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Parkinsonism & Related Disorders Sep 2023The human immunodeficiency virus (HIV) causes movement disorders in persons living with HIV (PLH). (Review)
Review
BACKGROUND
The human immunodeficiency virus (HIV) causes movement disorders in persons living with HIV (PLH).
OBJECTIVES AND METHODS
We conducted a systematic review on the spectrum of movement disorders in PLH using standard terms for each of the phenomenologies and HIV.
RESULTS
Movement disorders in PLH were commonly attributed to opportunistic infections (OI), dopamine receptor blockade reactions, HIV-associated dementia (HAD), presented during seroconversion, developed due to drug reactions or antiretroviral therapy (ART) itself and lastly, movement disorders occurred as a consequence of the HIV-virus. Parkinsonism in ART naïve PLH was associated with shorter survival, however when Parkinsonism presented in PLH on ART, the syndrome was indistinguishable from Idiopathic Parkinson's disease and responded to therapy. Tremor was often postural due to HAD, drugs or OI. Generalized chorea was most frequent in HIV encephalopathy and toxoplasmosis gondii caused most cases of hemichorea. Ataxia was strongly associated with JCV infection, ART efavirenz toxicity or due to HIV itself. Dystonia was reported in HAD, secondary to drugs and atypical facial dystonias. Both cortical/subcortical and segmental/spinal origin myoclonus were noted mainly associated with HAD. In patients with HIV related opsoclonus-myoclonus-ataxia-syndrome, seroconversion illness was the commonest cause of followed by IRIS and CSF HIV viral escape phenomenon.
CONCLUSIONS
Aetiology of movement disorders in PLH depend on the treatment state. Untreated, PLH are prone to develop OI and HAD and movement disorders. However, as the number of PLH on ART increase and survive longer, the frequency of ART and non-AIDS related complications are likely to increase.
Topics: Humans; HIV; Myoclonus; Movement Disorders; HIV Infections; Parkinson Disease; Parkinsonian Disorders; Ataxia
PubMed: 37532621
DOI: 10.1016/j.parkreldis.2023.105774 -
Movement Disorders : Official Journal... May 2021Parkinson's disease (PD) is a genetically complex neurodegenerative disease with ~20 genes known to contain mutations that cause PD or atypical parkinsonism. Large-scale...
BACKGROUND
Parkinson's disease (PD) is a genetically complex neurodegenerative disease with ~20 genes known to contain mutations that cause PD or atypical parkinsonism. Large-scale next-generation sequencing projects have revolutionized genomics research. Applying these data to PD, many genes have been reported to contain putative disease-causing mutations. In most instances, however, the results remain quite limited and rather preliminary. Our aim was to assist researchers on their search for PD-risk genes and variant candidates with an easily accessible and open summary-level genomic data browser for the PD research community.
METHODS
Sequencing and imputed genotype data were obtained from multiple sources and harmonized and aggregated.
RESULTS
In total we included a total of 102,127 participants, including 28,453 PD cases, 1650 proxy cases, and 72,024 controls.
CONCLUSIONS
We present here the Parkinson's Disease Sequencing Browser: a Shiny-based web application that presents comprehensive summary-level frequency data from multiple large-scale genotyping and sequencing projects https://pdgenetics.shinyapps.io/VariantBrowser/. Published © 2021 This article is a U.S. Government work and is in the public domain in the USA. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: DNA; Humans; Mutation; Neurodegenerative Diseases; Parkinson Disease; Parkinsonian Disorders
PubMed: 33497488
DOI: 10.1002/mds.28488 -
Journal of Parkinson's Disease 2017The MDS-UPDRS (Movement Disorders Society - Unified Parkinson's Disease Rating Scale) is the most widely used scale for rating impairment in PD. Subscores measuring... (Review)
Review
BACKGROUND
The MDS-UPDRS (Movement Disorders Society - Unified Parkinson's Disease Rating Scale) is the most widely used scale for rating impairment in PD. Subscores measuring bradykinesia have low reliability that can be subject to rater variability. Novel technological tools can be used to overcome such issues.
OBJECTIVE
To systematically explore and describe the available technologies for measuring limb bradykinesia in PD that were published between 2006 and 2016.
METHODS
A systematic literature search using PubMed (MEDLINE), IEEE Xplore, Web of Science, Scopus and Engineering Village (Compendex and Inspec) databases was performed to identify relevant technologies published until 18 October 2016.
RESULTS
47 technologies assessing bradykinesia in PD were identified, 17 of which offered home and clinic-based assessment whilst 30 provided clinic-based assessment only. Of the eligible studies, 7 were validated in a PD patient population only, whilst 40 were tested in both PD and healthy control groups. 19 of the 47 technologies assessed bradykinesia only, whereas 28 assessed other parkinsonian features as well. 33 technologies have been described in additional PD-related studies, whereas 14 are not known to have been tested beyond the pilot phase.
CONCLUSION
Technology based tools offer advantages including objective motor assessment and home monitoring of symptoms, and can be used to assess response to intervention in clinical trials or routine care. This review provides an up-to-date repository and synthesis of the current literature regarding technology used for assessing limb bradykinesia in PD. The review also discusses the current trends with regards to technology and discusses future directions in development.
Topics: Biomedical Technology; Extremities; Humans; Hypokinesia; Neurology; Parkinson Disease
PubMed: 28222539
DOI: 10.3233/JPD-160878 -
Parkinsonism & Related Disorders Jan 2016Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Despite... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. PD is a complex syndrome with different clinical subtypes and a wide variability in disorder course. In order to deliver better clinical management of PD patients and discovery of novel therapies, there is an urgent need to find sensitive, specific, and reliable biomarkers. The development of biomarkers will not only help the scientific community to identify populations at risk, but also facilitate clinical diagnosis. Furthermore, these tools could monitor progression, which could ultimately deliver personalized therapeutic strategies. The field of biomarker discovery in PD has attracted significant attention and there have been numerous contributions in recent years. Although none of the parameters have been validated for clinical practice, some candidates hold promise. This review summarizes recent advances in the development of PD biomarkers and discusses new strategies for their utilization.
Topics: Animals; Biomarkers; Disease Progression; Humans; Neuroimaging; Parkinson Disease
PubMed: 26439946
DOI: 10.1016/j.parkreldis.2015.09.048 -
Journal of Parkinson's Disease 2015This review describes the oculo-visual problems likely to be encountered in Parkinson's disease (PD) with special reference to three questions: (1) are there visual... (Review)
Review
This review describes the oculo-visual problems likely to be encountered in Parkinson's disease (PD) with special reference to three questions: (1) are there visual symptoms characteristic of the prodromal phase of PD, (2) is PD dementia associated with specific visual changes, and (3) can visual symptoms help in the differential diagnosis of the parkinsonian syndromes, viz. PD, progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degeneration (CBD)? Oculo-visual dysfunction in PD can involve visual acuity, dynamic contrast sensitivity, colour discrimination, pupil reactivity, eye movement, motion perception, and visual processing speeds. In addition, disturbance of visuo-spatial orientation, facial recognition problems, and chronic visual hallucinations may be present. Prodromal features of PD may include autonomic system dysfunction potentially affecting pupil reactivity, abnormal colour vision, abnormal stereopsis associated with postural instability, defects in smooth pursuit eye movements, and deficits in visuo-motor adaptation, especially when accompanied by idiopathic rapid eye movement (REM) sleep behaviour disorder. PD dementia is associated with the exacerbation of many oculo-visual problems but those involving eye movements, visuo-spatial function, and visual hallucinations are most characteristic. Useful diagnostic features in differentiating the parkinsonian symptoms are the presence of visual hallucinations, visuo-spatial problems, and variation in saccadic eye movement dysfunction.
Topics: Humans; Ocular Motility Disorders; Parkinson Disease; Vision Disorders; Visual Perception
PubMed: 26599301
DOI: 10.3233/JPD-150686 -
International Journal of Molecular... Feb 2024Parkinson's disease (PD) is associated with various deficits in sensing and responding to reductions in oxygen availability (hypoxia). Here we summarize the evidence... (Review)
Review
Parkinson's disease (PD) is associated with various deficits in sensing and responding to reductions in oxygen availability (hypoxia). Here we summarize the evidence pointing to a central role of hypoxia in PD, discuss the relation of hypoxia and oxygen dependence with pathological hallmarks of PD, including mitochondrial dysfunction, dopaminergic vulnerability, and alpha-synuclein-related pathology, and highlight the link with cellular and systemic oxygen sensing. We describe cases suggesting that hypoxia may trigger Parkinsonian symptoms but also emphasize that the endogenous systems that protect from hypoxia can be harnessed to protect from PD. Finally, we provide examples of preclinical and clinical research substantiating this potential.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Parkinsonian Disorders; Dopaminergic Neurons; Hypoxia; Oxygen
PubMed: 38339038
DOI: 10.3390/ijms25031759 -
Journal of Biomedicine & Biotechnology 2012Parkinson's disease (PD) is a common disorder, and the diagnosis of Parkinson's disease is clinical and relies on the presence of characteristic motor symptoms. The... (Review)
Review
Parkinson's disease (PD) is a common disorder, and the diagnosis of Parkinson's disease is clinical and relies on the presence of characteristic motor symptoms. The accuracy of the clinical diagnosis of PD is still limited. Functional neuroimaging using SPECT technique is helpful in patients with first signs of parkinsonism. The changes detected may reflect the disease process itself and/or compensatory responses to the disease, or they may arise in association with disease- and/or treatment-related complications. This paper addresses the value of SPECT in early differential diagnosis of PD and its potential as a sensitive tool to assess the pathophysiology and progression, as well as the therapeutic efficacy of PD.
Topics: Brain Chemistry; Humans; Molecular Imaging; Parkinson Disease; Tomography, Emission-Computed, Single-Photon
PubMed: 22529704
DOI: 10.1155/2012/412486 -
Neurobiology of Disease Jan 2023The early differential diagnosis of Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), including corticobasal degeneration (CBD) and progressive...
The early differential diagnosis of Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), is challenging because of an overlap of clinical features and the lack of reliable biomarkers. Neural-derived extracellular vesicles (NDEVs) isolated from blood provide a window into the brain's biochemistry and may assist in distinguishing between PD and APS. We verified in a case-control study whether oligomeric α-Synuclein and Tau aggregates isolated from NDEVs could allow the differential diagnosis of these conditions. Blood sampling and clinical data, including disease duration, motor severity, global cognition, and levodopa equivalent daily dose (LEDD), were collected from patients with a diagnosis of either PD (n = 70), PSP (n = 21), or CBD (n = 19). NDEVs were isolated from serum by immunocapture using an antibody against the neuronal surface marker L1CAM; oligomeric α-Synuclein and aggregated Tau were measured by ELISA. NDEVs analyses showed that oligomeric α-Synuclein is significantly augmented in PD compared to APS, whereas Tau aggregates are significantly increased in APS compared to PD (p < 0.0001). ROC analyses showed that these two biomarkers have a "good" power of classification (p < 0.0001 for both proteins), with high sensitivity and specificity, with NDEVs concentration of Tau aggregates and oligomeric α-Synuclein being respectively the best biomarker for PD/PSP and PD/CBD diagnostic differentiation. Logistic and multiple regression analysis confirmed that NDEVs-derived oligomeric α-Synuclein and Tau aggregates differentiate PD from CBD and PSP (p < 0.001). Notably, a positive correlation between NDEVs oligomeric α-Synuclein and disease severity (disease duration, p = 0.023; Modified H&Y, p = 0.015; UPDRS motor scores, p = 0.004) was found in PD patients and, in these same patients, NDEVs Tau aggregates concentration inversely correlated with global cognitive scores (p = 0.043). A minimally invasive blood test measuring the concentration of α-synuclein and Tau aggregates in NDEVs can represent a promising tool to distinguish with high sensitivity and specificity PD from CBD or PSP patients. Optimization and validation of these data will be needed to confirm the diagnostic value of these biomarkers in distinguishing synucleinopathies from taupathies.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Case-Control Studies; Parkinsonian Disorders; Supranuclear Palsy, Progressive; Extracellular Vesicles; Biomarkers; tau Proteins
PubMed: 36481435
DOI: 10.1016/j.nbd.2022.105947 -
Journal of Parkinson's Disease 2015Parkinson's disease (PD) is currently clinically defined by a set of cardinal motor features centred on the presence of bradykinesia and at least one additional motor... (Review)
Review
Parkinson's disease (PD) is currently clinically defined by a set of cardinal motor features centred on the presence of bradykinesia and at least one additional motor symptom out of tremor, rigidity or postural instability. However, converging evidence from clinical, neuropathological, and imaging research suggests initiation of PD-specific pathology prior to appearance of these classical motor signs. This latent phase of neurodegeneration in PD is of particular relevance in relation to the development of disease-modifying or neuroprotective therapies which would require intervention at the earliest stages of disease. A key challenge in PD research, therefore, is to identify and validate markers for the preclinical and prodromal stages of the illness. Currently, several nonmotor symptoms have been associated with an increased risk to develop PD in otherwise healthy individuals and ongoing research is aimed at validating a variety of candidate PD biomarkers based on imaging, genetic, proteomic, or metabolomic signatures, supplemented by work on tissue markers accessible to minimally invasive biopsies. In fact, the recently defined MDS research criteria for prodromal PD have included combinations of risk and prodromal markers allowing to define target populations of future disease modification trials.
Topics: Biomarkers; Humans; Parkinson Disease; Prodromal Symptoms
PubMed: 26485429
DOI: 10.3233/JPD-150685 -
Biomolecules Jan 2023We investigated retinal structure changes in patients with Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and controls,...
We investigated retinal structure changes in patients with Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and controls, and explored the value of this method in differential diagnosis. Spectral domain optical coherence tomography (SD-OCT) was used to measure peripapillary retinal nerve fiber layer (pRNFL) thickness, and macular thickness and volume. PSP patients showed higher temporal pRNFL thickness than PD and MSA patients. Peripapillary RNFL thickness could be used for discriminating PSP from MSA and PD. PD and MSA patients showed retinal thinning in the foveal center circle and nasal inner sectors compared to controls. Macular thickness and volume could be used for discriminating MSA from PD. There were negative correlations between disease duration and OCT parameters in PD, MSA, and PSP, independent of age, sex ratio, and the side of the eye. PD and atypical parkinsonism correlate with specific patterns of retina alterations. OCT could be a biomarker for differential diagnosis and progression evaluation of parkinsonian syndrome.
Topics: Humans; Parkinson Disease; Retina; Parkinsonian Disorders; Retinal Degeneration; Multiple System Atrophy
PubMed: 36830588
DOI: 10.3390/biom13020218