Reduced intraepidermal nerve fiber density in patients with REM sleep behavior disorder.
Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) has been increasingly acknowledged to be an initial specific manifestation of alpha-synucleinopathies such as Parkinson's disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB). Recent findings suggest that cutaneous abnormalities like small fiber neuropathy and alpha-synuclein deposition might reflect brain pathology and might function as early biomarkers in PD. This is the first study to elucidate whether iRBD patients already suffer from distinctive cutaneous features.



We examined skin punch biopsies from the distal leg of 18 iRBD patients and 22 age- and sex-matched controls using immunohistochemistry and microscopy. Further clinical evaluation included structured interviews, clinical motor and non-motor questionnaires and rating scales (e.g. Unified Parkinson's disease rating scale [UPDRS], non-motor symptoms questionnaire [NMS-Quest] and Beck Depression Inventory, Epworth Sleepiness Scale, evaluation of cognitive and olfactory functioning as well as blood samples.



Intraepidermal nerve fiber density (IEFND) was reduced in iRBD patients compared to controls (p = 0.037), whereas the axon swelling ratio did not differ between groups. Patients with iRBD reported non-motor symptoms more frequently than controls (UPDRS I, NMS-Quest). Olfaction and daytime sleepiness differed between both groups, whereas there were no differences regarding cognition.



These in vivo findings demonstrate small fiber neuropathy in iRBD patients that are associated with non-motor symptoms indicating that peripheral abnormalities may occur early in iRBD. However, the prognostic value has to be further investigated in longitudinal studies.
Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
Wiebke
W
Schrempf
Institute of Neuropathology, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.
Istvan
I
Katona
Department of Neurology, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany; Jülich Aachen Research Alliance (JARA) BRAIN Institute II, Research Center Jülich GmbH and RWTH Aachen, Germany.
Imis
I
Dogan
Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany.
Verena V
VV
Felbert
Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
Miriam
M
Wienecke
Department of Neurology, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany; Jülich Aachen Research Alliance (JARA) BRAIN Institute II, Research Center Jülich GmbH and RWTH Aachen, Germany.
Julia
J
Heller
Department of Neurology, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.
Andrea
A
Maier
Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany; German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307 Dresden, Germany.
Andreas
A
Hermann
Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
Katharina
K
Linse
Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
Moritz D
MD
Brandt
Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany.
Heinz
H
Reichmann
Department of Neurology, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany; Jülich Aachen Research Alliance (JARA) BRAIN Institute II, Research Center Jülich GmbH and RWTH Aachen, Germany.
Jörg B
JB
Schulz
Department of Neurology, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.
Johannes
J
Schiefer
Department of Neurology, Philipps University Marburg, Germany.
Wolfgang H
WH
Oertel
Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany; Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany; German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307 Dresden, Germany; Department of Neurology, University of Rostock, 18147 Rostock, Germany.
Alexander
A
Storch
Institute of Neuropathology, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.
Joachim
J
Weis
Department of Neurology, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany; Jülich Aachen Research Alliance (JARA) BRAIN Institute II, Research Center Jülich GmbH and RWTH Aachen, Germany. Electronic address: kreetz@ukaachen.de.
Kathrin
K
Reetz
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology* / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D020187:REM Sleep Behavior Disorder / Q000473:pathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D055815:Young Adult
C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase
Alpha-synucleinopathies; Neuropathy; Parkinson’s disease; Skin biopsy; iRBD