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James Parkinson

James Parkinson. Born in 1755; died 1824. Lived entire life in London. • Political reformer • Paleontologist • Physician. 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

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James Parkinson

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  1. James Parkinson • Born in 1755; died 1824. • Lived entire life in London. • Political reformer • Paleontologist • Physician

  2. 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

  3. “Before Concluding these pages, it may be proper to observe once more, that an important object proposed to be obtained by them is, the leading of the attention of those who humanely employ anatomical examination in detecting the causes and nature of diseases, particularly to this malady. By their benevolent labours its real nature may be ascertained, and appropriate modes of relief, or even of cure, pointed out.” James Parkinson An Essay on the Shaking Palsy, 1817

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  5. Lewy Body Lewy, 1913 • Described intraneuronal inclusions (Lewy bodies).

  6. LEWY BODY NEURON

  7. 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.

  8. Arvid Carlsson

  9. 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.

  10. Oleh Hornykiewicz

  11. Dopamine Hornykiewcz, 1960 • Found that dopamine was depleted in striatum of people with PD.

  12. CAUDATE PUTAMEN

  13. L-DOPA Cotzias, 1967 • First convincing evidence that D,L- DOPA, a precursor of dopamine, reversed parkinsonism.

  14. 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.

  15. Single Gene Mutations and PD I

  16. Genetics • Discovering alpha-synuclein mutation or gene duplication as causes of PD • Recognizing alpha-synuclein is a component of Lewy bodies

  17. Interneuronal Lesions Related to Parkinson’s Disease Braak et al., 2003

  18. Braak’s Staging for Parkinson’s Disease Braak et al., 2006

  19. Myocardial 18F-Dopamine Scans Normal Parkinson 08/25/99 01/18/01 Li et al., 2002

  20. Cardial Pexus in PD Iwanga et al., 2000

  21. 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%

  22. Autonomic Nervous System as Portal for Pathogen or Toxin? Braak et al., 2003

  23. 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.

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