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Autonomic dysfunction in Parkinson's disease and its correlates to medication and dopamine transporter binding

Abstract
Patients with idiopathic Parkinson's disease (PD) may suffer from autonomic nervous system dysfunction
even in the early phase of the disease. We assessed the autonomic cardiovascular and sudomotor regulation in
de novo PD patients with and without medication. We also measured the dopamine (DAT)
and serotonin transporter (SERT) uptake in the PD patients using
2β-carboxymethoxy-3β-(4-iodophenyl)tropane
(β-CIT) SPECT and studied the clinical correlates of the uptake. Sixty PD patients were included in the
study and randomised to receive levodopa, bromocriptine or selegiline (n=20 in each) as their treatment.
Thirty patients were examined with β-CIT SPECT. The results of the patients were compared with those of
healthy controls and within the subgroups at different time points.


Cardiovascular autonomic regulation was assessed using standard cardiovascular reflex tests at
baseline, after six months' medication and following a 6-week washout period. The heart rate (HR) and blood
pressure (BP) regulation was impaired in PD patients at baseline, and PD medications modified the responses
further. Bromocriptine and selegiline, in contrast to levodopa, increased the orthostatic BP fall and
suppressed the BP response to isometric exercise. The long-term cardiovascular autonomic function was
evaluated from ambulatory ECG recordings by analysis of traditional spectral and non-spectral components of
HR fluctuation together with two-dimensional vector analysis and power-law relationship analysis of the HR
dynamics. All spectral measures and the slope of the power-law relationship demonstrated impaired tonic
cardiovascular regulation in the PD patients.


Sympathetic sudomotor activity was evaluated using the sympathetic skin response (SSR). The
major finding was suppression of the SSR amplitudes with an inverse correlation to clinical disability,
whereas PD medication seemed to have only minor effects. The changes in amplitude and repetitiveness of the
SSRs with normal adaptation suggest deficits at several levels of the SSR reflex arc.


DAT uptake, assessed by β-CIT SPECT, was diminished in the striatum and especially the
putamen
of the PD patients, and correlated with the results of the cardiovascular reflex tests and ambulatory ECG
recordings. Simultaneous measurement of SERT binding demonstrated decreased SERT availability in the
thalamic and frontal areas.


The results demonstrate disturbances of the reflectory and tonic cardiovascular autonomic regulation caused
by PD itself. PD medications further modify the reflectory responses. The degenerative process in PD also
involves the sympathetic sudomotor pathway. β-CIT SPECT provides a useful method for simultaneous
assessment
of DAT and SERT binding, demonstrating the deficit of serotonin metabolism in PD.

Identiferoai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5963-7
Date17 April 2001
CreatorsHaapaniemi, T. (Tarja)
PublisherUniversity of Oulu
Source SetsUniversity of Oulu
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion
Formatapplication/pdf
Rightsinfo:eu-repo/semantics/openAccess, © University of Oulu, 2001
Relationinfo:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234

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