The Shaking Palsy Observations based on 6 cases • 1 case with no follow-up Observations • Gait and Posture (flexed posture and festination) • Described bradykinesia but did not name
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
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 Recognizing alpha-synuclein is a component of Lewy bodies
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.
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