underlying neuropathological process of neurodegenerative Parkinson syndromes more specific into account. Specifically, future therapies will target the aggregation of aggregation-prone proteins such as alpha-synuclein and tau, the degradation of pathological aggregates, and the spreading of pathological protein aggregates throughout the brain. Many of these approaches are already in (pre)clinical development. In addition, anti-inflammatory approaches are in development. Furthermore, drug-repurposing is a feasible approach to shorten the developmental process of new drugs.
Topics: Biomarkers; Brain; Humans; Parkinson Disease; Parkinsonian Disorders; Supranuclear Palsy, Progressive
PubMed: 35695938
DOI: 10.1007/s00702-022-02520-6 -
International Review of Neurobiology 2017The term palliative care (PC) is defined as a collection of interventions and strategies that helps to improve and sustain the quality of life of patients and caregivers... (Review)
Review
The term palliative care (PC) is defined as a collection of interventions and strategies that helps to improve and sustain the quality of life of patients and caregivers in situations and scenarios associated with life-threatening illness. This is usually implemented by means of early identification and treatment of relevant motor and nonmotor issues such as pain, sleep, and autonomic dysfunction, dementia, and depression. In addition, a holistic PC program also includes delivery of physical, psychosocial, and spiritual support. PC as a specific discipline, as well as a treatment strategy for long-term neurological conditions such as Parkinson's disease (PD), is relatively new, but very important as neurodegenerative disorders in the United Kingdom alone affects approximately 10 million people and there are over 130,000 people with PD. With longer life expectancy, the burden of long duration and late stage PD is even more evident, bringing in focus the need for PC. However, the concept of PC in PD is still poorly defined and although there are pockets of excellence, the strategy is poorly implemented into routine clinical practice. The variable progressive nature of the disease, the heterogeneity of clinical subtypes, and also the burden of nonmotor symptoms create challenges for effective PC delivery in PD, but recent clinical trials have started addressing PC in PD and are to be welcomed.
Topics: Autonomic Nervous System Diseases; Depression; Humans; Pain; Pain Management; Palliative Care; Parkinson Disease; Parkinsonian Disorders; Quality of Life; Sleep Wake Disorders
PubMed: 28805571
DOI: 10.1016/bs.irn.2017.05.014 -
Journal of Parkinson's Disease 2023Little is known about the burden of parkinsonism and Parkinson's disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is...
BACKGROUND
Little is known about the burden of parkinsonism and Parkinson's disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis.
OBJECTIVE
The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries.
METHODS
12,865 participants aged 65 years and older from the 10/66 population-based cohort study were analysed. Baseline assessments were conducted in 2003-2007 and followed-up 4 years later. Parkinsonism and PD were defined using current clinical criteria or self-reported diagnosis. Logistic regression models assessed the association between parkinsonism/PD with baseline health service use (community-based care or hospitalisation in the last 3 months) and Cox proportional hazards regression models with incident dependency (subjective assessment by interviewer based on informant interview) and mortality. Separate analyses for each country were combined via fixed effect meta-analysis.
RESULTS
At baseline, the prevalence of parkinsonism and PD was 7.9% (n = 934) and 2.6% (n = 317), respectively. Only parkinsonism was associated with hospital admission at baseline (OR 1.89, 95% CI 1.30-2.74). Among 7,296 participants without dependency at baseline, parkinsonism (HR 2.34, 95% CI 1.81-3.03) and PD (2.10, 1.37-3.24) were associated with incident dependency. Among 10,315 participants with vital status, parkinsonism (1.73, 1.50-1.99) and PD (1.38, 1.07-1.78) were associated with mortality. The Higgins I2 tests showed low to moderate levels of heterogeneity across countries.
CONCLUSIONS
Our findings show that older people with parkinsonism or PD living in Latin America have higher risks of developing dependency and mortality but may have limited access to health services.
Topics: Aged; Humans; Cohort Studies; Latin America; Parkinson Disease; Parkinsonian Disorders; Patient Acceptance of Health Care
PubMed: 37742660
DOI: 10.3233/JPD-230114 -
Brain : a Journal of Neurology Jul 2019Sleep disturbances may signal presence of prodromal parkinsonism, including Parkinson's disease. Whether general sleep quality or duration in otherwise healthy subjects...
Sleep disturbances may signal presence of prodromal parkinsonism, including Parkinson's disease. Whether general sleep quality or duration in otherwise healthy subjects is related to the risk of parkinsonism remains unclear. We hypothesized that both worse self-reported sleep quality and duration, as well as a longitudinal deterioration in these measures, are associated with the risk of parkinsonism, including Parkinson's disease. In the prospective population-based Rotterdam Study, we assessed sleep quality and duration with the Pittsburgh Sleep Quality Index in 7726 subjects (mean age 65 years, 57% female) between 2002 and 2008, and again in 5450 subjects between 2009 and 2014. Participants were followed until 2015 for a diagnosis of parkinsonism and Parkinson's disease. Outcomes were assessed using multiple modalities: interviews, physical examination, and continuous monitoring of pharmacy records and medical records of general practitioners. We used Cox regression to associate sleep, and changes in sleep over time, with incident parkinsonism and Parkinson's disease, adjusting for age, sex, education and smoking status. Over 64 855 person-years in 13 years of follow-up (mean: 8.4 years), 75 participants developed parkinsonism, of whom 47 developed Parkinson's disease. We showed that within the first 2 years of follow-up, worse sleep quality {hazard ratio (HR) 2.38 per standard deviation increase [95% confidence interval (CI 0.91-6.23)]} and shorter sleep duration [HR 0.61 per standard deviation increase (95% CI 0.31-1.21)] related to a higher risk of parkinsonism. Associations of worse sleep quality [HR 3.86 (95% CI 1.19-12.47)] and shorter sleep duration [HR 0.48 (95% CI 0.23-0.99)] with Parkinson's disease were more pronounced, and statistically significant, compared to parkinsonism. This increased risk disappeared with longer follow-up duration. Worsening of sleep quality [HR 1.76 per standard deviation increase (95% CI 1.12-2.78)], as well as shortening of sleep duration [HR 1.72 per standard deviation decrease (95% CI 1.08-2.72)], were related to Parkinson's disease risk in the subsequent 6 years. Therefore, we argue that in the general population, deterioration of sleep quality and duration are markers of the prodromal phase of parkinsonism, including Parkinson's disease.
Topics: Aged; Comorbidity; Disease Progression; Female; Humans; Longitudinal Studies; Male; Middle Aged; Netherlands; Parkinson Disease; Parkinsonian Disorders; Prodromal Symptoms; Prospective Studies; Risk Factors; Sleep Wake Disorders; Time Factors
PubMed: 31038176
DOI: 10.1093/brain/awz113 -
Current Neurology and Neuroscience... Sep 2018Patients with Parkinson's disease (PD) often display gastrointestinal and genitourinary autonomic symptoms years or even decades prior to diagnosis. These symptoms are... (Review)
Review
PURPOSE OF REVIEW
Patients with Parkinson's disease (PD) often display gastrointestinal and genitourinary autonomic symptoms years or even decades prior to diagnosis. These symptoms are thought to be caused in part by pathological α-synuclein inclusions in the peripheral autonomic and enteric nervous systems. It has been proposed that the initial α-synuclein aggregation may in some PD patients originate in peripheral nerve terminals and then spread centripetally to the spinal cord and brainstem. In vivo imaging methods can directly quantify the degeneration of the autonomic nervous system as well as the functional consequences such as perturbed motility. Here, we review the methodological principles of these imaging techniques and the major findings in patients with PD and atypical parkinsonism.
RECENT FINDINGS
Loss of sympathetic and parasympathetic nerve terminals in PD can be visualized using radiotracer imaging, including I-MIBG scintigraphy, and F-dopamine and C-donepezil PET. Recently, ultrasonographical studies disclosed reduced diameter of the vagal nerves in PD patients. Radiological and radioisotope techniques have demonstrated dysmotility and prolonged transit time throughout all subdivisions of the gastrointestinal tract in PD. The prevalence of objective dysfunction as measured with these imaging methods is often considerably higher compared to the prevalence of subjective symptoms experienced by the patients. Degeneration of the autonomic nervous system may play a key role in the pathogenesis of PD. In vivo imaging techniques provide powerful and noninvasive tools to quantify the degree and extent of this degeneration and its functional consequences.
Topics: Autonomic Nervous System; Humans; Parkinson Disease; Parkinsonian Disorders; Positron-Emission Tomography; Radionuclide Imaging; Tomography, Emission-Computed, Single-Photon
PubMed: 30232650
DOI: 10.1007/s11910-018-0889-4 -
Movement Disorders : Official Journal... Apr 2023Development of disease-modifying therapeutic trials of progressive supranuclear palsy (PSP) urges the need for sensitive fluid biomarkers.
BACKGROUND
Development of disease-modifying therapeutic trials of progressive supranuclear palsy (PSP) urges the need for sensitive fluid biomarkers.
OBJECTIVES
The objectives of this study were to explore the utility of plasma biomarkers in the diagnosis, differential diagnosis, and assessment of disease severity, brain atrophy, and tau deposition in PSP.
METHODS
Plasma biomarkers were measured using a single-molecule array in a cohort composed of patients with PSP, Parkinson's disease (PD), multiple system atrophy with predominant parkinsonism (MSA-P), and healthy controls (HCs).
RESULTS
Plasma neurofilament light chain (NfL) outperformed other plasma makers (ie, glial fibrillary acidic protein [GFAP], phosphorylated-tau 181 [p-tau181], amyloid-β 1-40, amyloid-β 1-42) in identifying PSP from HC (area under the curve [AUC] = 0.904) and from MSA-P (AUC = 0.711). Plasma GFAP aided in distinguishing PSP from HC (AUC = 0.774) and from MSA-P (AUC = 0.832). It correlated with brainstem atrophy and higher regional tau accumulation. However, plasma p-tau181 neither helped in diagnosis nor was it associated with clinical or neuroimaging measures.
CONCLUSIONS
Plasma NfL and GFAP showed different values in differentiating PSP from HC or controls with other forms of neurodegenerative parkinsonism and detecting disease severity, brain atrophy, or tau deposition in PSP. © 2023 International Parkinson and Movement Disorder Society.
Topics: Humans; Biomarkers; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Positron-Emission Tomography; Supranuclear Palsy, Progressive; tau Proteins
PubMed: 36781585
DOI: 10.1002/mds.29339 -
Parkinsonism & Related Disorders Jan 2018The question whether DLB and PDD are distinct disorders has been debated in several forums. The two disorders, once parkinsonism is present in DLB, cannot be... (Review)
Review
INTRODUCTION
The question whether DLB and PDD are distinct disorders has been debated in several forums. The two disorders, once parkinsonism is present in DLB, cannot be distinguished on clinical or pathological grounds. The conundrum exists for those DLB patients who do not yet have parkinsonism, and raises the parallel with patients who have Rapid Eye Movement Behavior Disorder but have not yet manifested parkinsonian signs.
METHODS
A literature review was summarized to justify classification as a single disorder.
RESULTS
Most clinical observations and trials point to these disorders, once parkinsonism is present in DLB, are identical.
CONCLUSION
This article notes the advantage to clinical research and treatment by considering these two syndromes as the same so that medications approved for PDD and for PD psychosis can be extended to DLB patients and that resources for PD research and support can be also used for DLB.
Topics: Biomedical Research; Humans; Lewy Body Disease; Parkinson Disease
PubMed: 28756177
DOI: 10.1016/j.parkreldis.2017.07.013 -
Journal of Parkinson's Disease 2023Sleep disturbances are common in parkinsonian disorders; however, whether sleep disorders affect individuals with early-onset parkinsonism and whether they differ from...
BACKGROUND
Sleep disturbances are common in parkinsonian disorders; however, whether sleep disorders affect individuals with early-onset parkinsonism and whether they differ from individuals with typical-onset parkinsonism is unknown.
OBJECTIVE
To compare the prevalence and incidence of sleep disorders before and after parkinsonian motor symptom onset between individuals with early onset parkinsonism (age ≤50 at motor symptom onset) and typical-onset parkinsonism (age >50 at motor symptom onset).
METHODS
We used a population-based, 1991 to 2015 incident-cohort study of parkinsonism including 38 patients with early-onset and 1,001 patients with typical-onset parkinsonism. Presence or absence and type of sleep disorder as well as the relationship between motor and sleep symptoms were abstracted from the medical records. Rates of sleep disorders before and after onset of parkinsonism were compared with logistic regression and Cox proportional hazards models.
RESULTS
The prevalence of sleep disorders prior to the onset of parkinsonism in early vs. typical parkinsonism (24% vs. 16% p = 0.19) and incidence of sleep disorders after parkinsonism onset (5.85 cases per 100 person-years vs. 4.11 cases per 100 person-years; HR 1.15 95% CI: 0.74-1.77) were similar between the two groups. Early-onset parkinsonism had a higher risk for developing post-motor insomnia compared with typical-onset parkinsonism (HR 1.73, 95% CI: 1.02-2.93); the risk for developing all other sleep disorders considered was similar between groups.
CONCLUSION
Sleep disorders are common in individuals with early-onset parkinsonism and occur with similar frequency to those with typical-onset parkinsonism, except for insomnia, which was more frequent in the early-onset group.
Topics: Humans; Cohort Studies; Parkinson Disease; Sleep Initiation and Maintenance Disorders; Parkinsonian Disorders; Sleep; Sleep Wake Disorders
PubMed: 37742659
DOI: 10.3233/JPD-230045