Parkinson's Disease Flashcards
What is the annual incidence of PD?
1/8000
What is the prevalence of PD?
1/800
What percentage of over 65s are affected by PD?
1%
What is the median age of onset of PD?
60
What is roughly the time from PD disease onset to death?
15 years
What is the classical pathology of PD? Be specific
Loss of pigmented neurons in ventrolateral tier of SNPC with alpha synuclein inclusions in surviving nigral neurons (Lewy Bodies)
What percentage of PD cases present before age 45?
Roughly 15%
How much more likely are non-smokers to get PD than smokers?
Twice as likely
What is the major environmental toxin linked loosely to a PD like picture?
MPTP
9 major iatrogenic (drug) causes of Parkinsonism?
Antipsychotics Prochlorperazine Metaclopramide Several CCBs Amiodarone Valproate Lithium Ciclosporin Chloroquine
5 major degenerative differentials for PD?
PSP MSA Vascular Parkinsonism - diffuse subcortical white matter ischaemia DLB Acute vascular Parkinsonism
What are the 4 key diagnostic features of PD?
Fatiguable bradykinesia with slowing of initiation of movements
Postural instability
Rigidity
Coarse, slow resting tremor (pill rolling)
What are the 4 major differentials for the PD rest tremor?
Severe essential
Holmes tremor/rubral tremor
Dystonic tremor
Neuropathic tremor
How might rigidity in early PD manifest as a complaint?
Muscle stiffness and aching discomfort
How would you describe the rigidity in PD?
Lead pipe
What early complaints might be heard in PD?
Difficulty with fine motor - doing up buttons, stirring, wiping, brushing teeth, getting things out of pockets…
Muscle aches and stiffness
Dragging or slowness of a limb
Tremor
What defines early onset in PD?
Less than 40 (/45)
What prodromal features of PD may be seen?
Major depressive illness or stress may unmask
Fatigue
Bradykinesia, mental inflexibility
Autonomic Sx
Frozen shoulder, low back pain (?due to mobility problems)
REM sleep behaviour disorder
Anosmia
What is Braak’s hypothesis?
That PD begins in the peripheral autonomic system, olfactory bulb and dorsal nucleus of vagus before spreading rostrally in a prion like mechanism
What is the name of the hypothesis that PD starts in the autonomic and olfactory system?
Braak’s hypothesis
What autonomic Sx may be seen early in PD?
Thermodysregulation
Dribbling saliva e.g. At night onto pillow
Colonic motility disturbance and constipation
Erectile dysfunction
What does vertical saccadic slowing suggest in the context of Parkinsonism?
PSP
What does delay in initiation of vertical saccades in the context of Parkinsonism suggest?
CBD
What do horizontal square wave jerks and gaze evoked nystagmus suggest in the context of Parkinsonism?
MSA
How may speech differentiate types of Parkinsonism?
Monotonous and quiet in PD
Growly and slow in PSP
Nasal and whining in MSA
What eyelid signs may suggest PSP?
Eyelid apraxia
Near-absent spontaneous blinking
What should babinski signs in Parkinsonism without cervical spondylotic myelopathy/prev stroke make you think about?
Is it MSA (maybe PSP)
Genetic pallidopyramidal syndrome e.g. Hallervorden-Spatz (PKAN) or another NBAI such as Kufor-Rakeb syndrome or PLA2G6 neuroaxonal dystrophy
Why is lying and standing BP after 2 mins important in assessing PD?
Postural hypotension of over 20 systolic may suggest increasing risk of falls if starting on dopaminergic meds
What should significant orthostasis preceding Parkinsonism make you think about?
Is it MSA-P
What might be a useful way to distinguish between PD and essential tremor on exam?
Get patient to hold arms/hands outstretched - latent interval of a few seconds before tremor appears in PD vs tremor present straight away in essential
What is the possibly arbitrary definition of DLB?
Dementia occurring within the first year of onset of Parkinsonism or before onset
What rating scales may be useful in analysing disease response for PD especially early on?
UPDRS (parts 2 and 3)
What might make you reconsider a presumptive PD diagnosis?
Poor response to therapy (750mg/day LDopa) at 4 months, having doubled dose at 3 months
What constitutes a formal acute levodopa challenge?
250mg of levodopa/benserazide with finger tapping and timed walking tests at baseline and 1 hour then 2 hours
With all PD meds stopped overnight beforehand and domperidone if nauseous
What should be done for a bradykinetic-rigid predominant phenotype of presumed PD that hasn’t responded to initial LDopa therapy? Looking for what?
MRI
Hot cross bun sign in pons, pontocerebellar atrophy, hyperintense putaminal rim on T2 - MSA
Midbrain and superior cerebellar peduncle atrophy (hummingbird/penguin sign) - PSP
Vascular Parkinsonism - subcortical white matter ischaemia and striatocapsular infarcts
Secondary Parkinsonism e.g. Basal ganglia calcification
What might be a good investigation for predominantly tremulous patients with suspected PD?
DAT scan, as normal DAT excludes PD
2 important surgical causes of Parkinsonism?
Supratentorial meningiomas
Communicating hydrocephalus
What is the middle cerebellar peduncle sign and what does it suggest?
Increased white matter T2 signal in middle cerebellar peduncle
With tremor, ataxia and Parkinsonism suggests fragile X premutation (FRXTAS) esp if FH/male patient
What is ephedrone toxicity and what can it cause? Where is it a major problem?
Subacute bradykinesia, severe dysarthria, dystonic posturing and walking and severe postural instability with backwards falls
Due to illicit ephedrone IV injection, made from sudafed (pseudoephedrine)
Big in Eastern Europe
What is the initial maintenance dose of L dopa?
50mg TDS
/62.5mg TDS if with a DDCI (carbidopa/benserazide)
What is the max L dopa dose per day with aim to reduce long term side effects?
600mg/day
What is the main role of L dopa sparing agents?
To avoid on-off phenomena and end of dose deterioration, and also peak dose choreoathetosis
What is the best drug to reduce dyskinesias in PD?
Amantadine
What drugs might be useful for off-period dystonia in earlier onset PD patients?
Anticholinergics
Commonly used MAO-B inhibitors in PD?
Selegiline
Rasagiline
What are commonly used COMT inhibitors?
Entacapone
Tolcapone
What are commonly used dopamine agonists?
Rotigotine - patch
Ropinerole
Pramipexole
Apomorphine
What might be a reasonable starting drug for patients with mild motor disability only in PD?
Rasagiline - a MAO-B inhibitor
What are the 3 best methods of managing refractory motor fluctuations for PD?
Apomorphine subcut administration
Duo-dopa - continuous intrajejunal L dopa administration through a gastrojejunostomy
DBS - usually bilateral STN
Managing insomnia in PD?
Nocturnal dopaminergic drug dose
Clonazepam
Low dose amitriptyline
Sleep hygiene
Management of depression in PD?
Noradrenergic reuptake inhibitors e.g. Duloxetine
Amitriptyline or nortryptiline
Management of REM sleep behaviour disorder in PD?
Melatonin
Clonazepam
Management of daytime sleepiness in PD e.g. Due to dopamine agonist therapy?
Modafinil
Management of psychosis in PD?
Reduce doses of antiPD drugs, consider clozapine quetiapine or Aripiprazole and cholinomimetics
Management of constipation in PD?
Macrogol - osmotic laxative
Faecal softeners
Management of urinary urgency in PD?
Bladder stabilisers e.g. Tolterodine, trospium
Desmopressin if nocturia
Management of ED in PD?
Sildenafil
Management of rigidity/dystonia pain in PD?
Clonazepam, Anticholinergics
Management of restless legs in PD?
Dopamine agonists
Management of orthostatic hypotension in PD?
Increase water and salt
Fludrocortisone
Ephedrine/midodrine
Management of drooling in PD?
Atropine eye drops sublingually (0.5%)
Botulinum toxin injections into salivary glands
Management of excessive sweating in PD?
Propranolol
Propantheline
What is Stalevo?
L dopa plus carbidopa plus entacapone
What is madopar?
Co-beneldopa
What is sinemet?
Co-careldopa
What is azilect?
Rasagiline
What is a commonly used anticholinergic in PD?
Trihexiphenidyl
How is Parkin PD inherited?
AR
How does Parkin PD differ to idiopathic?
More benign, with restricted SN lesion but not alpha synuclein
Early onset and slowly progressive with no Anosmia, leg presentation and common rest tremor
How is LRRK2 PD inherited? What is the mutation? What about its penetrance?
AD
G2019S
Incomplete penetrance but a susceptibility gene seen in sporadic PD fairly often
How is LRRK2 different to Parkin PD?
It is an alpha synucleinopathy so is more like IPD
What percentage of PD patients get dementia by terminal stages/over 70 years?
40%
