scholarly journals An early diagnosis is not the same as a timely diagnosis of Parkinson's disease

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1106 ◽  
Author(s):  
Richard Nathaniel Rees ◽  
Anita Prema Acharya ◽  
Anette Schrag ◽  
Alastair John Noyce

Parkinson’s disease is a common neurodegenerative condition that has significant costs to the individual patient and to society. The pathology starts up to a decade before symptoms are severe enough to allow a diagnosis using current criteria. Although the search for disease-modifying treatment continues, it is vital to understand what the right time is for diagnosis. Diagnosis of Parkinson’s disease is based on the classic clinical criteria, but the presence of other clinical features and disease biomarkers may allow earlier diagnosis, at least in a research setting. In this review, we identify the benefits of an early diagnosis, including before the classic clinical features occur. However, picking the right point for a “timely” diagnosis will vary depending on the preferences of the individual patient, efficacy (or existence) of disease-modifying treatment, and the ability for health systems to provide support and management for individuals at every stage of the disease. Good evidence for the quality-of-life benefits of existing symptomatic treatment supports the argument for earlier diagnosis at a time when symptoms are already present. This argument would be significantly bolstered by the development of disease-modifying treatments. Benefits of early diagnosis and treatment would affect not only the individual (and their families) but also the wider society and the research community. Ultimately, however, shared decision-making and the principles of autonomy, beneficence, and non-maleficence will need to be applied on an individual basis when considering a “timely” diagnosis.

Author(s):  
Richard A. Walsh

Multiple system atrophy represents a form of atypical parkinsonism that is challenging to manage and results in rapidly progressive disability and dependence in the absence of effective disease-modifying or symptomatic therapies. Two syndromes are recognized, both associated with autonomic dysfunction—MSA-C and MSA-P, with a predominance of parkinsonian and cerebellar features, respectively. Magnetic resonance imaging can assist with an early diagnosis, demonstrating certain features that can be considered diagnostic in the right clinical context. The typical changes described may not be apparent on an initial scan, so it is worth repeating imaging 1 or 2 years later if the clinical features and course are typical of multiple system atrophy.


2020 ◽  
Vol 2 (1) ◽  
Author(s):  
D. Berg ◽  
K. Eggert ◽  
B. Haslinger ◽  
J. Kassubek ◽  
B. Mollenhauer ◽  
...  

Abstract Background The advent of therapeutic strategies designed to modify the disease course in Parkinson’s disease has raised great expectations in the currently conducted clinical trials. However, we see ethical challenges in the cooperation of industry and clinical partners, specifically evident in the way recruitment is performed. We here discuss the different positions and challenges of all involved to set the stage for a study and recruitment culture taking into account the expectations of all: (i) patients and their caregivers, ready to take the considerable burden of clinical trials in hope for the development of disease-modifying treatments; (ii) physicians and study nurses, obligated to the patients’ well-being and benefit who accompany and supervise patients closely as basis for the performance of elaborate clinical trials (iii) industrial partners, investing years of efforts and finances to develop new treatments. Conclusions We conclude that the current competitive race for enrollment in clinical studies in PD is challenging the primary goal to ensure patients’ benefit and formulate requests to the industrial partners to encounter these concerns.


2020 ◽  
Vol 26 (37) ◽  
pp. 4738-4746
Author(s):  
Mohan K. Ghanta ◽  
P. Elango ◽  
Bhaskar L. V. K. S.

Parkinson’s disease is a progressive neurodegenerative disorder of dopaminergic striatal neurons in basal ganglia. Treatment of Parkinson’s disease (PD) through dopamine replacement strategies may provide improvement in early stages and this treatment response is related to dopaminergic neuronal mass which decreases in advanced stages. This treatment failure was revealed by many studies and levodopa treatment became ineffective or toxic in chronic stages of PD. Early diagnosis and neuroprotective agents may be a suitable approach for the treatment of PD. The essentials required for early diagnosis are biomarkers. Characterising the striatal neurons, understanding the status of dopaminergic pathways in different PD stages may reveal the effects of the drugs used in the treatment. This review updates on characterisation of striatal neurons, electrophysiology of dopaminergic pathways in PD, biomarkers of PD, approaches for success of neuroprotective agents in clinical trials. The literature was collected from the articles in database of PubMed, MedLine and other available literature resources.


Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 715
Author(s):  
Emilio Fernández-Espejo ◽  
Fernando Rodríguez de Fonseca ◽  
Juan Suárez ◽  
Eduardo Tolosa ◽  
Dolores Vilas ◽  
...  

Background. Salivary α-synuclein (aSyn) and its nitrated form, or 3-nitrotyrosine-α-synuclein (3-NT-αSyn), hold promise as biomarkers for idiopathic Parkinson’s disease (IPD). Nitrative stress that is characterized by an excess of 3-nitrotyrosine proteins (3-NT-proteins) has been proposed as a pathogenic mechanism in IPD. The objective is to study the pathological role of native αSyn, 3-NT-αSyn, and 3-NT-proteins in the saliva and submandibulary glands of patients with IPD. Methods. The salivary and serum αSyn and 3-NT-proteins concentration is evaluated with ELISA in patients and controls. Correlations of αSyn and 3-NT-proteins content with clinical features of the disease are examined. Immunohistochemical 3-NT-αSyn expression in submandibulary gland sections is analyzed. Results. (a) Salivary concentration and saliva/serum ratios of native αSyn and 3-NT-proteins are similar in patients and controls; (b) salivary αSyn and 3-NT-proteins do not correlate with any clinical feature; and (c) three patterns of 3-NT-αSyn-positive inclusions are observed on histological sections: rounded “Lewy-type” aggregates of 10–25 µm in diameter, coarse deposits with varied morphology, and spheroid inclusions or bodies of 3–5 µm in diameter. “Lewy-type” and coarse inclusions are observed in the interlobular connective tissue of the gland, and small-sized bodies are located within the cytoplasm of duct cells. “Lewy-type” inclusions are only observed in patients, and the remaining patterns of inclusions are observed in both the patients and controls. Conclusions. The patients’ saliva presents a similar concentration of native αSyn and 3-nitrotyrosine-proteins than that of the controls, and no correlations with clinical features are found. These findings preclude the utility of native αSyn in the saliva as a biomarker, and they indicate the absence of nitrative stress in the saliva and serum of patients. As regards nitrated αSyn, “Lewy-type” inclusions expressing 3-NT-αSyn are observed in the patients, not the controls—a novel finding that suggests that a biopsy of the submandibulary gland, if proven safe, could be a useful technique for diagnosing IPD. Finally, to our knowledge, this is also the first description of 3-NT-αSyn-immunoreactive intracytoplasmic bodies in cells that are located outside the nervous system. These intracytoplasmic bodies are present in duct cells of submandibulary gland sections from all subjects regardless of their pathology, and they can represent an aging or involutional change. Further immunostaining studies with different antibodies and larger samples are needed to validate the data.


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