Cardiac sympathetic denervation preceding motor signs in Parkinson disease

Abstract

There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex-cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[(18)F]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The results lead us to hypothesize that cardiac noradrenergic denervation and decreased baroreflex-cardiovagal function may occur early in the pathogenesis of PD.

FIGURE 1

Thoracic 6-[¹⁸F]fluorodopamine (¹⁸FDA) and ¹³N-ammonia (¹³NH₃) images in July 2001 and November 2005. Note absence of left ventricular myocardial 6-[¹⁸F]fluorodopamine-derived radioactivity at both times, indicating cardiac sympathetic denervation. Myocardial perfusion, as indicated by ¹³NH₃-derived radioactivity, was normal.

FIGURE 2

Beat-to-beat heart rate and blood pressure responses to the Valsalva maneuver (12-second duration, 30 mm Hg) in July 2001 and November 2005. In the latter recording, note progressive decline in blood pressure during Phase II, smaller pressure overshoot, and delayed return of pressure toward baseline in Phase IV, consistent with worsening baroreflex-sympathoneural function. Heart rate responses during and after the maneuver were also smaller in 2005 than in 2001, despite larger changes in blood pressure, consistent with worsening baroreflex-cardiovagal function.

FIGURE 3

Individual values for septal myocardial 6-[¹⁸F]fluorodopamine-derived radioactivity, in normal control subjects (white circles), patients with Parkinson disease without sympathetic neurocirculatory failure (PD no SNF, green circles), patients with Parkinson disease and sympathetic neurocirculatory failure (PD + SNF, blue circles), and the case reported here (large green circle). Dashed line shows the normal mean value and light green shaded area 2 standard deviations from the normal mean. Note markedly decreased 6-[¹⁸F]fluorodopamine-derived radioactivity in the current case.