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Neurocirculatory and nigrostriatal abnormalities in Parkinson disease from LRRK2 mutation

From the Clinical Neurocardiology Section (D.S.G., R.I., C.H.) and Medical Neurology Branch (E.P., M.H.), National Institutes on Neurological Disorders and Stroke, Genetic Disease Research Branch (G.L.), National Human Genome Research Institute, and Laboratory of Neurogenetics (C.C., J.H., A.S.), National Institute on Aging, NIH, Bethesda, MD.

Address correspondence and reprint requests to Dr Goldstein, NINDS, NIH, 10 Center Dr. MSC-1620, Bldg. 10, Rm. 6N252, Bethesda, MD 20892-1620 goldsteind{at}ninds.nih.gov

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 -synuclein or by -synuclein gene triplication also features cardiac sympathetic denervation and baroreflex failure.

Methods: Here we report results of cardiac sympathetic neuroimaging by 6-[¹⁸F]fluorodopamine PET, baroreflex testing based on beat-to-beat hemodynamic responses to the Valsalva maneuver, and nigrostriatal neuroimaging using 6-[¹⁸F] 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-[¹⁸F] 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-[¹⁸F] 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.

e-Pub ahead of print on July 11, 2007, at www.neurology.org.

Supported in part by the intramural programs of the National Institute on Neurological Diseases and Stroke and the National Institute on Aging, NIH, Department of Health and Human Services.

Disclosure: The authors report no conflicts of interest.

Received February 16, 2007. Accepted in final form April 19, 2007.

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