Parkinson's disease
How loss of dopamine-producing neurones in the substantia nigra disturbs the basal ganglia circuit that releases movement, causing slowness, stiffness and tremor, and why other symptoms often come first.
By the end, you can
- Describe the nigrostriatal pathway and the role of the basal nuclei in selecting and scaling movement.
- Explain the loss of dopaminergic neurones and the accumulation of alpha-synuclein in Lewy bodies.
- Use the simplified direct and indirect pathway model to explain why dopamine loss reduces movement.
- Relate bradykinesia, rigidity and rest tremor, and non-motor symptoms, to the underlying changes.
- Recognise the classic appearances, staging systems and tests of Parkinson’s disease, and explain how dopaminergic and other treatments act on the failing circuit.
What it is
Parkinson’s disease is a progressive neurodegenerative disease in which dopaminergic neurones of the substantia nigra are lost and the protein alpha-synuclein accumulates in neurones as Lewy bodies. It causes parkinsonism (bradykinesia with rigidity and/or rest tremor), along with many non-motor features. Parkinsonism has other causes, such as some drugs and other degenerative diseases.
2 types to tell apart
- Sporadic
- Most cases, with no single cause: ageing, genetic susceptibility and environmental factors combine.
- Genetic
- A minority, often younger at onset, linked to variants in genes such as LRRK2, GBA1, SNCA (which encodes alpha-synuclein) and PRKN.
US spelling: fibres → fibers.
Normal function
The basal nuclei and the release of movement
The basal nuclei lie deep in each hemisphere. The and together form the striatum, which receives input from the cortex; the is their main output, which projects to the . The thalamus in turn drives the motor areas of the cortex, whose fibres descend in the .
The output nuclei normally hold the thalamus under steady inhibition, keeping unwanted movements switched off. When a movement is chosen, the circuit briefly lifts that inhibition for the right muscles, releasing the movement and setting its speed and size.
In the midbrain, pigmented neurones of the substantia nigra (pars compacta) send dopamine-releasing fibres to the striatum: the nigrostriatal pathway. Dopamine tunes the striatum so that chosen movements are released readily.
Underlying change · Step 1 of 4
Dopaminergic neurones are lost
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 2 of 4
Too much brake on the thalamus
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 4
Slowness, stiffness and tremor
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 4 of 4
A disease of more than movement
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .