Non motor subtypes and Parkinson's disease

Abstract

Word count abstract: 163 Word count manuscript: 2839 References: 30 2 AbstractNon motor symptoms (NMS) represent a significant burden in Parkinson's disease (PD) with numerous studies highlighting the importance of NMS both in "pre-motor" phase of PD as well as throughout the disease course. In part this has led the international Parkinson and Movement Disorder Society (IPMDS) task force to attempt a re-definition of PD incorporating NMS and not base the diagnosis solely on motor symptoms. While motor subtypes within PD have been recognized and researched, recent, clinical and neurobiological research suggests the existence of discrete non-motor subtypes in PD, particularly in untreated (drug naïve) and early PD patients. Several independent observers have reported specific "clusters of NMS dominant PD" using a data driven approach in early and untreated PD patients while others have reported on the burden of NMS in untreated PD and specific NMS dominant phenotypes in untreated or treated PD using observational case series based data. In this review we report on specific NMS dominant phenotypes of PD as described in the literature using clinical observational studies and address pathophysiological concepts. A proposal for several NMS subtypes are reported combining clinical reports with, where possible, evidence base supporting probable biomarkers.

Unmet needs in Parkinson's disease: New horizons in a changing landscape

“…Indeed, there have been significant advances in understanding the pathophysiology of PD over the past decades and it is now better understood that the disease follows a defined clinical pattern, with a range of NMS defining the pre-motor phase [8]. In the prodromal stage, the most common NMS manifestations are olfactory impairment and raid eye movement behavior disorder while other features such as constipation, somnolence, apathy, fatigue may also be present [9].…”

“…In one recent proposal, Sauerbier et al suggested at least seven distinct NMS dominant subtypes of PD: Cognitive dominant, apathy dominant, depression/anxiety dominant, sleep dominant, pain dominant, fatigue dominant and autonomic dominant [8]. Within this scheme, sleep-dominant and autonomic-dominant subtypes are grouped into a 'brainstem phenotype,' where the underlying pathology is thought to involve the brainstem and olfactory route.…”

“…Within this scheme, sleep-dominant and autonomic-dominant subtypes are grouped into a 'brainstem phenotype,' where the underlying pathology is thought to involve the brainstem and olfactory route. Likewise, the cognitive dominant subtype is thought to reflect lateonset disease where cortical pathology predominates and the depression, fatigue and pain dominant subtypes are grouped under a 'limbic phenotype' where the olfactory route predominates [8]. The stability of non-motor subtypes has not been studied and it is probable that non-motor subtypes will also change throughout the disease course.…”

Clinical and Pathophysiological Considerations of Gait Limitations and High Prevalence of Falls, in Elderly with Most Common, Disabling Neurological Diseases

“…Overlapping between groups was seen in many objective features of gait and balance. Several independent observers have reported (in early and untreated PD subjects) specific "clusters of non-motor symptoms dominant phenotype of PD" [26]. Patients with the PIGD subtype (predominantly characterized by axial motor involvement and increased cognitive impairment) are predisposed to falls, contrasting with the TD subjects [27].…”

“…Patients with the PIGD subtype (predominantly characterized by axial motor involvement and increased cognitive impairment) are predisposed to falls, contrasting with the TD subjects [27]. These clinical particularities raised the supposition of different neuropathology, genetic and etiologic influences, distinct neurotransmitter systems, and functional imaging aspects [25][26][27][28].…”