Parkinson's Disease

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Introduction

a simple case introducing clincial presentation and calling for a differential diagnosis. To get students thinking.

phenothiazines, used in the treatment of schizophrenia, can cause drug-induced parkinsonism, which is reversible
MPTP can result from improper synthesis of opioids and is cytotoxic for dopaminiergic neurons

degeneration of dopaminergic neurons in the substantia nigra compacta, leading to increased inhibition of the globus pallidus externa. This causes increased inhibitory output of the globus pallidus interna, in part due to increased excitation by the subthalamic nucleus

A reduction of thalamic input to the motor cortex leads to rigidity and bradykinesia

Lewy bodies and alpha-synuclein (Ch 4) appear to be involved in some cases of PD.

bradykinesia - decreased amplitude and velocity of voluntary movement
akinesia - impaired initiation of movement
rigidity
tremor - typically rest tremor; usually in one upper limb first, then spreading to ipsilateral lower limb
gait postural disturbances
- shuffling (festinating) gait, flexed posture
- freezing
- impaired balance
dementia
TRAP - tremor, rigidity, akesia, postural instability

symptoms vary from being 'off' to being 'dyskinetic' over time

L-dopa (sinamet) together with carbidopa
amantadine is an antiviral with better tolerance but less effectiveness than L-dopa
work only as long as dopaminergic neurons remain - perhaps 15 years

Dopamine receptor agonists
- directly activiate D2 receptors in striatum
- bromocriptine
- do not require dopaminergic neurons

Surgical procedures:

pallidotomy
deep brain stimulation of subthalamic nuclei using electricity to inhibit - this leads decreased globus pallidus signaling
neural transplantation

Case #2 - a small story wrapping it all up and asking about esp management.

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