Cardiac sympathetic denervation precedes nigrostriatal loss in the E46K mutation of the α-synuclein gene (SNCA)

Tijero, Beatriz; Gómez‐Esteban, Juan Carlos; Llorens, V.; Lezcano, Elena; González-Fernández, M.C.; Pancorbo, Marian M. de; Ruíz‐Martínez, Javier; Cembellín, José Carlos; Zarranz, J.J.

doi:10.1007/s10286-010-0068-4

Cited by 44 publications

(20 citation statements)

References 9 publications

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“…In contrast, for SNCA gene mutation carriers, myocardial sympathetic innervation ratios have been found to be abnormal from very early stages [18,23]. All these data suggest that normal cardiac uptake of MIBG might be of potential diagnostic value to indicate the absence of Lewy body pathology [12,13] in Parkinsonism.…”

Section: Discussionmentioning

confidence: 61%

Autonomic involvement in Parkinsonian carriers of PARK2 gene mutations

Tijero

Gabilondo

Lezcano

et al. 2015

Parkinsonism & Related Disorders

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Section: Discussionmentioning

confidence: 61%

Autonomic involvement in Parkinsonian carriers of PARK2 gene mutations

Tijero

Gabilondo

Lezcano

et al. 2015

Parkinsonism & Related Disorders

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“…8,9 Indeed, cardiac sympathetic involvement seems to occur in the early stages of PD, 10 possibly before the onset of motor clinical symptoms, as described in patients carrying high-penetrance genetic mutations of PD. 11,12 By contrast, NOH is frequently detected later during advanced stages of PD. Furthermore, in early stages of the disease there is no correlation between the symptoms of orthostatic intolerance and myocardial MIBG scintigraphy measures in PD.…”

Section: Introductionmentioning

confidence: 86%

Cardiocirculatory manifestations in Parkinson's disease patients without orthostatic hypotension

et al. 2015

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The objective of this study was to characterize cardiac sympathetic denervation in Parkinson's disease (PD) patients without neurogenic orthostatic hypotension (NOH), both in terms of hemodynamics and in its relation with vascular denervation. We studied 20 PD patients without NOH. We analyzed the heart rate and blood pressure variability during various physical maneuvers. The following parameters were calculated: expiratory-inspiratory ratio, stroke volume, cardiac output, cardiac index, left ventricular ejection time, left ventricular work index, thoracic fluid content, total peripheral resistance and baroreflex sensitivity (BRS). We also measured direct and spectral derivatives of cardiac (cardiovagal) parasympathetic function. Myocardial I-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed and early and late heart/mediastinum uptake ratios were analyzed. We observed that the late heart/mediastinum uptake ratio was 1.33±0.21. This parameter was correlated with years since diagnosis (correlation coefficient:-0.485; P=0.05), Unified Parkinson's Disease Rating Scale (UPDRS) III score (cc:-0.564; P=0.02) and pressure recovery time in the Valsalva maneuver (cc: 0.61; P<0.001). At rest, it was correlated with BRS (cc:0.75; P=0.003) and low-frequency diastolic blood pressure (LFDBP; cc: 0.58;P=0.017). We found no correlations with any of the cardiography impedance variables. In linear regression models, the variable that best correlated with MIBG results was LFDBP. Our results support that in absence of NOH the degree of denervation of the heart does not produce any effect on its inotropic function. Moreover, BRS and LFDBP can be used as an indirect measure of cardiac sympathetic denervation at rest.

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“…In vivo imaging of sympathetic denervation in PD patients is accomplished with radiolabeled ligands for both the norepinephrine transporter (expressed at the plasma membrane of sympathetic neurons) and VMAT2 [146–150]. Sympathetic denervation may occur prior to the onset of motor symptoms of PD, with noradrenergic denervation of the heart paralleling the dopaminergic denervation of the striatum [149, 151]. …”

Section: Vmat2 As a Peripheral Biomarker Of Pdmentioning

confidence: 99%

Vesicular Integrity in Parkinson’s Disease

Alter

Lenzi

Bernstein

et al. 2013

Curr Neurol Neurosci Rep

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The defining motor characteristics of Parkinson’s disease (PD) are mediated by the neurotransmitter dopamine (DA). Dopamine molecules spend most of their lifespan stored in intracellular vesicles awaiting release and very little time in the extracellular space or the cytosol. Without proper packaging of transmitter and trafficking of vesicles to the active zone, dopamine neurotransmission cannot occur. In the cytosol, dopamine is readily oxidized; excessive cytosolic dopamine oxidation may be pathogenic to nigral neurons in PD. Thus, factors that disrupt vesicular function may impair signaling and increase the vulnerability of dopamine neurons. This review outlines the many mechanisms by which disruption of vesicular function may contribute to the pathogenesis of PD. From direct inhibition of dopamine transport into vesicles by pharmacological or toxicological agents to alterations in vesicle trafficking by PD-related gene products, variations in the proper compartmentalization of dopamine can wreak havoc on a functional dopamine pathway. Findings from patient populations, imaging studies, transgenic models, and mechanistic studies will be presented to document the relationship between impaired vesicular function and vulnerability of the nigrostriatal dopamine system. Given the deleterious effects of impaired vesicular function, strategies aimed at enhancing vesicular function may be beneficial in the treatment of PD.

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Cardiac sympathetic denervation precedes nigrostriatal loss in the E46K mutation of the α-synuclein gene (SNCA)

Abstract: This example of monogenic autosomal dominant parkinsonism due to an alpha-synuclein mutation favours the hypothesis that peripheral autonomous nervous system involvement occurs earlier than the CNS degeneration.

Cited by 44 publications

References 9 publications

Autonomic involvement in Parkinsonian carriers of PARK2 gene mutations

Autonomic involvement in Parkinsonian carriers of PARK2 gene mutations

Cardiocirculatory manifestations in Parkinson's disease patients without orthostatic hypotension

Vesicular Integrity in Parkinson’s Disease

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