Parkinson's Disease Flashcards
What is Parkinson’s disease?
It is defined as a progressive neurodegenerative condition caused by a reduction of dopaminergic neurons in the substantia nigra pars compacta of the basal ganglia
This results in a reduction in dopamine levels and therefore dysregulation of the basal ganglia
What is the basal ganglia? What are its three functions?
It is a group of structures situated in the middle of the brain
To coordinate habitual movements
To control voluntary movements
To learn specific movement patterns
What is the substantia nigra? What is its function?
It forms a component of the basal ganglia
It produces dopamine
What is dopamine? What is its function?
Neurotransmitter
It is essential for the correct functioning of the basal ganglia
What are the five risk factors associated with Parkinson’s disease?
Increasing Age > 65 Years Old
Male Gender
Family History
Dopamine Antagonist Drugs
Vascular Disease
What are the three genes associated with Parkinson’s disease?
LLRK
Parkin
Glucocerebrosidase (GBA)
Is the LLRK gene - autosomal dominant or autosomal recessive?
Autosomal dominant
When does the LLRK gene result in the onset of Parkinson’s disease?
Late onset
Is the Parkin gene - autosomal dominant or autosomal recessive?
Autosomal recessive
When does the Parkin gene result in the onset of Parkinson’s disease?
Early onset
Name three dopamine antagonist drugs that can cause Parkinson’s disease
Memantine
Metoclopramide
Antipsychotics
Which antipsychotic can cause Parkinson’s disease?
Haloperidol
What is a characteristic feature of Parkinson’s clinical features?
Asymmetrical
What are the triad of clinical features associated with Parkinson’s disease?
Bradykinesia
Tremor
Rigidity
What is another term for bradykinesia?
Hypokinesia
What is bradykinesia?
It describes slowness of movements, with a decrease in amplitude through repetition
What are the three features of Parkinson’s bradykinesia?
Micrographia
Shuffling Gait
Hypomimia
What is micrographia?
It is is defined as handwriting getting smaller and smaller
What are the three features of a shuffling gait?
It describes individuals taking small steps when walking, in which their foot doesn’t fully lift up from the ground
They will also have difficulty in turning around when standing
They will have reduced arm swinging
What is hypomimia?
It describes reduced facial movements and facial expressions
What tremor is Parkinson’s disease?
A unilateral ‘pill rolling tremor’
What is a pill rolling tremor?
A tremor in which individuals appear to be rolling a pill between their index finger and thumb
When does the Parkinson’s tremor become worse?
At rest
When does the Parkinson’s tremor improve?
When conducting voluntary movements
What is the frequency of Parkinson’s tremor? What does this mean?
3 -5 Hz
The tremor occurs between three to five times a second
What is rigidity?
It is defined as a resistance to passive movement of a joint, due to stiffness and tension in the muscles
What are the two types of rigidity associated with Parkinson’s?
Lead Pipe Rigidity
Cogwheel Rigidity
What is lead pipe rigidity?
It is defined as a constant resistance to motion throughout the entire range of movement
What is cogwheel rigidity?
It is defined as a resistance to movements that is intermittent through its range of motion, resulting in small jerky movements
What are the six additional clinical features associated with Parkinson’s?
Depression
REM Sleep Behaviour Disorder
Anosmia
Postural Instability
Autonomic Dysfunction
Cognitive Impairment
What is REM sleep behaviour disorder?
It is defined as a loss of atonia during the REM phase of sleep, causing motor enactment of dreams
What is atonia?
It is defined as a loss of muscle tone
What is anosmia?
It is defined as a loss of the sense of smell
What autonomic dysfunction feature is associated with Parkinson’s disease?
Postural hypotension
What dermatological condition is Parkinson’s disease associated with?
Seborrhoeic dermatitis
What cause of Parkinson’s disease presently differently?
Drug induced Parkinsonism
How does drug induced parkinsonism present?
The motor clinical features present rapidly and bilaterally
The features of rigidity and tremor are uncommon
What is the pharmacological management option for tremor in drug-induced parkinsonism?
Procyclidine
How do we diagnose Parkinson’s?
There are no specific investigations that can be conducted
Instead, diagnosis is clinically based using the ‘UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria’
In cases where patients present with suspected Parkinson’s disease, what is the most appropriate next step?
We refer to neurology
What investigation is used to diagnose Parkinson’s when the diagnosis is unclear?
123I-FP-CIT single photon emission computed tomography (SPECT) scan
How does the caudate appear on a normal SPECT scan?
Symmetrical comma experience
What are SPECT scan results in grade one Parkinson’s?
There is an asymmetrical loss of dopaminergic cells in the putamen
What are SPECT scan results in grade two Parkinson’s?
There is bilateral loss of dopaminergic cells in the putamen
What are SPECT scan results in grade three Parkinson’s?
There is bilateral loss of dopaminergic cells in the putamen and a reduction within the caudate
What investigation can definitively diagnose Parkinson’s disease?
Post mortem biopsy
What is a sign of Parkinson’s disease on biopsy?
Lewy bodies within the basal ganglia
Who should initiate pharmacological management of Parkinson’s disease?
Specialists
What are the five pharmacological management options of Parkinson’s disease?
Levodopa
Dopamine agonists
Monoamine oxidase-B (MAO-B) inhibitors
Catechol-O-methyltransferase (COMT) inhibitors
Antimuscarinics
What is levodopa?
It is a precursor of synthetic dopamine, which converts into dopamine once it crosses the blood brain barrier
When do we prescribe levodopa to manage Parkinson’s?
In cases where clinical features impose on the patient’s quality of life, it is recommended as the first line management option
It is also recommended once other pharmacological options have been deemed ineffective
What do we usually prescribe with levodopa? Why?
Peripheral decarboxylase inhibitors
These drugs prevent levodopa being broken down in the body before it reaches the blood brain barrier, and thus reduces side effect development
Name two peripheral decarboxylase inhibitors
Carbidopa
Benserazide
What is the drug name for combined levodopa and benserazide?
Co-Benyldopa
What is the drug name for combined levodopa and carbidopa?
Co-Careldopa
How effective is levodopa in managing the symptoms of Parkinson’s?
It is the most effective pharmacological management option
However, this efficacy decreases over time
Why does levodopa become less effective with time?
This is due to the fact that as there is an increased loss in dopaminergic nerve cells in the brain, less absorption of the medication can occur
What are the seven common side effects of levodopa?
‘On-Off Effect’
Dyskinesia
Nausea & Vomiting
Arrythmias
Postural Hypotension
Red Urine Discolouration
Psychosis
What side effect occurs when the dosage of levodopa is deemed too high?
Dyskinesia
What is dyskinesia?
It is defined as abnormal movements associated with excessive motor activity
What are the three types of dyskinesia?
Dystonia
Chorea
Athetosis
What is dystonia?
It refers to excessive muscle contraction leading to abnormal postures or exaggerated movements
What is chorea?
It refers to abnormal involuntary movements that can be jerking and random
What is athetosis?
It refers to involuntary twisting or writhing movements usually in the fingers, hands or feet
Why do we not suddenly stop levodopa? What should be done instead?
It can result in acute dystonia
In individuals who take levodopa orally, we administer a dopamine agonist patch to gradually wean patients off
What should be administered in cases where patients still suffer from clinical features despite optimal levodopa?
The addition of a dopamine agonist, MAO‑B inhibitor or catechol‑O‑methyl transferase (COMT) inhibitor as an adjunct
What are dopamine agonists?
They mimic dopamine in the basal ganglia and stimulate the dopamine receptors
When do we prescribe dopamine agonists to manage Parkinson’s?
When the Parkinson’s disease is not affecting the patient’s quality of life
Name four dopamine agonists
Bromocriptine
Ropinirole
Cabergoline
Apomorphine
How effective are dopamine agonists in managing the symptoms of Parkinson’s?
These drugs are less effective than levodopa in symptomatic relief
How are dopamine agonists used to manage Parkinson’s?
They are usually recommended to delay the use of levodopa and are then used in combination with it to reduce the dose that is required to control symptoms
What are the six common side effects of dopamine agonists?
Pulmonary Fibrosis
Retroperitoneal Fibrosis
Cardiac Fibrosis
Impulse Control Disorders
Daytime Drowsiness
Hallucinations
Due to the side effects of fibrosis being associated dopamine agonists, what four investigations do we conduct?
ESR bloods
Creatinine bloods
ECHO
CXR
What is impulse control disorder?
It involves development of addictive gambling, compulsive shopping and excessively increased interest in sex
What are monoamine oxidase enzymes?
They break down neurotransmitters, such as dopamine, serotonin and adrenaline
What is the function of monoamine oxidase-B (MAO-B)?
It acts specifically to break down dopamine and does not act on serotonin or adrenaline
What is the function of MAO-B inhibitors?
They inhibit MAO-B and therefore prevent the breakdown of dopamine
Name two MAO-B inhibitors
Selegiline
Rasagiline
How effective are MAO-B inhibitors in managing the symptoms of Parkinson’s?
These drugs are less effective than levodopa in symptomatic relief
How are MAO-B inhibitors used to manage Parkinson’s?
They are usually recommended to delay the use of levodopa and are then used in combination with it to reduce the dose that is required to control symptoms
What are COMT enzymes?
They metabolise levodopa in the brain and body
What drug class do COMT inhibitors belong to?
Decarboxylase drugs
What is the function of COMT inhibitors?
They prevent the breakdown of levodopa within the body
Name two COMT inhibitors
Entacapone
Tolcapone
When are COMT inhibitors used to manage Parkinson’s?
They are recommended in individuals who are in the later stages of Parkinson’s disease
What are antimuscarinics?
They are involved in the inhibition of cholinergic receptors
Name three antimuscarinics
Procyclidine
Benzotropine
Benzhexol
How are antimuscarinics used to manage Parkinson’s?
They are used to treat drug-induced parkinsonism, specifically relieving clinical features of tremor and rigidity
What is the aim of Parkinson’s management?
There is currently no cure for Parkinson’s disease
The aim of management is to relieve clinical features, maintain the patient’s quality of life and fulfil their wishes with disease progression
What phenomenon do patients experience during pharmacological management of Parkinson’s?
On-off phenomenon
What is the on-off phenomenon?
It describes motor performance being varied throughout treatment
The ‘on’ phase refers to periods in which normal motor function is obtained and the ‘off’ phase refers to periods in which there is restricted motor function
What are Parkinson’s plus syndromes?
They are defined as a group of neurodegenerative diseases that feature the classical motor symptoms of Parkinson’s disease, with additional features that distinguish them from idiopathic Parkinson’s disease
Name four Parkinson’s plus syndromes
Multiple System Atrophy (MSA)
Lewy Body Dementia
Progressive Supranuclear Palsy (PSP)
Corticobasal Degeneration (CBS)
What is MSA?
It is a rare condition in which there is degeneration of neurones in multiple systems of the brain
It tends to affect the basal ganglia as well as multiple other areas of the brain
What are the five clinical features associated with MSA?
Parkinson’s
Tachycardia
Syncope
Erectile Dysfunction
Cerebellar Dysfunction
What is Lewy body dementia?
It is a condition in which there is an accumulation of Lewy bodies, which are deposits of alpha synuclein proteins, within the brain
What are the four clinical features associated with Lewy body dementia?
Parkinsonism
Visual hallucinations
Fluctuations in cognitive impairment
Sleep disturbances
What is progressive supranuclear palsy (PSP)?
It is defined as neurodegeneration that results in increased level of the tau protein within the brain
The tau protein is usually broken down before it reaches high levels, however in PSP this physiological process doesn’t occur, and levels increase above threshold
What are the four clincial features associatde with progressive supranuclear palsy?
Postural Instability
Vertical Gaze Impairment
Parkinsonism
Frontal Lobe Dysfunction
What clinical feature differentiates PSP from idiopathic Parkinson’s?
Eye movement abnormalities
What is corticobasal degeneration (CBS)?
It is defined as neurodegeneration that results in increased level of the tau protein within the cerebral cortex and basal ganglia
The tau protein is usually broken down before it reaches high levels, however in PSP this physiological process doesn’t occur, and levels increase above threshold
What two clinical features differentiate CBS from idiopathic Parkinson’s?
Cognitive impairment
Unilateral apraxia
What is apraxia?
It refers to the inability to perform learned movements on command, even though the command is understood and there is a willingness to perform the movement
