-
The American Journal of Medicine Jul 2019Parkinson's disease is a progressive neurodegenerative disease characterized by tremor and bradykinesia and is a common neurologic ailment. Male sex and advancing age... (Review)
Review
Parkinson's disease is a progressive neurodegenerative disease characterized by tremor and bradykinesia and is a common neurologic ailment. Male sex and advancing age are independent risk factors and, as the population ages, is taking an increasing toll on productivity and medical resources. There are a number of other extrapyramidal conditions that can make the diagnosis challenging. Unlike other neurodegenerative diseases, idiopathic Parkinson's disease has effective treatments that mitigate symptoms. Medications can improve day-to-day function and, in cases where medication does not give a sustained benefit or has significant side effects, treatments like deep brain stimulation result in improved quality of life.
Topics: Antiparkinson Agents; Diagnosis, Differential; Humans; Parkinson Disease; Parkinsonian Disorders
PubMed: 30890425
DOI: 10.1016/j.amjmed.2019.03.001 -
RoFo : Fortschritte Auf Dem Gebiete Der... Dec 2021Diagnosis of Parkinson's disease and atypical parkinsonism is based on clinical evaluation of the patient's symptoms and on magnetic resonance imaging (MRI) of the... (Review)
Review
BACKGROUND
Diagnosis of Parkinson's disease and atypical parkinsonism is based on clinical evaluation of the patient's symptoms and on magnetic resonance imaging (MRI) of the brain, which can be supplemented by nuclear medicine techniques. MRI plays a leading role in the differentiation between Parkinson's disease and atypical parkinsonism. While atypical parkinsonism is characterized by relatively specific MRI signs, imaging of Parkinson's disease previously lacked such signs. However, high-field MRI and new optimized MRI sequences now make it possible to define specific MRI signs of Parkinson's disease and have significant potential regarding differentiated imaging, early diagnosis, and imaging of disease progression.
METHODS
PubMed was selectively searched for literature regarding the definition and discussion of specific MRI signs of Parkinson's disease, as well as the most common types of atypical parkinsonism with a leading motor component. No time frame was set, but the search was particularly focused on current literature.
RESULTS
This review article discusses the different MRI signs of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. The pathogenesis of the MRI signs is described, and imaging examples are given. The technical aspects of image acquisition are briefly defined, and the different signs are discussed and compared with regard to their diagnostic significance according to current literature.
CONCLUSION
The MRI signs of Parkinson's disease, which can be defined with high-field MRI and new optimized MRI sequences, enable differentiated structural image interpretation and consecutive diagnostic workup. Despite the fact that the signs are in need of further validation by bigger studies, they have the potential to achieve significant diagnostic relevance regarding the imaging of Parkinson's disease and atypical parkinsonism.
KEY POINTS
· High-field MRI and specialized sequences make it possible to define specific MRI signs for neurodegenerative disorders. · Cerebral alterations can be detected in prodromal stages of Parkinson's disease. · The combination of specific MRI signs makes it possible to differentiate between Parkinson's disease and atypical parkinsonism.
CITATION FORMAT
· Aludin S, Schmill LA. MRI Signs of Parkinson's Disease and Atypical Parkinsonism. Fortschr Röntgenstr 2021; 193: 1403 - 1410.
Topics: Humans; Magnetic Resonance Imaging; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders; Supranuclear Palsy, Progressive
PubMed: 34034347
DOI: 10.1055/a-1460-8795 -
Journal of Parkinson's Disease 2018Neurological disorders are now the leading source of disability globally, and the fastest growing neurological disorder in the world is Parkinson disease. From 1990 to... (Review)
Review
Neurological disorders are now the leading source of disability globally, and the fastest growing neurological disorder in the world is Parkinson disease. From 1990 to 2015, the number of people with Parkinson disease doubled to over 6 million. Driven principally by aging, this number is projected to double again to over 12 million by 2040. Additional factors, including increasing longevity, declining smoking rates, and increasing industrialization, could raise the burden to over 17 million. For most of human history, Parkinson has been a rare disorder. However, demography and the by-products of industrialization have now created a Parkinson pandemic that will require heightened activism, focused planning, and novel approaches.
Topics: Aging; Global Health; Humans; Pandemics; Parkinson Disease; Parkinsonian Disorders; Survival Rate
PubMed: 30584159
DOI: 10.3233/JPD-181474 -
Neuron Jan 2015Understanding the function of genes mutated in hereditary forms of Parkinson's disease yields insight into disease etiology and reveals new pathways in cell biology.... (Review)
Review
Understanding the function of genes mutated in hereditary forms of Parkinson's disease yields insight into disease etiology and reveals new pathways in cell biology. Although mutations or variants in many genes increase the susceptibility to Parkinson's disease, only a handful of monogenic causes of parkinsonism have been identified. Biochemical and genetic studies reveal that the products of two genes that are mutated in autosomal recessive parkinsonism, PINK1 and Parkin, normally work together in the same pathway to govern mitochondrial quality control, bolstering previous evidence that mitochondrial damage is involved in Parkinson's disease. PINK1 accumulates on the outer membrane of damaged mitochondria, activates Parkin's E3 ubiquitin ligase activity, and recruits Parkin to the dysfunctional mitochondrion. Then, Parkin ubiquitinates outer mitochondrial membrane proteins to trigger selective autophagy. This review covers the normal functions that PINK1 and Parkin play within cells, their molecular mechanisms of action, and the pathophysiological consequences of their loss.
Topics: Humans; Mitochondria; Mitophagy; Parkinson Disease; Parkinsonian Disorders; Protein Kinases; Proteolysis; Ubiquitin-Protein Ligases
PubMed: 25611507
DOI: 10.1016/j.neuron.2014.12.007 -
Journal of Parkinson's Disease 2022Early-onset parkinsonism (EO parkinsonism), defined as subjects with disease onset before the age of 40 or 50 years, can be the main clinical presentation of a variety... (Review)
Review
Early-onset parkinsonism (EO parkinsonism), defined as subjects with disease onset before the age of 40 or 50 years, can be the main clinical presentation of a variety of conditions that are important to differentiate. Although rarer than classical late-onset Parkinson's disease (PD) and not infrequently overlapping with forms of juvenile onset PD, a correct diagnosis of the specific cause of EO parkinsonism is critical for offering appropriate counseling to patients, for family and work planning, and to select the most appropriate symptomatic or etiopathogenic treatments. Clinical features, radiological and laboratory findings are crucial for guiding the differential diagnosis. Here we summarize the most important conditions associated with primary and secondary EO parkinsonism. We also proposed a practical approach based on the current literature and expert opinion to help movement disorders specialists and neurologists navigate this complex and challenging landscape.
Topics: Diagnosis, Differential; Humans; Middle Aged; Neurologists; Parkinson Disease; Parkinsonian Disorders
PubMed: 34569973
DOI: 10.3233/JPD-212815 -
International Journal of Molecular... Nov 2020Parkinson's disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated mechanisms are pivotal to the pathogenicity and progression of the disease. In this review, we highlight the binary role of microglia activation in the pathophysiology of the disorder, both neuroprotective and neuromodulatory. We present how the expression of several cytokines implicated in dopaminergic neurons (DA) degeneration could be used as biomarkers for PD. Viral infections have been studied and correlated to the disease progression, usually operating as trigger factors for the inflammatory process. The gut-brain axis and the possible contribution of the peripheral bowel inflammation to neuronal death, mainly dopaminergic neurons, seems to be a main contributor of brain neuroinflammation. The role of the immune system has also been analyzed implicating a-synuclein in the activation of innate and adaptive immunity. We also discuss therapeutic approaches concerning PD and neuroinflammation, which have been studied in experimental and in vitro models and data stemming from epidemiological studies.
Topics: Animals; Autoimmunity; Biomarkers; Cytokines; Dopaminergic Neurons; Humans; Inflammation; Microglia; Nerve Degeneration; Parkinson Disease; Parkinsonian Disorders; Signal Transduction; Virus Diseases; alpha-Synuclein
PubMed: 33182554
DOI: 10.3390/ijms21228421 -
Genes Mar 2022Parkinson's disease may be caused by a single pathogenic variant (monogenic) in 5-10% of cases, but investigation of these disorders provides valuable pathophysiological... (Review)
Review
Parkinson's disease may be caused by a single pathogenic variant (monogenic) in 5-10% of cases, but investigation of these disorders provides valuable pathophysiological insights. In this review, we discuss each genetic form with a focus on genotype, phenotype, pathophysiology, and the geographic and ethnic distribution. Well-established Parkinson's disease genes include autosomal dominant forms (, , and ) and autosomal recessive forms (, and ). Furthermore, mutations in the gene are a key risk factor for Parkinson's disease, and there have been major developments for X-linked dystonia parkinsonism. Moreover, atypical or complex parkinsonism may be due to mutations in genes such as , , , , , and . Furthermore, numerous genes have recently been implicated in Parkinson's disease, such as , , , , and . Additionally, we discuss the role of heterozygous mutations in autosomal recessive genes, the effect of having mutations in two Parkinson's disease genes, the outcome of deep brain stimulation, and the role of genetic testing. We highlight that monogenic Parkinson's disease is influenced by ethnicity and geographical differences, reinforcing the need for global efforts to pool large numbers of patients and identify novel candidate genes.
Topics: DNA-Binding Proteins; Genetic Testing; Genotype; Humans; Membrane Proteins; Parkinson Disease; Parkinsonian Disorders; Phenotype; Transcription Factors
PubMed: 35328025
DOI: 10.3390/genes13030471 -
Journal of Parkinson's Disease 2018Recent epidemiological observations have drawn attention to the rapid rise in the burden caused by Parkinson's disease over the past years, emphasizing that Parkinson's...
Recent epidemiological observations have drawn attention to the rapid rise in the burden caused by Parkinson's disease over the past years, emphasizing that Parkinson's disease is a matter of serious concern for our future generations. A recent report by Public Health England corroborates this message, by providing new insight on trends in deaths associated with neurological diseases in England between 2001 to 2014. The report indicates that mortality associated with Parkinson's disease and related disorders increased substantially between 2001 and 2014. This trend is partially explained by increased longevity in the population. However, it is possible that changes in exposure to risk factors, recent improvements in multidisciplinary care (leading to prolonged survival), and improved diagnostic awareness or improved registration also influenced the observed trend. Furthermore, patients with Parkinson's disease and related disorders were found to die at an advanced age, and the majority die in a care home or hospital, despite a preponderant preference for many patients and their families to spend their last days at home. To combat these concerning observations, future efforts should be focused on providing resources for vulnerable elderly Parkinson patients, avoiding unplanned hospital admissions and out-of-home deaths as much as possible. Possible solutions include a community-based network of specifically trained allied health therapists, personal case managers for Parkinson patients, dedicated Parkinson nursing homes, and improved centralised support services from university clinics to regional community hospitals aimed at facilitating optimal wide-scale care delivery.
Topics: Cause of Death; Delivery of Health Care; Humans; Parkinson Disease; Parkinsonian Disorders; Risk; Survival Rate
PubMed: 30149463
DOI: 10.3233/JPD-181374 -
Deutsches Arzteblatt International Feb 2016Aside from idiopathic Parkinson syndrome (Parkinson's disease), there are a number of other, so-called atypical parkinsonian syndromes: dementia with Lewy bodies (DLB),... (Review)
Review
BACKGROUND
Aside from idiopathic Parkinson syndrome (Parkinson's disease), there are a number of other, so-called atypical parkinsonian syndromes: dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). DLB is a common disease, with a prevalence of 0.4% (400 cases per 100 000 persons) in the elderly; MSA and PSP both have a prevalence of 5 to 10 per 100 000 persons, while the prevalence of CBD is about 1 per 100 000.
METHODS
This review is based on pertinent publications retrieved by a selective literature search.
RESULTS
The atypical parkinsonian syndromes are synucleinopathies and tauopathies, i.e., disorders characterized by the abnormal deposition of the proteins α-synuclein and tau. The site of deposition is correlated with the clinical features. In DLB, synuclein is mainly deposited in neocortical neurons, with some brain stem involvement as well. The main clinical features are dementia and, later on, parkinsonism. In MSA, synuclein is deposited in oligodendrocytes, mainly in the cerebellum but also in the brain stem; the main clinical feature is autonomic dysfunction combined with parkinsonism or cerebellar ataxia. Synucleinopathies often impair REM (rapid eye movement) sleep. PSP and CBD, on the other hand, are primary tauopathies. PSP usually causes predominantly supranuclear vertical gaze palsy and early postural instability with falls, less commonly parkinsonism (PSP-P) or frontotemporal dementia (PSP-FTD) as its most prominent feature. CBD typically manifests itself as markedly asymmetrical parkinsonism with apraxia or cortical sensory disturbance. At present, there is no accepted causal treatment for any of these disorders; the available symptomatic treatments are of limited efficacy and are supported only by low-level evidence.
CONCLUSION
Causal treatments for neurodegenerative diseases are now being developed and tested, and thus a molecular diagnosis is desirable. This will require the cooperation of primary care physicians with specialized centers.
Topics: Diagnosis, Differential; Evidence-Based Medicine; Humans; Parkinson Disease; Parkinsonian Disorders; Treatment Outcome
PubMed: 26900156
DOI: 10.3238/arztebl.2016.0061 -
Journal of Parkinson's Disease 2021Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson's disease (PD). Initially originating from... (Review)
Review
Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson's disease (PD). Initially originating from the observation that mitochondrial toxins cause PD, findings from genetic PD supported a contribution of mitochondrial dysfunction to the disease. Here, proteins encoded by the autosomal recessively inherited PD genes Parkin, PTEN-induced kinase 1 (PINK1), and DJ-1 are involved in mitochondrial pathways. Additional evidence for mitochondrial dysfunction stems from models of autosomal-dominant PD due to mutations in alpha-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2). Moreover, patients harboring alterations in mitochondrial polymerase gamma (POLG) often exhibit signs of parkinsonism. While some molecular studies suggest that mitochondrial dysfunction is a primary event in PD, others speculate that it is the result of impaired mitochondrial clearance. Most recent research even implicated damage-associated molecular patterns released from non-degraded mitochondria in neuroinflammatory processes in PD. Here, we summarize the manifold literature dealing with mitochondria in the context of PD. Moreover, in light of recent advances in the field of personalized medicine, patient stratification according to the degree of mitochondrial impairment followed by mitochondrial enhancement therapy may hold potential for at least a subset of genetic and idiopathic PD cases. Thus, in the second part of this review, we discuss therapeutic approaches targeting mitochondrial dysfunction with the aim to prevent or delay neurodegeneration in PD.
Topics: Animals; Humans; Mitochondrial Diseases; Parkinson Disease
PubMed: 33074190
DOI: 10.3233/JPD-201981