Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson’s disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls. Skin biopsy was taken at C7, Th10, and the upper and lower leg. Presynaptic dopamine transporter imaging using FP-CIT-SPECT was performed in all patients with RBD and in 11 patients with PD. All RBD patients underwent olfactory function testing. The likelihood ratio (LR) for prodromal PD was calculated for each patient based on published research criteria. Skin serial sections were assessed by double-immunofluorescence labelling with antibodies to pSer129-alpha-syn under blinded conditions. P-alpha-syn was visualized in 10/18 patients with RBD (sensitivity of 55.6%) and in 20/25 early PD patients (sensitivity of 80%) but in none of the controls (specificity of 100%). The percentage of dermal structures innervated by p-alpha-syn-positive fibres was negatively correlated with dopamine transporter binding in the FP-CIT-SPECT (ρ = −0.377, p = 0.048), with olfactory function (ρ = −0.668, p = 0.002), and positively correlated with the total LR for RBD to present prodromal PD (ρ = 0.531, p = 0.023). Dermal p-alpha-syn can be considered a peripheral histopathological marker of synucleinopathy and can be detected in a subgroup of RBD patients presumably representing prodromal PD. Dermal p-alpha-syn is detectable in RBD patients without PD motor symptoms, thereby stratifying a patient group that is of great interest for clinical trials testing disease-modifying drugs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-017-1684-z) contains supplementary material, which is available to authorized users.
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Background: Choosing the adequate systemic treatment for melanoma is driven by clinical parameters and personal preferences. Objective: Evaluation of the impact of disease and treatment on the daily life of patients receiving systemic therapy for melanoma. Methods: A German-wide, cross-sectional comparative study was conducted at 13 specialized skin cancer centres from 08/2020 to 03/2021. A questionnaire was distributed to assess patients' perception of disease and symptoms, the impact of their current treatment on quality of life (QOL) and activities, adverse events (AEs),
Zusammenfassung
Der kutane metastatische Morbus Crohn (MMC) ist eine seltene, aber herausfordernde dermatologische Manifestation des Morbus Crohn (MC). Die Hautläsionen, die nicht in Kontinuität zum Gastrointestinaltrakt stehen, sind histologisch durch nicht verkäsende Granulome charakterisiert. Der MMC ist abzugrenzen von den weitaus häufigeren kutanen Manifestationen des MC, die perianal oder seltener peristomal mit direkter Ausdehnung vom Darm auf die angrenzende Haut auftreten. Die vielgestaltige klinische Morphologie zusammen mit dem Umstand, dass das Auftreten vor der Erstdiagnose eines MC liegen kann, birgt die Gefahr von Fehldiagnosen, verzögerter Behandlung und einer unterschätzten Prävalenz wegen mangelnder Erfassung. Aufgrund der geringen Fallzahlen und fehlender randomisierter kontrollierter Studien bleibt die Erkrankung eine therapeutische Herausforderung. Wir führten daher eine systematische Literaturrecherche durch und identifizierten 264 publizierte pädiatrische sowie erwachsene Fälle von MMC und berichten zusätzlich über drei eigene Fälle. Diese Übersichtsarbeit fasst klinische Merkmale, Konzepte zur vermuteten Ätiopathologie, histologische Befunde, Differenzialdiagnosen und Behandlungsmöglichkeiten für den MMC zusammen.
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