ORCID Profile
0000-0002-5403-1959
Current Organisation
Philipps University of Marburg
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Publisher: Frontiers Media SA
Date: 09-08-2021
DOI: 10.3389/FNEUR.2021.710572
Abstract: Background: Pathogenic variants in the Leucine-rich repeat kinase 2 ( LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2 -linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions. Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data. Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood s les (to obtain DNA, RNA, serum lasma, immune cells), urine as well as household dust. We plan to enroll 1,000 participants internationally: 300 with LRRK2 -linked PD, 200 with LRRK2 pathogenic variants but without PD, 100 PD patients with pathogenic variants in the GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without pathogenic variants. Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part. The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating, Hoehn & Yahr, and Schwab & England Scales, the Brief Smell Identification Test, and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction, and quality of life questionnaires, the Pittsburgh Sleep Quality Inventory, and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales. The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th, 2021). Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2 -linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivity Clinical Trial Registration: ClinicalTrials.gov , NCT04214509.
Publisher: Springer Science and Business Media LLC
Date: 25-05-2020
DOI: 10.1186/S12883-020-01788-Z
Abstract: Cerebellar degeneration as a consequence of a malignancy is a rare condition most commonly related to the presence of anti-Yo, anti-Hu, and anti-Tr/DNER antibodies. In recent years, several reports have indicated Zinc-finger protein 4 (Zic4) antibodies being associated with paraneoplastic cerebellar degeneration (PCD) in patients with small cell lung carcinoma. However, the prevalence and the significance of Zic4-antibodies may be underestimated due to their co-occurrence with more frequent antibodies such as anti-Hu. A literature review of isolated Zic4 mediated paraneoplastic syndromes yielded 14 cases reporting mainly benign clinical courses when treated early. We present the case of a 67-year-old woman with progressive Zic4 antibody mediated PCD and rhombencephalitis. Immunomodulatory treatment, including intravenous methylprednisolone, plasmaphereses, and intravenous immunoglobulin (IVIG) was administered. Small cell lung cancer (SCLC) was detected, lobectomy performed and cyclophosphamide started. Despite this considerable therapeutic effort, rhombencephalitis led to defiant dysautonomia. Paraneoplastic syndromes related to isolated Zic4 antibodies are rare and typically show a benign clinical course. Here, we present the first case of a rapidly progressive isolated Zic4 associated PCD and rhombencephalitis. Despite considerable therapeutic efforts, the patient passed away on autonomic dysfunction, highlighting the significance of Zic4 associated disease.
Publisher: Cold Spring Harbor Laboratory
Date: 25-04-2023
DOI: 10.1101/2023.04.25.23289088
Abstract: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for motor and non-motor symptoms in advanced Parkinson’s disease (PD). However, considerable interin idual variability of outcomes exists. Neuroimaging based biomarkers, such as neurite orientation dispersion and density imaging (NODDI), a biophysical model based MRI-technique, have been proposed to predict clinical outcomes and therefore inform preoperative patient counselling. To detect microstructural properties of brain areas associated with short-term non-motor outcomes following STN-DBS in PD. In this prospective open-label study, 37 PD patients underwent diffusion MRI and comprehensive clinical assessments at preoperative baseline and 6-month follow-up. Neurite density index (NDI), orientation dispersion index (ODI), and fractional anisotropy (FA) were derived. Whole brain voxel-wise analysis assessed associations between microstructural metrics and non-motor outcomes corrected for multiple comparisons using a permutation-based approach. Intact microstructure within specific areas including right insular cortex, right putamen, right cingulum, and bilateral corticospinal tract were associated with greater postoperative improvement of non-motor symptom burden. Furthermore, microstructural properties of distinct brain regions were associated with postoperative changes in sleep, attention/memory, and urinary symptoms. Microstructural properties of distinct brain areas predict non-motor outcomes in DBS for PD. Therefore, diffusion MRI can support preoperative patient counselling and treatment selection by identifying patients with above-or below-average non-motor responses.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David Pedrosa.