Parkinson's Disease Flashcards
(44 cards)
1
Q
4 cardinal clinical features of parkinson’s disease:
A
- tremor
- cogwheel rigidity
- bradykinesia
- postural abnormalities
2
Q
Clinical Features of Parkinson’s Disease:
A
- tremor
- cogwheel rigidity
- bradykinesia
- postural abnormalities
- unilateral at onset
- reduced arm swing
- shuffling, festinating gait
- falls
- micrographia
- non-motor symptoms: anosmia,
constipation, abnormal dreams,
urinary symptoms - neuro-psych symptoms: anxiety,
depression, psychosis and
dementia
3
Q
Diagramatic Representation of Symptoms and Signs in Idiopathic Parkinson’s Disease:
A
insert diagram
4
Q
What are the basal ganglia?
A
An area of the fore and midbrain known to be involved in control of movement and motor learning
5
Q
Main components of the basal ganglia:
A
- caudate nucleus
- putamen
- globus pallidus
also substantia nigra and subthalamic nucleus have an anatomical and functional relationship shared with neostriatum
6
Q
Neuroanatomy-basal Ganglia:
A
insert diagram
7
Q
What is the primary afferent source of the basal ganglia?
A
From the cerebral cortex (somatosensory and primary motor cortex)
8
Q
Direct and Indirect Pathways of Basal Ganglia:
A
insert diagram
9
Q
Incidence of Parkinson’s Disease:
- females
- age
- males
A
- 37.6 per 100,000
- increases with age
- 61.2 per 100,000
10
Q
Parkinson’s Disease: Pathophysiology:
A
- loss of dopamine containing
neurons of the Pars Compacta of
the Substantia Nigra - neurons lose dark melanin
granules with a concurrent loss of
dopamine in nigrostriatal
pathways and neostriatum - definitive diagnosis would require
identification of alpha synuclein
within lewy bodies - lewy bodies present in surviving
neurons only in substantia nigra;
which is the differentiating feature
between dementia with lewy
bodies and parkinson’s disease - clinical signs and symptoms are
seen after 70-80% nigral neurons
and corresponding granules and
dopamine are lost
11
Q
Parkinson’s Disease: Aetiology:
A
- unknown
- genetics (15% of patients have
familial hereditary parkinson’s) - environmental toxins
12
Q
Parkinson’s Disease: Genes:
A
- SNCA = responsible for alpha
synuclein production; deposited in
clumps in Lewy bodies - PARK2 = makes protein parkin,
which has a role in cell breakdown
and recycling proteins - PARK7 = found in rare early-onset
Parkinson’s Disease, protect
against mitochondrial stress - PINK1, LRRK2
- Autosomal Dominant or Recessive
13
Q
Neuropathology:
A
(affects gut as well)
14
Q
Parkinson’s Disease forms part of a spectrum of disorders associated with lewy bodies.
What is the difference between a patient with “Parkinson’s Disease with Dementia” and a patient with “Dementia with Lewy Bodies”?
A
- Parkinson’s Disease with
Dementia will have the onset of
Parkinson’s disease/parkinsonism
first and dementia AT LEAST A
YEAR AFTER - Dementia with Lewy Bodies will
have parkinsonism and then
dementia occurring WITHIN A YEAR
15
Q
Lewy Body Dementia:
A
- often presents with cognitive
impairment - visual hallucinations are common
- fluctuates
- lewy bodies found sub-cortically
and cerebral cortex - anti-parkinsonian treatments
make the hallucinations worse - and the neuroleptics make the
extra-pyramidal symptoms
16
Q
Parkinson’s Disease: Treatment Overview:
A
- pharmacological
- therapy: physio, Tai Chi, pilates
- surgical: deep brain stimulation
- supportive: social prescribers
17
Q
Core Drug: L-Dopa: Mechanism of Action:
A
- passes through BBB as a pre-
cursor of dopamine - converted to dopamine in the
brain - replenishes the lost dopamine in
the neostriatum - used to treat Parkinson’s Disease
18
Q
In the UK Gold-standard pharmacological treatment for Parkinson’s Disease?
A
- L-dopa
and one of the following:
- carbidopa
- benserazide
- co-careldopa (L-dopa + carbidopa)
- co-beneldopa (L-dopa +
benserazide)
19
Q
Carbidopa and Benserazide are
A
dopamine-decarboxylase inhibitors
inhibits the peripheral conversion of L-dopa to dopamine
increases the amount of L-dopa available to brain tissue
20
Q
Core Drug: L-dopa: Side Effects:
A
- initially very well tolerated and
effective - low dosage and slow
- nausea, GI side effects
- postural hypotension
- long term complications after 7-8
years:
- motor fluctuations
- dyskinesias-hyperkinetic
involuntary movements - neuro-psychiatric complications:
- confusion
- hallucinations
- psychosis
21
Q
Core Drug: L-dopa: Drug Class:
A
Anti-parkinsonians
Dopamine precursor
22
Q
Core Drug: Ropinirole: Drug Class:
A
Anti-parkinsonians
Dopamine Agonist
23
Q
Core Drug: Ropinirole: Mechanism of Action:
A
- direct stimulation of dopaminergic
receptors - increased production of dopamine
24
Q
Core Drug: Ropinirole: Side Effects:
A
- postural hypotension (more)
- more GI side effects
- dopamine dysregulation
syndrome/impulse control
disorder: gambling, hypersexuality
warn patient and relatives - excessive daytime sleepiness:
DVLA
25
What is the first line anti-parkinsonian drug for Parkinson's patients under 60?
Ropinirole
takes longer to get to a therapeutic dose
causes less tardive dyskinesias (less long term side effects) but more when initially started
26
Core Drug: Rasgiline: Drug Class:
Anti-parkinsonians
MAO-B inhibitor (monoamine oxidase B)
27
Core Drug: Rasgiline: Mechanism of Action:
- selective inhibitor of Monoamine
Oxidase B (MAO-B)
- blocks dopamine metabolism in
the CNS
- used in early disease; prolongs
time before l-dopa or dopamine
agonist required
- adjunctive to L-dopa to prevent
end of dose deterioration; when L-
dopa effects stop lasting till the
next dose
28
Core Drug: Rasgiline: Side Effects:
- abdominal pain
- depression
- sleep disorders
- vomiting
29
Core Drug: Entacapone: Drug Class:
Anti-parkinsonians
Catechol-o-methyltransferase inhibitors (COMT inhibitors)
30
Core Drug: Entacapone: Mechanism of Action:
- inhibits catechol-o-
methyltransferase (COMT) enzyme
- blocks dopamine metabolism
- extends benefits of L-dopa
31
Deep Brain Stimulation:
- used for complex/late stage
parkinson's disease
- electrodes implanted into globus
pallidus or subthalamic nuclei
- used to treat motor symptoms
- indicated in on/off fluctuations or
L-dopa induced dyskinesias
- long lasting
to be eligible more than 30% of day must be spent in dyskinesia
Side Effects: executive function, verbal fluency decreases, apathy
32
Core Drug: Entacapone: Side Effects:
- abdominal pain
- confusion
- GI side effects
- dizziness
- dry mouth
- vomiting
33
What main treatments throughout different stages of parkinson's disease?
- early = dopamine agonist =
rasgillne
- mid = L-dopa
- late = deep brain stimulation or
apomorphine
34
Late Stage Complex Parkinson's Disease and Apomorphine:
- dopamine agonist
- subcutaneous injection
- used wit L-dopa
- lasts 40mins
- sudden and unpredicatable
changes in symptoms
- dyskinesia
- off period not controlled by other
drugs
side effects: sleepy, hallucinations, impulse behaviours, hypotension,
cardiac disorders
35
Complex Stage Parkinson's Disease and Duodopa:
- gel form of levodopa
- directly delivered via a tube into
the intestine
- fewer motor fluctuation
- overall improved quality of life
36
Other Parkinsonian Syndromes: MSA, PSP:
- Multiple System Atrophy (MSA):
- early falls
- autonomic, cerebellar,
parkinsonian variant
- immunecytochemistry
demonstrating alpha synuclein
inclusions in the glia
- Progressive Supranuclear Palsy
(PSP):
- early falls
- failure of vertical eye
movements
- dysarthria
- tau pathology showing
neurofibrillary tangles within
neurons
37
Tic Disorders:
- sudden, stereotyped movements
or sounds which occur at irregular
intervals
- linked to increased dopaminergic
activity in basal ganglia
- abnormality in the cortico-
striato-thalamocortical circuits
- disinhibition of excitatory
neurons in thalamus resulting
in hyperexcitability of cortical
motor areas
associated with basal ganglia dysfunction
38
Gilles de la Tourette's Syndrome:
- presents in childhood age 7+
- more common in males x4
- motor tics in cranial/orbital region
- vocal tics
- associated with ADHD, OCD
39
Is chorea, dystonia, tremors, tics and myoclonus bradykinetic disorder?
Hyperkinetic
all suppressable slightly
due to increased dopaminergic activity in basal ganglia
parkinsons is bradykinetic
40
Chorea:
- hyperkinetic
- increased dopaminergic activity in
basal ganglia
- rapid, irregular, involuntary dance
like movements that flow
randomly from one body region to
another
most common form is huntington's disease
41
Huntington's Disease:
- progressive disorder
- presents with either psychiatric or
neurological symptoms
- autosomal dominant
- key to diagnosis is family history
- expanded trinucleotide (CAG)
repeat on chromosome 4, coding
for huntington protein
- whole genome sequency
- atrophy of caudate nucleus,
putamen, globus pallidus and a
degree of cerebral atrophy
42
Apart from genetic causes, what are other causes of chorea?
- vascular
- systemic lupus erythematosus
- auto-immune encephalitis
- toxoplasmosis
43
Dystonia:
- abnormal twisting posture often
facial
- may be associated with jerky
tremor
- pathophysiology not fully
understood: PET scans suggest
abnormal activity in motor cortex
- abnormal dopaminergic activity in
basal ganglia supported by:
- dystonia caused by blocked
dopamine receptors
- some are levodopa induced
44
Hyperkinetic movement disorder treatments: (core drugs)
- dopamine receptor blocking
agents = typical antipsychotics =
core drugs: Haloperidol,
Chlorpromazine
- Core Drugs: atypical anti-
psychotics: Clozapine,
Olanzapine, Aripiprazole
