The aggregation of α-synuclein (α-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Postmortem analyses of α-syn pathology, especially that of PD, have suggested that aggregates progressively spread from a few discrete locations to wider brain regions. The neuron-to-neuron propagation of α-syn has been suggested to be the underlying mechanism by which aggregates spread throughout the brain. Many cellular and animal models has been created to study cell-to-cell propagation. Recently, it has been shown that a single injection of preformed fibrils (PFFs) made of recombinant α-syn proteins into various tissues and organs of many different animal species results in widespread α-syn pathology in the central nervous system (CNS). These PFF models have been extensively used to study the mechanism by which aggregates spread throughout the brain. Here, we review what we have learned from PFF models, describe the nature of PFFs and the neuropathological features, neurophysiological characteristics, and behavioral outcomes of the models.
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Oro-pharyngeal dysphagia is a common symptom in patients with Parkinson’s disease (PD) and related disorders, even in their early stage of diseases. Dysphagia in these patients has been underdiagnosed, probably due to poor the self-awareness of the conditions and the underuse of validated tools and objective instruments for assessment. The early detection and intervention of dysphagia are closely related to improving the quality of life and decreasing the mortality rate in these patients. The purpose of this paper is to give an overview of the characteristics of dysphagia, including the epidemiology, pathophysiology, and clinical symptomatology, in patients with PD compared with other parkinsonian disorders and movement disorders. The management of dysphagia and future research directions related to these disorders are also discussed.
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Objective The provisional diagnosis of progressive supranuclear palsy (PSP) depends on a combination of typical clinical features and specific MRI findings, such as atrophy of the tegmentum in the midbrain. Atrophy of the superior cerebellar peduncle (SCP) distinguishes PSP from other types of parkinsonism. Histological factors affect the conventional fluid-attenuated inversion recovery (FLAIR) signals, such as the extent of neuronal loss and gliosis.
Methods We investigated patients with PSP to verify the percentage of patients with various PSP phenotypes presenting a high signal intensity in the SCP. Three interviewers, who were not informed about the clinical data, visually inspected the presence or absence of a high signal intensity in the SCP on the FLAIR images. We measured the pixel value in the SCP of each patient. Clinical characteristics were evaluated using the Mann-Whitney test, followed by the χ2 test.
Results Ten of the 51 patients with PSP showed a high signal intensity in the SCP on FLAIR MRI. Higher pixel values were observed within the SCP of patients with a high signal intensity in the SCP than in patients without a high signal intensity (p < 0.001). The sensitivity and specificity of the high signal intensity in the SCP of patients with PSP was 19.6% and 100%, respectively. This finding was more frequently observed in patients with PSP with Richardson’s syndrome (PSP-RS) (25.7%) than other phenotypes (6.2%).
Conclusion The high signal intensity in the SCP on FLAIR MRI might be an effective diagnostic tool for PSP-RS.
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Diffusion tractography of superior cerebellar peduncle and dentatorubrothalamic tracts in two autopsy confirmed progressive supranuclear palsy variants: Richardson syndrome and the speech-language variant Rodolfo G. Gatto, Peter R. Martin, Farwa Ali, Heather M. Clark, Joseph R. Duffy, Rene L. Utianski, Hugo Botha, Mary M. Machulda, Dennis W. Dickson, Keith A. Josephs, Jennifer L. Whitwell NeuroImage: Clinical.2022; 35: 103030. CrossRef
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Objective Impulse control disorders (ICDs) in Parkinson’s disease (PD) are mostly related to dopamine replacement therapy (DRT); however, drug-naïve PD patients have also frequently experienced impulsivity. This phenomenon makes clinicians hesitate treating patients with DRT. In this study, we assessed the effect of impulsivity on quality of life (QOL) in drug-naïve PD patients.
Methods Two hundred three newly diagnosed, nonmedicated PD patients were enrolled, and they received structured clinical interviews, physical examinations and validated questionnaires to evaluate motor and nonmotor symptoms and QOL. Impulsivity was evaluated using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale (QUIP-RS).
Results Thirty-eight patients (18.7%) had impulsivity with QUIP-RS scores ≥ 1 and 4 patients (2.0%) were diagnosed with combined ICDs. Motor and nonmotor symptoms were significantly correlated with the Parkinson’s Disease Questionnaire-39 summary index. Female sex and QUIP-RS scores were also correlated with QOL in drug-naïve PD patients.
Conclusion The results of the present study showed that impulsivity negatively influences QOL in early drug-naïve PD patients. In addition, more severe motor and nonmotor symptoms were also associated with lower QOL. Such findings complicate treatment but provide valuable information for managing early PD.
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Objective Multiple System Atrophy (MSA) and progressive supranuclear palsy (PSP) are rapidly progressive forms of degenerative Parkinsonism. The difficulties of diagnosing MSA and PSP in their early stages may lead to delayed referral to appropriate specialists and distress to patients, as well as delaying symptomatic treatment and participation in clinical trials. This work aimed to describe the symptoms that patients with MSA and PSP developed and plot their emergence relative to final diagnosis using a median onset in months.
Methods Forty-seven patients from the United Kingdom with MSA or PSP diagnosed by a movement disorder specialist were interviewed with carers or relatives to establish milestone onset. This was corroborated using clinical notes and letters.
Results In the MSA cohort (n = 23), autonomic symptoms (median 5.5 months before diagnosis) and falls (median 1 month before diagnosis) were the two clinical milestones which occurred before diagnosis. In the PSP cohort (n = 24), falling was the only milestone which occurred before diagnosis (median of 18.5 months).
Conclusion This Study Shows That Psp Patients Experience Falling More Than A Year And A Half An Average Before Receiving A Diagnosis And Although Msa Patients Also Tended To Fall, This Was Much Closer To The Time Of Diagnosis. Further Work With Larger Cohorts May Illustrate Whether These Preliminary Findings Can Be Generalised To Guide Diagnosis And Management.
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