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Background Parkinson's disease (PD) patients exhibit deficits in saccade performance, pupil function, and blink rate. Isolated REM (rapid eye movement) Sleep Behavior Disorder (RBD) is a harbinger to PD making them candidates to investigate for early oculomotor abnormalities as PD biomarkers. Objectives We tested whether saccade, pupillary, and blink responses in RBD were similar to PD. Methods RBD (n = 22), PD (n = 22) patients, and healthy controls (CTRL) (n = 74) were studied with video-based eye-tracking. Results RBD patients did not have significantly different saccadic behavior compared to CTRL, but PD patients differed from CTRL and RBD. Both patient groups had significantly lower blink rates, dampened pupil constriction, and dilation responses compared to CTRL. Conclusion RBD and PD patients had altered pupil and blink behavior compared to CTRL. Because RBD saccade parameters were comparable to CTRL, pupil and blink brain areas may be impacted before saccadic control areas, making them potential prodromal PD biomarkers. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinson's disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD-related pattern were each associated with increased risk of conversion to PD. The objective of this study was to study the relationship between the PD-related pattern, dopamine transporter binding, and olfaction in idiopathic REM sleep behavior disorder. Methods In this cross-sectional study, 21 idiopathic REM sleep behavior disorder subjects underwent 18F-fluorodeoxyglucose PET, dopamine transporter imaging, and olfactory testing. For reference, we included 18F-fluorodeoxyglucose PET data of 19 controls, 20 PD patients, and 22 patients with dementia with Lewy bodies. PD-related pattern expression z-scores were computed from all PET scans. Results PD-related pattern expression was higher in idiopathic REM sleep behavior disorder subjects compared with controls (P = 0.048), but lower compared with PD (P = 0.001) and dementia with Lewy bodies (P

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 material The online version of this article (doi:10.1007/s00401-017-1684-z) contains supplementary material, which is available to authorized users.

Augmented spinal nociception during the "off" phase has been observed early in Parkinson's disease further increasing with disease duration. To find out whether increased spinal nociception represents a premotor feature, experimental pain sensitivity was assessed in idiopathic REM-sleep behavior disorder (IRBD) patients with or without signs of a neurodegenerative disorder compared to early Parkinson's disease (ePD) patients and healthy controls (HC). Spinal nociception as measured by the nociceptive flexion reflex (NFR) and experimental pain sensitivity as measured by heat and electrical pain thresholds were determined in 14 IRBD, 15 ePD patients in the medication-defined "off" state and 27 HC in an explorative cohort study. No significant differences between IRBD and HC were found with regard to spinal nociception (NFR) and experimental pain sensitivity. However, IRBD patient with anosmia and/or abnormal DaTSCAN tended to increased experimental pain sensitivity. In contrast, early PD patients exhibited increased NFR responses compared to HC, and a tendency for increased spinal nociception compared to IRBD patients. Increased spinal nociception may represent an early but not a premotor, non-motor feature of PD. Whether increased pain sensitivity already presents a premotor feature should be assessed in further studies.

Parkinson's disease (PD) is a frequent neurodegenerative process in old age. Accumulation and aggregation of the lipid-binding SNARE complex component α-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA neurotoxicity have been intensely investigated. In view of the physiological roles of SNCA in blood to modulate vesicle release, we studied blood samples from a new large pedigree with SNCA gene duplication (PARK4 mutation) to identify effects of SNCA gain of function as potential disease biomarkers. Downregulation of complexin 1 (CPLX1) mRNA was correlated with genotype, but the expression of other Parkinson's disease genes was not. In global RNA-seq profiling of blood from presymptomatic PARK4 indviduals, bioinformatics detected significant upregulations for platelet activation, hemostasis, lipoproteins, endocytosis, lysosome, cytokine, Toll-like receptor signaling and extracellular pathways. In PARK4 platelets, stimulus-triggered degranulation was impaired. Strong SPP1, GZMH and PLTP mRNA upregulations were validated in PARK4. When analysing individuals with rapid eye movement sleep behavior disorder, the most specific known prodromal stage of general PD, only blood CPLX1 levels were altered. Validation experiments confirmed an inverse mutual regulation of SNCA and CPLX1 mRNA levels. In the 3'-UTR of the CPLX1 gene we identified a single nucleotide polymorphism that is significantly associated with PD risk. In summary, our data define CPLX1 as a PD risk factor and provide functional insights into the role and regulation of blood SNCA levels. The new blood biomarkers of PARK4 in this Turkish family might become useful for PD prediction.

Hintergrund Die REM-Schlaf-Verhaltensstorung (RBD) ist eine Parasomnie, die durch den Verlust der im REM-Schlaf normalerweise vorliegenden Muskelatonie gekennzeichnet ist. Uber 80 % der Patienten mit idiopathischer RBD entwickeln im spateren Verlauf eine α-Synukleinopathie, d. h. eine Parkinson-Krankheit, eine Demenz mit Lewy-Korpern oder in selteneren Fallen eine Multisystematrophie. Die RBD stellt somit ein hochspezifischer praklinischer Marker dieser neurodegenerativen Erkrankungen dar. Ziel muss es sein, die pramotorische Phase dieser neurodegenerativen Parkinson-Syndrome soweit zu charakterisieren, um zukunftig die Krankheitsprogression mit krankheitsmodifizierenden Therapieansatzen beeinflussen zu konnen. Das erfordert gleichsam eine moglichst fruhe Differenzierung der verschiedenen Verlaufsformen.

Hintergrund Ghrelin und andere Peptidhormone des Gastrointestinaltrakts beeinflussen Stoffwechselprozesse und die Motilitat des Verdauungstraktes. Viele dieser Peptidhormone wirken zusatzlich uber eine Bindung an spezifische Rezeptoren im zentralen Nervensystem (ZNS) auf Prozesse wie Gedachtnisfunktion, Stimmung, Belohnungsverhalten und Schlaf. Die Ausschuttung der Peptidhormone des Gastrointestinaltrakts wird uber unterschiedliche Mechanismen gesteuert. Der N. vagus spielt hierbei eine wichtige Rolle.

Die REM(„rapid eye movement”)-Schlaf-Verhaltensstorung („REM sleep behavior disorder“, RBD) ist definiert als eine Parasomnie, die einerseits durch einen intermittierenden, elektromyographisch nachweisbaren Verlust der REM-Schlaf-assoziierten Atonie und andererseits durch das Auftreten ausgepragter motorischer Aktivitat wahrend des Traumens (in der Regel mit aggressivem Inhalt) charakterisiert ist. Epidemiologische Daten uber die Pravalenz von RBD sind wenig aussagekraftig. Die RBD kann idiopathisch oder symptomatisch sein. Fur ihre Diagnose ist eine Video-Audio-Polysomnographie essenziell. Pharmakologisch stehen fur ihre Behandlung hauptsachlich Clonazepam und Melatonin zur Verfugung. Aktuelle Studien belegen, dass Betroffene mit einer idiopathischen RBD ein auf bis zu 80 % erhohtes spezifisches Risiko haben, in 10 bis 20 Jahren eine neurodegenerative Erkrankung vom α-Synukleinopathie-Typ (Parkinson-Krankheit, Demenz vom Lewy-Korper-Typ, Multisystematrophie) zu entwickeln. Die vorliegende Arbeit liefert eine kurze Ubersicht uber die Klinik, Epidemiologie, Pathophysiologie, Diagnose und Therapie der RBD.

Die Parkinson-Krankheit (PK) ist die zweithaufigste neurodegenerative Erkrankung des alteren Menschen. Sie ist definiert durch die Kardinalsymptome Akinese, Rigor und Ruhetremor. Neben diesen motorischen Symptomen treten aber auch nichtmotorische Symptome wie Depression, Hyposmie, autonome Storungen und spezifische Schlafstorungen auf. Viele PK-Patienten leiden schon vor dem Zeitpunkt der neurologischen Diagnosestellung unter nichtmotorischen Symptomen. Diese Prodromalphase kann unterschiedlich lang sein. Nach bisherigen Studien erreicht als prodromale Marker die hochste Sensitivitat die Hyposmie gefolgt von autonomer Dysfunk­tion (Obstipation), eine hohe Spezifitat wird durch die REM-Schlaf-Verhaltensstorung erreicht. Mit dieser Ausnahme sind die Spezifitaten aller bisherigen klinischen prodromalen Marker gering. Sogenannte Biomarker, die das Auftreten der motorischer PK-Symptome voraussagen, sind in der klinischen Routine bisher nicht etabliert. Neue Marker oder die Kombination von verschiedenen Markern konnten moglicherweise eine bessere prognostische Aussage ermoglichen, und insbesondere bei der Identifizierung von geeigneten Patienten fur krankheitsmodifizierende Therapiestudien hilfreich sein.

Background Idiopathic REM sleep behavior disorder is a prodromal stage of Parkinson's disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD‐related pattern were each associated with increased risk of conversion to PD. The objective of this study was to study the relationship between the PD‐related pattern, dopamine transporter binding, and olfaction in idiopathic REM sleep behavior disorder. Methods In this cross‐sectional study, 21 idiopathic REM sleep behavior disorder subjects underwent 18F‐fluorodeoxyglucose PET, dopamine transporter imaging, and olfactory testing. For reference, we included 18F‐fluorodeoxyglucose PET data of 19 controls, 20 PD patients, and 22 patients with dementia with Lewy bodies. PD‐related pattern expression z‐scores were computed from all PET scans. Results PD‐related pattern expression was higher in idiopathic REM sleep behavior disorder subjects compared with controls (P = 0.048), but lower compared with PD (P = 0.001) and dementia with Lewy bodies (P

We report on two pregnant women who either had de novo restless legs syndrome (RLS) or had marked enhancement of preexisting RLS symptoms during pregnancy. Both patients had ferritin values

Les douleurs sont tres communes dans la maladie de Parkinson (MP) et souvent associees a la maladie. La prevalence des douleurs augmente avec la progression clinique de la MP, de facon egalement parallele avec l’augmentation de la nociception spinale, qui est deja exageree au debut de la maladie. Pour savoir si l’augmentation de la nociception spinale et de la sensibilite a la douleur est un signe precoce precedant les signes moteurs dans la MP, nous avons explore des patients atteints de troubles comportementaux en sommeil paradoxal (TCSP ou REM Behavior Disorder [RBD]). En effet, les TCSP pourraient representer un stade preliminaire au developpement d’une maladie neurodegenerative comme la MP. Nous avons compare des patients TCSP avec des patients atteints de MP dans leurs 5 premieres annees. La nociception spinale etait mesuree au moyen de l’enregistrement du reflexe nociceptif de flexion (Nociceptive Flexion Reflex [NFR]) et la sensibilite a la douleur etait evaluee par un seuil electrique et un seuil thermique au chaud. Les patients atteints de TCSP ne presentaient pas d’anomalies quant aux mesures de nociception spinale et de sensibilite a la douleur, en dehors des patients presentant ouvertement des signes de maladie neurodegenerative (objectives au DATSCAN). Ce dernier groupe avait une sensibilite augmentee a la douleur experimentale provoquee, en comparaison avec un groupe temoin. A l’inverse, les patients atteints de MP montraient une elevation de la nociception spinale. L’augmentation de la sensibilite a la douleur pourrait etre un signe d’atteinte precedant l’atteinte motrice, alors que l’augmentation de la nociception spinale pourrait representer une atteinte non-motrice precoce de la MP.