Neurocirculatory and nigrostriatal abnormalities in Parkinson disease from LRRK2 mutation

Background: Patients with Parkinson disease (PD) often have cardiac sympathetic denervation and failure of neurocirculatory regulation by baroreflexes. Familial PD caused by mutation of the gene encoding alpha-synuclein or by alpha-synuclein gene triplication also features cardiac sympathetic denervation and baroreflex failure. Methods: Here we report results of cardiac sympathetic neuroimaging by 6-[F-18] fluorodopamine PET, baroreflex testing based on beat-to-beat hemodynamic responses to the Valsalva maneuver, and nigrostriatal neuroimaging using 6-[F-18] fluorodopa PET in a proband with mutation of the gene encoding leucine-rich repeat kinase 2(LRRK2), the most common genetic abnormality identified so far in familial PD. Results: The patient had no detectable 6-[F-18] fluorodopamine-derived radioactivity in the left ventricular myocardium, a progressive fall in blood pressure during the Valsalva maneuver and no pressure overshoot after release of the maneuver, and decreased 6-[F-18] fluorodopa-derived radioactivity bilaterally in the putamen and substantia nigra. Conclusion: This patient with Parkinson disease (PD) caused by LRRK2 mutation had evidence of cardiac sympathetic denervation, baroreflex-sympathoneural and baroreflex-cardiovagal failure, and nigrostriatal dopamine deficiency, a pattern resembling that in the sporadic disease. The results fit with the concept that in LRRK2 PD, parkinsonism, cardiac sympathetic denervation, and baroreflex failure can result from a common pathogenetic process.