6.1 Flashcards
(12 cards)
- What are the cardinal motor symptoms of Parkinson disease?
The cardinal motor symptoms include resting tremor, bradykinesia (slowness of movement), rigidity (increased resistance to passive movement), and postural instability.
- What are some common non-motor symptoms observed in Parkinson disease patients?
Non-motor symptoms may include sleep disturbances, constipation, loss of smell, depression, anxiety, cognitive changes, autonomic dysfunction (e.g., hypotension), and impaired speech or swallowing.
- What are the primary pathological hallmarks of Parkinson disease?
The disease is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra and the deposition of aggregated, insoluble a-synuclein in the form of Lewy bodies within affected neurons.
- How does the deposition of a-synuclein contribute to Parkinson disease pathology?
In a healthy brain, a-synuclein functions at synapses. In Parkinson disease, it misfolds, aggregates into oligomers and eventually into large, insoluble fibrils forming Lewy bodies, leading to neuronal dysfunction and cell death.
- What proportion of Parkinson disease cases are idiopathic versus genetic, and what does this imply about its aetiology?
Approximately 90% of Parkinson disease cases are idiopathic (of unknown cause), while about 10% are familial. This indicates a complex aetiology that involves a mix of genetic predisposition and environmental factors.
- Which risk factors are known to increase the likelihood of developing Parkinson disease?
Risk factors include advanced age, male sex, REM sleep behavior disorder, environmental exposures (such as pesticides, solvents, and air pollution), rural living, and genetic susceptibility. Conversely, factors like exercise, a Mediterranean diet, and coffee/tea consumption have been associated with reduced risk.
- How do changes in the dopamine pathways of the basal ganglia create the motor symptoms of Parkinson disease?
Degeneration of dopamine neurons in the substantia nigra leads to reduced dopamine levels in the dorsal striatum, which disrupts the balance between the direct (movement-facilitating) and indirect (movement-inhibiting) pathways, resulting in bradykinesia, rigidity, and impaired movement initiation.
- What is the role of the basal ganglia’s direct and indirect pathways in normal movement, and how are they affected in Parkinson disease?
In healthy individuals, the direct pathway facilitates movement, whereas the indirect pathway inhibits movement. In Parkinson disease, the loss of dopaminergic input weakens the direct pathway and/or overactivates the indirect pathway, leading to reduced movement (bradykinesia) and rigidity.
- What are some of the proposed molecular mechanisms behind the degeneration of substantia nigra dopamine neurons?
Proposed mechanisms include mitochondrial dysfunction, oxidative stress, neuroinflammation, protein aggregation (especially of a-synuclein), lysosomal dysfunction, and imbalances in metal ions—factors that together create a self-perpetuating neurodegenerative cascade.
- How does the “Parkinson’s Iceberg” concept help conceptualize the disease’s clinical presentation?
The “Parkinson’s Iceberg” illustrates that the overt motor symptoms (resting tremor, bradykinesia, rigidity) represent only the visible tip of the disease. Beneath the surface lie a variety of non-motor symptoms (such as depression, sleep disturbances, gastrointestinal and autonomic dysfunctions) that significantly affect quality of life but are less apparent.
- Why is the clinical diagnosis of Parkinson disease largely based on observation and treatment response?
Because there is no definitive diagnostic biomarker currently available, Parkinson disease is diagnosed based on a constellation of clinical motor and non-motor symptoms and a favorable response to dopaminergic treatments.
- Summarize how the degeneration of basal ganglia movement circuits leads to Parkinson disease symptoms.
Loss of dopaminergic neurons in the substantia nigra decreases stimulation of the direct pathway and increases inhibition via the indirect pathway of the basal ganglia. This imbalance leads to reduced initiation and execution of movement (bradykinesia), as well as rigidity and other motor disturbances characteristic of Parkinson disease.
