Parkinson Disease

Summary

Parkinson disease is a neurodegenerative disorder that affects motion and cognition. It is caused by loss of dopamine-producing neurons in the substantia nigra, which in rare cases may be caused by MPTP, a component of illicit drugs. Parkinson disease causes an imbalance of three important neurotransmitters: Dopamine and serotonin levels decrease, while acetylcholine levels increase in the brain. Clinically, patients with Parkinson disease present with a classic resting or pill-rolling tremor, shuffling gait, micrographia, bradykinesia, and dementia. They can also present with cogwheel rigidity and postural instability. The diagnosis of Parkinson disease is usually clinical, but may be supplemented by the finding of Lewy bodies in neurons, which are composed of aggregated alpha-synuclein proteins.

Key Points

• Parkinson Disease (PD)
  • Pathophysiology
    • Loss of dopaminergic neurons in the substantia nigra (pars compacta, SNc)
      • Loss of balance between dopamine and acetylcholine in brain; resulting in improper muscle movement
    • May be caused by MPTP
      • Component in illegal drugs, metabolized to MPP+, is toxic to neurons in SNc
  • Neurotransmitter Changes
    • Increased ACh
    • Decreased Dopamine
    • Decreased Serotonin
  • Presentation
    • Bradykinesia/Akinesia
      • Hypokinesis refers to slowing of movements
    • Resting Tremor
      • 4-6 Hz “pill rolling” hand tremor is characteristic
      • Usually asymmetric in distribution; typically involves hands and feet
      • Tremor disappears with voluntary movement (hence, resting)
    • Cogwheel rigidity
      • Pulsing resistance to muscle movements
    • Postural instability
      • Feeling of imbalance; tendency to fall
    • Shuffling gait
    • Small handwriting (micrographia)
    • Dementia
      • Late finding of illness
  • Diagnosis
    • Mainly diagnosed by clinical signs and symptoms
    • Brain biopsy
      • Depigmentation of substantia nigra pars compacta
        • Due to loss of dopaminergic neurons
      • Lewy Bodies
        • Intracellular eosinophilic inclusions in neurons
        • Composed of alpha-synuclein
        • Also seen in Lewy Body Dementia
  • Treatment
    • Direct intravenous dopamine is not used because dopamine cannot cross the blood-brain-barrier
    • Carbidopa-Levodopa
      • Most effective treatment; but reserved for last due to limited effectiveness over time
      • L-DOPA converted into dopamine in brain
    • Selegiline/Rasagiline and Tolcapone
      • Prevents dopamine breakdown
    • Benztropine/Trihexyphenidyl
      • Reduces tremor
      • Decreases excess cholinergic activity
    • Bromocriptine
      • Ergot dopamine agonist
      • Can help delay the need to start carbidopa-levodopa
    • Amantadine
      • Increases dopamine availability and decreases dopamine reuptake
    • Deep Brain Stimulation
      • High frequency deep brain stimulation may help restore function to basal ganglia
      • Reserved for end-stage Parkinson Disease no longer responsive to pharmacotherapy
  • Parkinson-plus Syndromes
    • These syndromes display parkinsonism but are usually more widespread neurodegenerative conditions
    • Multiple System Atrophy (Shy Drager Syndrome)
      • Parkinsonism
      • Autonomic instability
        • postural instability, with syncope and hypotension is classic
        • Impotence and incontinence may be seen
      • Widespread neurological deficits
    • Progressive Supranuclear Palsy (PSP)
      • Neurodegeneration of the midbrain and frontal subcortical white matter
      • Presents with
        • Gait dysfunction and falls
        • Cognitive impairment
        • Vertical gaze palsy
      • Neuropathology
        • Shows deposits of abnormally phosphorylated tau proteins
    • Corticobasal degeneration