Highlights • These consensus criteria update the 2003 diagnostic criteria for RLS/WED. • A new essential criterion, differential diagnosis, improves diagnostic specificity. • The clinical ...significance of RLS/WED is determined by a new specifier. • A course specifier classifies RLS/WED as chronic-persistent or intermittent. • The pediatric diagnostic criteria have been merged with the adult criteria.
To investigate the frequency, phenomenology, and associated risk factors of REM sleep behavior disorder (RBD) in Parkinson disease (PD).
An unselected cohort of sleep-disturbed patients with PD ...(n=457) was investigated with video-supported polysomnography. We determined the frequency of RBD and analyzed the influence of age, clinical disease features, disease duration, cognitive and physical impairment, medication, comorbidity, and sleep architecture.
The overall frequency of RBD was 46%. According to our cohort and modified definition, there was no preferred PD subtype for RBD (p=0.142). There was no gender preference (p=0.770). RBD was associated with older age (p=0.000). Adjusted for age and gender, patients with PD and RBD had longer disease duration (p=0.024), higher Hoehn & Yahr stages (p=0.002), more falls (p=0.018), more fluctuations (p=0.005), more psychiatric comorbidity (p=0.026), and a higher dose of levodopa (p=0.002). The presence of RBD was related to slightly increased sleep efficiency (p=0.007), a higher amount of REM sleep (p=0.000), and more periodic leg movements during sleep (p=0.019).
RBD is a frequent and clinically relevant nocturnal disturbance for all stages of PD. It increases with age and disease duration and may contribute to the nocturnal problems of patients with PD and their bed partners.
Immune-related alterations in Parkinson's disease (PD) can be monitored by assessing peripheral biological fluids that show that specific inflammatory pathways contribute to a chronic ...pro-inflammatory status. This pro-inflammatory activity is hypothesized to be already present in the prodromal stages of PD. These pathways maintain and reinforce chronic neurodegeneration by stimulating cell activation and proliferation what triggers the pro-inflammatory status as well. The gut microbiome possibly contributes to inflammatory pathways and shows specific differences in fecal samples from PD compared to healthy controls. In PD, Bacteroides abundance correlates with inflammatory markers in blood and motor impairment. Increased pro-inflammatory and decreased anti-inflammatory bacterial colonization can lead to changes in the metabolic pathways of amino acids, inducing increased membrane permeability, described as a leaky gut, enabling advanced contact between immune cells and gut microbiome and potentially a spreading of neuroinflammation through the body via the blood. Increased cytokine blood levels in PD are correlated with disease severity, motor symptoms, and clinical phenotypes.
α-synuclein is a central player in PD-associated inflammation, inducing specific T-cell activity and triggering microglial activation in the central nervous system (CNS). Misfolded α-synuclein propagation possibly results in the spreading of aggregated α-synuclein from neuron to neuron leading to a sustained neuroinflammation. This is supported by age-dependent defects of protein uptake in microglia and monocytes, so-called “inflammaging”, including α-synuclein oligomers, as the key pathological protein in PD.
Genetic risk markers and inherited forms of PD are also associated with inflammation, which is highly relevant for potential therapeutical targets.
The documented associations of inflammatory markers and clinical phenotypes indicate a pro-inflammatory concept of specific PD pathophysiology here. An in-depth understanding of inflammatory mechanisms in PD from bottom (gut) to top (CNS) and vice versa is needed to design novel immunomodulatory approaches to delay or even stop PD. Future studies focusing on structured protocols in large patient cohorts with appropriate control groups and comparative analysis among studies will aid the discovery of novel candidate biomarkers.
•Specific characteristics in PD gut microbiome induces metabolic changes and increased membrane permeability: “leaky gut”.•The "leaky gut" enables advanced contact between immune cells and gut microbiome.•Immune-related alterations in PD can be monitored in biological fluids from the periphery, already in prodromal stages.•α-synuclein induces specific T-cell activity, triggering microglial activation and possibly sustained neuroinflammation.•“inflammaging” in PD supports age-dependent defects in microglia and monocytes, including α-synuclein oligomer uptake.•Some genetic risk markers and inherited PD forms are associated with inflammation.
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