Harvey's Garden

Parkinson disease

3 min read

Epidemiology

Etiology

Parkinson disease

  • Idiopathic
  • Contributing genetic factors include:
    • α-Synuclein (SNCA)
      • α-Synuclein constitutes the major component of Lewy bodies. In addition to mutations, duplication/triplication of the wild-type gene can also cause PD (due to increased production of the normal protein).

Pathophysiology

Mnemonic

PArkinson’s Disease = doPAmine Dowm Alzheimer Disease = Acetylcholine Down

  • Progressive dopaminergic neuron degeneration in the substantia nigra (part of the basal ganglia) and the locus coeruleus → dopamine deficiency at the respective receptors of the striatum with interrupted transmission to the thalamus and motor cortex → motor symptoms of PD
  • Serotonin and noradrenaline depletion (in the raphe nuclei): likely cause of depressive symptoms
  • Acetylcholine surplus (in the nucleus basalis of Meynert): likely cause of dyskinesia

Clinical features

Motor signs

  • Parkinsonism
    • Bradykinesia: slowed movements in combination with decreased amplitude/speed when moving
    • Resting tremor (4–6 Hz)
      • Oftentimes the presenting symptom
      • Pill-rolling tremor that subsides with voluntary movements but increases with stress
    • Rigidity: increased and persistent resistance to passive joint movement that is independent of speed
      • Cogwheel rigidity
  • Postural instability
    • Imbalance and tendency to fall
  • Parkinsonian gait: shuffling gait with quickened and shortened steps

Diagnostics

Pathology

  • Lewy bodies
    • Aggregates of misfolded α-synuclein and other proteins, such as ubiquitin and neurofilament protein within the neural cell bodies
    • Appear histologically as intracellular hyaline eosinophilic globules
    • May be found in brainstem, substantia nigra, and cortex
    • Also seen in Lewy body dementia

  • Image A: An eosinophilic cytoplasmic inclusion (Lewy body; blue overlay) is visible inside a neuron. There is a large accumulation of neuromelanin (brown granules; green overlay).
  • Image B: A neurite staining positive for α-synuclein is visible in the center of the image (Lewy neurite; yellow overlay).

Treatment

Nonergot dopamine receptor agonists

  • Pramipexole, Ropinirole, Apomorphine
  • Consider as initial treatment in younger patients, especially those with risk factors for levodopa-induced dyskinesia.
  • Some patients develop impulse control disorders with compulsive gambling or hypersexuality.

Tip

  • Ergot dopamine agonists (cabergoline and bromocriptine) are not recommended in Parkinson disease or restless leg syndrome, but are first-line treatment in Prolactinoma and Hyperprolactinemia.
    • Primarily due to a higher risk of serious side effects, specifically fibrotic reactions affecting the heart valves and lungs.
    • The doses used for Prolactinoma and Hyperprolactinemia are generally lower than for Parkinson’s, leading to a lower risk of fibrotic side effects, making the benefit-risk balance more favorable.

Anticholinergic drugs (muscarinic antagonists)

  • Benztropine, Trihexyphenidyl, Biperiden
  • Beneficial regarding tremor and rigidity but does not improve bradykinesia

Deep brain stimulation (DBS)

  • In PD, the lack of dopamine leads to overactivity in the indirect pathway. Key players here are the STN and the GPi.
  • Indications
    • Severe motor symptoms or refractory tremor
    • Decrease in dosage of medication because of adverse effects
  • Procedure
    • Stereotactic implantation of stimulating electrode(s) targeting the subthalamic nucleus or internal globus pallidus
    • Controlled remotely

Parkinson-plus syndromes

Dementia with Lewy bodies

  • Epidemiology
    • Second most common form of neurodegenerative dementia (10–20% of dementia cases)
  • Diagnosis requires two of the following
    • Cognitive fluctuations
    • Visual hallucinations
    • Parkinsonism

Graph View

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