Constipation distinguishes different clinical-biochemical patterns in de novo Parkinson's disease

Parkinson’s disease motor progression in relation to the timing of REM sleep behavior disorder presentation: an exploratory retrospective study

“…PD is a heterogeneous syndrome characterized by the misfolding, aggregation, and subsequent cell-to-cell propagation of pathological α -synuclein inclusions, which share some similarities with prions (Conti et al 2022 ). According to the recent “α-Synuclein Origin and Connectome Model (SOC Model)” of PD, the α -synuclein pathology starts in a single location, the body, or the brain, and then propagates symmetrically or asymmetrically, depending on the origin of the accumulation, defining two types of PD: a “brain first” subtype and a “body first” subtype (Grillo et al 2022 ; Horsager et al 2022 ; Bovenzi et al 2023 ; Schirinzi et al 2023 ).…”

“…Along with primary motor features, namely bradykinesia, tremor, and rigidity, which directly result from nigrostriatal dopaminergic degeneration, PD is characterized by a wide range of non-motor symptoms (NMS) related to a heterogeneous impairment of multiple neurotransmitter networks (Schirinzi et al 2019 ). NMS, such as REM sleep behavior disorder (RBD), constipation, autonomic dysfunction, neuropsychiatric manifestations, and cognitive disturbances, might appear at different time points throughout the progression of PD, mirroring the trajectory of non-dopaminergic systems involvement (Rocchi et al 2021 ; Bellini et al 2022 ; Grillo et al 2022 ). RBD, which is characterized by the loss of physiological muscle atonia during REM sleep and motor activity associated with dream enactment, represents one of the most frequent NMS of PD, with a medium incidence of 42.3% in all PD patients (Boeve et al 2007 ).…”

Constipation and pain in Parkinson’s disease: a clinical analysis

“…It is extensively recognized that individuals with PD exhibit lower levels of physical activity in comparison to healthy individuals (von Rosen et al 2021 ). Thus, despite constipation in PD basically reflects the degeneration of the enteric nervous system by the Lewy Body pathology (Grillo et al 2022 ), physical inactivity may contribute to it. Constipation may long precede the onset of motor symptoms, suggesting that, at least in some cases, neurodegeneration may proceed bottom-up, from the enteric or peripheral autonomic nervous system to the brain (the so called “body-first” hypothesis) (Horsager et al 2022 ).…”

“…One of the most frequent and complaining non-motor symptoms is constipation, which affects up to 80% of PD patients, 20–30% in the early premotor phase (Picillo et al 2021 ; Grillo et al 2022 ). Although considered a condition simply associated with the disease, the latest evidence suggests that prodromal constipation might mark a specific PD neuropathological subtype (the so-called “body-first”) (Horsager et al 2022 ; Grillo et al 2022 ).…”

“…One of the most frequent and complaining non-motor symptoms is constipation, which affects up to 80% of PD patients, 20–30% in the early premotor phase (Picillo et al 2021 ; Grillo et al 2022 ). Although considered a condition simply associated with the disease, the latest evidence suggests that prodromal constipation might mark a specific PD neuropathological subtype (the so-called “body-first”) (Horsager et al 2022 ; Grillo et al 2022 ). Some authors speculate that in the “body-first” PD subtype, α-synuclein forms in the enteric nerve terminals or in the peripheral autonomic nervous system and then spreads via pons to the midbrain, thereby affecting non-dopaminergic nuclei along the route, including locus coeruleus and the raphe area, before substantia nigra is involved (Braak et al 2003 , 2004 ).…”