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Tidsskrift For Den Norske Laegeforening... Feb 2017
Topics: Humans; Parkinson Disease; Parkinsonian Disorders; Terminology as Topic
PubMed: 28225240
DOI: 10.4045/tidsskr.16.0915 -
Journal of Parkinson's Disease 2023The Parkinson's disease (PD) research field has seen the advent of several promising biomarkers and a deeper understanding of the clinical features of the disease from... (Review)
Review
The Parkinson's disease (PD) research field has seen the advent of several promising biomarkers and a deeper understanding of the clinical features of the disease from the earliest stages of pathology to manifest disease. Despite progress, a biologically based PD staging system does not exist. Such staging would be a useful framework within which to model the disease, develop and validate biomarkers, guide therapeutic development, and inform clinical trials design. We propose that the presence of aggregated neuronal α-synuclein, dopaminergic neuron dysfunction/degeneration, and clinical signs and symptoms identifies a group of individuals that have Lewy body pathology, which in early stages manifests with what is now referred to as prodromal non-motor features and later stages with the manifestations of PD and related Lewy body diseases as defined by clinical diagnostic criteria. Based on the state of the field, we herein propose a definition and staging of PD based on biology. We present the biologic basis for such a staging system and review key assumptions and evidence that support the proposed approach. We identify gaps in knowledge and delineate crucial research priorities that will inform the ultimate integrated biologic staging system for PD.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Lewy Body Disease; Lewy Bodies; Nerve Degeneration; Biomarkers; Prodromal Symptoms; Biological Products
PubMed: 37066922
DOI: 10.3233/JPD-225111 -
Journal of Parkinson's Disease 2023The etiologies of Parkinson's disease (PD) remain unclear. Some, such as certain genetic mutations and head trauma, are widely known or easily identified. However, these... (Review)
Review
The etiologies of Parkinson's disease (PD) remain unclear. Some, such as certain genetic mutations and head trauma, are widely known or easily identified. However, these causes or risk factors do not account for the majority of cases. Other, less visible factors must be at play. Among these is a widely used industrial solvent and common environmental contaminant little recognized for its likely role in PD: trichloroethylene (TCE). TCE is a simple, six-atom molecule that can decaffeinate coffee, degrease metal parts, and dry clean clothes. The colorless chemical was first linked to parkinsonism in 1969. Since then, four case studies involving eight individuals have linked occupational exposure to TCE to PD. In addition, a small epidemiological study found that occupational or hobby exposure to the solvent was associated with a 500% increased risk of developing PD. In multiple animal studies, the chemical reproduces the pathological features of PD.Exposure is not confined to those who work with the chemical. TCE pollutes outdoor air, taints groundwater, and contaminates indoor air. The molecule, like radon, evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected. Despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited. Here, through a literature review and seven illustrative cases, we postulate that this ubiquitous chemical is contributing to the global rise of PD and that TCE is one of its invisible and highly preventable causes. Further research is now necessary to examine this hypothesis.
Topics: Animals; Trichloroethylene; Parkinson Disease; Solvents; Risk Factors
PubMed: 36938742
DOI: 10.3233/JPD-225047 -
Journal of Parkinson's Disease 2019Parkinson's disease (PD) is a highly heterogeneous disorder, which probably consists of multiple subtypes. Aggregation of misfolded alpha-synuclein and propagation of... (Review)
Review
Parkinson's disease (PD) is a highly heterogeneous disorder, which probably consists of multiple subtypes. Aggregation of misfolded alpha-synuclein and propagation of these proteinacious aggregates through interconnected neural networks is believed to be a crucial pathogenetic factor. It has been hypothesized that the initial pathological alpha-synuclein aggregates originate in the enteric or peripheral nervous system (PNS) and invade the central nervous system (CNS) via retrograde vagal transport. However, evidence from neuropathological studies suggests that not all PD patients can be reconciled with this hypothesis. Importantly, a small fraction of patients do not show pathology in the dorsal motor nucleus of the vagus. Here, it is hypothesized that PD can be divided into a PNS-first and a CNS-first subtype. The former is tightly associated with REM sleep behavior disorder (RBD) during the prodromal phase and is characterized by marked autonomic damage before involvement of the dopaminergic system. In contrast, the CNS-first phenotype is most often RBD-negative during the prodromal phase and characterized by nigrostriatal dopaminergic dysfunction prior to involvement of the autonomic PNS. The existence of these subtypes is supported by in vivo imaging studies of RBD-positive and RBD-negative patient groups and by histological evidence- reviewed herein. The present proposal provides a fresh hypothesis-generating framework for future studies into the etiopathogenesis of PD and seems capable of explaining a number of discrepant findings in the neuropathological literature.
Topics: Autonomic Nervous System; Central Nervous System; Dopamine; Humans; Parkinson Disease; Prodromal Symptoms; alpha-Synuclein
PubMed: 31498132
DOI: 10.3233/JPD-191721 -
Sensors (Basel, Switzerland) Feb 2020Rigidity is one of the cardinal symptoms of Parkinson´s disease (PD). Present in up 89% of cases, it is typically assessed with clinical scales. However, these...
Rigidity is one of the cardinal symptoms of Parkinson´s disease (PD). Present in up 89% of cases, it is typically assessed with clinical scales. However, these instruments show limitations due to their subjectivity and poor intra- and inter-rater reliability. To compile all of the objective quantitative methods used to assess rigidity in PD and to study their validity and reliability, a systematic review was conducted using the Web of Science, PubMed, and Scopus databases. Studies from January 1975 to June 2019 were included, all of which were written in English. The Strengthening the Reporting of observational studies in Epidemiology Statement (STROBE) checklist for observational studies was used to assess the methodological rigor of the included studies. Thirty-six studies were included. Rigidity was quantitatively assessed in three ways, using servomotors, inertial sensors, and biomechanical and neurophysiological study of muscles. All methods showed good validity and reliability, good correlation with clinical scales, and were useful for detecting rigidity and studying its evolution. People with PD exhibit higher values in terms of objective muscle stiffness than healthy controls. Rigidity depends on the angular velocity and articular amplitude of the mobilization applied. There are objective, valid, and reliable methods that can be used to quantitatively assess rigidity in people with PD.
Topics: Electromyography; Humans; Joints; Movement; Muscle Rigidity; Muscles; Observational Studies as Topic; Parkinson Disease
PubMed: 32041374
DOI: 10.3390/s20030880 -
Journal of Parkinson's Disease 2018Cognitive dysfunction is one of the most prevalent non-motor symptoms in Parkinson's disease (PD), often experienced as more debilitating for patients and caregivers...
BACKGROUND
Cognitive dysfunction is one of the most prevalent non-motor symptoms in Parkinson's disease (PD), often experienced as more debilitating for patients and caregivers than motor problems. Therefore, a deeper understanding of the course of cognitive decline and the identification of valid progression markers for Parkinson's disease dementia (PDD) is essential.
OBJECTIVE
This systematic review summarizes the current state of knowledge on cognitive decline over time by reporting effect sizes of cognitive changes in neuropsychological tests.
METHODS
1368 studies were identified by a PubMed database search and 25 studies by additionally scanning previous literature. After screening all records, including 69 full-text article reviews, 12 longitudinal studies on the progression of cognitive decline in PD met our criteria (e.g., sample size ≥50 patients).
RESULTS
Only a few studies monitored cognitive decline over a longer period (>4 years). Most studies focused on the evaluation of change in global cognitive state by use of the Mini-Mental State Examination, whereas the use of neuropsychological tests was highly heterogenic among studies. Only one study evaluated patients' cognitive performance in all specified domains (executive function, attention & working memory, memory, language, and visual-spatial function) allowing for diagnosis of cognitive impairment according to consensus guidelines. Medium to strong effect sizes could only be observed in studies with follow-up intervals of four years or longer.
CONCLUSIONS
The results emphasize the need for the assessment of larger PD cohorts over longer periods of follow-up with a comprehensive neuropsychological battery.
Topics: Attention; Cognition; Cognition Disorders; Disease Progression; Executive Function; Humans; Language; Memory, Short-Term; Neuropsychological Tests; Parkinson Disease
PubMed: 29914040
DOI: 10.3233/JPD-181306 -
Journal of Parkinson's Disease 2021In Parkinson's disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity...
BACKGROUND
In Parkinson's disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity with potential contribution for the knowledge of disease pathophysiology, natural history and therapeutic development. There have been many studies of PD subtypes but their impact remains unclear with limited application in research or clinical practice.
OBJECTIVE
To critically evaluate PD subtyping systems.
METHODS
We conducted a systematic review of PD subtypes, assessing the characteristics of the studies reporting a subtyping system for the first time. We completed a critical appraisal of their methodologic quality and clinical applicability using standardized checklists.
RESULTS
We included 38 studies. The majority were cross-sectional (n = 26, 68.4%), used a data-driven approach (n = 25, 65.8%), and non-clinical biomarkers were rarely used (n = 5, 13.1%). Motor characteristics were the domain most commonly reported to differentiate PD subtypes. Most of the studies did not achieve the top rating across items of a Methodologic Quality checklist. In a Clinical Applicability Checklist, the clinical importance of differences between subtypes, potential treatment implications and applicability to the general population were rated poorly, and subtype stability over time and prognostic value were largely unknown.
CONCLUSION
Subtyping studies undertaken to date have significant methodologic shortcomings and most have questionable clinical applicability and unknown biological relevance. The clinical and biological signature of PD may be unique to the individual, rendering PD resistant to meaningful cluster solutions. New approaches that acknowledge the individual-level heterogeneity and that are more aligned with personalized medicine are needed.
Topics: Humans; Parkinson Disease; Precision Medicine; Prognosis
PubMed: 33682731
DOI: 10.3233/JPD-202472 -
Journal of Parkinson's Disease 2017Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and effective treatment modality for selected patients with Parkinson's disease (PD). Since... (Review)
Review
Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and effective treatment modality for selected patients with Parkinson's disease (PD). Since its advent, systematic exploration of the effect of stimulation parameters including the stimulation intensity, frequency, and pulse width have been carried out to establish optimal therapeutic ranges. This review examines published data on these stimulation parameters in terms of efficacy of treatment and adverse effects. Altering stimulation intensity is the mainstay of titration in DBS programming via alterations in voltage or current settings, and is characterised by a lower efficacy threshold and a higher side effect threshold which define the therapeutic window. In addition, much work has been done in exploring the effects of frequency modulation, which may help patients with gait freezing and other axial symptoms. However, there is a paucity of data on the use of ultra-short pulse width settings which are now possible with technological advances. We also discuss current evidence for the use of novel programming techniques including directional and adaptive stimulation, and highlight areas for future research.
Topics: Deep Brain Stimulation; Humans; Parkinson Disease; Subthalamic Nucleus; Treatment Outcome
PubMed: 28505983
DOI: 10.3233/JPD-171077 -
Journal of Parkinson's Disease 2023Despite its devastating disease burden and alarming prevalence, the etiology of Parkinson's disease (PD) remains to be completely elucidated. PD is characterized by the... (Review)
Review
Despite its devastating disease burden and alarming prevalence, the etiology of Parkinson's disease (PD) remains to be completely elucidated. PD is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and this correlates with the accumulation of misfolded α-synuclein. While the aggregation of α-synuclein in the form of Lewy bodies or Lewy neurites is a well-established intraneuronal hallmark of the disease process, our understanding of the glial contribution to aberrant α-synuclein proteostasis is lacking. In this regard, restoring astrocyte function during early PD could offer a promising therapeutic avenue and understanding the involvement of astrocytes in handling/mishandling of α-synuclein is of particular interest. Here, we explore the growing body of scientific literature implicating aberrant astrocytic α-synuclein proteostasis with the seemingly inexorable pathological sequelae typifying PD. We also provide a perspective on how heterogeneity in the morphological relationship between astrocytes and neurons will need to be considered in the context of PD pathogenesis.
Topics: Astrocytes; alpha-Synuclein; Parkinson Disease; Humans; Animals; Protein Aggregates
PubMed: 38007674
DOI: 10.3233/JPD-230284 -
Tidsskrift For Den Norske Laegeforening... May 2024Parkinson's disease is characterised by the core motor symptoms: bradykinesia, rigidity and tremor. The disease also has a number of non-motor symptoms, such as visual... (Review)
Review
Parkinson's disease is characterised by the core motor symptoms: bradykinesia, rigidity and tremor. The disease also has a number of non-motor symptoms, such as visual impairment. Patients may experience blurred vision, sensitivity to light, difficulties in reading, and a subjective feeling of rapid eye fatigue. The visual impairments also affect the patients' motor skills, as vision compensates for poor postural control and difficulty initiating movement. It is important to identify common but frequently underdiagnosed visual impairment, and initiate measures that can increase quality of life and pattern of movement. In this clinical review we present the most common visual impairments in Parkinson's disease, as well as providing advice for improved visual function.
Topics: Humans; Parkinson Disease; Vision Disorders; Quality of Life
PubMed: 38747667
DOI: 10.4045/tidsskr.23.0716