Parkinson's Disease Flashcards
Clinical diagnostic features for PD
- Rest tremor
- rigidity
- Bradykinesia/ Akinesia
(± postural reflexes decreased - imbalance)
2 of the 3 features are required for diagnosis 1 of the 2 has to be bradykinesia
Definition of bradykinesia (in PD)
Slowness of movement AND decrement in amplitude or speed (or progressive hesitations/halts) as movements are continued.
Fatiguing in PD vs non PD movement disorders
In parkinsonism caused by PD, a decline in either speed or amplitude is seen as movements are continued, a feature sometimes not observed in parkinsonism caused by alternate conditions.
Non-Motor Sx PD
3 stages of early PD
- Preclinical PD
- neurodegenerative processes have commenced, but there are no evident symptoms or signs - Prodromal PD
- symptoms and signs are present, but are yet insufficient to define disease - Clinical PD
- diagnosis of PD based on presence of classical motor signs
Main RFs for PD
Smoking
FHx
Age
Major prodromal features of PD
- RBD (REM sleep behaviour disorder)
- hyposmia
- anxiety
- constipation
Diagnosis of REM sleep Behaviour Disorder
- movements of the body or limbs associated with dreaming
- plus at least one of the following:
– potentially harmful sleep behaviour
– dreams that appear to be acted out
– sleep behaviour that disrupts sleep continuity
What are Lewy bodies made of
alphasynuclein (alpha-SN) and several other proteins
Anatomical progression of PD
advances in an orderly sequence, starting in the medulla and the olfactory bulb, then spreads upwards to substantia nigra, then finally into the cortex
AE of levodopa
Nausea
Orthostatic hypotension
Confusion , Hallucinations
Sleepiness and sleep attacks
Motor fluctuations and dyskinesia
Impulse control disorders - worsens
Anti-emetics in PD
Use domperidone or ondansetron
Avoi:
metoclopramide, prochlorperazine
Issues with ergot dopamine issues
cardiac/lung/retroperitoneal fibrosis
Unavailability
Just use no-ergot derivatives
Nonergot dopamine agonists
apomorphine (subcutaneous)
pramipexole
ropinirole
rotigotine (transdermal)
piribedil
Dopamine agonist AE
Nausea
Orthostatic hypotension
- worse than with
Dopamine agonist AE
Nausea
Orthostatic hypotension
- worse than with levodopa
Confusion and hallucinations
Sleepiness and sleep attacks
Peripheral oedema, ankle swelling, facial oedema
Skin irritation/rash – Rotigotine (10%)
Impulse control disorders
- higher propensity than levodopa
Features of impulse control disorders
- Pathological gambling (more in males)
- Hypersexuality
- Compulsive (binge) eating
- Compulsive shopping (more in females)
Punding
stereotyped repetitive behaviours
Often associated with marked dyskinesias and off-state dysphoria and with over-use of levodopa
compulsive performance of repetitive, mechanical tasks, such as assembling and disassembling, collecting, or sorting household objects
Punding
stereotyped repetitive behaviours
Often associated with marked dyskinesias and off-state dysphoria and with over-use of levodopa
compulsive performance of repetitive, mechanical tasks, such as assembling and disassembling, collecting, or sorting household objects
MAO inhibitor examples in PD
- Selegiline
- Rasagiline
Good/ Bad aspects of each PD drug class in early PD
Levodopa
- well tolerated and most effective/potent
- Increased short-term dyskinesia rate with levodopa but no difference long-term
Dopamine agonists
– medium potency, less well tolerated, less dyskinesia
MAOI-B’s
- very well tolerated, low potency, low dyskinesia
Timing of dyskinesias with levodopa
Peak dose
* 30-60 min post Ldopa
* Chorea
* entire body/upper half
* Often not aware
End of dose
* 3-4 hours post Ldopa or early morning
* Dystonia
* Often foot
* Often painful
Management PEAK dose dyskinesia with levodopa
- reduce levodopa dose size
- add amantadine
- add dopamine agonist and reduce levodopa
- stop entacapone
Management END of dose dyskinesia with levodopa
- add entacapone or selegiline
- decrease dose interval
- increase levodopa dose size
- add amantadine
- add dopamine agonist
Amantadine and dyskinesias
- 24% reduction in dyskinesias
- improved “off” motor performance
- no change in “on” performance
Skin change with amantadine
Levido reticularis
harmless but relatively common
COMT inhibitors for PD
Tolcapone
– Regular LFT testing mandatory
– Scripts have to be written by specialist
Entacapone (Comtan)
Amantadine MOA
NMDA glutamate receptor antagonist
weak anticholinergic, and љ dopamine release
AE amantadine
insomnia, livedo
reticularis, confusion, leg oedema, blurred vision
Anti-cholinergics in PD
all specific anti-muscarinic
benztropine,
procyclidine,
benzhexol
AE Anti-cholinergics in PD
esp. dry mouth and cognitive impairment also, blurred vision, urinary retention
?? promotes amyloid plaque deposition
? risk factor for dementia
RBD treatment
- Clonazepam
- Melatonin
- increases REM sleep atonia levels
- useful in those with comorbid OSA or dementia.
Incidence of Parkinson’s dementia in PD
~ 10% per year
Dementia in PD - treatment
- cholinesterase inhibitors
– rivastigmine
– donepezil
– no evidence for benefit in PD-MCI - memantine
- no convincing evidence (yet) for cognitive training or physical exercise or diet, hearing aids
Treatment of Psychosis in Parkinson’s
Hallucinations
– benign hallucinations of presence are common (don’t treat)
– usually visual, but can be tactile, auditory (treat unless rare)
- Paranoid psychosis – must be treated urgently!
Step wise progression of management
1. quetiapine
2. reduce PD drugs one by one, starting with the least potent; levodopa should be maintained
3. cholinesterase inhibitors (donepezil) if dementia/confusion
4. clozapine if ongoing psychosis
DBS location and effects
- Thalamic surgery (historically done)
– good mainly for tremor - Deeper - Pallidal, subthalamic surgeries have more global effect
Selection criteria fo DBS in PD
–Typical PD
will never be better than. their best L.dopa response
–Medically healthy
–No dementia
–No psychosis or severe hallucinations
–<70 yrs
RED Flags in movement disorder (For not Parkinson’s disease)
- No tremor
- symmetric signs
- early falls (in the first year)
- dysphagia or marked speech problems
- urinary incontinence
- early dementia
Subforms of MSA
MSA-C: cerebellar predominant form
– nystagmus, dysarthria, ataxia
- MSA-: parkinsonism predominant form
– mainly akinetic-rigid (symmetric rigidity, little tremor, poor postural reflexes).
Main clues for MSA-P
- erectile failure (Men)
- urinary incontinence (Women)
- postural hypotension
Other
* not much tremor
* early instability
* pyramidal/cerebellar signs
* poor response to levodopa
* more rapid progression
Pathophys MSA
Alphasynucleinopathy
antecollis
Flexed neck
MSA on MRI
HOT cross bun sign
- in the pons
Putaminal ring sign
- quite specific
Subtypes of PSP
Classic PSP - “Richardson’s syndrome“
* characterised by the classic features of PSP:
– early onset of falls
– supranuclear down gaze palsy (or slow vertical saccades)
– postural instability
– Frontal dementia.
“PSP-Parkinsonism” (PSP-P)
* characterised by:
– asymmetric onset
– tremor
– response to levodopa
– Better prognosis.
PSP on MRI
Hummingbird sign
- wasting of the midbrain
Pathology in CBS
- Commonest pathology is corticobasal degeneration (a tauopathy) but may be due to other pathologies:
– PSP
– Pick disease
– AD
– DLB
– Creutzfeld–Jakob disease
Commonest presentation of CBS.
Features of CBS
a useless rigid jerking arm.
Other features
– asymmetric akinetic-rigid syndrome
– apraxia
– frontal lobe dementia
– ± limb pain/cortical sensory loss
– ± myoclonus
– ± alien limb phenomenon
– ± oculomotor apraxia (delay in launching saccades
– ± supranuclear gaze palsy (not as severe as PSP, often issues intiating)
Drugs -> Drug induced PD
- Neuroleptics
- Antiemetics
- Lithium
Clues for drug induced PD clinically
- Symptoms and signs often symmetric
- Tremor may be absent
Arteriosclerotic Parkinsonism
Clinical presentation
- Superficial appearance of parkinsonism
- “lower half parkinsonism”
- expressive face
- normal arm swing
- pyramidal signs (hyperreflexia, extensor plantars)
- rigidity is gegenhalten or spastic
- tremor – absent or postural
