scholarly journals Diagnostic value of skin RT-QuIC in Parkinson’s disease: a two-laboratory study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Anastasia Kuzkina ◽  
Connor Bargar ◽  
Daniela Schmitt ◽  
Jonas Rößle ◽  
Wen Wang ◽  
...  

AbstractSkin α-synuclein deposition is considered a potential biomarker for Parkinson’s disease (PD). Real-time quaking-induced conversion (RT-QuIC) is a novel, ultrasensitive, and efficient seeding assay that enables the detection of minute amounts of α-synuclein aggregates. We aimed to determine the diagnostic accuracy, reliability, and reproducibility of α-synuclein RT-QuIC assay of skin biopsy for diagnosing PD and to explore its correlation with clinical markers of PD in a two-center inter-laboratory comparison study. Patients with clinically diagnosed PD (n = 34), as well as control subjects (n = 30), underwent skin punch biopsy at multiple sites (neck, lower back, thigh, and lower leg). The skin biopsy samples (198 in total) were divided in half to be analyzed by RT-QuIC assay in two independent laboratories. The α-synuclein RT-QuIC assay of multiple skin biopsies supported the clinical diagnosis of PD with a diagnostic accuracy of 88.9% and showed a high degree of inter-rater agreement between the two laboratories (92.2%). Higher α-synuclein seeding activity in RT-QuIC was shown in patients with longer disease duration and more advanced disease stage and correlated with the presence of REM sleep behavior disorder, cognitive impairment, and constipation. The α-synuclein RT-QuIC assay of minimally invasive skin punch biopsy is a reliable and reproducible biomarker for Parkinson’s disease. Moreover, α-synuclein RT-QuIC seeding activity in the skin may serve as a potential indicator of progression as it correlates with the disease stage and certain non-motor symptoms.

2020 ◽  
Vol 13 (5) ◽  
pp. 508-523 ◽  
Author(s):  
Guan‐Hua Huang ◽  
Chih‐Hsuan Lin ◽  
Yu‐Ren Cai ◽  
Tai‐Been Chen ◽  
Shih‐Yen Hsu ◽  
...  

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040527
Author(s):  
Julia C Greenland ◽  
Emma Cutting ◽  
Sonakshi Kadyan ◽  
Simon Bond ◽  
Anita Chhabra ◽  
...  

IntroductionThe immune system is implicated in the aetiology and progression of Parkinson’s disease (PD). Inflammation and immune activation occur both in the brain and in the periphery, and a proinflammatory cytokine profile is associated with more rapid clinical progression. Furthermore, the risk of developing PD is related to genetic variation in immune-related genes and reduced by the use of immunosuppressant medication. We are therefore conducting a ‘proof of concept’ trial of azathioprine, an immunosuppressant medication, to investigate whether suppressing the peripheral immune system has a disease-modifying effect in PD.Methods and analysisAZA-PD is a phase II randomised placebo-controlled double-blind trial in early PD. Sixty participants, with clinical markers indicating an elevated risk of disease progression and no inflammatory or immune comorbidity, will be treated (azathioprine:placebo, 1:1) for 12 months, with a further 6-month follow-up. The primary outcome is the change in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale gait/axial score in the OFF state over the 12-month treatment period. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life. In addition, peripheral and central immune markers will be investigated through analysis of blood, cerebrospinal fluid and PK-11195 positron emission tomography imaging.Ethics and disseminationThe study was approved by the London-Westminster research ethics committee (reference 19/LO/1705) and has been accepted by the Medicines and Healthcare products Regulatory Agency (MHRA) for a clinical trials authorisation (reference CTA 12854/0248/001–0001). In addition, approval has been granted from the Administration of Radioactive Substances Advisory Committee. The results of this trial will be disseminated through publication in scientific journals and presentation at national and international conferences, and a lay summary will be available on our website.Trial registration numbersISRCTN14616801 and EudraCT- 2018-003089-14.


2021 ◽  
Author(s):  
Milan Nigam ◽  
Ines Ayadi ◽  
Camille Noiray ◽  
Ana Catarina Branquino‐Bras ◽  
Erika Herraez Sanchez ◽  
...  

2021 ◽  
pp. 135901
Author(s):  
Alma Cristina Salas-Leal ◽  
Sergio M. Salas-Pacheco ◽  
Alfredo Pérez Gavilán-Ceniceros ◽  
Francisco X. Castellanos-Juárez ◽  
Edna M. Méndez-Hernández ◽  
...  

2021 ◽  
Vol 36 ◽  
pp. 153331752110213
Author(s):  
Anamaria Jurcau ◽  
Vharoon Sharma Nunkoo

Background: The study aims at identifying features predictive of early onset of dementia in Parkinson’s disease (PD). Methods: 103 non-demented PD patients were evaluated on various scales at baseline and 89 patients at 3-year follow-up. Results: By the end of the study 43.8% of patients developed dementia. The development of dementia was linked to the baseline Mini Mental State Examination score (Pearson coefficient r = .404, p = 0.013), the presence of autonomic dysfunctions (r = −.621, p < 0.001) and insomnia (r = −.526, p = 0.001). A binary logistic regression analysis showed that the development of dementia was correlated strongly with the presence of autonomic dysfunctions (95% CI 2.60 to 52.83, p < 0.001), and insomnia (95% CI 0.60 to 0.95, p = 0.017). Conclusion: Patients with signs of autonomic dysfunction and insomnia are at higher risk for developing dementia and deserve closer monitoring of cognitive symptoms.


2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Chen Tian ◽  
Genliang Liu ◽  
Liyan Gao ◽  
David Soltys ◽  
Catherine Pan ◽  
...  

2021 ◽  
pp. jnnp-2020-323939
Author(s):  
Umer Akbar ◽  
Robert Brett McQueen ◽  
Julienne Bemski ◽  
Julie Carter ◽  
Elizabeth R Goy ◽  
...  

Parkinson’s disease and related disorders (PDRD) are the second most common neurodegenerative disease and a leading cause of death. However, patients with PDRD receive less end-of-life palliative care (hospice) than other illnesses, including other neurologic illnesses. Identification of predictors of PDRD mortality may aid in increasing appropriate and timely referrals. To systematically review the literature for causes of death and predictors of mortality in PDRD to provide guidance regarding hospice/end-of-life palliative care referrals. We searched MEDLINE, PubMed, EMBASE and CINAHL databases (1970–2020) of original quantitative research using patient-level, provider-level or caregiver-level data from medical records, administrative data or survey responses associated with mortality, prognosis or cause of death in PDRD. Findings were reviewed by an International Working Group on PD and Palliative Care supported by the Parkinson’s Foundation. Of 1183 research articles, 42 studies met our inclusion criteria. We found four main domains of factors associated with mortality in PDRD: (1) demographic and clinical markers (age, sex, body mass index and comorbid illnesses), (2) motor dysfunction and global disability, (3) falls and infections and (4) non-motor symptoms. We provide suggestions for consideration of timing of hospice/end-of-life palliative care referrals. Several clinical features of advancing disease may be useful in triggering end-of-life palliative/hospice referral. Prognostic studies focused on identifying when people with PDRD are nearing their final months of life are limited. There is further need for research in this area as well as policies that support need-based palliative care for the duration of PDRD.


Author(s):  
F. Sartucci ◽  
T. Bocci ◽  
M. Santin ◽  
P. Bongioanni ◽  
G. Orlandi

Abstract Background and rationale Histopathological studies revealed degeneration of the dorsal motor nucleus of the vagus nerve (VN) early in the course of idiopathic Parkinson’s disease (IPD). Degeneration of VN axons should be detectable by high-resolution ultrasound (HRUS) as a thinning of the nerve trunk. In order to establish if the VN exhibits sonographic signs of atrophy in IPD, we examined patients with IPD compared with age-matched controls. Material and methods We measured the caliber (cross-sectional area, CSA) and perimeter of the VN in 20 outpatients with IPD (8 females and 12 males; mean age 73.0 + 8.6 years) and in age-matched controls using HRUS. Evaluation was performed by blinded raters using an Esaote MyLab Gamma device in conventional B-Mode with an 8–19 MHz probe. Results In both sides, the VN CSA was significantly smaller in IPD outpatients than in controls (right 2.37 + 0.91, left 1.87 + 1.35 mm2 versus 6.0 + 1.33, 5.6 + 1.26 mm2; p <0.001), as well as the perimeter (right 5.06 + 0.85, left 4.78 + 1.74 mm versus 8.87 + 0.86, 8.58 + 0.97 mm; p <0.001). There were no significant correlations between VN CSA and age, the Hoehn and Yahr scale, L-dopa therapy, and disease duration. Conclusion Our findings provide evidence of atrophy of the VNs in IPD patients by HRUS. Moreover, HRUS of the VN represent a non-invasive easy imaging modality of screening in IPD patients independent of disease stage and duration and an interesting possible additional index of disease.


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