Parkinsons Flashcards
What is Parkinson’s disease?
Parkinson’s disease is a progressive neurodegenerative disorder caused by a loss of nerve cells in the substantia nigra, which is part of the basal ganglia responsible for regulating motor signaling. This leads to a reduction in dopamine, which plays a vital role in regulating movement.
What are the cardinal symptoms of Parkinson’s disease?
Motor Symptoms:
- Bradykinesia (slow movement)
- Tremor (resting tremor, pin rolling, diminished by activity)
- Involuntary movement (Dyskinesias)
- Rigidity (increased muscle tone, stiffness/pain)
- Trouble walking
- Postural instability (reduced balance, fixed posture, reduced trunk rotation)
- Painful uncontrolled muscle contractions (Dystonias)
Non-motor Symptoms:
- Cognitive impairment
- Mental health disorders
- Dementia
- Sleep disorders
- Pain
- Loss of sense of smell
- Sweating and melanoma
- Gastrointestinal issues
What is the pathophysiology of Parkinson’s disease?
Direct Pathway (Facilitates Movement):
- Motor cortex sends excitatory signals (glutamate) to the striatum.
- Striatum sends inhibitory signals (GABA) to the globus pallidus internal and substantia nigra pars reticulata.
- This reduces inhibition on the thalamus, allowing it to send excitatory signals (glutamate) to the motor cortex, promoting movement.
Indirect Pathway (Inhibits Movement):
- Striatum sends inhibitory signals (GABA) to the globus pallidus externus.
- Globus pallidus externus inhibits the subthalamic nucleus (GABA).
- Subthalamic nucleus excites the globus pallidus internus (glutamate), which inhibits the thalamus (GABA), reducing movement.
What happens to the pathways in Parkinson’s disease?
In the basal ganglia there is a direct pathway which stimulates movement and an indirect pathway which inhibits movement
- Degeneration of dopamine-producing neurons in the substantia nigra (pars compacta).
Dopamine normally:
* Stimulates the direct pathway (which increases movement & allows appropriate initiation and execution of movement).
* Inhibits the indirect pathway (which appropriately reduces excessive movement).
Without dopamine:
* Less stimulation of the direct pathway (reduces speed and amplitude of movement when faster movement or amplitude would be indicated ).
* More activity in the indirect pathway (casuing excessive movement inhibition that is not indicated or wanted).
What causes the degeneration of dopamine-producing neurons in the substantia nigra (pars compacta)?
The degeneration is caused by the accumulation of alpha-synuclein, a protein that affects neurotransmitter release and the regulation of synaptic vesicles.
What is bradykinesia in Parkinson’s disease?
- Bradykinesia results from basal ganglia dysfunction, neurodegeneration of dopamine producing neurons and an imbalance between the direct and indirect pathways.
- Loss of dopamine reduces activity in the direct pathway, which normally promotes movement, and increases activity in the indirect pathway, which inhibits movement.
- This imbalance disrupts the brain’s ability to prepare and execute movement, leading to slower reaction times and abnormal motor command retrieval.
Direct - reduction in activity = decreased speed and amplitude of movement
Indirect- increased activity = slow reaction time & abnormal motor comman retrieval
What is freezing of gait in Parkinson’s disease?
Freezing of gait is a phenomenon where individuals with Parkinson’s disease experience brief episodes where they cannot initiate or continue walking, often feeling as though their feet are “frozen” to the ground. These episodes typically occur during turning, approaching doorways, or other challenging walking tasks.
Pathophysiology of FOG?
Impact of Dopamine Deficiency:
* Reduced direct pathway activity (due to dopamine loss) leads to difficulty initiating or executing movement, contributing to the freezing episodes where patients cannot start or continue walking, particularly during challenging tasks like turning or approaching doorways.
* Increased indirect pathway activity leads to excessive inhibition of movement, further impairing the ability to move smoothly, especially during transitions like turning or starting to walk.
What is festination in Parkinson’s disease?
Rapid, small steps, done in an attempt to keep the centre of gravity in between the feet while the trunk leans forward involuntarily and shift the centre of gravity forward’. This can lead to an increase in falls
What is the pathophysiology of festination?
Basal Ganglia Dysfunction:
* The basal ganglia is responsible for automatic motor control and motor cue production.
* Dopamine depletion in PD leads to defective motor cue production, causing abnormal movement sequencing.
Direct and Indirect Pathways: Loss of dopamine reduces stimulation of the direct pathway (which promotes movement) impairing normal movement initiation and increases activity in the indirect pathway (which inhibits movement), contributing to poor motor control causing difficulty regulating gait
What causes muscle weakness in Parkinson’s disease?
- Dopamine deficiency in PD leads to tonic reduction in thalamic activity, which decreases motor cortex excitation. This results in less neuronal drive and impaired muscle activation, contributing to muscle weakness. This can over time lead to secondary adaptive changes in the muscle causing disuse atrophy and stiffness, reducing cross sectional area, density of muscle fibres, number of motor units, shortening of opposing muscle groups, increased resistance to contraction in agonists.
- Pre-CNS pathology weakness- ageing, sedentary lifestyle, other pathologies (OA, RA, Diabetes)
What is rigidity in Parkinson’s disease?
Cogwheel Rigidity:
* A type of muscle rigidity characterized by a ratchet-like, jerky resistance to passive movement, typically seen in Parkinson’s disease. It results from a combination of muscle stiffness and involuntary muscle contractions, often associated with tremors.
Lead Pipe Rigidity:
* A form of muscle rigidity where there is constant, uniform resistance to passive movement throughout the entire range of motion, as if bending a lead pipe. This type of rigidity is typical in Parkinson’s disease and differs from the jerky resistance seen in cogwheel rigidity.
How does dopamine affect rigidity?
Dopamine normally:
* Stimulates the direct pathway (increases movement appropriate initiation and execution).
* Inhibits the indirect pathway (reduces inhibition of movement, appropriately reduces excessive movement).
Without dopamine:
* Less stimulation of the direct pathway (reducing movement initiation and coordination).
* More activity in the indirect pathway (increasing movement inhibition leading to rigidity).
Thalamus role
The thalamus acts as a relay station, transmitting signals between the basal ganglia and the motor cortex to regulate movement. It helps modulate motor function by filtering and relaying motor commands
