Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update—I. Hypokinetic-rigid movement disorders

Journal of Neural Transmission, Journal Year: 2019, Volume and Issue: 126(8), P. 933 - 995

Published: June 18, 2019

Language: Английский

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Pedunculopontine Nucleus Degeneration Contributes to Both Motor and Non-Motor Symptoms of Parkinson’s Disease

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 10

Published: Jan. 15, 2020

Parkinson's disease (PD) is a neurodegenerative disorder characterized by hypokinetic motor features; however, patients also display non-motor symptoms like sleep disorders. The standard treatment for PD dopamine replacement with L-DOPA; many symptoms, including gait deficits and disorders are unresponsive to L-DOPA. Notably, these have been linked aberrant activity in the pedunculopontine nucleus (PPN). Of late, clinical trials involving PPN deep brain stimulation (DBS) employed alleviate deficits. Although preclinical evidence implicating cholinergic neurons dysfunction was initially promising, DBS fell short of expected outcomes. One reason failure may be that heterogenous consists GABAergic, cholinergic, glutamatergic project diverse array structures. Second, unsuccessful because susceptible mitochondrial dysfunction, lewy body pathology, degeneration PD. Therefore, pharmaceutical or gene-therapy strategies targeting specific neuronal populations projections could better intractable symptoms. Unfortunately, how their respective influence nonmotor remains enigmatic. Herein we discuss normal cellular neuroanatomical features PPN, differential susceptibility PD-related insults, give an overview literature suggesting role Finally, identify future approaches directed towards

Language: Английский

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Striatal Acetylcholine–Dopamine Imbalance in Parkinson Disease: In Vivo Neuroimaging Study with Dual-Tracer PET and Dopaminergic PET–Informed Correlational Tractography

Journal of Nuclear Medicine, Journal Year: 2021, Volume and Issue: 63(3), P. 438 - 445

Published: July 16, 2021

Previous studies of animal models Parkinson9s disease (PD) suggest an imbalance between striatal acetylcholine (ACh) and dopamine (DA), although other have questioned this. To our knowledge, there are no previous in vivo neuroimaging examining ACh-DA PD patients. Using cholinergic dopaminergic PET (¹⁸F-FEOBV ¹¹C-DTBZ, respectively) correlational tractography, aim was to investigate the interaction at two levels loss subjects: integrity nigrostriatal white matter tract; presynaptic-terminal level. Methods: The study involved 45 subjects with mild moderate (36 men, 9 women; mean age, 66.3 ± 6.3 years, duration, 5.8 3.6; Hoehn Yahr stage, 2.2 0.6) 15 control (9 6 69.1 8.6 years). imaging performed using standard protocols. We first estimated tracts by incorporating molecular information from ¹¹C-DTBZ into fiber tracking process tractography (based on quantitative anisotropy, QA; a measure tract integrity). Subsequently, we used voxel-based correlation test association QA each cerebral hemisphere ¹⁸F-FEOBV distribution volume ratio (DVR) subjects. same analysis for DVR 12 subregions (presynaptic-terminal level). Results: Unlike subregions, most affected (MA) showed negative cluster (p corrected= 0.039). also found that within this higher group compared (P = 0.01). Cross-validation analyses confirmed these findings. increase bradykinesia ratings associated increased MA (r=0.41, P 0.006). Conclusion: Our results provide evidence existence early may avenue testing effects therapeutic strategies aimed restoring PD.

Language: Английский

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Regional cerebral cholinergic nerve terminal integrity and cardinal motor features in Parkinson’s disease

Brain Communications, Journal Year: 2021, Volume and Issue: 3(2)

Published: April 1, 2021

Clinical effects of anti-cholinergic drugs implicate cholinergic systems alterations in the pathophysiology some cardinal motor impairments Parkinson's disease. The topography affected deficits and domain specificity are poorly understood. disease patients (n = 108) underwent clinical assessment vesicular acetylcholine transporter [18F]-fluoroethoxybenzovesamicol PET imaging. Volumes-of-interest-based analyses included detailed thalamic cerebellar parcellations. Successful sampling for most small-sized parcellations was available 88 patients. A data-driven approach, stepwise regression using forward selection method, used to identify brain regions associating with domain-specific ratings. Regressions scores model-selected followed by confounder analysis age onset, duration levodopa equivalent dose were performed. Among 7 model-derived postural instability gait difficulties three retained significance variable analysis: medial geniculate nucleus (standardized β -0.34, t -3.78, P 0.0003), lateral (β -0.32, -3.4, 0.001) entorhinal cortex -0.23, -2.6, 0.011). sub-analysis non-episodic demonstrated significant nucleus, globus pallidus pars interna. 6 tremor two vermis section lobule VIIIb -0.22, -2.4, 0.021) putamen -2.3, 0.024). None variables rigidity survived analysis. Two out four distal limb bradykinesia externa 0.36, 3.9, 0.0097) paracentral 0.26, 2.5, 0.013). Emphasizing utility a systems-network conception features, our results consistent specific basal forebrain corticopetal, peduncupontine-laterodorsal tegmental complex, vestibular pathways, against background nigrostriatal dopaminergic deficits, contributing significantly instability, difficulties, features Our suggest distinct consequences degeneration complex afferents both segments pallidus. Non-specific regional nerve terminal associations likely reflect more multifactorial signalling mechanisms smaller contributions from pathways.

Language: Английский

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Mapping Cholinergic Synaptic Loss in Parkinson’s Disease: An [18F]FEOBV PET Case-Control Study

Journal of Parkinson s Disease, Journal Year: 2022, Volume and Issue: 12(8), P. 2493 - 2506

Published: Nov. 1, 2022

Cholinergic degeneration is strongly associated with cognitive decline in patients Parkinson's disease (PD) but may also cause motor symptoms and olfactory dysfunction. Regional differences are striking reflect different PD related progression patterns.To map quantify the regional cerebral cholinergic alterations non-demented patients.We included 15 early-moderate stage age- sex-matched healthy controls for [18F]FEOBV positron emission tomography imaging. We quantitated variations using VOI-based analyses which were supported by a vertex-wise cluster analysis. Correlations between imaging data clinical neuropsychological explored.We found significantly decreased uptake global neocortex (38%, p = 0.0002). The most severe reductions seen occipital posterior temporo-parietal regions (p < 0.0001). analysis corroborated these findings. All subcortical structures showed modest non-significant reductions. Motor (postural instability gait difficulty) cognition (executive function composite z-score) correlated (thalamus cingulate cortex/insula/hippocampus, respectively), correlations not statistically significant after multiple comparison correction. A strong correlation was interhemispheric asymmetry, symptom asymmetry of extremities (r 0.84, 0.0001).Cortical prominent patients, more subtle structures. suggest uneven involvement nuclei brain represent window to follow progression. asymmetric neocortical indicates that unilateral parallels ipsilateral dopaminergic degeneration.

Language: Английский

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