Cardiac sympathetic denervation in symptomatic and asymptomatic carriers of the E46K mutation in the ¦Á synuclein gene

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• 作者：Beatriz Tijero^a ; ¹ ; ^{beatriz_tijero@hotmail.com} ; Juan Carlos Gó ; mez-Esteban^a ; ¹ ; ^{juancarlos.gomezesteban@gmail.com} ; Elena Lezcano^a ; Carmen Ferná ; ndez-Gonzá ; lez^b ; Johanne Somme^a ; Veró ; nica Llorens^c ; Ana Mart&#237 ; nez^d ; Javier Ruiz-Mart&#237 ; nez^e ; Nerea Foncea^f ; Iné ; s Escalza^f ; Koldo Berganzo^a ; M.A. Aniel-Quiroga^g ; Veró ; nica Ruiz^a ; Nuria Terá ; nⁱ ; Horacio Kaufmann^h ; Juan Jose Zarranz^a
• 关键词：Parkinson disease ; Autonomic disorders ; Synuclein gene ; E46K mutation
• 刊名：Parkinsonism and Related Disorders
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：19
• 期：1
• 页码：95-100
• 全文大小：508 K

文摘

Objective

The aim of this study was to analyze autonomic function and cardiac sympathetic innervation in symptomatic and asymptomatic carriers of the E46K alpha-synuclein gene (SNCA) mutation.

Patients and methods

Autonomic function tests were performed in six patients, four of whom were symptomatic carriers (ages: 46, 59, 52 and 28-years) and two who were asymptomatic carriers (ages: 52 and 29 years). Autopsy studies were performed on an additional two symptomatic carriers not eligible for autonomic testing.

Patients completed the SCOPA autonomic questionnaire, and underwent the head-up tilt test accompanied by measurements of plasma norepinephrine. Valsalva maneuver and deep breathing tests, along with recording of sympathetic skin response (SSR) and cardiac MIBG scintigraphy were carried out. Myocardial tissue sections removed from the two autopsied cases were subjected to routine histological staining and immunohistochemical processing with monoclonal antibodies against tyrosine hydroxylase and alpha-synuclein.

Results

Both the four symptomatic and the older asymptomatic carriers reported abnormalities in the SCOPA questionnaire and had markedly diminished cardiac MIBG uptake. Plasma norepinephrine in the supine and tilted positions was normal in all subjects. Only one patient had significant orthostatic hypotension. There was a complete absence of tyrosine hydroxylase immunostaining in the myocardium of the two autopsied cases.

Interpretation

We have found imaging and histological evidence of cardiac sympathetic denervation in symptomatic and asymptomatic carriers of the E46K alpha-synuclein gene mutation. The sympathetic denervation appears to be organ-specific, with selective affectation of the heart given that plasma norepinephrine levels and blood pressure were normal.