2-Year Natural Decline of Cardiac Sympathetic Innervation in Idiopathic Parkinson Disease Studied with C-11-Hydroxyephedrine PET

摘要

The objective of this study was to detect regional patterns of cardiac sympathetic denervation in idiopathic Parkinson disease (IPD) using C-11-hydroxyephedrine (C-11-HED) PET and determine the denervation rate over 2 y. Methods: We obtained 62 cardiac C-11-HED PET scans in 39 patients (30 men and 9 women; mean age +/- SD, 61.9 +/- 5.9 y), including 23 patients with follow-up scans at 2 y. We derived C-11-HED retention indices (Rls; mL of blood/min/mL of tissue) reflecting nerve density and integrity for 480 left ventricular (LV) sectors. We compared IPD patients with 33 healthy controls using z score analysis; RI values <= 2.5 SDs were considered abnormal. We expressed global and regional LV denervation as the percentage extent of z score severity and severity extent product (SEP) on 9-segment bullseye maps and decline in cardiac sympathetic innervation as the 2-y difference in SEP (diff-SEP). Results: Baseline C-11-HED PET in the 39 IPD patients revealed an RI mean of 0.052 +/- 0.022 mL of blood/min/mL of tissue. In comparison with data from normal controls, 12 patients had normal C-11-HED PET, 5 showed mild denervation (percentage extent < 30%), and 22 had moderate to severe denervation (percentage extent > 30%, z score 2.5 SD). In the 23 paired PET scans, worsening cardiac denervation (global diff-SEP > 9) occurred in 14 of 23 (60.9%) patients over 2 y, including percentage LV abnormality (59% increasing to 66%), z-severity (-2.4 down to 2.5), and SEP (-195 to 227) (P = 0.0062). We found a mean annual decline of 4.6% +/- 5.6 (maximum, 13%) in C-11-HED retention from a baseline global RI mean of 0.0481 +/- 0.0218 to 0.0432 +/- 0.0220 (P = 0.0009). At baseline, 5 patients with normal uptake had no interval change; 3 with mild denervation developed interval decline in lateral and inferior segments (diff-SEP 82 to 99) compared with anterior and septal segments (-65 to 79), whereas the reverse pattern occurred in 15 patients with severe baseline denervation. Conclusion: Progressive decline in cardiac sympathetic neural integrity in IPD patients occurs at a modest rate over 2 y on C-11-HED scans with marked heterogeneity and a regional pattern of involvement and decline.