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Seminars in Neurology Apr 2017The overlap of signs and symptoms between Parkinson's disease and the atypical parkinsonian syndromes, such as progressive supranuclear palsy, multiple system atrophy,... (Review)
Review
The overlap of signs and symptoms between Parkinson's disease and the atypical parkinsonian syndromes, such as progressive supranuclear palsy, multiple system atrophy, corticobasal syndrome and dementia with Lewy bodies, can render clinical diagnoses challenging. The continued evolution of diagnostic criteria to reflect the increasingly recognized heterogeneous presentations of these diseases further complicates timely recognition and diagnosis. In this review, we provide a diagnostic approach to the classic atypical parkinsonian syndromes, with an emphasis on the key clinical and pathological features of each and the recognition of “red flags” in the setting of recent advances in diagnosis and treatment.
Topics: Animals; Humans; Lewy Body Disease; Multiple System Atrophy; Parkinson Disease; Supranuclear Palsy, Progressive
PubMed: 28511262
DOI: 10.1055/s-0037-1602422 -
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 -
The Journals of Gerontology. Series A,... Jun 2021There is paucity of data about African American (AA) patients with Parkinson's disease (PD) and parkinsonism which may precede PD in older adults. Prior studies suggest...
BACKGROUND
There is paucity of data about African American (AA) patients with Parkinson's disease (PD) and parkinsonism which may precede PD in older adults. Prior studies suggest that there are lower rates of PD in the AA population, with more cognitive impairment in AA with PD. This study aimed to investigate differences in PD, parkinsonism, and cognition between White and AA populations in 3 longitudinal epidemiologic cohort studies of aging.
METHODS
This study examined parkinsonism, PD frequency, and cognition of community-dwelling older individuals in 3 longitudinal epidemiologic cohort studies. Parkinsonism was based on an exam utilizing the modified Unified Parkinson's Disease Rating Scale performed by a nurse. PD was based on self-report, medications used for treatment of PD, and examination findings. Cognition was assessed using 19 performance-based tests that assess 5 cognitive domains.
RESULTS
AA participants were less likely to have parkinsonism compared to Whites, even with age and gender differences. Frequency of PD was not significant between groups. AA were more likely to have lower cognitive scores as compared to Whites. AA were less likely to have parkinsonism even with controlling for cognitive differences between groups.
CONCLUSIONS
Parkinsonian signs are present among AA in the community at lower rates than in White individuals. Cognitive profiles of AA and Whites with parkinsonism may be different, suggesting differing contributions of pathology to cognitive decline and parkinsonism between groups. Additional research is needed to understand the progression of parkinsonism to PD, as well as to understanding the cognitive differences in AA with parkinsonism.
Topics: Black or African American; Aged; Aged, 80 and over; Chicago; Cognition Disorders; Female; Humans; Independent Living; Longitudinal Studies; Male; Parkinson Disease; Parkinsonian Disorders; Risk Factors
PubMed: 33631006
DOI: 10.1093/gerona/glab042 -
Biochemical Society Transactions Feb 2023The prevalence of neurological diseases is currently growing due to the combination of several factor, including poor lifestyle and environmental imbalance which enhance... (Review)
Review
The prevalence of neurological diseases is currently growing due to the combination of several factor, including poor lifestyle and environmental imbalance which enhance the contribution of genetic factors. Parkinson's disease (PD), a chronic and progressive neurological condition, is one of the most prevalent neurodegenerative human diseases. Development of models may help to understand its pathophysiology. This review focuses on studies using invertebrate models to investigate certain chemicals that generate parkinsonian-like symptoms models. Additionally, we report some preliminary results of our own research on a crustacean (the crab Ucides cordatus) and a solitary ascidian (Styela plicata), used after induction of parkinsonism with 6-hydroxydopamine and the pesticide rotenone, respectively. We also discuss the advantages, limits, and drawbacks of using invertebrate models to study PD. We suggest prospects and directions for future investigations of PD, based on invertebrate models.
Topics: Humans; Animals; Parkinsonian Disorders; Parkinson Disease; Rotenone; Invertebrates; Disease Models, Animal
PubMed: 36645005
DOI: 10.1042/BST20221172 -
Journal of Parkinson's Disease 2023Patient perspectives on meaningful symptoms and impacts in early Parkinson's disease (PD) are lacking and are urgently needed to clarify priority areas for monitoring,...
BACKGROUND
Patient perspectives on meaningful symptoms and impacts in early Parkinson's disease (PD) are lacking and are urgently needed to clarify priority areas for monitoring, management, and new therapies.
OBJECTIVE
To examine experiences of people with early-stage PD, systematically describe meaningful symptoms and impacts, and determine which are most bothersome or important.
METHODS
Forty adults with early PD who participated in a study evaluating smartwatch and smartphone digital measures (WATCH-PD study) completed online interviews with symptom mapping to hierarchically delineate symptoms and impacts of disease from "Most bothersome" to "Not present," and to identify which of these were viewed as most important and why. Individual symptom maps were coded for types, frequencies, and bothersomeness of symptoms and their impacts, with thematic analysis of narratives to explore perceptions.
RESULTS
The three most bothersome and important symptoms were tremor, fine motor difficulties, and slow movements. Symptoms had the greatest impact on sleep, job functioning, exercise, communication, relationships, and self-concept- commonly expressed as a sense of being limited by PD. Thematically, most bothersome symptoms were those that were personally limiting with broadest negative impact on well-being and activities. However, symptoms could be important to patients even when not present or limiting (e.g., speech, cognition).
CONCLUSION
Meaningful symptoms of early PD can include symptoms that are present or anticipated future symptoms that are important to the individual. Systematic assessment of meaningful symptoms should aim to assess the extent to which symptoms are personally important, present, bothersome, and limiting.
Topics: Adult; Humans; Parkinson Disease; Tremor; Cognition; Exercise; Hypokinesia
PubMed: 37212071
DOI: 10.3233/JPD-225068 -
Neuromodulation : Journal of the... Oct 2023Falls in extrapyramidal disorders, particularly Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP), are key milestones... (Review)
Review
BACKGROUND
Falls in extrapyramidal disorders, particularly Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP), are key milestones affecting patients' quality of life, incurring increased morbidity/mortality and high healthcare costs. Unfortunately, gait and balance in parkinsonisms respond poorly to currently available treatments. A serendipitous observation of improved gait and balance in patients with PD receiving spinal cord stimulation (SCS) for back pain kindled an interest in using SCS to treat gait disorders in parkinsonisms.
OBJECTIVES
We reviewed preclinical and clinical studies of SCS to treat gait dysfunction in parkinsonisms, covering its putative mechanisms and efficacies.
MATERIALS AND METHODS
Preclinical studies in animal models of PD and clinical studies in patients with PD, PSP, and MSA who received SCS for gait disorders were included. The main outcome assessed was clinical improvement in gait, together with outcome measures used and possible mechanism of actions.
RESULTS
We identified 500 references, and 45 met the selection criteria and have been included in this study for analysis. Despite positive results in animal models, the outcomes in human studies are inconsistent.
CONCLUSIONS
The lack of blind and statistically powered studies, the heterogeneity in patient selection and study outcomes, and the poor understanding of the underlying mechanisms of action of SCS are some of the limiting factors in the field. Addressing these limitations will allow us to draw more reliable conclusions on the effects of SCS on gait and balance in extrapyramidal disorders.
Topics: Humans; Parkinson Disease; Spinal Cord Stimulation; Quality of Life; Parkinsonian Disorders; Multiple System Atrophy; Gait
PubMed: 37452800
DOI: 10.1016/j.neurom.2023.06.003 -
Cells Feb 2023Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of Lewy bodies in the basal ganglia,... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of Lewy bodies in the basal ganglia, resulting in movement impairment referred to as parkinsonism. However, the etiology of PD is not well known, with genetic factors accounting only for 10-15% of all PD cases. The pathogenetic mechanism of PD is not completely understood, although several mechanisms, such as oxidative stress and inflammation, have been suggested. Understanding the mechanisms of PD pathogenesis is critical for developing highly efficacious therapeutics. In the PD brain, dopaminergic neurons degenerate mainly in the basal ganglia, but recently emerging evidence has shown that astrocytes also significantly contribute to dopaminergic neuronal death. In this review, we discuss the role of astrocytes in PD pathogenesis due to mutations in α-synuclein (PARK1), DJ-1 (PARK7), parkin (PARK2), leucine-rich repeat kinase 2 (LRRK2, PARK8), and PTEN-induced kinase 1 (PINK1, PARK6). We also discuss PD experimental models using neurotoxins, such as paraquat, rotenone, 6-hydroxydopamine, and MPTP/MPP+. A more precise and comprehensive understanding of astrocytes' modulatory roles in dopaminergic neurodegeneration in PD will help develop novel strategies for effective PD therapeutics.
Topics: Humans; Parkinson Disease; Astrocytes; Parkinsonian Disorders; Lewy Bodies; Dopamine; Mutation
PubMed: 36831289
DOI: 10.3390/cells12040622 -
Journal of Parkinson's Disease 2018In vivo gene therapy for neurodegenerative disorders has turned out to be a formidable challenge. It is a field not much older than twenty years, but we were many who... (Review)
Review
In vivo gene therapy for neurodegenerative disorders has turned out to be a formidable challenge. It is a field not much older than twenty years, but we were many who would have predicted a much easier path towards the clinic using this treatment modality. For Parkinson's disease patients, this has meant a frustrating wait, seeing many promising therapies being forgotten after a few pre-clinical proof-of-concept studies. The reasons for this are both scientific and economical. However, this is slowly but surely changing and over the next two decades we will see a very exciting development in this field. In a foreseeable future, gene therapy will be a very natural component of many clinical therapies, not least in Parkinson's disease.
Topics: Brain; Genetic Therapy; Humans; Parkinson Disease
PubMed: 30584164
DOI: 10.3233/JPD-181485 -
Neuroscience and Biobehavioral Reviews Jan 2022Understanding the pathophysiological mechanism of Parkinson's disease (PD) in the subthalamic nucleus (STN) has become a critical issue since deep brain stimulation... (Review)
Review
Understanding the pathophysiological mechanism of Parkinson's disease (PD) in the subthalamic nucleus (STN) has become a critical issue since deep brain stimulation (DBS) in this region has been proven as an effective treatment for this disease. The STN possesses a special ability to switch from the spike to the burst firing mode in response to dopamine deficiency in parkinsonism, and this STN burst is considered an electrophysiological signature of the cortico-basal ganglia circuit in the brains of PD patients. This review focuses on the role of STN burst firing in the pathophysiology of PD and during DBS. Here, we review existing literature on how STN bursts originate and the specific factors affecting their formation; how STN burst firing causes motor symptoms in PD and how interventions can rescue these symptoms. Finally, the similarities and differences between the two electrophysiological hallmarks of PD, STN burst firing and beta-oscillation, are discussed. STN burst firing should be considered as a pathophysiological target in PD during treatment with DBS.
Topics: Basal Ganglia; Deep Brain Stimulation; Humans; Parkinson Disease; Parkinsonian Disorders; Subthalamic Nucleus
PubMed: 34856222
DOI: 10.1016/j.neubiorev.2021.11.044 -
Neuroscience Bulletin Oct 2017Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as... (Review)
Review
Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as hyposmia, constipation, REM sleep behavior disorder and depression may antecede these motor symptoms for years. It would be ideal, if we had a biomarker which would allow to predict who with one or two of these pre-motor symptoms will develop the movement disorder Parkinson's disease (PD). Thus, it is interesting to learn that biopsies of the submandibular gland or colon biopsies may be a means to predict PD, if there is a high amout of abnormally folded alpha-synuclein and phosphorylated alpha-synuclein. This would be of relevance if we would have available means to stop the propagation of abnormal alpha-synuclein which is otherwise one of the reasons of this spreading disease PD.
Topics: Constipation; Depression; Early Diagnosis; Humans; Olfaction Disorders; Parkinson Disease; REM Sleep Behavior Disorder
PubMed: 28776303
DOI: 10.1007/s12264-017-0159-5