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European Journal of Neurology Jan 2020Parkinson disease (PD) is the most common neurodegenerative movement disorder. In Europe, prevalence and incidence rates for PD are estimated at approximately... (Review)
Review
Parkinson disease (PD) is the most common neurodegenerative movement disorder. In Europe, prevalence and incidence rates for PD are estimated at approximately 108-257/100 000 and 11-19/100 000 per year, respectively. Risk factors include age, male gender and some environmental factors. The aetiology of the disease in most patients is unknown, but different genetic causes have been identified. Although familial forms of PD account for only 5%-15% of cases, studies on these families provided interesting insight on the genetics and the pathogenesis of the disease allowing the identification of genes implicated in its pathogenesis and offering critical insights into the mechanisms of disease. The cardinal motor symptoms of PD are tremor, rigidity, bradykinesia/akinesia and postural instability, but the clinical picture includes other motor and non-motor symptoms. Its diagnosis is principally clinical, although specific investigations can help the differential diagnosis from other forms of parkinsonism. Pathologically, PD is characterized by the loss of dopaminergic neurons in the pars compacta of the substantia nigra and by accumulation of misfolded α-synuclein, which is found in intra-cytoplasmic inclusions called Lewy bodies. Currently available treatments offer good control of motor symptoms but do not modify the evolution of the disease. This article is intended to provide a comprehensive, general and practical review of PD for the general neurologist.
Topics: Europe; Humans; Incidence; Parkinson Disease; Prevalence; Risk Factors; Substantia Nigra
PubMed: 31631455
DOI: 10.1111/ene.14108 -
Advances in Clinical and Experimental... Jul 2017The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The... (Review)
Review
The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The publications on the problem discuss a wide range of methods of physiotherapy that can be used in order to reduce the degree of disability and alleviate the symptoms associated with the disease. The complexity of the disease, the difficulty in determining the appropriate treatment and a wide range of symptoms require a comprehensive approach to the patient, which would include both pharmacology and neurorehabilitation. Rehabilitation, which includes psychotherapy and symptomatic therapy, is regarded nowadays as the best form of treatment for multiple sclerosis. An indepth diagnostic assessment of functional status and prognosis should be carried out before the start of the rehabilitation process. The prognosis should take into account the mental state, the neurological status and the awareness of the patient. The kinesiotherapy program in multiple sclerosis is based on a gradation of physiotherapy which assumes a gradual transition from basic movements to more complex ones till global functions are obtained. The most appropriate form of treatment is functional rehabilitation combined with physical procedures. Recent reports indicate the need for aerobic training to be included in the rehabilitation program. The introduction of physical activities, regardless of the severity of the disease, will reduce the negative effects of akinesia, and thus increase the functional capabilities of all body systems.
Topics: Exercise; Humans; Multiple Sclerosis; Physical Therapy Modalities; Prognosis
PubMed: 28691412
DOI: 10.17219/acem/62329 -
Journal of Internal Medicine Nov 2022Parkinson's disease (PD) is a progressive neurodegenerative illness with both motor and nonmotor symptoms. Deep brain stimulation (DBS) is an established safe... (Review)
Review
Parkinson's disease (PD) is a progressive neurodegenerative illness with both motor and nonmotor symptoms. Deep brain stimulation (DBS) is an established safe neurosurgical symptomatic therapy for eligible patients with advanced disease in whom medical treatment fails to provide adequate symptom control and good quality of life, or in whom dopaminergic medications induce severe side effects such as dyskinesias. DBS can be tailored to the patient's symptoms and targeted to various nodes along the basal ganglia-thalamus circuitry, which mediates the various symptoms of the illness; DBS in the thalamus is most efficient for tremors, and DBS in the pallidum most efficient for rigidity and dyskinesias, whereas DBS in the subthalamic nucleus (STN) can treat both tremors, akinesia, rigidity and dyskinesias, and allows for decrease in doses of medications even in patients with advanced stages of the disease, which makes it the preferred target for DBS. However, DBS in the STN assumes that the patient is not too old, with no cognitive decline or relevant depression, and does not exhibit severe and medically resistant axial symptoms such as balance and gait disturbances, and falls. Dysarthria is the most common side effect of DBS, regardless of the brain target. DBS has a long-lasting effect on appendicular symptoms, but with progression of disease, nondopaminergic axial features become less responsive to DBS. DBS for PD is highly specialised; to enable adequate selection and follow-up of patients, DBS requires dedicated multidisciplinary teams of movement disorder neurologists, functional neurosurgeons, specialised DBS nurses and neuropsychologists.
Topics: Deep Brain Stimulation; Dyskinesias; Humans; Parkinson Disease; Quality of Life; Treatment Outcome; Tremor
PubMed: 35798568
DOI: 10.1111/joim.13541 -
Handbook of Clinical Neurology 2017Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The spectrum of tau pathologies expands beyond the... (Review)
Review
Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The spectrum of tau pathologies expands beyond the traditionally discussed disease forms like Pick disease, progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. Emerging entities and pathologies include globular glial tauopathies, primary age-related tauopathy, which includes neurofibrillary tangle dementia, chronic traumatic encephalopathy (CTE), and aging-related tau astrogliopathy. Clinical symptoms include frontotemporal dementia, corticobasal syndrome, Richardson syndrome, parkinsonism, pure akinesia with gait freezing and, rarely, motor neuron symptoms or cerebellar ataxia. Some disorders show specific neuroimaging features, while examination of the cerebrospinal fluid awaits markers for in vivo stratification of cases. The possibility of cell-to-cell propagation is a novel aspect of the pathogenesis of tauopathies, which is partly reflected by the hierarchic involvement of anatomic regions. This concept might have relevance for the development of therapies. For cost-effective screening for tau pathologies in neuropathologic practice, examination of the hippocampus, amygdala, and basal ganglia is recommended. Uncommon morphologies or unusually extensive forms of tau pathologies should raise the suspicion of a genetic background. Ongoing multidisciplinary studies are needed to understand the whole spectrum and significance of tau pathologies.
Topics: Animals; Brain; Humans; Tauopathies; tau Proteins
PubMed: 28987182
DOI: 10.1016/B978-0-12-802395-2.00025-0 -
International Review of Neurobiology 2019Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized pathologically by 4 repeat tau deposition in various cell types and anatomical regions.... (Review)
Review
Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized pathologically by 4 repeat tau deposition in various cell types and anatomical regions. Richardson's syndrome (RS) is the initially described and one of the clinical phenotypes associated with PSP pathology, characterized by vertical supranuclear gaze paly in particular downwards, postural instability with early falls and subcortical frontal dementia. PSP can manifest as several other clinical phenotypes, including PSP-parkinsonism, -pure akinesia with gait freezing, -frontotemporal dementia, - corticobasal syndrome, - speech/language impairment. RS can also have a pathologic diagnosis other than PSP, including corticobasal degeneration, FTD-TDP-43 and others. New clinical diagnostic criteria take into account this phenotypic variability in an attempt to diagnose the disease earlier, given the current lack of a validated biomarker. At present, therapeutic options for PSP are symptomatic and insufficient. Recent large neuroprotective trials have failed to provide a positive clinical outcome, however, have led to the design of better studies that are ongoing and hold promise for a neuroprotective treatment for PSP.
Topics: Humans; Supranuclear Palsy, Progressive
PubMed: 31779824
DOI: 10.1016/bs.irn.2019.10.013 -
Neuroscience and Biobehavioral Reviews Sep 2016Parkinson's disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (akinesia and bradykinesia, tremor and rigidity), PD patients show... (Review)
Review
Parkinson's disease (PD) is characterized by a range of motor symptoms. Besides the cardinal symptoms (akinesia and bradykinesia, tremor and rigidity), PD patients show additional motor deficits, including: gait disturbance, impaired handwriting, grip force and speech deficits, among others. Some of these motor symptoms (e.g., deficits of gait, speech, and handwriting) have similar clinical profiles, neural substrates, and respond similarly to dopaminergic medication and deep brain stimulation (DBS). Here, we provide an extensive review of the clinical characteristics and neural substrates of each of these motor symptoms, to highlight precisely how PD and its medical and surgical treatments impact motor symptoms. In conclusion, we offer a unified framework for understanding the range of motor symptoms in PD. We argue that various motor symptoms in PD reflect dysfunction of neural structures responsible for action selection, motor sequencing, and coordination and execution of movement.
Topics: Deep Brain Stimulation; Dopamine Agents; Gait; Humans; Motor Activity; Parkinson Disease; Speech
PubMed: 27422450
DOI: 10.1016/j.neubiorev.2016.07.010 -
Cells Dec 2020Parkinson's disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and... (Review)
Review
Parkinson's disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and postural instability due to a loss of nigrostriatal dopaminergic neurons. Although the pathogenesis in sporadic PD remains unknown, there is a consensus on the involvement of non-neuronal cells in the progression of PD pathology. Astrocytes are the most numerous glial cells in the central nervous system. Normally, astrocytes protect neurons by releasing neurotrophic factors, producing antioxidants, and disposing of neuronal waste products. However, in pathological situations, astrocytes are known to produce inflammatory cytokines. In addition, various studies have reported that astrocyte dysfunction also leads to neurodegeneration in PD. In this article, we summarize the interaction of astrocytes and dopaminergic neurons, review the pathogenic role of astrocytes in PD, and discuss therapeutic strategies for the prevention of dopaminergic neurodegeneration. This review highlights neuron-astrocyte interaction as a target for the development of disease-modifying drugs for PD in the future.
Topics: Animals; Antioxidants; Astrocytes; Disease Progression; Dopamine; Dopaminergic Neurons; Humans; Inflammation; Mitochondria; Nerve Degeneration; Neuroglia; Neurons; Neuroprotection; Oxidative Stress; Parkinson Disease; Signal Transduction; alpha-Synuclein
PubMed: 33297340
DOI: 10.3390/cells9122623 -
Journal of Medical Genetics Sep 2021Fetal akinesia and arthrogryposis are clinically and genetically heterogeneous and have traditionally been refractive to genetic diagnosis. The widespread availability...
BACKGROUND
Fetal akinesia and arthrogryposis are clinically and genetically heterogeneous and have traditionally been refractive to genetic diagnosis. The widespread availability of affordable genome-wide sequencing has facilitated accurate genetic diagnosis and gene discovery in these conditions.
METHODS
We performed next generation sequencing (NGS) in 190 probands with a diagnosis of arthrogryposis multiplex congenita, distal arthrogryposis, fetal akinesia deformation sequence or multiple pterygium syndrome. This sequencing was a combination of bespoke neurogenetic disease gene panels and whole exome sequencing. Only class 4 and 5 variants were reported, except for two cases where the identified variants of unknown significance (VUS) are most likely to be causative for the observed phenotype. Co-segregation studies and confirmation of variants identified by NGS were performed where possible. Functional genomics was performed as required.
RESULTS
Of the 190 probands, 81 received an accurate genetic diagnosis. All except two of these cases harboured class 4 and/or 5 variants based on the American College of Medical Genetics and Genomics guidelines. We identified phenotypic expansions associated with and . We describe a total of 50 novel variants, including a novel missense variant in the recently identified gene for arthrogryposis with brain malformations.
CONCLUSIONS
Comprehensive gene panels give a diagnosis for a substantial proportion (42%) of fetal akinesia and arthrogryposis cases, even in an unselected cohort. Recently identified genes account for a relatively large proportion, 32%, of the diagnoses. Diagnostic-research collaboration was critical to the diagnosis and variant interpretation in many cases, facilitated genotype-phenotype expansions and reclassified VUS through functional genomics.
Topics: Alleles; Amino Acid Sequence; Amino Acid Substitution; Arthrogryposis; Chromosome Mapping; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genomics; Genotype; High-Throughput Nucleotide Sequencing; Humans; Magnetic Resonance Imaging; Male; Mutation; Pedigree; Phenotype; Sequence Analysis, DNA; Exome Sequencing
PubMed: 33060286
DOI: 10.1136/jmedgenet-2020-106901 -
Journal of Parkinson's Disease 2020Pain is a very frequent symptom with influence on the quality of life in Parkinson's disease (PD), but is still underdiagnosed and commonly treated only... (Review)
Review
Pain is a very frequent symptom with influence on the quality of life in Parkinson's disease (PD), but is still underdiagnosed and commonly treated only unsystematically. Pain etiology and pain character are often complex and multi-causal, and data regarding treatment recommendations are limited. Pain can be primarily related to PD but frequently it is associated with secondary diseases, such as arthrosis of the spine or joints. However, even basically PD-unrelated pain often is amplified by motor- or non-motor PD symptoms, such as akinesia or depression. Beyond an optimization of anti-parkinsonian treatment, additional pain treatment strategies are usually needed to properly address pain in PD. A careful pain history and diagnostic work-up is essential to rate the underlying pain pathophysiology and to develop a targeted therapeutic concept. This review gives an overview on how pain is treated in PD patients and how patients assess the effectiveness of these therapies; here, the manuscript focuses on pathophysiology-driven suggestions for a multimodal pain management in clinical practice.
Topics: Analgesics; Antiparkinson Agents; Humans; Pain; Pain Management; Pain Measurement; Parkinson Disease; Quality of Life
PubMed: 32568113
DOI: 10.3233/JPD-202069 -
Journal of Visualized Experiments : JoVE Oct 2021Motor symptoms of Parkinson's disease (PD)-bradykinesia, akinesia, and tremor at rest-are consequences of the neurodegeneration of dopaminergic neurons in the substantia...
Motor symptoms of Parkinson's disease (PD)-bradykinesia, akinesia, and tremor at rest-are consequences of the neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and dopaminergic striatal deficit. Animal models have been widely used to simulate human pathology in the laboratory. Rodents are the most used animal models for PD due to their ease of handling and maintenance. Moreover, the anatomy and molecular, cellular, and pharmacological mechanisms of PD are similar in rodents and humans. The infusion of the neurotoxin, 6-hydroxydopamine (6-OHDA), into a medial forebrain bundle (MFB) of rats reproduces the severe destruction of dopaminergic neurons and simulates PD symptoms. This protocol demonstrates how to perform the unilateral microinjection of 6-OHDA in the MFB in a rat model of PD and shows the motor deficits induced by 6-OHDA and predicted dopaminergic lesions through the stepping test. The 6-OHDA causes significant impairment in the number of steps performed with the contralateral forelimb.
Topics: Animals; Disease Models, Animal; Dopamine; Dopaminergic Neurons; Medial Forebrain Bundle; Oxidopamine; Parkinson Disease; Rats; Substantia Nigra
PubMed: 34779439
DOI: 10.3791/62923