Abstract
The functional anatomy of the reticular formation (RF) encompasses a constellation of brain regions which are reciprocally connected to sub-serve a variety of functions. Recent evidence indicates that neuronal degeneration within one of these regions spreads synaptically along brainstem circuitries. This is exemplified by the recruitment of various brainstem reticular nuclei in specific Parkinson’s disease (PD) phenotypes, and by retrospective analysis of lethargic post-encephalitic parkinsonism. In fact, the spreading to various monoamine reticular nuclei can be associated with occurrence of specific motor and non-motor symptoms (NMS). This led to re-consider PD as a brainstem monoamine disorder (BMD). This definition surpasses the anatomy of meso-striatal motor control to include a variety of non-motor domains. This concept clearly emerges from the quite specific clinical-anatomical correlation which can be drawn in specific paradigms of PD genotypes. Therefore, this review article focuses on the genetics and neuroanatomy of three PD genotypes/phenotypes which can be selected as prototype paradigms for a differential recruitment of the RF leading to differential occurrence of NMS: (i) Parkin-PD, where NMS are rarely reported; (ii) LRRK2-PD and slight SNC point mutations, where the prevalence of NMS resembles idiopathic PD; (iii) Severe SNCA point mutations and multiplications, where NMS are highly represented.
Highlights
In the process of re-defining Parkinson’s disease (PD) a task force is working on various symptoms which, despite being unrelated to the extra-pyramidal motor system, are considered as fundamental features of PD (Poewe, 2008; Fornai and Ruggieri, 2013; Marras and Chaudhuri, 2016; Wei et al, 2016)
We proposed the definition of brainstem monoamine disorder (BMD) as more balanced to define the neuroanatomy of PD
SNCA duplications lead to various non-motor symptoms (NMS) albeit with lower prevalence compared with carriers of four SNCA copies, but still higher compared with idiopatic PD (i-PD)
Summary
In the process of re-defining Parkinson’s disease (PD) a task force is working on various symptoms which, despite being unrelated to the extra-pyramidal motor system, are considered as fundamental features of PD (Poewe, 2008; Fornai and Ruggieri, 2013; Marras and Chaudhuri, 2016; Wei et al, 2016). Brain areas, which control extra-pyramidal motor systems concomitantly, affect other neurological and psychiatric domains This is evident when examining several reticular brainstem nuclei, whose functions affect both extrapyramidal motor circuitries and a variety of non-motor domains during the neuropathology of sporadic PD (S-PD; Fornai and Ruggieri, 2013). There is an appreciable site-specificity, which connects neuroanatomy with the onset of NMS and this works as a general model to build a clinical anatomical correlation within various PD syndromes Within this context, progress in neurogenetics provided a powerful tool to improve PD nosography since specific gene/protein alterations connect quite with clusters of both motor and NMS, which in turn, are related to a damage in quite selective brain areas. This resembles most SNCA point mutations but p.G51D, as well as S-PD patients (Figure 1)
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