Cardiovascular dysautonomia in de novo Parkinson's disease
Introduction
Parkinson's disease (PD) is characterized by resting tremor, rigidity, bradykinesia, and gait disturbance. It is an important degenerative disease because of its high prevalence [1]. The pathological hallmark of PD is loss of nigrostrial dopaminergic neurons [2]. Significant dysfunction, such as constipation and orthostatic and postprandial hypotension, can occur in progressive PD; however, the autonomic dysfunction in PD is less severe than that in multiple system atrophy [3], [4], [5], [6].
Recent studies have shown that sympathetic noradrenergic dysfunction has a clinical importance in PD; orthostatic hypotension occurs in 20–50% of patients with PD and can contribute to falls and other accidental trauma [7], [8], [9]. Sympathetic dysfunction due to abnormal cardiac and peripheral sympathetic innervation in patients who have PD with orthostatic hypotension can lead to disturbances resulting from the loss of postganglionic sympathetic nervous fibers; norepinephrine concentrations are lower in these patients than in patients who have PD without orthostatic hypotension [10], [11], [12].
Myocardial concentrations of radioiodinated metaiodobenzylguanidine (MIBG) are also decreased in PD [13], [14], [15]. MIBG is a physical analogue of noradrenaline that is transported into sympathetic nerve terminals [16]. MIBG imaging has been used to assess efferent postganglionic neuronal function in the heart [17]. Many authors have concluded that the sympathetic nervous disturbance in PD is caused by postganglionic lesions [13], [14], [15]. However, the pathogenesis of the parasympathetic nervous dysfunction in PD remains unclear. The cardiac parasympathetic nervous system may be relatively preserved in patients with PD. In fact, many studies have shown that the baroreceptor reflex in patients who have early stage PD without orthostatic hypotension is not severely impaired [18], [19]. Cardiovagal efferent innervation, which produces a reflex bradycardia, is mainly mediated by the nucleus ambiguus, which does not appear to suffer cell loss in patients with PD [20].
The aims of this study were 1) to determine whether cardiovascular dysfunction occurs in previously untreated early stage PD and 2) to examine whether the development of cardiovascular autonomic deregulation involves mainly the sympathetic nervous system, including cardiac and noradrenergic function, or the cardiovagal nervous system.
Section snippets
Study groups
The subjects were 44 patients with de novo PD (17 men and 27 women, age 66.1 ± 6.3 years, range 41–89 years) with a disease duration of 1–9 years (mean 2 years). The diagnosis of PD was based on the assessments of three neurologists according to the criteria of Calne et al. [21]. The diagnoses were retrospectively confirmed by clinical observation over a period of at least 3 years. No patient had abnormal findings on magnetic resonance imaging, including evidence of brain ischemia, brain stem
123I-MIBG myocardial scintigraphy in de novo PD
H / M ratios of the early and delayed images were significantly lower in the patients with PD than in the control subjects (early: 1.77 ± 0.34 (PD) vs. 2.49 ± 0.21 (control), delayed: 1.65 ± 0.42 (PD) vs. 2.40 ± 0.26 (control), p < 0.001 for both). The H / M ratios of the early and delayed images in the patients with PD decreased gradually with an increase in disease severity graded according to Hoehn–Yahr stage (Table 1).
Hemodynamic autonomic function using the Valsalva maneuver
BRSII and IVp were significantly smaller in patients with PD than in control (BRSII: 1.9
Discussions
Our results show that the cardiac MIBG uptake of patients with PD was lower than that of control. This finding is in accordance with the results of previous studies [13], [14], [15]. In our patients, MIBG uptake was reduced even in early stage PD. MIBG uptake gradually decreased with increasing disease severity. A reduced norepinephrine level at rest, denervation hypersensitivity to norepinephrine infusions, and reduced cardiac MIBG uptake indicated that the sympathetic failure was caused by
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Cited by (74)
Principles and Practice of Movement Disorders
2021, Principles and Practice of Movement DisordersCardiovascular dysfunction in untreated Parkinson's disease: A multi-modality assessment
2016, Journal of the Neurological SciencesCitation Excerpt :This alteration, which is not related to the duration or severity of parkinsonian symptoms, may be present from the early disease stages [7,8] and has been confirmed in post-mortem studies [9]. However, the lack of overt cardiovascular symptoms, in many cases associated with reduced cardiac MIBG uptake [10], makes it difficult to correlate this imaging abnormality with a clinically relevant symptomatology [10,11]. In addition, there is lack of information on the phenotypic peculiarities of left ventricular function and exercise tolerance in PD.
Retrospective analysis of parkinsonian patients exhibiting normal <sup>123</sup>I-MIBG cardiac uptake
2015, Journal of the Neurological SciencesHyposmia and cardiovascular dysautonomia correlatively appear in early-stage Parkinson's disease
2014, Parkinsonism and Related DisordersCardiovascular autonomic nervous system evaluation in Parkinson disease and multiple system atrophy
2014, Journal of the Neurological SciencesCitation Excerpt :This finding was consistent with the presence of more severe orthostatic hypotension in our MSA patients, but is somehow in contrast with the demonstration that impairment of post-ganglionic sympathetic noradrenergic innervations, as documented with cardiac sympathetic imaging using single photon emission computed tomography (SPECT) scanning with 123I-metaiodiobenzylguanidine (123I-MIBG) [14,41], occurs in PD with autonomic failure, but not in MSA. On the other hand, simultaneous HRVa and polysomnography have shown that in the early phase of PD a reduced sympathetic activity during non-REM and REM sleep phases can occur, before the onset of clinically evident autonomic dysfunction, as a consequence of postganglionic noradrenergic denervation [42,43]. Also the results of another recent study [44], evidence that the LF/HF ratio and the short-term fractal exponent α1, indexes of sympathovagal balance, were significantly decreased in both MSA and PD patients.
Sympathetic neuroimaging
2013, Handbook of Clinical NeurologyCitation Excerpt :This concept predicts that imaging evidence of cardiac sympathetic denervation may be a premotor biomarker of Parkinson disease. Although such evidence can precede the movement disorder by several years (Goldstein et al., 2007) and is apparent in at least some patients with de novo Parkinson disease (Oka et al., 2006, 2011) or incidental Lewy body disease (Orimo et al., 2008b), the frequency and consistency of this abnormality as an antecedent of parkinsonism have not yet been determined (Goldstein et al., 2011a). Cardiac sympathetic neuroimaging and postmortem neuropathological findings have linked α-synucleinopathy with noradrenergic denervation in Lewy body diseases (Orimo et al., 2008b).