James Parkinson The Shaking Palsy Observations based on 6 cases

James Parkinson

The Shaking Palsy

• Observations based on 6 cases

• • 2 cases with follow-up

• • 1 case with no follow-up

• • 3 cases seen on the streets of London

• Observations

• • Rest Tremor

• • Gait and Posture

• (flexed posture and festination)

• • Described bradykinesia but did not name

• • Missed rigidity

Lewy Body

• Lewy, 1913

• Described intraneuronal inclusions (Lewy bodies).

Substantia Nigra

• Von Economo, 1918

• Noted involvement of substantia nigra in encephalitis lethargica.

• Tretiakoff, 1919

• Described neuronal loss in substantia nigra in Parkinson’s disease.

Arvid Carlsson

Dopamine

• Carlsson, 1957

• Found high concentrations of dopamine in striatum.

• Deduced that dopamine was a neurotransmitter and not a precursor for norepinephrine.

• Depletion of dopamine produced akinesia in rabbits which could be reversed by L-DOPA.

Oleh Hornykiewicz

Dopamine

• Hornykiewcz, 1960

• Found that dopamine was depleted in striatum of people with PD.

L-DOPA

• Cotzias, 1967

• First convincing evidence that D,L- DOPA, a precursor of dopamine, reversed parkinsonism.

Parkinson’s Disease: 20th Century

• PD defined by motor symptoms (rest tremor, rigidity and bradykinesia).

• Loss of dopamine explained clinical features of the disease.

• Search for etiology of PD focused on unique features of dopamine neurons that led to their selective degeneration.

Genetics

• Discovering alpha-synuclein mutation or gene duplication as causes of PD

• Recognizing alpha-synuclein is a component of Lewy bodies

Lewy Body Pathology in Autonomic Nervous System in PD

• Hypothalamus – 100%

• Intermediolateral columns – 96%

• Sympathetic ganglia – 96%

• Dorsal motor nucleus X – 100% ?

• Sacral parasympathetic ganglia – 100%

• Enteric nervous system (VIP neurons) – 93%

Parkinson’s Disease: 21st Century

• PD recognized as a multisystem disorder with wide spread pathology.

• Loss of dopamine may occur later in disease process and primarily explains motor symptoms.

• Search for etiology of PD is no longer focused on unique features of dopamine neurons that lead to cell death.