Premotor Parkinson’s disease

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Parkinson’s disease (PD) is characterized by typical motor symptoms. However, recent studies show several non-motor features that may precede the development of the motor symptoms of PD. The best known premotor symptoms include hyposmia, REM sleep behavior disorder (RBD), constipation, and depression; other symptoms are excessive daytime somnolence, orthostatic hypotension and symptomatic hypotension, erectile or urinary dysfunction, musculoskeletal symptoms, pain, and global cognitive deficit. In this review, we summarize currently available diagnostic methods for these symptoms. We also briefly summarize neuroimaging, polyneuropathy, peripheral markers, and cerebrospinal fluid biomarkers that may be used in the early diagnosis of PD.




INTRODUCTION

Parkinson’s disease (PD) is characterized by typical motor symptoms caused by degeneration of the substantia nigra. However, recent studies show that Lewy pathology in PD is not only present in the midbrain; it is a diffuse synucleinopathy affecting both the central and peripheral nervous system, spreading in a caudo-rostral pattern1,2. This widespread pathology results in a number of nonmotor symptoms, some of which may be present for years before the development of the typical motor symptoms of PD.

The Movement Disorders Society proposed research diagnostic criteria for prodromal PD in 2015 (ref.3 ) and updated them in 2019 (, ref.4 ). These criteria comprise symptoms with a predictive value for developing PD that has been documented in prospective studies. The criteria have been validated on the general population5, REM sleep behavior disorder patients6, and LRRK2 mutation carriers7; the criteria seem to be a promising tool in identifying PD in the premotor stage5,8,9.

The best known premotor symptoms of PD include hyposmia, REM sleep behavior disorder (RBD), constipation, and depression; other non-motor features are excessive daytime somnolence, orthostatic hypotension, and symptomatic hypotension, erectile or urinary dysfunction, and global cognitive deficit. Pain, sometimes accompanied by musculoskeletal symptoms, may also occur in the premotor phase of PD.

The aim of this review is to summarize the currently available methods for diagnosing the premotor symptoms of PD which may help in the early diagnosis of PD.




*Olfactory functions
*Autonomic dysfunction
*Constipation
*Erectile dysfunction
*Urinary dysfunction
*Orthostatic hypotension and symptomatic hypotension
*REM sleep behavior disorder (RBD) and excessive daytime somnolence
*Depression
*Cognitive deficit
*Pain
*Small fiber neuropathy
*Neuroimaging
*Peripheral markers
*Cerebrospinal fluid







In conclusion, recent studies show that there are several non-motor symptoms with predictive value for the
development of PD. They are currently being tested in research settings due to the lack of effective neuroprotective therapy. However, as soon as an adequate treatment is available, it will be a priority for clinicians to establish the diagnosis of PD in the early/premotor stages in order to preserve the patients’ quality of life.
 

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