Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) are linked to striatal angiogenesis in rodent models.
• Angiogenesis can increase cerebral blood flow (CBF) responses to hypercapnia.
• Documenting microvascular changes in living humans with PD is challenging.

Purpose of the Study:

• To investigate if hypercapnic CBF responses are abnormally increased in PD patients with LID compared to non-dyskinetic PD patients (NLID) and healthy controls.
• To explore the relationship between hypercapnic CBF responses and levodopa-induced CBF responses in the basal ganglia.
• To determine if these vascular changes correlate with motor disability or symptom duration in PD.

Main Methods:

• Utilized H215O Positron Emission Tomography (PET) to measure CBF in 24 unmedicated PD subjects (12 LID, 12 NLID) and 12 healthy controls.
• Scanned subjects under normocapnic and hypercapnic conditions.
• Compared hypercapnic CBF responses with levodopa-induced CBF responses in the same individuals.

Main Results:

• Significantly greater hypercapnic CBF responses were observed in the posterior putamen of LID subjects compared to NLID and healthy controls.
• Hypercapnic CBF responses in the posterior putamen correlated with off-state motor disability.
• Levodopa-mediated CBF responses correlated with symptom duration, but not motor disability.

Conclusions:

• This study provides the first in vivo human evidence linking levodopa-induced dyskinesias in Parkinson's disease to microvascular alterations in the basal ganglia.
• Abnormal hypercapnic vasoreactivity in the posterior putamen is associated with LID and motor disability in PD.
• Distinct vascular mechanisms may underlie motor disability and dyskinesias in Parkinson's disease.