Pattern of cardiac sympathetic denervation in idiopathic Parkinson disease studied with 11C hydroxyephedrine PET

Abstract

Purpose: To determine whether cardiac sympathetic denervation in idiopathic Parkinson disease (IPD) affects the left ventricle in a distinct regional pattern versus a more global pattern with use of carbon 11 (11C) meta-hydroxyephedrine (HED) positron emission tomography (PET).

Materials and methods: This prospective study was approved by the institutional review board and was compliant with HIPAA. Informed consent was obtained from all subjects. Cardiac PET was performed with 11C HED in 27 patients with IPD (20 men and seven women aged 50-74 years; mean age, 62 years±6 [standard deviation]). 11C HED retention indexes (RIs), which reflect nerve density and integrity, were determined. RIs for 33 healthy control subjects (15 men and 18 women aged 20-78 years; mean age, 47 years±17) were used as a control database. Patients with IPD were compared with control subjects by using z score analysis. Global and segmental measurements of sympathetic denervation were expressed as percentage extent, z score severity, and severity-extent product (SEP). Group comparisons were performed with the Student t test.

Results: The mean 11C HED RI was 0.086 mL of blood per minute per milliliter tissue±0.015 for control subjects and 0.043 mL of blood per minute per milliliter tissue±0.016 for patients with IPD (P<0001). When compared with normative data from the control database, profound cardiac denervation (global extent>50%) was seen in most patients (19 of 27 patients, 70%). Four patients had normal 11C HED studies and four had mild denervation (global extent<25%). The mean global denervation extent was 62%±38, the mean severity z score was -2.7±1.2, and the mean SEP was -202±131 (range, -358 to 0). Segmental analysis revealed relative sparing of anterior and proximal septal segments (mean extent, 48%-51%; mean severity z score, -2.47 to -2.0; mean SEP, -167 to -139), with lateral and proximal inferior segments more severely affected (mean extent, 68%-73%; mean severity z score, -2.8 to -2.62; mean SEP, -271 to -230). Patients with normal findings or preserved denervation did not significantly differ in mean age (t=1.09) or disease duration (t=0.44) compared to patients with severe sympathetic denervation.

Conclusion: Cardiac sympathetic denervation in IPD is extensive, with a segmental pattern that involves the proximal lateral left ventricular wall most severely, with relative sparing of the anterior and proximal septal walls.

Figure 1:

Summary of functional sympathetic cardiac PET and nigrostriatal PET neuroimaging protocols.

Figure 2:

Transaxial parametric DTBZ PET VMAT2 binding images at level of striatum show normal intense uptake in control subject (left) and asymmetric predominant putaminal losses in patient with IPD (right).

Figure 3:

A, B, Comparison polar maps of mean HED RI in, A, control subjects and, B, patients with IPD demonstrate severe global cardiac sympathetic denervation in patients with IPD. C, Segmental z score severity polar map generated by means of sector-to-sector comparison of HED RI in patients with IPD and control subjects shows the “characteristic” regional pattern of sympathetic denervation in IPD. Proximal lateral wall is most severely affected, with relative sparing of anterior and proximal septal walls. There is concordance in segmental distribution on both the z score severity polar map and, D, the frequency polar map representing the percentage of patients with IPD with an abnormal sector z score of 2.5 or less (ie, number of patients/27 3 100) displayed on a color scale of 0%–100%.

Figure 4:

Bull’s-eye plots obtained with nine-segment model summarize segmental distribution of sympathetic denervation with respect to mean percentage extent, z score severity, and SEP in comparison to global mean measurements. Mean global denervation extent was 62% 6 38 (range, 0%–100%), mean severity z score was −2.7 ± 1.2 (range, −3.6 to −2.5), and mean SEP was −202 ± 131 (range, −358 to 0). Lateral wall displays greater extent and more severe reduction of ¹¹C HED retention compared with anterior and proximal septal walls.