Parkinsons Disease
Epidemiology:
Mean
onset 55 years
Pathology:
Loss of pigmented neurons in substantia nigra. About 80%
must be depleted before symptoms occur.
Clinical
History
Fatigue, tremor (pill-rolling), ↓mobility, problems walking, falling
Late features:
Mask-like facies, monotonous tone, oblinking, dysarthria,
dysphagia, micrographia, ↓ADLs, autonomic dysfuntion (↑sweating)
ΔΔ for tremor:
Benign essential (intention, bilateral, FH, better w alcohol),
cerebellar (intention, faster as approach target)
Examination:
TRAP = Tremor, Rigidity, Akinesia, Posture
Tremor:
pill rolling, occurs at rest, unilateral at first
Rigidity:
cogwheel
Akinesia:
initiating movement, turning, festinant gait = fast small steps, no
arm swinging
Posture:
stooped
Treatment
POSSET, psychiatric (association with dementia and depression), SALT
(when swallowing fails)
Drugs: Enhance dopamine transmission
Levodopa
Indicated
for those over 65+ starting when independence compromised. Often
withheld in the early stages because prolonged use it becomes less
effective. Given with a peripheral decarboxylase inhibitor
(carbidopa/benserazide) to ↓GI side effects.
Side effects:
-
Dyskinesia
-
Nausea
& vomiting: treated with carbidopa, antiemetics e.g.
domperidone
(NB: but not those anti-emetics which affect dopaminergic transmission
e.g. metoclopramide)
-
Postural hypotension: discontine
anti-hypertensives, compression stockings, fludrocortisone, consider
multiple system atrophy as an alternative diagnosis
-
Psychiatric: e.g. confusion/hallucinations
-
On/off
phenomenon: early wearing off of dose, dyskinesia at peak doses.
Treated with the addition of other drugs such as entacapone,
selegelline, and dopamine agonists.
-
Compulsive behaviour: controversial
Other Drugs
MAOIs
(e.g. selegeline): early PD
Catechol-O-Methyl
Transferase (COMT) inhibitors
(e.g. entacapone): inhibit
COMT in periphery thus increasing the
bioavailability of L-DOPA by facilitating its transmission across the
blood-brain barrier
Dopamine agonists
(e.g. bromocriptine, apomorphine): first line for the under 65s. Side
effects: same as L-DOPA.
Natural history
Relatively normal life span, many die of old age. Postural instability
is an omnious sign.
Parkinsonism
Parkinsons can be idiopathic (Parkinson's Disease) or associated with
other disorders:
-
Drug induced: neuroleptics, metoclopramide, cyclizine,
valproate, stemitil. Akinetic-rigid (no tremor)
-
Progressive
supranuclear palsy: Changes in personality. Eye movement disorders:
clssically can't look down so has problems reading & going down
stairs
-
Multiple system atrophy: rigidity (symmetrical in both
legs), facial dystonia, cerebellar signs, dysarthria, postural
hypotension
-
Repeated head trauma
-
Pseudo-parkinsonism: small vessel infarcts, vascular risk
factors, stepwise
-
Lewy body: presents with dementia
