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Parkinsonism & Related Disorders Jun 2024Alpha-synucleinopathies are prevalent neurological disorders that cause significant disability, leading to progressive clinical deterioration that is currently managed...
Alpha-synucleinopathies are prevalent neurological disorders that cause significant disability, leading to progressive clinical deterioration that is currently managed solely through symptomatic treatment. Efforts to evaluate disease-modifying therapies during the established stage of the disease have not yielded positive outcomes in terms of clinical or imaging efficacy endpoints. However, alpha-synucleinopathies have a long prodromal phase that presents a promising opportunity for intervention with disease-modifying therapies. The presence of polysomnography-confirmed REM sleep behavior disorder (RBD) is the most reliable risk factor for identifying individuals in the prodromal stage of alpha-synucleinopathy. This paper discusses the rationale behind targeting idiopathic/isolated RBD in disease-modifying trials and outlines possible study designs, including strategies for patient stratification, selection of biomarkers to assess disease progression and patient eligibility, as well as the identification of suitable endpoints. Additionally, the potential targets for disease-modifying treatment in alpha-synucleinopathies are summarized.
PubMed: 38943771
DOI: 10.1016/j.parkreldis.2024.107042 -
Stem Cell Research Jun 2024Recent studies reported that the mutation in the THAP11 gene (THAP11) could be responsible for the inborn vitamin deficiency known as cobalamin disorder, by affecting...
Recent studies reported that the mutation in the THAP11 gene (THAP11) could be responsible for the inborn vitamin deficiency known as cobalamin disorder, by affecting the expression of the enzyme MMACHC, key in the cobalamin metabolism. However, the specifics of the molecular mechanism are largely unknown. In here we generated genetically modified human pluripotent stem cell lines with THAP11 mutation, providing a new research tool for futher exploring the molecular mechanism. The established hPSC lines remain pluripotent, showing expression of OCT3/4, differentiation capacity to the three germ layers and displaying normal karyotype.
PubMed: 38943762
DOI: 10.1016/j.scr.2024.103483 -
Clinics (Sao Paulo, Brazil) Jun 2024
PubMed: 38943705
DOI: 10.1016/j.clinsp.2024.100425 -
NeuroRehabilitation 2024Parkinson's disease (PD) is a progressive neurodegenerative disorder diagnosed by motor symptoms of bradykinesia, in combination with tremor, rigidity, or postural...
BACKGROUND
Parkinson's disease (PD) is a progressive neurodegenerative disorder diagnosed by motor symptoms of bradykinesia, in combination with tremor, rigidity, or postural instability. Many studies document the effects of exercise-based interventions, but the benefit of different exercise types remains unclear.
OBJECTIVE
To provide a commentary on the Cochrane Review by Ernst et al. on the effectiveness of different types of physical exercise regarding motor signs, Quality of Life (QoL), and the occurrence of adverse events.
METHODS
A systematic search was performed in CENTRAL, MEDLINE, Embase, and other databases. The search was performed also in trial registries, conference proceedings, and reference list of identified studies.
RESULTS
The review included 154 RCTs (with 7837 participants). The network meta-analyses (NMAs) on the severity of motor signs and QoL included data from 60 (2721 participants) and 48 (3029 participants) trials, respectively. The evidence from the NMA suggests that dance, gait/balance/functional training probably have a moderate beneficial effect on the severity of motor signs, and multi-domain training probably has a small beneficial effect on the severity of motor signs. Endurance, aqua-based, strength/resistance, and mind-body training might have a small beneficial effect on the severity of motor signs. In addition, aqua-based training probably has a large beneficial effect on QoL, and mind-body, gait/balance/functional, and multi-domain training and dance might have a small beneficial effect on QoL.
CONCLUSIONS
Current evidence supports the promotion of physical exercise among people with PD, identifying only small differences between exercises in influencing the severity of motor signs and QoL.
Topics: Humans; Exercise Therapy; Parkinson Disease; Quality of Life; Systematic Reviews as Topic
PubMed: 38943407
DOI: 10.3233/NRE-246004 -
Journal of Parkinson's Disease Jun 2024
PubMed: 38943399
DOI: 10.3233/JPD-249006 -
Journal of Parkinson's Disease Jun 2024Natural health products have emerged as a potential symptomatic therapeutic approach for people with Parkinson's disease (PD).
BACKGROUND
Natural health products have emerged as a potential symptomatic therapeutic approach for people with Parkinson's disease (PD).
OBJECTIVE
To determine the prevalence of natural health product use, interest in natural health products, awareness of potential herb-drug interactions, and consultation of healthcare professionals regarding natural health products use among people with PD.
METHODS
Cross-sectional 4-item survey embedded in the PRIME-NL study, which is a population-based cohort of PD.
RESULTS
Of 367 people with PD, 36% reported having used natural health products to alleviate PD-related symptoms, with coffee, cannabis and turmeric being the most popular. Furthermore, 71% of people with PD were interested in learning more about natural health products. 39% of natural health products users were aware that these products could interact with PD medication and 39% had discussed their use with their healthcare professional.
CONCLUSIONS
Natural health products are commonly used to alleviate symptoms by people with PD, but most users are unaware that these products can interact with PD medication and do not discuss their consumption with their healthcare professional.
PubMed: 38943398
DOI: 10.3233/JPD-240102 -
Journal of Parkinson's Disease Jun 2024Reduced spontaneous blinking is a recognized Parkinson's disease (PD) feature. In contrast, voluntary blinking has been less studied and might serve as a measurable...
Reduced spontaneous blinking is a recognized Parkinson's disease (PD) feature. In contrast, voluntary blinking has been less studied and might serve as a measurable marker of facial bradykinesia. We tested 31 PD patients and 31 controls. Participants were filmed during conversation and a rapid blinking task. Both tasks were videorecorded to count the number of blinks per second. PD patients had lower blink rates. Rapid blinking accurately discriminated between groups with 77% sensitivity and 71% specificity. To conclude, rapid blinking may be a simple and quantifiable task of facial bradykinesia.
PubMed: 38943397
DOI: 10.3233/JPD-240005 -
Journal of Neurochemistry Jun 2024The synucleinopathies Parkinson disease (PD), multiple system atrophy (MSA), and the Lewy body form of pure autonomic failure (PAF) entail intra-cytoplasmic deposition...
The synucleinopathies Parkinson disease (PD), multiple system atrophy (MSA), and the Lewy body form of pure autonomic failure (PAF) entail intra-cytoplasmic deposition of the protein alpha-synuclein and pathogenic catecholaminergic neurodegeneration. Cerebrospinal fluid (CSF) levels of catecholamines and their metabolites are thought to provide a "neurochemical window" on central catecholaminergic innervation and can identify specific intra-neuronal dysfunctions in synucleinopathies. We asked whether there are CSF concentration gradients for catechols such as 3,4-dihydroxyphenylacetic acid (DOPAC), the main neuronal metabolite of dopamine, and if so whether the gradients influence neurochemical differences among synucleinopathies. In a retrospective cohort study, we reviewed data about concentrations of catechols in the first, sixth, and twelfth 1-mL aliquots from 33 PD, 28 MSA, and 15 PAF patients and 41 controls. There were concentration gradients for DOPAC, dopamine, norepinephrine, and 3,4-dihydroxyphenylglycol (the main neuronal metabolite of norepinephrine) and gradients in the opposite direction for 5-S-cysteinyldopa and 5-S-cysteinyldopamine. In all 3 aliquots, CSF DOPAC was low in PD and MSA compared with controls (p < 0.0001 each) and normal in PAF. Synucleinopathies differ in CSF catechols regardless of concentration gradients. Concentration gradients for 5-S-cysteinyl derivatives in opposite directions from the parent catechols may provide biomarkers of spontaneous oxidation in the CSF space.
PubMed: 38943336
DOI: 10.1111/jnc.16168 -
Movement Disorders Clinical Practice Jun 2024Primary mitochondrial diseases (PMDs) are the most common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. They can result from mutations in... (Review)
Review
BACKGROUND
Primary mitochondrial diseases (PMDs) are the most common inborn errors of energy metabolism, with a combined prevalence of 1 in 4300. They can result from mutations in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). These disorders are multisystemic and mainly affect high energy-demanding tissues, such as muscle and the central nervous system (CNS). Among many clinical features of CNS involvement, parkinsonism is one of the most common movement disorders in PMDs.
METHODS
This review provides a pragmatic educational overview of the most recent advances in the field of mitochondrial parkinsonism, from pathophysiology and genetic etiologies to phenotype and diagnosis.
RESULTS
mtDNA maintenance and mitochondrial dynamics alterations represent the principal mechanisms underlying mitochondrial parkinsonism. It can be present in isolation, alongside other movement disorders or, more commonly, as part of a multisystemic phenotype. Mutations in several nuclear-encoded genes (ie, POLG, TWNK, SPG7, and OPA1) and, more rarely, mtDNA mutations, are responsible for mitochondrial parkinsonism. Progressive external opthalmoplegia and optic atrophy may guide genetic etiology identification.
CONCLUSION
A comprehensive deep-phenotyping approach is needed to reach a diagnosis of mitochondrial parkinsonism, which lacks distinctive clinical features and exemplifies the intricate genotype-phenotype interplay of PMDs.
PubMed: 38943319
DOI: 10.1002/mdc3.14148 -
Movement Disorders Clinical Practice Jun 2024
PubMed: 38943269
DOI: 10.1002/mdc3.14156