Parkinsons Disease - Course, Natural History and Prognosis

The clinical effects of Parkinson’s Disease (PD) are visually obvious, but the underlying pathology of PD is still not fully understood. In this slide deck, the course, natural history and prognosis of PD are discussed, including infographics on prodromal PD as well as the stages of PD. Observational cohorts of PD progression are also used to identify related biomarkers.

This slide deck has been developed in collaboration with the former Lundbeck International Neuroscience Foundation.

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Course, Natural History and Prognosis

This presentation covers course, natural history and prognosis of Parkinson’s disease. The clinical effects of Parkinson’s disease (PD) are visually obvious, but the underlying pathology of PD is still not fully understood.

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The course of Parkinson’s disease

Parkinsons Disease – Course Natural History and Prognosis – slide 2

The course of Parkinson’s disease

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Parkinsons Disease – Course Natural History and Prognosis – slide 3

The journey of Parkinson’s disease

The clinical effects of Parkinson’s disease (PD) are visually obvious, but the underlying pathology of PD is still not fully understood.^{[McCann et al., 2016]} PD pathology is thought to spread from brain region to brain region over multiple long-distance…

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Parkinsons Disease – Course Natural History and Prognosis – slide 4

Clinical symptoms and time course of Parkinson’s disease progression

The progression of PD is generally slow, taking place over years (often many years).^{[Kalia & Lang, 2015]} While diagnosis tends to occur with the onset of motor symptoms, this can be preceded by a long prodromal phase of 15…

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Parkinsons Disease – Course Natural History and Prognosis – slide 5

Thresholds for the appearance of Parkinson’s disease symptoms

Regions of the brain that are particularly vulnerable to Lewy pathology and degeneration during the earliest phase of PD include the olfactory bulb, a critical component of the sense of smell; the locus coeruleus, which produces noradrenaline and regulates…

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Parkinsons Disease – Course Natural History and Prognosis – slide 6

The therapeutic benefits of modifying the disease course

While there have been major advances in the management and reduction of PD-related symptoms, there is still no effective way of preventing or slowing the underlying neurodegeneration.^{[Athauda & Foltynie, 2015; Ferreira et al., 2013]} As the disease becomes more…

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Change in levodopa response over time – ‘wearing-off’

Levodopa is the major symptomatic therapy for PD and provides benefit to virtually all patients.^{[Obeso et al., 2000]} During the so-called ‘honeymoon’ period, the effects of levodopa tend to be long-lasting and side effects are tolerable.^{[Obeso et al., 2000]}…

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Parkinsons Disease – Course Natural History and Prognosis – slide 8

Definitions of terms used in Parkinson’s disease

The slide includes some basic definitions of terms used to describe the course of PD.

References: Hametner E, Seppi K, Poewe W. The clinical spectrum of levodopa-induced motor complications. J Neurol 2010; 257 (Suppl 2): S268–275.

Kalia LV, Lang…

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Drug-induced dyskinesias in Parkinson’s disease

Levodopa-induced dyskinesias cover a broad clinical spectrum of different types of involuntary movements, ranging from chorea affecting the limbs, trunk, and head, slow dystonic movements, fixed dystonic postures, or (more rarely) myoclonus or ballism.^{[Hametner et al., 2010; Thanvi et…}

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Relationship between levodopa administration and motor fluctuations

As the extent of neurodegeneration in the substantia nigra becomes greater, its capacity to produce dopamine diminishes to the point where patients require larger doses of levodopa to maintain normal function.^{[Jenner, 2013]}

Motor complications, such dyskinesia and motor fluctuations,…

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Prodromal Parkinson’s disease

Parkinsons Disease – Course Natural History and Prognosis – slide 11

Prodromal Parkinson’s disease

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MDS research criteria for prodromal Parkinson’s disease

The Movement Disorder Society (MDS) research criteria for identification of prodromal PD were designed solely for research purposes since, for now at least, the lack of effective treatments that are able to halt the progression of prodromal PD makes…

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Parkinsons Disease – Course Natural History and Prognosis – slide 13

Distribution of α-synuclein pathology in Parkinson’s disease

The Lewy pathology and aggregated α-synuclein proteins associated with PD are not confined to the central nervous system (CNS); they can also be found in the peripheral nervous system at various sites around the body, such as the skin,…

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Parkinsons Disease – Course Natural History and Prognosis – slide 14

The gastrointestinal system and Parkinson’s disease

Neurons found in the enteric (gut) nervous system (ENS) require dopamine.^{[Rao & Gershon, 2016]} Without dopamine, these neurons cannot properly control gastrointestinal motility.^{[Rao & Gershon, 2016]} Animal studies have suggested that the ENS may be vulnerable to degeneration during…

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