New concepts in the pathogenesis and presentation of Parkinson’s disease

Abstract

Parkinson's disease (PD) was first described by James Parkinson in 1817. He noted the complex nature of this condition and that non-motor symptoms (NMS) underpinned the classic motor symptoms of PD. The concept of what PD is has therefore undergone substantial changes and it is now recognised that PD is a combined motor and non-motor syndrome and NMS are present during the prodromal phase of PD, starting up to 20 years before the first clinical motor signs emerge. PD may originate from pathology in the gut, olfactory bulb and lower brainstem rather than in the substantia nigra. Complex phenotypes of PD may exist where clinical NMS overshadow motor features. Therapy needs to be adjusted based on motor and non-motor loads, ideally using validated tools. Recently, a multimodal biomarker battery in PD has emerged and might play an important role in the future.

Non-Motor Symptoms Assessed by Non-Motor Symptoms Questionnaire and Non-Motor Symptoms Scale in Parkinson's Disease in Selected Asian Populations

“…NMS subtypes are now recognised, and the implicated neuropathology reflects the clinical expression [42,43,44]. In addition, NMS are a key determinant of QoL [45].…”

The Future of Parkinson’s Treatment – Personalised and Precision Medicine

“…7 Non-motor and motor clinical subtypes of PD are an emerging and important clinical concept that will also determine treatment of PD. [4][5][6] A cholinergic syndrome of PD would need a different treatment strategy to someone with a noradrenergic subtype of PD. 2 Relevant clinical, imaging and genetic biomarkers may help define and drive these subtype-specific treatments.…”

“…Clearly, in future, this approach needs to change and the concept of a holistic personalised medicine strategy combining several strands of genetic, therapeutic, personal and socio-economic variables needs to be embraced. 6,7 …”

Noninvasive Options for ‘Wearing-off’ in Parkinson’s Disease: A Clinical Consensus From a Panel of Uk Parkinson’s Disease Specialists

“…The annual incidence of PD in the UK is 15-20 individuals per 100,000 [2], with a significantly higher incidence in males (1.5 times greater) compared with females [3]. With an increasing aging population, the estimated prevalence of PD in the UK is expected to rise by approximately 18% in the next 7 years; however, about 7% of people living with PD in 2018 will be under 60 years old [4].This progressive disorder is characterized by motor symptoms (rigidity, bradykinesia, tremor, postural instability) [5] and a range of nonmotor symptoms (NMS) such as pain, constipation, problems with swallowing, depression, anxiety and cognitive impairment, which can occur from disease onset [6,7], and often before the onset of motor symptoms [8]. The gold standard treatment for PD is still considered to be levodopa (L-dopa) [9].…”