Case 7 - Parkinson's Flashcards
Outline the pathophysiology behind Parkinson’s Disease
Degradation of dopaminergic neurons in the substantia nigra –> dopamine deficiency –> motor symptoms of PD
What % of dopaminergic neurons in the substantia nigra must be depleted before motor symptoms of PD arise?
50% depletion
What % of Parkinson’s disease is thought to be genetic?
10-15%
List 4 risk factors for Parkinson’s Disease
- Lifestyle: smoking, obesity, high iron, low vitamin D
- Environmental: exposure to manganese and other substances
- History of TBI
(note that PD is considered idiopathic)
What is the typical age of onset and course of Parkinson’s disease?
Age of onset ~60 years old
Progressive over ~10 years
List 4 key clinical features of Parkinsonism (TRAP)
Tremor (resting)
Rigidity
Akinesia / bradykinesia
Postural instability
Mutations in which 4 genes can increase someone’s risk of developing PD?
SNCA gene (encodes alpha-synuclein)
GBA gene (most common)
Dardarin LRRK2 gene (most common cause of DOMINANTLY inherited PD)
Parkin PARK2 gene (most common cause of RECESSIVELY inherited PD)
List 4 clinical features that may appear during the Parkinson’s prodrome
- Constipation (earliest symptom!)
- Mood disorders (anxiety, depression, apathy)
- Anosmia
- Sleep disturbances (REM sleep behaviour disorder, restless leg syndrome)
The motor symptoms of Parkinson’s are usually ________ and ____________ (more prominent on one side).
The motor symptoms of Parkinson’s are usually UNILATERAL and ASYMMETRICAL (more prominent on one side).
Parkinsonism is due to impairment of which neural network? What is the function of this network?
Parkinsonism results from impairment of the extrapyramidal system
The function of the extrapyramidal system is to facilitate involuntary muscle function (e.g. reflexes, posture, coordination)
List 3 Parkinson-plus syndromes and a differentiating factor about each
- Vascular Parkinsonism: symmetric and limited to lower limbs, with no tremor
- Multiple system atrophy (MSA): symmetric, autonomic dysfunction is the first symptom
- Corcticobasal degeneration: alien limb phenomenon, upper limb apraxia as first symptom
For each of the 4 cardinal features of Parkinsonism (TRAP) explain how they are examined and how they can be accentuated
RESTING TREMOR - subsides on voluntary movements but increases with stress.
RIGIDITY - increased and persistent resistance to passive movement (cogwheel rigidity: ‘stalls’ when moved). Rigidity is also responsible for stooped posture and hypomimia.
AKINESIA/BRADYKINESIA - slowed movements in combination w/decreased amplitudes/speed when moving (e.g. when asked to perform rapidly alternating movements with the affected limb, the movements decrease in speed and amplitude)
POSTURAL INSTABILITY - imbalance, tendency to fall. Evaluated using the pull test.
Describe the gait abnormalities seen in a Parkinson’s patient
- SHUFFLING gait (with quickened, shortened steps)
- REDUCED arm swing
- FESTINATION: small, increasingly quick steps
- FREEZING: sudden inability to start or continue movements
- PROPULSION: forward-leaning posture (increased falls risk)
Rapid gait with short steps, interrupted by stopping and freezing
What is the froment manoeuvre?
The patient is asked to perform repetitive movements in the contralateral extremity (e.g., opening and closing of the left fist if the right side is examined) → subclinical rigidity becomes more pronounced and may be detected.
Which primitive reflex may be elicited in people with Parkinson’s disease?
Glabellar reflex
tapping between the eyebrows causes the patient to blink PERSISTENTLY
Handwriting in someone with Parkinson’s disease can become…?
Reduced (micrographia)
List 4 autonomic symptoms of Parkinson’s Disease
- Oily skin
- Sexual dysfunction
- Urinary urgency
- Orthostatic hypotension
List 4 neuropsychiatric symptoms of Parkinson’s Disease
- Depression
- Cognitive problems
- Apathy
- Behavioural changes (irritability, impulsivity)
How is Parkinson’s disease diagnosed?
CLINICALLY: Parkinsonism is a syndrome diagnosed by BRADYKINESIA, PLUS one of the following features:
- Rigidity
- Tremor (4 to 6 Hz)
- Postural instability (not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction)
Name 4 features that SUPPORT a diagnosis of Parkinson’s Disease (eTG).
- Unilateral rest tremor
- Excellent response to levodopa
- Progressing disorder w/persistent asymmetry
How can bradykinesia be elicited in a physical exam?
Decrementing bradykinesia
e.g. repetitive pronation and supination, opening and closing the fingers, closing the hands into a fist
Explain the difference between lead-pipe and cogwheel rigidity
Lead-pipe rigidity refers to a hypertonic state throughout the range of movement. Immediate resistance to reversal of direction of movement about a joint.
Cogwheel rigidity easier to detect and more common in the upper extremities. Combination of lead-pipe rigidity with tremor.
Re-emergent tremor
.
Much more commonly seen in PD
Name 4 features that would suggest a diagnosis OTHER than Parkinson’s Disease (eTG)
- Early dementia
- Early falls
- Other neurological signs (eg upper motor neurone signs, abnormal eye movements, cerebellar signs)
- Onset of symptoms coinciding with dopamine antagonist treatment (eg antipsychotic drugs, metoclopramide)
- No response to large doses of levodopa (if malabsorption is excluded)
- History of repeated strokes with stepwise progression of parkinsonian features
Imaging is not needed to diagnose PD. What is the role of imaging in a case of suspected PD?
To rule out other neurodegenerative conditions which can mimic Parkinson’s, e.g. MRIs to detect:
Progressive supranuclear palsy (PSP)
Multi-system atrophy
Options for medications when someone cannot swallow
Crushing (but not all can be crushed)
Neupro (rotigotine patch)
Non-pharmacological treatment
- Aerobic exercise programs (to maintain physical fitness: very important!)
Does disease-modifying therapy exist for Parkinson’s disease?
NO
All treatment is symptomatic (and hence will be based on the patient’s individual situation)
Why is levodopa not started in every patient, despite it being the most effective medication for Parkinsonism?
Principles of medication:
- Levodopa is our most effective treatment
- BUT is not started in everyone (esp. younger people) because as the disease progresses, it’s associated with fluctuations in response (‘on’ and ‘off’ periods)
- Levodopa has a short half-life, so the progression of the disease has an impact on this. Short half-life = unable to sustain as the disease progresses
Young people have to live with this disease for many years. Save them from living with the fluctuations earlier
Eventually, levodopa will have to be added with a non-levodopa since these drugs aren’t cutting it anymore
ACCEPTABILITY is also an issue.
Outline the main clinical differentiating factor between Parkinson’s Disease and Lewy body Dementia
PARKINSON’S: motor symptoms onset before dementia.
LEWY BODY DEMENTIA: dementia occurs concurrently with motor symptoms
What is the role of the basal ganglia?
Modifies ongoing activity in motor pathway (it has no direct effect on efferent motor neurons). This allows it to:
- inhibit muscle tone
- maintain purposeful activity + suppress useless/unwanted patterns of movement
What is the difference between levodopa and dopamine?
Levodopa can pass through the BBB; dopamine cannot.
Explain why levodopa must be administered alongside a peripheral decarboxylase inhibitor (e.g. carbidopa)
Levodopa can be converted to dopamine in the peripheral system by dopamine decarboxylase. If it is converted to dopamine, it is no longer able to cross the BBB, where it is needed.
Peripheral decarboxylase inhibitors prevent this conversion.
List the 4 core clinical features of DLB
- Fluctuating cognition with variations in alertness and attention
- REM sleep disturbances
- Visual hallucinations
- One or more spontaneous features of Parkinsonism
Name a symptom that occurs more commonly in DLB than AD and PD
Visual hallucinations
Memory loss is an early feature of which type of dementia?
Describe how this is different to other common forms of dementia
Alzheimer Disease.
Memory (especially of recent occurrences) is impaired much earlier in the disease course of AD compared with DLB and PD.
Discuss the long-term complications when using levodopa
COMPLICATIONS: most patients on levodopa eventually develop motor symptoms.
- Unpredictable and predictable motor patterns (e.g. wearing ‘off’)
- Dyskinesia (aka drug-induced chorea), dystonia
- Sudden loss of mobility
List 4 patient groups which are especially at risk of developing motor complications due to levodopa
- Younger patients
- Patients with more severe disease
- Patients who have had the disease for longer
- Those on higher doses of levodopa
How can the motor complications of levodopa be managed?
- Smaller, more frequent doses
- Take 1 hour before mealtimes (high protein meals can interfere with absorption)
- Adhering to regular dosing times
What is the ‘wearing off’ vs. ‘on’ of levodopa treatment?
‘On’ = levodopa is working, symptoms are under control
Wearing ‘off’ = symptoms of PD returning before the next dose of levodopa
Why is metoclopramide not used for patients with Parkinson’s disease?
What can you use instead?
Metoclopramide is a dopamine antagonist and it can cross the BBB
Domperidone can be used instead. It is also a dopamine antagonist but it acts outside the chemoreceptor trigger zone, which is outside the BBB
Describe what is involved in an ACAT assessment.
- The aged care team has a phone call with you about your health, how you’re managing at home
- If they think My Aged Care serviced will be helpful for you, they will arrange a face-to-face assessment
- At the in-person assessment they will ask what support you have, your health and lifestyle + any concerns, how you’re managing at home, problems with memory or risks to safety
- You will either receive Residential Aged Care or a Home Care Package (4 levels)
https: //unitingsa.com.au/aged-care/acat-support/
When would you consider prescribing dopamine agonists for patients with Parkinson’s disease?
Which side effects would you need to warn these patients about?
- Younger patients
- Worried about long-term side effects of L-dopa
- Worried about too many tablets
- Can’t swallow
SIDE EFFECTS OF DOPAMINE AGONISTS: pathological eating, hoarding, gambling, sexual preoccupation, punding
Which patient groups should NOT receive dopamine agonists?
Those with a history of impulse control disorders (e.g. gambling problems)
Which dopamine agonists should be avoided in PD?
Ergot derivatives, e.g. cabergoline and bromocriptine, should be avoided
Non-ergot derivatives include: pramipexole, rotigotine
Multiple system atrophy is a Parkinson-plus syndrome. Name 3 features which differentiate it from PD.
- BILATERAL symptoms
- Cerebellar dysfunction
- EARLY autonomic dysfunction
- Hot cross bun sign on imaging
Vascular Parkinsonism is a Parkinson-plus syndrome. Name 3 features which differentiate it from PD.
- SYMMETRICAL/BILATERAL symptoms
- Limited to lower limbs
- Tremor absent
- CV RFs
Corticobasal degeneration is a Parkinson-plus syndrome. Name 3 features which differentiate it from PD.
- Alien limb phenomenon
- Upper limb clumsiness (apraxia) is the first symptom
- Markedly asymmetric (I guess this part is like PD)
What is the pull test and which feature of Parkinsonism is it evaluating?
Pull test = standing behind the patient and jerking them backwards by the shoulders. Patients w/parkinson’s will require several steps backwards to right themselves, or may fall over.
It is testing for postural instability.
In which body part does the Parkinsonian tremor typically manifest?
Hands
But can also involve the legs, lips, jaw, and tongue
Name 2 other types of drugs used in the treatment of PD (not levodopa or dopamine agonists)
Enzyme inhibitors: COMT inhibitors and MAO-B inhibitors
What is the surgical options for treatment of Parkinson’s?
High-frequency deep-brain stimulation
Detail the MOTOR side effects of long-term levodopa usage
Levodopa is the most effective drug for treating motor symptoms of PD, but there are unavoidable motor complications. These include:
- HYPOKINESIA: freezing (sudden inability to move), on-off phenomenon (phases of good mobility, “on” phases, alternate with phases of poor mobility, “off” phases)
- DYSKINESIA: dystonia (involuntary muscle contractions that cause twitching)
What is an akinetic crisis?
Severe dopamine deficiency leading to inability to move. Can be due to L-DOPA discontinuation or lack of L-DOPA absorption
Describe the psychiatric side effects of levodopa
- Hallucinations (often visual)
- Anxiety, insomnia, agitation
- Aggressive behaviour
