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Handbook of Clinical Neurology 2021This chapter provides a review of mood, emotional disorders, and emotion processing deficits associated with diseases that cause movement disorders, including... (Review)
Review
This chapter provides a review of mood, emotional disorders, and emotion processing deficits associated with diseases that cause movement disorders, including Parkinson's disease, Lewy body dementia, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia with parkinsonism, Huntington's disease, essential tremor, dystonia, and tardive dyskinesia. For each disorder, a clinical description of the common signs and symptoms, disease progression, and epidemiology is provided. Then the mood and emotional disorders associated with each of these diseases are described and discussed in terms of clinical presentation, incidence, prevalence, and alterations in quality of life. Alterations of emotion communication, such as affective speech prosody and facial emotional expression, associated with these disorders are also discussed. In addition, if applicable, deficits in gestural and lexical/verbal emotion are reviewed. Throughout the chapter, the relationships among mood and emotional disorders, alterations of emotional experiences, social communication, and quality of life, as well as treatment, are emphasized.
Topics: Humans; Huntington Disease; Movement Disorders; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Quality of Life
PubMed: 34389117
DOI: 10.1016/B978-0-12-822290-4.00015-3 -
Movement Disorders : Official Journal... Dec 2023Excessive glutamatergic transmission in the striatum is implicated in Parkinson's disease (PD) progression. Astrocytes maintain glutamate homeostasis, protecting from...
BACKGROUND
Excessive glutamatergic transmission in the striatum is implicated in Parkinson's disease (PD) progression. Astrocytes maintain glutamate homeostasis, protecting from excitotoxicity through the glutamate-aspartate transporter (GLAST), whose alterations have been reported in PD. Noninvasive brain stimulation using intermittent theta-burst stimulation (iTBS) acts on striatal neurons and glia, inducing neuromodulatory effects and functional recovery in experimental parkinsonism.
OBJECTIVE
Because PD is associated with altered astrocyte function, we hypothesized that acute iTBS, known to rescue striatal glutamatergic transmission, exerts regional- and cell-specific effects through modulation of glial functions.
METHODS
6-Hydroxydopamine-lesioned rats were exposed to acute iTBS, and the areas predicted to be more responsive by a biophysical, hyper-realistic computational model that faithfully reconstructs the experimental setting were analyzed. The effects of iTBS on glial cells and motor behavior were evaluated by molecular and morphological analyses, and CatWalk and Stepping test, respectively.
RESULTS
As predicted by the model, the hippocampus, cerebellum, and striatum displayed a marked c-FOS activation after iTBS, with the striatum showing specific morphological and molecular changes in the astrocytes, decreased phospho-CREB levels, and recovery of GLAST. Striatal-dependent motor performances were also significantly improved.
CONCLUSION
These data uncover an unknown iTBS effect on astrocytes, advancing the understanding of the complex mechanisms involved in TMS-mediated functional recovery. Data on numerical dosimetry, obtained with a degree of anatomical details never before considered and validated by the biological findings, provide a framework to predict the electric-field induced in different specific brain areas and associate it with functional and molecular changes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Rats; Animals; Astrocytes; Transcranial Magnetic Stimulation; Parkinsonian Disorders; Parkinson Disease; Corpus Striatum; Magnetic Phenomena
PubMed: 37700489
DOI: 10.1002/mds.29599 -
Parkinsonism & Related Disorders May 2024Our ability to define, understand, and classify Parkinson's disease (PD) has undergone significant changes since the disorder was first described in 1817. Clinical... (Review)
Review
Our ability to define, understand, and classify Parkinson's disease (PD) has undergone significant changes since the disorder was first described in 1817. Clinical features and neuropathologic signatures can now be supplemented by in-vivo interrogation of genetic and biological substrates of disease, offering great opportunity for further refining the diagnosis of PD. In this mini-review, we discuss the historical perspectives which shaped our thinking surrounding the definition and diagnosis of PD. We highlight the clinical, genetic, pathologic and biologic diversity which underpins the condition, and proceed to discuss how recent developments in our ability to define biologic and pathologic substrates of disease might impact PD definition, diagnosis, individualised prognostication, and personalised clinical care. We argue that Parkinson's 'disease', as currently diagnosed in the clinic, is actually a syndrome. It is the outward manifestation of any array of potential dysfunctional biologic processes, neuropathological changes, and disease aetiologies, which culminate in common outward clinical features which we term PD; each person has their own unique disease, which we can now define with increasing precision. This is an exciting time in PD research and clinical care. Our ability to refine the clinical diagnosis of PD, incorporating in-vivo assessments of disease biology, neuropathology, and neurogenetics may well herald the era of biologically-based, precision medicine approaches PD management. With this however comes a number of challenges, including how to integrate these technologies into clinical practice in a way which is acceptable to patients, promotes meaningful changes to care, and minimises health economic impact.
Topics: Humans; Parkinson Disease
PubMed: 38360507
DOI: 10.1016/j.parkreldis.2024.106041 -
Canadian Family Physician Medecin de... Jan 2023To provide family physicians an updated approach to the diagnosis of Parkinson disease (PD).
OBJECTIVE
To provide family physicians an updated approach to the diagnosis of Parkinson disease (PD).
SOURCES OF INFORMATION
Published guidelines on the diagnosis and management of PD were reviewed. Database searches were conducted to retrieve relevant research articles published between 2011 and 2021. Evidence levels ranged from I to III.
MAIN MESSAGE
Diagnosis of PD is predominantly clinical. Family physicians should evaluate patients for specific features of parkinsonism, then determine whether symptoms are attributable to PD. Levodopa trials can be used to help confirm the diagnosis and alleviate motor symptoms of PD. "Red flag" features and absence of response to levodopa may point to other causes of parkinsonism and prompt more urgent referral.
CONCLUSION
Access to neurologists and specialized clinics varies, and Canadian family physicians can be important players in facilitating early and accurate diagnosis of PD. Applying an organized approach to diagnosis and considering motor and nonmotor symptoms can greatly benefit patients with PD. Part 2 in this series will review management of PD.
Topics: Humans; Parkinson Disease; Levodopa; Canada; Parkinsonian Disorders; Patients
PubMed: 36693741
DOI: 10.46747/cfp.690120 -
Movement Disorders : Official Journal... Sep 2023PREDICT-PD is a United Kingdom population-based study aiming to stratify individuals for future Parkinson's disease (PD) using a risk algorithm. (Meta-Analysis)
Meta-Analysis
BACKGROUND
PREDICT-PD is a United Kingdom population-based study aiming to stratify individuals for future Parkinson's disease (PD) using a risk algorithm.
METHODS
A randomly selected, representative sample of participants in PREDICT-PD were examined using several motor assessments, including the motor section of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-III, at baseline (2012) and after an average of 6 years of follow-up. We checked for new PD diagnoses in participants seen at baseline and examined the association between risk scores and incident sub-threshold parkinsonism, motor decline (increasing ≥5 points in MDS-UPDRS-III) and single motor domains in the MDS-UPDRS-III. We replicated analyses in two independent datasets (Bruneck and Parkinson's Progression Markers Initiative [PPMI]).
RESULTS
After 6 years of follow-up, the PREDICT-PD higher-risk group (n = 33) had a greater motor decline compared with the lower-risk group (n = 95) (30% vs. 12.5%, P = 0.031). Two participants (both considered higher risk at baseline) were given a diagnosis of PD during follow-up, with motor signs emerging between 2 and 5 years before diagnosis. A meta-analysis of data from PREDICT-PD, Bruneck, and PPMI showed an association between PD risk estimates and incident sub-threshold parkinsonism (odds ratio [OR], 2.01 [95% confidence interval (CI), 1.55-2.61]), as well as new onset bradykinesia (OR, 1.69 [95% CI, 1.33-2.16]) and action tremor (OR, 1.61 [95% CI, 1.30-1.98]).
CONCLUSIONS
Risk estimates using the PREDICT-PD algorithm were associated with the occurrence of sub-threshold parkinsonism, including bradykinesia and action tremor. The algorithm could also identify individuals whose motor examination experience a decline over time. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; Parkinson Disease; Tremor; Hypokinesia; Mental Status and Dementia Tests; Algorithms; Disease Progression
PubMed: 37317903
DOI: 10.1002/mds.29496 -
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 -
Age and Ageing Oct 2023Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Ageing is considered to be the greatest risk factor for PD, with...
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Ageing is considered to be the greatest risk factor for PD, with a complex interplay between genetics and the environment. With population ageing, the prevalence of PD is expected to escalate worldwide; thus, it is of utmost importance to reduce the burden of PD. To date, there are no therapies to cure the disease, and current treatment strategies focus on the management of symptoms. Older adults often have multiple chronic diseases and geriatric syndromes, which further complicates the management of PD. Healthcare systems and care models necessary to address the broad needs of older PD patients are largely unavailable. In this New Horizon article, we discuss various aspects of PD from an ageing perspective, including disease management. We highlight recent advancements in PD therapies and discuss new care models with the potential to improve patient's quality of life.
Topics: Humans; Aged; Parkinson Disease; Quality of Life; Aging
PubMed: 37847793
DOI: 10.1093/ageing/afad186 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2024Evaluation of nocturia and its relationship with clinical characteristics of Parkinson's disease (PD) and dopaminergic therapy.
OBJECTIVE
Evaluation of nocturia and its relationship with clinical characteristics of Parkinson's disease (PD) and dopaminergic therapy.
MATERIAL AND METHODS
One hundred and thirteen patients with PD of I-III Hoehn and Yahr stage (H&Y) were examined using the following scales: IPSS, including nocturia domain, UPDRS, Sch&En, PDQ-39, MMSE, FAB BDI, STAI-S and STAI-T, PFS-16, NMSQuest, GDSS, GSRS, and orthotest.
RESULTS
Nocturia was detected in 93 patients. It depended on the age of the patients (rS=0.345; <0.001) and was more spread among women (=0.002). We obtained positive correlations of nocturia (<0.05) with: PDQ-39 (rS=0.296), H&Y (rS=0.223), UPDRS (rS=0.265) and its items (speech, walking disorders, standing up from chair, posture and postural stability), NMSQ (rS=0.318), FAB (rS= -0.359), BDI, STAI-S and STAI-T, PFS-16, gastrointestinal parameters and blood pressure in the supine position. No significant effect of dopaminergic therapy on the severity of nocturia was found. According to regression analysis (stepwise method), predictors of nocturia are depression, higher lying blood pressure, constipation and postural instability (R2=0.474).
CONCLUSIONS
Nocturia is the most common urological symptom in patients with PD and it significantly reduces the quality of life starting from the early stages of the disease. Nocturia increases as PD progresses, it is independent of dopaminergic medications, and it is directly associated with a number of parkinsonian symptoms (postural, frontal cognitive, affective and autonomic), which are partly dopamine-resistant. This indicates the common pathogenesis of nocturia and other symptoms of PD and the significant influence of polytransmitter imbalance.
Topics: Humans; Parkinson Disease; Female; Nocturia; Male; Aged; Middle Aged; Severity of Illness Index; Quality of Life; Aged, 80 and over
PubMed: 38676677
DOI: 10.17116/jnevro202412404148