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Case Study

Identifying data

A 64-year-old
architect
Chief Complaint

left-hand
tremor
at rest
Associated signs and
symptoms

stooped posture
a tendency to drag
his left leg when walking
slight unsteadiness
on turning
Personal Social History

He remains independent in all


activities of daily living
Physical examination
Hypomimia (flat facies)
Hypophonia
a rest tremor of the left
arm and leg,
mild rigidity in all limbs,
impaired rapid alternating
movements in the left limbs
Question

What is the likely diagnosis and prognosis,


He is started on a dopamine agonist, which he seems to
tolerate well, and the dose is gradually built up to the
therapeutic range. About a year later, he and his wife
return for follow-up. It now becomes apparent that he is
spending large sums of money, which he cannot afford, on
gambling and refuses to stop, despite his wifes entreaties.
To what is his condition due and how should it be
managed?
Parkinsons Disease

Parkinsonism (paralysis agitans) is a common


movement disorder that involves dysfunction in the
basal ganglia and associated brain structures. Signs
include rigidity of skeletal muscles, akinesia (or
bradykinesia), flat facies, and tremor at rest
(mnemonic RAFT).
Parkinson's disease itself is not fatal.
However, complications from the
disease are serious.
PATHOPHYSIOLOGY
Cerebral Cortex

Thalamus

Spinal
Cord

Basal Ganglia

Skeletal
Muscle
Protein Mitochondrial
Misfolding Dysfunction

DEATH OF DOPAMINERGIC
NEURONS

D1 receptor DECREASE dopamine in D2 receptor


(stimulatory) basal ganglia (inhibitory)

CAUDATE STRIATUM:
CAUDATE GLOBUS PALLIDUS INTERNA: Gabanergic neuron not
STRIATUM: gabanergic neuron inhibited
Gabanergic overactive
neuron not GLOBUS PALLIDUS
stimulated EXTERNA: Inhibits
Excessive gabanergic neuron
inhibitory input to
THALAMUS
SUBTHALAMIC NUCLEUS:
Glutaminergic neuron in
Suppression of THALAMO-
CORTICO-SPINAL
not inhibited
PATHWAY
Cerebral Cortex

Thalamus

Spinal
Cord

Basal Ganglia

Skeletal
Muscle
Suppression of THALAMO-
CORTICO-SPINAL
PATHWAY

Impaired skeletal muscle


movement

POSTURAL
TREMORS RIGIDITY BRADYKINESIA
INSTABILITY

Hypophonia Hypomimia Shuffling gait


Cardinal Features Secondary Features

Tremors
L hand tremor at rest Hypomimia

L arm and leg tremor at rest Hypophonia

Rigidity Shuffling gait


Mild rigidity in all limb Drag L leg when walking

Bradykinesia
Impaired rapid alternating
movements in L limbs
Postural Instability
Stooped posture
Slight unsteadiness on turning
Prognosis

Parkinsons disease is not a fatal illness. However, its a


degenerative disorder that usually progresses until it
leaves its patients completely debilitated. The condition
usually worsens over an average of 15 years.
The rate of progression and its course varies
among patients. The course is relatively benign
in some patients with little disability after
twenty years and may be more aggressive
among others who may be severely disabled
after ten years. Those with an early onset
Parkinsons disease have shorter life spans
than those with later-onset disease.
PHARMACOLOGY
The goal of medical management of
Parkinson disease is to provide control of
signs and symptoms for as long as possible
while minimizing adverse effects. Studies
demonstrate that a patient's quality of life
deteriorates quickly if treatment is not
instituted at or shortly after diagnosis
Dopamine Agonist
(pramipexole or ropinirole)
Rationale for using Dopamine Agonist

Dopamine agonists provide an effective alternative to


levodopa for the treatment of Parkinson's disease.

Allow initiation of levodopa therapy to be delayed so


deferring onset of levodopa associated treatment
complications such as:
fluctuations,
dyskinesias,
toxicity, or loss of efficacy
Dopamine agonists have longer plasma
half-life than levodopa; therefore, they
are expected to have a favorable effect
on motor complications
ADVERSE EFFECTS
About a year later, he and his wife return for
follow-up. It now becomes apparent that he
is spending large sums of money, which he
cannot afford, on gambling and refuses to
stop, despite his wifes entreaties. To what is
his condition due and how should it be
managed?
Impulse Control Disorders (DSM-IV)

Used to refer to a group of behaviors that


appear impulsive wherein patients act
without foresight and control
Pathological Gambling
Hypersexuality
Compulsive Shopping or Eating
Impulse Control Disorders (DSM-IV)

Triggered by dopamine agonist treatment


Conceptualized as behavioral addictions
associated w/ aberrant or excess stimulation
of dopaminergic reward mechanisms
Develops in patients within a year or more
after taking medication
Dopamine Receptor Agonist Drugs

D2 receptors
Tonically elevates dopamine levels and stimulate D2 receptors
Prevents learning from negative decision outcomes
Enhanced reward processing and decreased punishment processing
D3 receptors
Distributed within both motor and limbic circuits
Increased agonism of these receptors seems to weaken mechanisms that
would normally keep risky, pleasure-seeking behaviors in check
Explains the elevated risk for impulse control disorders
ICD Management

Most common is to lower the dosage of or to remove the


medication
ICDs usually subside in people who did not experience them before
taking dopamine agonist receptor medications
Some return to normal within a matter of days to a week, others
took weeks or months
But there are few patients wherein ICDs persist despite the
discontinuation of medications
Conclusion

Parkinsons disease is a common movement disorder that involves


dysfunction in the basal ganglia and associated brain structures.
caused by decrease dopamine levels
Signs include rigidity of skeletal muscles, akinesia (or bradykinesia),
flat facies, and tremor at rest (mnemonic RAFT).
Managed by taking medications such as levodopa or dopamine
receptor agonist drugs
Impulse Control disorder is a side effect of dopamine receptor
agonist drugs managed by lowering the dosage of or removing the
medication