Table 5.

Treatment of Manifestations in Individuals with VPS35-Related Parkinson Disease

Manifestation/ConcernTreatmentConsiderations/Other
Neurologic Levodopa in combination w/peripheral dopa decarboxylase inhibitor (carbidopa, benserazide):
1.

Immediate-release (IR) tablets

2.

Disintegrating tablets

3.

Controlled-release (CR) tablets

4.

Extended-release (ER) capsules

5.

Inhalation powder

6.

Enteral suspension (pump)

Dopamine agonists
1.

IR & CR tablets

2.

Subcutaneous injections & infusion pump (apomorphine)

3.

Transdermal patch (rotigotine)

Other drugs used in combination w/levodopa & dopamine agonists: inhibitors of catechol-O-methyltransferase or monoamine oxidase-B, anticholinergics, & amantadine.
  • A good levodopa response was seen in nearly all persons w/PARK-VPS35.
  • Since there is low risk of neuropsychiatric symptoms in PARK-VPS35, treatment w/dopamine agonist should be considered.
  • To ↓ or delay side effects (e.g., dyskinesias, hallucinations, impulse control disorder) of levodopa & dopaminergic medication, doses should not exceed levels required for satisfactory clinical response.
  • In younger persons, treatment w/dopamine agonists should be given preference.
  • PT &/or OT to improve &/or maintain gross motor & fine motor skills.
  • Speech therapy
Dyskinesias Treatment options:
  • Reduction of levodopa dose
  • Use of dopamine receptor agonists
  • Deep brain stimulation
  • Continuous application of levodopa or apomorphine
Deep brain stimulation & apomorphine pump may be considered for persons who develop motor fluctuations & disabling dyskinesia.
Neuropsychiatric manifestations
  • Atypical neuroleptic agents such as low-dose clozapine, quetiepine, or pimavanserin & reduction of dopaminergic therapy can ↓ delusions & hallucinations.
  • Standard treatments for depression
Dementia Treatment w/cholinesterase inhibitor (rivastigmine) should be considered.
Orthostasis Consider treatment w/droxidopa, midodrine, fludrocortisone.
Constipation Symptomatic treatment

From: VPS35-Related Parkinson Disease

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