Week 3 - Parkinsonism Flashcards
1
Q
What is the triad of Parkinsonism?
A
- Bradykinesia (most important)
- Rigidity (muscular)
- Tremor (rest)
Note: postural + gait instability is not part of the triad but is an important symptom of parkinsonism
2
Q
How is parkinsonism different to Parkinson’s disease?
A
Parkinsonism = syndrome of features; bradykinesia, rigidity, tremor, postural instability etc.
Parkinson’s disease = one of many causes of parkinsonism and the disease for which parkinsonism syndrome of symptoms is named
3
Q
Which drugs can cause parkinsonism?
A
- Phenothiazines e.g. chlorpromazine, prochlorperazine (tpical anti-psychotics)
- Butyrophenones: haloperidol, droperidol (typical anti-psychotics)
-
Metoclopramide (D2 antagonist anti-emetic) - can exacerbate parkinsonism as it crosses the BBB –> thus can counteract action of levodopa in Parkinson’s disease
- Note: Domperidone is also a dopamine antagonist anti-emetic but doesn’t cross BBB = safe in Parkinson’s disease
4
Q
What non-drug causes of parkinsonism can you name?
A
- Parkinson’s disease
- Parkinson’s Plus syndromes (features of Parkinson’s + other features):
- Vascular Parkinsonism
- Progressive supranuclear palsy (PSP)
- Multiple System Atrophy (MSA)
- Lewy Body Dementia
- Corticobasal degeneration
- Wilson’s disease
- Post-encephalitis
- Dementia Pugilistica (secondary to chronic head trauma e.g. boxing)
- Toxins: carbon monoxide, MPTP (causes permanent parkinson’s)
5
Q
What protein are Lewy body aggregates composed of?
A
α-synuclein protein
6
Q
What are the criteria for diagnosis of parkinsonism?
A
-
Bradykinesia (slowness of initiation of voluntary movement with progressive ↓ in speed + amplitude of repetitive actions) AND 1 or more of the following:
- Muscular rigidity
- Resting temor
- Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction
7
Q
What are the criteria for diagnosis of Parkinson’s disease?
(UK Parkinson’s disease society brain bank criteria)
A
3 or more of the following features:
- Unilateral onset
- Rest tremor present
- Progressive disorder
- Persistent asymmetry (affecting side of onset the most)
- Excellent response to levodopa
- Severe levodopa-induced chorea
- Levodopa response for 5 years or more
- Clinical course of 10 years or more
8
Q
What are the 1. epideimiology and 2. the motor features of Parkinson’s disease?
A
- Epidemiology
- men (x2) vs women
- mean age of diagnosis = 65 yrs
- Motor features
- Triad
- Bradykinesia - short, shuffling steps, reduced arm swing, difficulty initiating movement
- Tremor - worse at rest, stressed or tired, pill-rolling
- Rigidity - lead pipe / cog-wheel
- Gait
- Festinant / fenestrated gait
- This means difficulty initiating gait and once mobile, rapid short steps with accelerating speed, often with a stooped, forward leaning posture.
- Shuffling gait
- Difficulty turning
- Reduced arm swing
- Freezing → patients find doorways, patterned carpets and other obstructions exacerbate freezing. They often have to adopt ways to overcome freezing such as counting out loud, using metronomes or using other auditory or visual cues
- Festinant / fenestrated gait
-
Postural instability
- suggested by the ‘pull test’ — a tendency to fall backwards after a sharp pull from the examiner. This may be suggestive of Parkinson’s disease if unrelated to primary visual, cerebellar, vestibular, or proprioceptive dysfunction.
-
Hypokinesia (poverty of movement)
- Hypomimia → Reduced facial expression, arm swing, or blinking.
- Difficulty with fine movements such as buttoning clothes and opening jars
- micrographia → small cramped handwriting
- hypophonia → quiet voice
- camptocormia → stooped posture
- Triad
9
Q
Which symptoms appear first in Parkinson’s disease; motor or non-motor?
A
Non-motor features
e.g. constipation, RBD, depression, hyposmia (↓ smell)
10
Q
What are the key features of essential tremor?
A
- Familial - autosomal dominant
- Postural tremor - worse on movement / if arms outstretched
- Symmetrical - e.g. both upper limbs, may also be in legs and jaw
- Improves with alcohol + rest
- NO bradykinesia!!
11
Q
What are the 3 types of action tremors?
A
- Postural
- Occurs during maintenance of a posture against gravity e.g. arms out
- Increases with voluntary action
- Intention
- Elicited by movement towards a target (e.g. your finger)
- An action tremor that is classically worse at the terminal portion of the targeted movement
- Task-specific
12
Q
Tremors can be categorised based on when they are worst - for the following are they worse at: rest, on movement or intention
- Parkinsonism
- Dystonic tremor
- Exaggerated phsyiological tremor
- Hyperthyroidism
- Essential tremor
- Drug induced tremor
- Cerebellar disorders
A
Worse at rest:
- Parkinsonism
Worse on movement:
- Dystonic tremor
- Exaggerated phsyiological tremor
- Hyperthyroidism
- Essential tremor
- Drug induced tremor
Worse on intention:
- Cerebellar disorders
13
Q
What is an intention temor?
A
A coarse tremor which increases in amplitude as an extremity approaches the endpoint of deliberate and visually guided movement (temor is often perpendicular to the direction of movement)
E.g. worsens when trying to pick up a pen
- Found in:
- Cerebellar disorders
- MS
- Ataxia
- Fragile X syndrome
- Chronic alcoholism
14
Q
How can an essential temor be managed?
A
Often it doesn’t require management
- Propranolol = 1st line - can ↓ tremor
15
Q
What are the distinctive features and management of vascular parkinsonism?
A
Features:
- Predominantly affects lower limbs
- Tremor less common
- Lower limb rigidity
- Hypomimia
Management:
- ~ 50% respond to levodopa
16
Q
What are the distinctive features and management of dementia with Lewy bodies?
A
Features:
- Triad:
- Dementia
- Parkinsonism
- Visual hallucinations (may have other features such as delusions)
- Fluctuations in alertness
- Disorders of REM sleep
Diagnosis:
- Clinical Hx
- SPECT (single-photon emission computed tomography) - commercially called DaTscan, 90% sensitivity and 100% specificity
Management:
- Acetylcholinesterase inhibitors e.g donepezil, rivastigmine
- Memantine (?NMDA-receptor blocker)
17
Q
What are the distinctive features and management of drug induced parkinsonism?
A
Features:
- Hx of dopamine blocking drugs e.g. antipsychotics, metoclopramide
- Symmetrical rigidity
- Hypomimia
Management:
- Stop offending medication (if possible) - liaise with psychiatry
18
Q
What are the distinctive features and management of Multi-systems atrophy?
A
MSA = degeneration of the basal ganglia + other areas
Types:
- MSA-P = Predominant parkinsonism features
- MSA-C = Predominant cerebellar features
Features:
- Symmetrical parkinsonism
- Prominent early autonomic disturbances
- Atonic bladder - causing urinary retention then overflow incontinence
- Postural hypotension
- Sexual dysfunction
- Constipation
- Abnormal sweating
- Cerebellar dysfunction e.g. ataxia
-
Hot Cross Bun sign (transverse T2 weighted MRI) - seen in MSA-C
- Due to selective loss of myelinated transverse pontocerebellar fibres
Management:
- Levodopa + supportative treatments
19
Q
What are the distinctive features and management of progressive supranuclear palsy?
A
Features:
- Parkinsonism
- Vertical gaze impairment (down gaze worse than up gaze - pts complain of difficulty reading or going down stairs)
- Early falls
- Truncal rigidity
- Slurring of speech
- Cognitive impairment
- ↓ in mid brain volume (MRI) - humming bird sign (preserved pons forms the body and the atrophied midbrain forms the head)
Management:
- Early SALT review
- Poor response to L-dopa
20
Q
What are the distinctive features and management of normal pressure hydrocephalus?
A
Features:
- Triad of:
- Dementia
- Gait disorder
- Bladder instability (incontinence)
- Hydrocephalus on neuro-imaging
Management:
- Diagnostic LP + CSF removal
- Ventriculo-peritoneal shunt
21
Q
What are the distinctive features and management of cortico-basal degeneration?
A
Features:
- Asymmetrical parkinsonism
- Dyspraxia (development coordination disorder)
- Alien limb phenomenon
Management:
- Symptomatic management
- Responds poorly to L-dopa
22
Q
There is a long list of exclusion criteria for PD (presence of which suggests it’s not PD) - try and name some.
A
Presence of 1 or more suggests an alternative to PD:
- Hx of repeated strokes with stepwise progression of parkinsonian features
- Hx of repeated head injury
- Hx of definite encephalitis
- Antipsychotic or dopamine-depleting drugs
- > 1 affected relative
- Sustained remission of symptoms
- -ve response to large doses of levodopa (if malabsorption is excluded)
- Strictly unilateral features after 3 years
- Other neurological signs: Babinski sign, early severe dementia with language disturbance, early severe autonomic involvement, supranuclear gaze palsy, cerebellar signs
23
Q
NICE have produced a simple guidance table for symptomatic control of PD - study it on the otherside.
A
24
Q
- Is Parkinson’s disease more common in men or women?
- How does smoking affect PD?
- How do pesticides + heavy metals affects PD?
A
- Men > women
- Smoking is protective
- Pesticides + heavy metals = risk factors
25
What categories of drugs are used to manage PD?
1. **Levodopa** / Co-beneldopa (Levodopa + dopa decarboxylase inhibitor, in this case benserazide)
* use with peripheral dopa decarboxylase inhibitors - carbidopa or benserazide
2. **Dopamine agonists** e.g. Ropinirole, pramipexole, rotigotine (trandermal patch) and apomorphine (not related to opiods - can only be used sub-cut)
3. **MAO-B inhibitor** (monoamine oxiadase B) e.g. rasagaline, selegiline
4. **COMT inhibitor** (catechol‑O‑methyl transferase) e.g. entacapone, tolcapone
Note: Consider **glycopyrronium bromide** to manage drooling of saliva in people with Parkinson's disease
26
What are common side effects of levodopa?
* Dyskinesia (involuntary writhing movements)
* 'On-off' effect i.e. symptoms controlled after levodopa dose but the duration of ↓ symptoms goes down over time
* Nausea
* Dry mouth
* Confusion
* Psychotic symptoms: hallucinations and delusions
* Postural hypotension
* Palpitations
* Excessive sleepiness / drowsiness
27
Why is it important to not acutely stop levodopa treatment e.g. admitted to hospital and can't take medication orally?
Not taking levodopa (or Parkinson's medication in general) on time or failing to take it can induce;
1. **Dystonia** = abnormal muscle tone, muscular spasm, abnormal posture
2. **Akinesia** = loss / impairment of the power of voluntary movement
3. **Neuroleptic malignant syndrome** = pyrexic, rigidity, hypertension, tachycardia, tachypnoea, confusion / agitated delirium, variable BP and sweating
* Often caused by anti-psychotics, but also withdrawal of dopaminergic drugs
A dopamine agonist patch (**rotigotine**) can be given as rescue medication until a route of usual medication is established.
28
What are some common side effects of dopamine-receptor agonists?
* Associated with pulmonary, retroperitoneal and cardiac fibrosis
* CXR, ESR, creatinine and echo before treatment + pt to be monitored
* Impulse control disorders e.g. gambling, overeating, hypersexuality etc.
* Nausea / vomiting
* Excessive daytime sleepiness
* More likely than levodopa to cause hallucinations (older pts)
* Postural hypotension
29
When can you consider deep brain stimulation for PD management?
Only if the patient's PD is **adanced** and their **symptoms can't be controlled** by best **medical therapy**
30
If excessive sleepiness is caused by PD medication, how can this be managed and what should you suggest the patient stop doing?
1. **Adjust medication** to reduce sleepiness
2. Consider **Modafinil** (hightens arousal + weak dopamine re-uptake inhibitor)
3. Suggest patient **not drive**
31
If orthostatic hypotension develops due to PD medication, how can this be managed?
1. **Review medication** to identify potential non-PD drug cause
2. Modify dosage of PD drugs / other drugs to reduce orthostatic hypotension
3. Consider **Midodrine** (peripheral alpha-adrenergic receptor agonist --\> ↑ arterial resistance and thus ↑ BP)
32
The mnemonic '**DANISH**' is useful in remembering **symptoms** of **cerebellar disease / pathology** - what does each letter stand for?
* **D** - Dysdiodochokinesia, dysmetria (past-pointing), pts may appear 'Drunk'
* **A** - Ataxia
* **N** - Nystagmus (lesion is on ipsilateral side to eye affected)
* **I** - Intention tremor
* **S** - Slurred staccacto speech, scanning dysarthria (spoken words broken up into seperate syllables, often with pauses)
* **H** - Hypotonia
33
What are some causes of a syndrome of cerebellar symptoms?
* **Stroke**
* **Alcohol**
* Multiple sclerosis
* Hypothyroidism
* Drugs:
* Phenytoin, lead poisoning
* Neoplastic e.g. cerebellar hemangioblastoma
* Genetic e.g. Friedreich's ataxia (autosomal recessive, difficulty walking, loss of sensations in limbs, impaired speech, HOCM)
34
What are the non-motor features of PD?
→ these may **precede** motor symptoms by years
* **Psychiatric** symptoms:
* Depression
* Anxiety
* Dementia
* Psychosis
* Psychosis and confusion – often a feature in the development of PDD or DLB
* **_Fatigue_**
* Reduced sense of smell.
* Cognitive impairment.
* Sleep disturbance → **_RBD_** (REM sleep behaviour disorder)
* Intense, vivid dreams
* Talking or moving in sleep
* Constipation
* Postural hypotension
35
What are the features of Late PD
* Dysphagia
* Falls
* Speech dysfunction
* Urinary incontinence
* Constipation
* Bilateral motor symptoms (starts unilateral)
36
Who is more susceptible to behaviour changes\* with dopamine agonists?
\*include gambling, overeating, hypersexuality, overspending and collecting/ hobbying
1. dopamine agonist therapy
2. a history of **previous impulsive** behaviours
3. a history of **alcohol consumption** and/or **smoking**
37
What safety advice should be given to someone newly diagnosed with PD?
1. Inform the DVLA and car insurance - this may not stop you driving
2. Medication counselling - esp not to suddenly stop levadopa for any reason
38
What is levadopa normally prescribed with? Why?
* usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine
* this allows a greater proportion of peripheral levodopa to cross the blood–brain barrier for central nervous system effect and reduces peripheral side-effects
