Week 7 - Parkinson's Flashcards
How many people are currently affected by Parkinson’s disease in Australia?
40,000
How many people worldwide suffer from Parkinson’s disease?
10 million
What are the major symptoms of parknson’s disease?
Bradykinesia
Tremor
Rigidity
What is the anchor feature of parkinsonism?
Bradykinesia
What is bradykinesia an umbrella term for?
Reduced movement speed
Amplitude (hypokinesia)
and slowness of movement initiation
What are some examples of bradykinesia?
Gross movements ae slowed such as
rising from chair, walking
fine movements such as tapping fingers
handwriting small and imprecise
What is a resting tremor?
Shaking that occurs in relaxed muscles (typically in extremities such as hands
Fingers demonstrate a twitching motion while at rest
What is rigidity?
Described as cogwheel rigidity because the increases muscle tension that feels ratchet-like when resistance is applied
What is dysarthria?
Weakness in the muscles used for speech, which often causes slowed or slurred speech. A late feature of parkinsons
What is dysphagia?
A late feature of PD
Difficulty swallowing foods or liquids
What are postural deformities in parkinsons?
A stooped posture with flexion of the trunk
What is dystonia?
Involuntary muscle contractions that cause repetitive or twisting movements
Rare feaure of idiopathic PD
Not uncommon in autosomal recessive forms with young-onset disease
how common is dementia in idiopathic parkinsons?
Common late feature
affects70-80% of patients after prolonged disease lasting 10 or more years
What are the risk factors for dementia in parkinsons disease??
Age
Longer duration of disease
being male
having visual hallucinations
older age of onset of parkinsons
family history
more severe motor symptoms
How is parkinson’s dementia different from Alzheimers disease?
Dementia is a hallmark of alzheimers where as dementia may or may not occur in people with parkinsons
Dementia has greater social and occuptional impact in parkinsons as there are motor and cognitive impairments
How common are depressive symptoms in parkinsons?
30-40% of patients experience low mood and lack of interest/pleasure (Anhedonia)
How common is anxiety in people with parkinsons?
affects up to 40% of patients
Some people may experience: generalised anxiety disorder, anxiety attacks social avoidance OCD
Parkinsons is primarily linked to a central dopamine deficit, what other neurodegenerative events may also occur?
noradrenergic nuclei
serotoninergic nuclei
cholinergic nuclei
What is the most common type of psychotic symptom in parkinsons?
Visual hallucinations
Delusional behaviour
What percentage of parkinsons patients experience psychotic symptoms?
up to 50%
What are the two groups of parkinsons?
degenerative parkinsonism
symptomatic or secondary parkinsonism
What is degenerative parkinsonism?
a variety of sporadic and genetic degenerative diseases cause neurodegeneration
What is symptomatic or secondary parkinsonism?
Caused by non-degerative lesions of the same system or other sites of striatopallidothalamic-cortical motor circuitry
Which type of parkinson’s disease is likely to be multifactorial and is considered to be environmental as well as genetic?
sporadic or idiopathic
What are the different kinds of symptomatic parkinsonism?
infectious
toxic
drug-induced
brain tumours
metabolic
How is the aetiology of neurogenerative and symptomatic forms of parkinsonism usually defined?
in terms of functional or structural disorders
affecting nigrostriatal dopamine transmission and/or downstream signalling pathways
What brain areas contain the brain structures of the basal ganglia?
telencephalon
diencephalon
mesencephalon
What forebrain structures are involved in the basal ganglia?
caudate nucleus
putamen
nucleus accumbens (or ventral striatum)
Globus pallidus
What two brain structures of the basal ganglia are considered to be functionally equivalent to each other?
caudate nucleus
putamen
Most mammals only have a single nucleus called the _____.
Striatum
What are the two segments of the globus pallidus?
internal (or medial) segment
External (or lateral) segment
Where is the subthalamic nucleus located?
part of the diencephalon
located just below the thalamus
Where is the substantia nigra located?
midbrain
What are the two distinct parts of the substantia nigra?
pars compacta (SNpc)
pars reticulata (SNpr)
What structure is the source of a clinically important dopaminergic pathway to the striatum?
pars compacta
What happens if there is a loss of neurons in the pars compacta?
cause of parkisons disease
this pathway referred to as nigrostriatal dopamine pathway
What is the dopamine pathway from the pars compacta to the striatum referred to?
nigrostriatal dopamine pathway
What are the two pathways in the basal ganglia that control the fine tuning of voluntary motor activities?
direct excitatory pathway
indirect inhibitory pathway
What happens when the direct excitatory and indirect inhibitory pathways are stimulated?
they have antagonistic net effects
stimulation of direct pathway: activation of motor cortex
stimulation of indirect pathway: inhibition of motor cortex
How does dopamine act on the direct pathway neurons?
activating dopamine D1 receptors
these receptors are linked to Gs proteins which stimulate cell activity through activation of adenylyl cyclase
how does dopamine act on the indirect pathway neurons?
Activating dopamine D2 receptors
these receptors are coupled to Gi proteins which inhibit cell activity by decreasing adenlyl cyclase activity
D1 and D2 receptors are expressed on two separate populations, what does this mean?
A change in dopaminergic tone alters the output of the striatum
In parkinsons, which areas are hyperactive and cause thalamocortical projections to be inhibited?
STN (subthalamic nucleus)
GPi (globus pallidus)
What is levodopa (L-dopa)?
The most effective symptomatic treatment of parkinsons
What are the limitations of levodopa?
“dopa resistant” motor symptoms (postural abnormalities, freezing episodes, speech impairment)
“dopa resistant” non-motor signs (autonomic dysfunction, mood and cognitive impairment etc)
Drug related side effects (especially psychosis, motor fluctuations and dyskinesias)
What are some other types of pharmacological treatments of parkinsons (aside from levodopa)?
Dopamine agonists
COMT inhibitors
MAO-B inhibitors
Anticholinergics
Amantadine
How do dopamine agonists treat parkinsons?
Idea is to stimulate dopamine receptors directly
Dopamine agonists are not a potent as levodopa and may be less likely to cause dyskinesias
How do COMT inhibitors treat parkinsons?
used in combination with levodopa
block the action of enzymes that break down levodopa
How do MAO-B inhibitors treat parkinsons?
Stop the breakdown of dopamine in the brain
How do anticholinergics treat parkinsons?
Helpful for tremor and may ease dystonia associated with wearing-off or peak-dose effect of levodopa
How does amantadine treat parkinsons?
Antiviral drug used for people who may have developed dyskinesias following long-term use of levodopa
What is deep-brain stimulation?
surgical technique
treat severe cases of PD
during times of extreme tremor the patient can activate the pacemaker which stimulates the subthalamic nucleus
stops tremor activity by bradykinesia and rigidity often persist
