Parkinson's Disease Flashcards
4 cardinal clinical features of parkinson’s disease:
- tremor
- cogwheel rigidity
- bradykinesia
- postural abnormalities
Clinical Features of Parkinson’s Disease:
- 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
Diagramatic Representation of Symptoms and Signs in Idiopathic Parkinson’s Disease:
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What are the basal ganglia?
An area of the fore and midbrain known to be involved in control of movement and motor learning
Main components of the basal ganglia:
- caudate nucleus
- putamen
- globus pallidus
also substantia nigra and subthalamic nucleus have an anatomical and functional relationship shared with neostriatum
Neuroanatomy-basal Ganglia:
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What is the primary afferent source of the basal ganglia?
From the cerebral cortex (somatosensory and primary motor cortex)
Direct and Indirect Pathways of Basal Ganglia:
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Incidence of Parkinson’s Disease:
- females
- age
- males
- 37.6 per 100,000
- increases with age
- 61.2 per 100,000
Parkinson’s Disease: Pathophysiology:
- 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
Parkinson’s Disease: Aetiology:
- unknown
- genetics (15% of patients have
familial hereditary parkinson’s) - environmental toxins
Parkinson’s Disease: Genes:
- 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
Neuropathology:
(affects gut as well)
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”?
- 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
Lewy Body Dementia:
- 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
Parkinson’s Disease: Treatment Overview:
- pharmacological
- therapy: physio, Tai Chi, pilates
- surgical: deep brain stimulation
- supportive: social prescribers
Core Drug: L-Dopa: Mechanism of Action:
- 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
In the UK Gold-standard pharmacological treatment for Parkinson’s Disease?
- L-dopa
and one of the following:
- carbidopa
- benserazide
- co-careldopa (L-dopa + carbidopa)
- co-beneldopa (L-dopa +
benserazide)
Carbidopa and Benserazide are
dopamine-decarboxylase inhibitors
inhibits the peripheral conversion of L-dopa to dopamine
increases the amount of L-dopa available to brain tissue
Core Drug: L-dopa: Side Effects:
- 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
Core Drug: L-dopa: Drug Class:
Anti-parkinsonians
Dopamine precursor
Core Drug: Ropinirole: Drug Class:
Anti-parkinsonians
Dopamine Agonist
Core Drug: Ropinirole: Mechanism of Action:
- direct stimulation of dopaminergic
receptors - increased production of dopamine
Core Drug: Ropinirole: Side Effects:
- postural hypotension (more)
- more GI side effects
- dopamine dysregulation
syndrome/impulse control
disorder: gambling, hypersexuality
warn patient and relatives - excessive daytime sleepiness:
DVLA
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
Core Drug: Rasgiline: Drug Class:
Anti-parkinsonians
MAO-B inhibitor (monoamine oxidase B)
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
Core Drug: Rasgiline: Side Effects:
- abdominal pain
- depression
- sleep disorders
- vomiting
Core Drug: Entacapone: Drug Class:
Anti-parkinsonians
Catechol-o-methyltransferase inhibitors (COMT inhibitors)
Core Drug: Entacapone: Mechanism of Action:
- inhibits catechol-o-
methyltransferase (COMT) enzyme - blocks dopamine metabolism
- extends benefits of L-dopa
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
Core Drug: Entacapone: Side Effects:
- abdominal pain
- confusion
- GI side effects
- dizziness
- dry mouth
- vomiting
What main treatments throughout different stages of parkinson’s disease?
- early = dopamine agonist =
rasgillne - mid = L-dopa
- late = deep brain stimulation or
apomorphine
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
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
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
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
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
Is chorea, dystonia, tremors, tics and myoclonus bradykinetic disorder?
Hyperkinetic
all suppressable slightly
due to increased dopaminergic activity in basal ganglia
parkinsons is bradykinetic
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
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
Apart from genetic causes, what are other causes of chorea?
- vascular
- systemic lupus erythematosus
- auto-immune encephalitis
- toxoplasmosis
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
- dystonia caused by blocked
Hyperkinetic movement disorder treatments: (core drugs)
- dopamine receptor blocking
agents = typical antipsychotics =
core drugs: Haloperidol,
Chlorpromazine - Core Drugs: atypical anti-
psychotics: Clozapine,
Olanzapine, Aripiprazole
