Parkinson’s Disease: Causes and Treatment
Explain the mechanisms underlying Parkinson’s disease., How do current pharmacological treatments such as levodopa and dopamine agonists help alleviate symptoms and what are the limitations of long-term therapy?, What role does deep brain stimulation (DBS) play in managing advanced Parkinson’s disease and how do non-motor symptoms impact the overall quality of life for affected individuals?
Parkinson’s Disease: Mechanisms and Management
1. Pathophysiology
- Parkinson’s disease (PD) is a neurodegenerative disorder caused by the progressive loss of dopaminergic neurons in the substantia nigra of the basal ganglia.
- Reduced dopamine levels impair motor control, leading to bradykinesia, rigidity, tremors, and postural instability.
- Accumulation of Lewy bodies (alpha-synuclein aggregates) contributes to neuronal dysfunction and disease progression.
2. Pharmacological Treatments
- Levodopa (L-DOPA): A dopamine precursor that improves motor symptoms but loses effectiveness over time and causes motor fluctuations (wearing-off) and dyskinesias.
- Dopamine Agonists (e.g., pramipexole, ropinirole): Stimulate dopamine receptors but may cause impulse control disorders and hallucinations.
- MAO-B Inhibitors (e.g., selegiline, rasagiline): Slow dopamine breakdown to enhance its effects.
- COMT Inhibitors (e.g., entacapone): Prolong levodopa action by reducing its metabolism.
3. Deep Brain Stimulation (DBS)
- DBS involves implanting electrodes in the subthalamic nucleus or globus pallidus interna to modulate abnormal neural activity.
- Effective for motor fluctuations and medication-resistant tremors, but not all patients are candidates.
- Risks include infection, cognitive decline, and speech difficulties.
4. Non-Motor Symptoms and Quality of Life
- PD also affects mood (depression, anxiety), sleep (REM sleep disorder), cognition (dementia), and autonomic functions (orthostatic hypotension, constipation).
- Non-motor symptoms often cause more disability than motor symptoms and require multidisciplinary management.
Conclusion
Parkinson’s disease remains progressive and incurable, but levodopa, dopamine agonists, and DBS can significantly improve motor function. Addressing non-motor symptoms is essential for enhancing the overall quality of life in affected individuals.APA