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Published online before print July 11, 2007, doi:10.1212/01.wnl.0000268696.57912.64)
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Received February 16, 2007
Accepted April 19, 2007

Neurocirculatory and nigrostriatal abnormalities in Parkinson disease from LRRK2 mutation

D. S. Goldstein MD, PhD*, R. Imrich MD, PhD, E. Peckham DO, C. Holmes CMT, G. Lopez MD, C. Crews , J. Hardy PhD, A. Singleton PhD, and M. Hallett MD

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.


* To whom correspondence should be addressed. E-mail: goldsteind{at}ninds.nih.gov.

ABSTRACT 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-[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.




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O. A. Ross, M. Toft, K. Haugarvoll, A. Chen-Plotkin, W. Yuan, C. Anderson, E. M. Wood, H.I. Hurtig, C. Clark, B.L. Miller, et al.
CORTICOBASAL SYNDROME AND PRIMARY PROGRESSIVE APHASIA AS MANIFESTATIONS OF LRRK2 GENE MUTATIONS
Neurology, July 22, 2008; 71(4): 303 - 304.
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