Johoney Be L.

Jumawan
XU-JPRSM, Senior Clerk

The second most common neurodegenerative disease

Mean age of onset = 60 years
Frequency increases with aging

Rest tremor
Rigidity
Bradykinesia
Gait impairment

Freezing of gait
Postural instability
Speech difficulty
Autonomic disturbances

Sensory alterations
Mood disorders
Sleep dysfunction
Cognitive impairment
Dementia
Degeneration of dopaminergic neurons in the
substantia nigra pars compacta (SNc)

Reduced striatal dopamine

Intracytoplasmic proteinaceous inclusions
(Lewy bodies)
typical macroscopic findings:
pallor of the substantia nigra and locus ceruleus

Robbins & Cotran Pathologic Basis of Disease, 18
th
edition
Microscopic findings:
loss of the pigmented, catecholaminergic neurons in the
2 regions, associated with gliosis.



Lewy Bodies
- intracytoplasmic proteinaceous
inclusions
-composed of fine filaments. These
filaments are composed of -synuclein.
also affects:
cholinergic neurons
(nucleus basalis of
Meynert)
norepinephrine neurons
(locus coeruleus)
serotonin neurons (raphe
nuclei of brainstem)
neurons of: olfactory
system, cerebral
hemispheres, spinal cord &
peripheral autonomic NS
most significant mechanism:

Protein Misfolding and accumulation
Mitochondrial dysfunction

characterized by Lewy bodies and Lewy nitrites

STRIATUM- major input region of the basal ganglia
GPi and SNr- major output regions

output of the basal ganglia:
provides inhibitory tone to thalamic and brainstem
neurons motor systems in the cerebral cortex and
spinal cord (regulate motor function)


Dopaminergic projections from SNc neurons

modulate neuronal firing
stabilize the basal ganglia network.
Basal Ganglia
Organization
Dopamine denervation

increased firing of neurons in the STN and Gpi

excessive inhibition of the thalamus
reduced activation of cortical motor systems
development of parkinsonian features

Reduced uptake of
striatal
dopaminergic
markers particularly
in the posterior
putamen
Imaging of the
brain dopamine
system

Parkinsonism- symptom complex manifested by
bradykinesia with rigidity and/or tremor

Parkinsons disease is the most common form of
parkinsonism
LEVODOPA
- a dopamine precursor
- the mainstay of therapy and the most effective
treatment for PD

DOPAMINE AGONISTS
(Ropinirole, Pramipexole, Rotigotine, Apomorphine)
-act directly on dopamine receptors

MONOAMINE OXIDASE TYPE B
(MAO-B INHIBITORS)
- Selegeline, Rasagiline
- block central dopamine metabolism and increase
synaptic concentrations of the neurotransmitter

COMT INHIBITORS
-increases the elimination of half-life of levodopa and
enhances its brain availability



AMANTADINE
- has antiparkinsonian effects



SURGICAL TREATMENT
- Pallidotomy
- Deep Brain Stimulation

NONPHARMACOLOGICAL THERAPY
- maintain social and intellectual activities
- Education, Attention to home safety
- need for caregivers
Current
Management

Treatment
Algorithm for the
management of
Parkinsons Disease


Harrisons Principle
of Internal
Medicine, 18e
Thank You :p