Parkinsonian

Doxycycline, a semi-synthetic tetracycline, is a widely used antibiotic for treating mild-to-moderate infections, including skin problems. However, its anti-inflammatory and antioxidant properties, combined with its ability to interfere with α-synuclein aggregation, make it an attractive candidate for repositioning in Parkinson's disease. Nevertheless, the antibiotic activity of doxycycline restricts its potential use for long-term treatment of Parkinsonian patients. In the search for non-antibiotic tetracyclines that could operate against Parkinson's disease pathomechanisms, eighteen novel doxycycline derivatives were designed...

INTRODUCTION: Prescribing cascade is a condition in which a drug administered to a patient causes an adverse reaction that is misinterpreted as a new condition, resulting in the addition of a new drug. CASE PRESENTATION: Here, we report the case of an elderly female patient who suffered from metabolic, neurologic, and urinary consequences of a prescribing cascade of antiemetic, antiepileptic, and dopaminergic drugs. While levosulpiride caused Parkinsonian symptoms, the dopaminergic drugs and valproate caused refractory hyponatremia followed by altered sensorium, and clidinium contributed to urinary retention...

The objective of this systematic review was to determine the prevalence of dysphagia and aspiration in people with progressive supranuclear palsy (PSP). A search of six electronic databases was performed from inception to April 2022. No context restrictions were set. All primary research comprising figures to derive a prevalence rate were included. Two independent reviewers screened search results. Data were extracted by one reviewer. Conflicts were resolved by discussion with a third reviewer. The quality of included studies was assessed using the JBI Checklist for Prevalence Studies...

OBJECTIVES: SLC6A1 -related disorders encompass heterogeneous neuropsychiatric manifestations through GABAergic dysregulation, without any specific abnormalities on brain MRI, nor evidence of dopaminergic cell loss on I123 -FP-β-CIT SPECT. We report here a case of globus pallidus lesions and dopaminergic denervation in a patient with a pathogenic SLC6A1 variant. METHODS: A 26-year-old female patient with intellectual disability, behavioral, and psychiatric disorders treated by neuroleptics for many years developed a parkinsonian syndrome associated with mild hand dystonia and chorea...

The internal globus pallidus (GPi) is a major source of tonic GABAergic inhibition to the motor thalamus. In parkinsonism, the firing rate of GPi neurons is increased, and their pattern switches from a tonic to a burst mode, two pathophysiological changes associated with increased GABAergic pallidothalamic activity. In this study, we used high-resolution 3D electron microscopy to demonstrate that GPi terminals in the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM), the two main GPi-recipient motor thalamic nuclei in monkeys, undergo significant morphometric changes in parkinsonian monkeys including (1) increased terminal volume in both nuclei; (2) increased surface area of synapses in both nuclei; (3) increased number of synapses/GPi terminals in the CM, but not VApc; and (4) increased total volume, but not number, of mitochondria/terminals in both nuclei...

Analysis of coupling between the phases and amplitudes of neural oscillations has gained increasing attention as an important mechanism for large-scale brain network dynamics. In Parkinson's disease (PD), preliminary evidence indicates abnormal beta-phase coupling to gamma-amplitude in different brain areas, including the subthalamic nucleus (STN). We analyzed bilateral STN local field potentials (LFPs) in eight subjects with PD chronically implanted with deep brain stimulation electrodes during upright quiet standing and unperturbed walking...

OBJECTIVE: This study aimed to elucidate brain areas mediated by oral anti-parkinsonian medicine that consistently show abnormal resting-state activation in PD and to reveal their functional connectivity profiles using meta-analytic approaches. METHODS: Searches of the PubMed, Web of Science databases identified 78 neuroimaging studies including PD OFF state (PD-OFF) versus (vs.) PD ON state (PD-ON) or PD-ON versus healthy controls (HCs) or PD-OFF versus HCs data...

BACKGROUND: Dynamin-related protein 1 (Drp1) plays a critical role in mitochondrial dynamics. Partial inhibition of this protein is protective in experimental models of neurological disorders such as Parkinson's disease and Alzheimer's disease. The protective mechanism has been attributed primarily to improved mitochondrial function. However, the observations that Drp1 inhibition reduces protein aggregation in such neurological disorders suggest the involvement of autophagy. To investigate this potential novel protective mechanism of Drp1 inhibition, a model with impaired autophagy without mitochondrial involvement is needed...

OBJECTIVE: The concomitant stimulation of the subthalamic nucleus and the substantia nigra pars reticulata is a promising approach to improve treatment of refractory axial symptoms in Parkinson`s disease. While dual stimulation of the subthalamic nucleus and the substantia nigra pars reticulata has previously shown beneficial effects on gait, the role of the substantia nigra, a crucial component of the basal ganglia circuitry, in cognitive functions such as attention an executive control remains underexplored...

BACKGROUND: Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease (PD). Previous studies have demonstrated that low-intensity transcranial ultrasound stimulation can significantly suppress the motor symptoms of PD. However, whether ultrasound stimulation can improve cognitive ability in PD and the related neural oscillation mechanism remain unclear to date. OBJECTIVE: To evaluate the effect of ultrasound stimulation on memory ability in PD and explore its neural oscillation mechanism...

OBJECTIVE: Passive monitoring of touchscreen interactions generates keystroke dynamic signals that can be used to detect and track neurological conditions such as Parkinson's disease (PD) and psychomotor impairment with minimal burden on the user. However, this typically requires datasets with clinically confirmed labels collected in standardized environments, which is challenging, especially for a large subject pool. This study validates the efficacy of a self-supervised learning method in reducing the reliance on labels and evaluates its generalizability...

OBJECTIVE: This study used network Meta-analysis to compare the effects of different transcranial magnetic stimulation (TMS) modalities on the effectiveness and long-term validity of improving cognitive function in Parkinson's patients. METHODS: Computer searches of the Cochrane Library, PubMed, Web of Science, Embass, CNKI and Wanfang Data were conducted to collect randomized controlled clinical studies on TMS to improve cognitive function in Parkinson's patients published from the time of library construction to December 2023...

Paraneoplastic movement disorders are diverse autoimmune neurological illnesses occurring in the context of systemic cancer, either in isolation or as part of a multifocal neurological disease. Movement phenomena may be ataxic, hypokinetic (parkinsonian), or hyperkinetic (myoclonus, chorea, or other dyskinetic disorders). Some disorders mimic neurodegenerative or hereditary illnesses. The subacute onset and coexisting nonclassic features of paraneoplastic disorders aid distinction. Paraneoplastic autoantibodies provide further information regarding differentiating cancer association, disease course, and treatment responses...

BACKGROUND: Parkinson's disease (PD) is characterized by death of dopaminergic neurons leading to dopamine deficiency, excessive α-synuclein facilitating Lewy body formation, etc. Latroeggtoxin-VI (LETX-VI), a proteinaceous neurotoxin discovered from the eggs of spider L. tredecimguttatus, was previously found to promote the synthesis and release of PC12 cells, showing a great potential as a drug candidate for PD. However, the relevant mechanisms have not been understood completely...

BACKGROUND: The clinical features and outcomes of post-COVID parkinsonism have not been organized systematically, and the possible correlations between COVID-19 and parkinsonism have not been elucidated. This scoping review addresses these two unmet needs. METHODS: We searched two databases (Pubmed, Embase) for all published cases of post-COVID parkinsonism. Data were extracted from eligible studies using standardized forms and predefined inclusion and exclusion criteria...

OBJECTIVE: Although human induced pluripotent stem cell (iPSC)-derived cell replacement for Parkinson's disease has considerable reparative potential, its full therapeutic benefit is limited by poor graft survival and dopaminergic maturation. Injectable biomaterial scaffolds, such as collagen hydrogels, have the potential to address these issues via a plethora of supportive benefits including acting as a structural scaffold for cell adherence, shielding from the host immune response and providing a reservoir of neurotrophic factors to aid survival and differentiation...

Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role...

BACKGROUND: Magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) VIM-thalamotomy has established efficacy and safety in tremor relief in patients with essential tremor and Parkinson's disease. The efficacy and safety in patients with atypical parkinsonism have not been reported. OBJECTIVE: To report on the efficacy and safety of FUS VIM-thalamotomy in 8 patients with parkinsonism, multiple system atrophy-Parkinsonian type (MSA-P) ( n  = 5), and dementia with Lewy bodies (DLB) ( n  = 3)...

Despite the prevalence of Parkinson's disease (PD), there are no clinically-accepted neuroimaging biomarkers to predict the trajectory of motor or cognitive decline or differentiate Parkinson's disease from atypical progressive parkinsonian diseases. Since abnormal connectivity in the motor circuit and basal ganglia have been previously shown as early markers of neurodegeneration, we hypothesize that patterns of interregional connectivity could be useful to form patient-specific predictive models of disease state and of PD progression...

Self-similar stochastic processes and broad probability distributions are ubiquitous in nature and in many man-made systems. The brain is a particularly interesting example of (natural) complex system where those features play a pivotal role. In fact, the controversial yet experimentally validated "criticality hypothesis" explaining the functioning of the brain implies the presence of scaling laws for correlations. Recently, we have analyzed a collection of rest tremor velocity signals recorded from patients affected by Parkinson's disease, with the aim of determining and hence exploiting the presence of scaling laws...