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Reported criteria and frequencies of orthostatic hypotension in Parkinson disease
Source publication
Patients with Parkinson's disease (PD) commonly have clinically significant orthostatic hypotension (OH). In such patients PD+OH might be confused with multiple system atrophy (MSA), in which OH is a frequent finding, or with pure autonomic failure (PAF), if OH preceded clinical manifestations of the movement disorder. This study addressed whether...
Contexts in source publication
Context 1
... Parkinson's disease (PD), orthostatic hypotension (OH) can pose a major management problem [10,27,81]. Studies have varied widely in reported frequencies of OH in PD (Table 1). In 5 relatively large studies in- volving more than 80 patients each, the frequency of OH ranged from 30 to 58 % [2,16,45,52,80]. ...
Context 2
... OH, defined by a fall in systolic blood pressure of at least 20 mm Hg and a fall in diastolic pressure of at least 5 mm Hg between the supine position (after 15 minutes of rest) and 5 minutes of upright posture. As noted in Table 1, despite a consensus statement on the de- finition of OH as an orthostatic fall in systolic blood pressure of at least 20 mm Hg and fall in diastolic pressure of at least 10 mm Hg [41], criteria actually used in PD research have varied, the most common criterion being an orthostatic decrease in systolic blood pressure of at least 20 mm Hg. ...
Similar publications
Background:
We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson's disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by...
In its early stages multiple system atrophy (MSA), a neurodegenerative movement disorder, can be difficult to differentiate from idiopathic Parkinson's disease (PD), and emphasis has been put on identifying premotor symptoms to allow for its early identification. The occurrence of vegetative symptoms in addition to motor impairment, such as orthost...
To clarify the progression of autonomic symptoms and functional deterioration in pure autonomic failure (PAF), particularly in comparison with multiple system atrophy (MSA).
The investigation involved eight patients with PAF (M/F = 7/1; mean age at onset, 57 years) and 22 with probable MSA matched for age at onset (M/F = 14/8; onset 56 years). Subj...
BACKGROUND: Parkinson's disease (PD) is a chronic, progressive, and debilitating disease, which affects over 1 million people in the United States. PD is characterized by a loss of voluntary and involuntary muscle control. As the disease progresses, additional complications can arise in the form of nomnotor and neurobehavioral symptoms. The traditi...
Citations
... Parkinson's disease (PD) is commonly accepted to be associated with various non-motor symptoms, including sleep disturbance, cognitive impairment, and autonomic dysfunction (1). Autonomic impairment associated with PD is characterized by clinical features of constipation, sweating, orthostatic hypotension (OH), and postprandial hypotension (PPH), even in the early phase (2). Cognitive impairment and OH are among the most frequent and troublesome non-motor symptoms in PD. ...
Introduction
Orthostatic hypotension (OH) frequently accompanies autonomic dysfunction and is an important risk factor for cognitive impairment in Parkinson's disease (PD). However, the association between different cognitive functions and OH in PD patients is not yet fully understood.
Methods
This study aimed to evaluate the scores of different cognitive domains and multiple parameters using different imaging techniques on PD patients with or without OH. A total number of 31 PD patients with OH (n = 20) and without OH (n = 11) were recruited from the Department of Neurology, Beijing Xuanwu Hospital for this study. All patients underwent beat-to-beat non-invasive blood pressure recordings and an active standing test to evaluate neurogenic OH and a global neuropsychological test to assess cognitive function. All patients underwent dynamic cerebral autoregulation (dCA) measurement, brain magnetic resonance imaging (MRI), and brain 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT).
Results
The results showed that OH patients had poor delayed recall verbal memory when compared with the PD patients without OH (1.75 ± 1.59 vs. 3.10 ± 1.73, p = 0.042). The dCA test indicated a significant difference in the right very low-frequency (VLF) gain between two groups (1.27 ± 0.17 vs. 1.10 ± 0.26, p = 0.045) and the brain 18F-FDG PET/CT indicated a significant difference in the SUV (right medial temporal lobe) to SUV (occipital lobe) ratio (0.60 ± 0.08 vs. 0.67 ± 0.11, p = 0.049). Meanwhile, these two imaging parameters were negatively correlated (p < 0.001). Furthermore, the score of a delayed recall verbal memory in the OH group was positively correlated with the right medial temporal lobe to occipital lobe ratio (p < 0.001) and was negatively correlated with the right VLF gain (p = 0.023).
Discussion
PD with OH patients had poor delayed recall memory, which might have been caused by the decreased metabolic dysfunction of specific medial temporal lobe due to the impaired dCA ability.
... In addition, previous research suggested that patients with PD have cardiac parasympathetic impairment along with sympathetic denervation (Awerbuch and Sandyk 1992;Shibata et al., 2009;Kim et al., 2014). Parkinson's disease has been associated with autonomic dysfunction (Visser et al., 2004;Goldstein 2006;Velseboer et al., 2011;Goldstein 2014), and cardiovascular autonomic control deficiencies have been suggested as possible underlying reasons for the drop in blood pressure upon standing (Barbic et al., 2007). PD affects not only the autonomic control of blood pressure but also skeletal muscle function (Inkster et al., 2003;Lavin et al., 2020). ...
Cardiac baroreflex and leg muscles activation are two important mechanisms for blood pressure regulation, failure of which could result in syncope and falls. Parkinson’s disease is known to be associated with cardiac baroreflex impairment and skeletal muscle dysfunction contributing to falls. However, the mechanical effect of leg muscles contractions on blood pressure (muscle-pump) and the baroreflex-like responses of leg muscles to blood pressure changes is yet to be comprehensively investigated. In this study, we examined the involvement of the cardiac baroreflex and this hypothesized reflex muscle-pump function (cardio-postural coupling) to maintain blood pressure in Parkinson’s patients and healthy controls during an orthostatic challenge induced via a head-up tilt test. We also studied the mechanical effect of the heart and leg muscles contractions on blood pressure. We recorded electrocardiogram blood pressure and electromyogram from 21 patients with Parkinson’s disease and 18 age-matched healthy controls during supine, head-up tilt at 70°, and standing positions with eyes open. The interaction and bidirectional causalities between the cardiovascular and musculoskeletal signals were studied using wavelet transform coherence and convergent cross mapping techniques, respectively. Parkinson’s patients displayed an impaired cardiac baroreflex and a reduced mechanical effect of the heart on blood pressure during supine, tilt and standing positions. However, the effectiveness of the cardiac baroreflex decreased in both Parkinson’s patients and healthy controls during standing as compared to supine. In addition, Parkinson’s patients demonstrated cardio-postural coupling impairment along with a mechanical muscle pump dysfunction which both could lead to dizziness and falls. Moreover, the cardiac baroreflex had a limited effect on blood pressure during standing while lower limb muscles continued to contract and maintain blood pressure via the muscle-pump mechanism. The study findings highlighted altered bidirectional coupling between heart rate and blood pressure, as well as between muscle activity and blood pressure in Parkinson’s disease. The outcomes of this study could assist in the development of appropriate physical exercise programs to reduce falls in Parkinson’s disease by monitoring the cardiac baroreflex and cardio-postural coupling effect on maintaining blood pressure.
... We recently described the prevalence of transient orthostatic hypotension (OH) in iRBD [5]. In addition to obstipation and olfactory dysfunction, OH is one of the most common autonomic features of α-SYN [6]. Regarding the onset and manifestation of PD in iRBD, there remains debate whether central or peripheral pathology is the first to appear. ...
Introduction
Studies have reported autonomic impairment in patients with idiopathic REM sleep behaviour disorder (iRBD), which is considered a prodromal stage of alpha-synucleinopathies. It is still debated whether central or peripheral pathologies are first manifestations of alpha-synucleinopathies. This study aimed to characterize autonomic and somatosensory function in iRBD patients.
Methods
This cross-sectional prospective case–control study included 17 iRBD patients (mean age 66.3 ± 9.2 years) and 16 healthy controls (HCs, 66.6 ± 11.3 years). Quantitative sensory testing, neurological and neuropsychological assessments, norepinephrine blood plasma levels, tilt table examination with orthostatic blood pressure, and heart rate variability were carried out. Longitudinal data of 10 iRBD patients, including neurological, neuropsychological, and tilt table examination, were assessed.
Results
iRBD patients more frequently presented with orthostatic dysfunction than HCs (70.6% vs. 6.3%, p < 0.0001). Supine norepinephrine plasma levels were normal, but lower in iRBD (249.59 ± 99.78 pg/ml iRBD, 354.13 ± 116.38 pg/ml HCs, p < 0.05). Quantitative sensory testing revealed impaired cold (CDT) and vibration detection thresholds (VDT) on the foot in iRBD (CDT foot iRBD − 1.24 ± 0.31, HCs − 9.89E-17 ± 0.25, VDT iRBD − 1.11 ± 0.47, HCs − 1.46E-16 ± 0.25, p < 0.05). Cold detection thresholds differed between the foot and hand among iRBD patients (foot − 1.24 ± 0.31, hand − 0.56 ± 0.25, p < 0.05). Longitudinal data revealed an increase in maximum systolic and diastolic orthostatic blood pressure changes and a decrease in the Valsalva ratio in the follow-up group ( p < 0.05).
Conclusion
This study revealed autonomic dysfunction with somatosensory impairment, and decreased norepinephrine levels in iRBD, which may serve as a possible prodromal marker for developing alpha-synucleinopathy.
... Parkinson's disease (PD) is a heterogeneous syndrome characterized by a combination of motor and non-motor symptoms, including depressive or anxious states, hyposomnia, sleep disturbance, or autonomic dysfunction. Also, autonomic dysfunction associated with PD is characterized by constipation, urinary dysfunction, decreased or impaired sweating, and cardiovascular events, such as orthostatic hypotension (OH), postprandial hypotension (PPH), supine hypertension, and nocturnal hypertension even in the earliest stages of PD [1]. Cardiovascular autonomic impairment is a severe sign of disease prognosis, and patients with PD and OH are at a greater risk of death than other patients with PD [2]. ...
Introduction
Orthostatic hypotension (OH) and abnormal blood pressure (BP) fluctuations occur mainly due to noradrenergic dysfunction and are clinically important in patients with Parkinson’s disease (PD). They lead to impairments of cognition function, daily activities, and quality of life. Some monoamine oxidase (MAO)-B inhibitors have a sympathomimetic amine, which can be attributed to OH. Therefore, we determined whether rasagiline, a common MAO-B inhibitor used in PD treatment, can contribute to cardiovascular autonomic BP dysregulation in patients with early or mild PD.
Methods
Nineteen patients with early or mild PD were recruited, and tilt test and 24-h ambulatory BP monitoring (ABPM) were performed before and after rasagiline administration. Early or mild PD was defined as patients with de novo (n = 4), levodopa (n = 10), dopamine agonist (n = 1), levodopa and one dopamine agonist (n = 2), levodopa and droxidopa (n = 1), and levodopa and istradefylline (n = 1). Furthermore, patients with motor fluctuation and multiple dopamine agonists were excluded from our study.
Results
OH and BP frequency were not significantly exacerbated before or after rasagiline administration. No significant differences of type in BP fluctuation on ABPM and the degree of nocturnal BP falls were found before and after rasagiline administration. The Unified Parkinson’s Disease Rating Scale motor score in patients (post-rasagiline administration) was significantly improved compared with before.
Conclusion
Rasagiline seems to be a suitable medication for Parkinsonian symptoms in patients with early and mild PD. It does not exacerbate cardiovascular autonomic responses, circadian rhythm of BP, or both.
... Although it is mainly characterized by motor manifestations, non-motor conditions often precede motor symptoms (Braak et al., 2003;Schapira et al., 2017). Autonomic dysfunction (AD) is diagnosed in 80% of patients with PD, and can be aggravated due to a denervation of autonomic pathways, causing orthostatic hypotension and cardiac autonomic imbalance (Orimo et al., 1999;Smit et al., 1999;Goldstein et al., 2000;Goldstein, 2006;Evatt et al., 2009;Velseboer et al., 2011;Schapira et al., 2017). In this way, finding a robust and sensitive quantitative technique that can perform a better characterization of possible electrophysiological biomarkers from ECG signals may represent a paradigm shift in the diagnosis and progression monitoring of this disease (van Dijk et al., 1993;Cersosimo and Benarroch, 2013). ...
... This chaoticity is also justified by considering the values of Dmax and TT of 6-OHDA (Wolf et al., 1991;Shibata et al., 2009). One possible origin of this physical constraint is the potential fluctuations due to atrial fibrillation (AF), caused by the decomposition of P-waves into many short waves (Goldstein, 2006). ...
A classic method to evaluate autonomic dysfunction is through the evaluation of heart rate variability (HRV). HRV provides a series of coefficients, such as Standard Deviation of n-n intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD), which have well-established physiological associations. However, using only electrocardiogram (ECG) signals, it is difficult to identify proper autonomic activity, and the standard techniques are not sensitive and robust enough to distinguish pure autonomic modulation in heart dynamics from cardiac dysfunctions. In this proof-of-concept study we propose the use of Poincaré mapping and Recurrence Quantification Analysis (RQA) to identify and characterize stochasticity and chaoticity dynamics in ECG recordings. By applying these non-linear techniques in the ECG signals recorded from a set of Parkinson’s disease (PD) animal model 6-hydroxydopamine (6-OHDA), we showed that they present less variability in long time epochs and more stochasticity in short-time epochs, in their autonomic dynamics, when compared with those of the sham group. These results suggest that PD animal models present more “rigid heart rate” associated with “trembling ECG” and bradycardia, which are direct expressions of Parkinsonian symptoms. We also compared the RQA factors calculated from the ECG of animal models using four computational ECG signals under different noise and autonomic modulatory conditions, emulating the main ECG features of atrial fibrillation and QT-long syndrome.
... In addition, previous research suggested that patients with PD have cardiac parasympathetic impairment along with sympathetic denervation (Awerbuch and Sandyk 1992;Shibata et al., 2009;Kim et al., 2014). Parkinson's disease has been associated with autonomic dysfunction (Visser et al., 2004;Goldstein 2006;Velseboer et al., 2011;Goldstein 2014), and cardiovascular autonomic control deficiencies have been suggested as possible underlying reasons for the drop in blood pressure upon standing (Barbic et al., 2007). PD affects not only the autonomic control of blood pressure but also skeletal muscle function (Inkster et al., 2003;Lavin et al., 2020). ...
Parkinson's disease (PD) is a progressive neurodegenerative disorder resulting in abnormal body movements. Postural instability is one of the primary motor symptoms of PD and contributes to falls. Measurement of postural sway through center of pressure (COP) data might be an objective indicator of Parkinson's disease. The goal of this work is to use machine learning to evaluate if different features of postural sway can differentiate PD patients from healthy controls. Time domain, frequency domain, time-frequency, and structural features were extracted from COP data collected from 19 PD patients and 13 healthy controls (HC). The calculated parameters were input to various machine-learning models to classify PD and HC. Random Forest outperformed the rest of the classifiers in terms of accuracy, false negative rate, F1-score, and precision. Time domain features had the best performance in differentiating PD from HC compared to other feature groups.
... Although it is mainly characterized by motor manifestations [3], non-motor conditions often precede motor symptoms [4]. Autonomic dysfunction (AD) is diagnosed in 80% of patients with PD [3,[5][6][7], and can be aggravated due to a denervation of autonomic pathways, causing orthostatic hypotension and cardiac autonomic imbalance [8]. In this way, finding a robust and sensitive quantitative technique that can perform a better characterization of possible electrophysiological biomarkers from ECG signals may represent a paradigm shift in the diagnosis and progression monitoring of this disease. ...
... One possible origin of this physical constraint is the potential fluctuations due to atrial fibrillation (AF), caused by the decomposition of P-waves into many short waves [8]. ...
A classic method to evaluate autonomic dysfunction is through the evaluation of heart rate variability (HRV). HRV provides a series of coefficients, such as SDNN (Standard Deviation of n-n intervals) and RMSSD (Root Mean Square of Successive Differences), which have well-established physiological associations. However, using only electrocardiogram (ECG) signals, it is difficult to identify proper autonomic activity, and the standard techniques are not sensitive and robust enough to distinguish pure autonomic modulation in heart dynamics from cardiac dysfunctions. By using Poincaré mapping and Recurrence Quantification Analysis (RQA), we were able to identify and characterize stochasticity and chaoticity dynamics in ECG recordings, using them to describe autonomic and heart dynamics. By applying these nonlinear techniques in the ECG signals recorded from a set of Parkinson disease animal model (6-OHDA), we show they present less variability in long time epochs and more stochasticity in short-time epochs, in their autonomic dynamics, when compared with those of the sham group. These results indicate that PD (Parkinson’s Disease) animal models present more “rigid heart rate” associated with “trembling ECG” and bradycardia, which are direct expressions of Parkinsonian symptoms. We also compared the RQA factors calculated from the ECG of animal models using four computational ECG signals under different noise and autonomic modulatory conditions, emulating atrial fibrillation and QT-long syndrome. We concluded, from Poincaré Map and RQA techniques, that PD animal models are more correlated with atrial fibrillation, with high variation according to autonomic modulation. As the Abstract should be able stand independantly of the main text, please do not abbreviate terms used only once in the Abstract.
... Goldstein et al. llevaron a cabo un estudio retrospectivo que incluyó 35 pacientes con EP, y encontraron HO en el 60 % de estos durante el primer año de inicio de síntomas parkinsonianos. Incluso, en cuatro pacientes la HO precedió al diagnóstico de EP, y en otros cuatro esta fue una de las manifestaciones predominantes al momento del diagnóstico (32). En un estudio retrospectivo, publicado recientemente, Fanciulli et al. encontraron al menos una forma de HO en el 41% de 173 pacientes con EP; 24% tenían HO transitoria y 19% tenían la forma clásica (30). ...
Parkinson's disease is the second most prevalent neurodegenerative disease in the world and is characterized by bradykinesia, tremor, rigidity, and postural instability. Although it has been considered as a motor system disease, it is currently considered as a complex neurological disease with different motor, non-motor, and autonomic manifestations. Cardiovascular manifestations in patients with Parkinson's disease are frequent and they have a great impact on quality of life. This article seeks to carry out a narrative review of the pathophysiological mechanisms and the main cardiovascular clinical manifestations in patients with Parkinson's disease.
... In PAF we predicted decreases in cortical norepinephrine and, based on post-mortem literature about SN neuronal loss (Table 2), variably decreased putamen dopamine. was not considered to be exclusionary (Goldstein, 2006;Kaufmann & Goldstein, 2013). Diagnostic categorization in terms of MSA and PAF was based on previously published consensus criteria (Kaufmann, 1996). ...
The synucleinopathies Parkinson's disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF) are characterized by intra‐cytoplasmic deposition of the protein alpha‐synuclein and by catecholamine depletion. PAF, which manifests with neurogenic orthostatic hypotension (nOH) and no motor signs of central neurodegeneration, can evolve into PD+nOH. The cerebrospinal fluid (CSF) levels of catecholamine metabolites may indicate central catecholamine deficiency in these synucleinopathies, but the literature is inconsistent and incomplete. In this retrospective cohort study we reviewed data about CSF catecholamines, the dopamine metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the norepinephrine metabolites 3,4‐dihydroxyphenylglycol (DHPG) and 3‐methoxy‐4‐hydroxyphenylglycol (MHPG). The compounds were measured in 36 patients with PD, 37 patients with MSA, and 19 patients with PAF and in 38 controls. Compared to the control group, the PD, MSA, and PAF groups had decreased CSF MHPG (p < .0001 each by Dunnett's post hoc test), DHPG (p = .004; p < .0001; p < .0001) and norepinephrine (p = .017; p = .0003; p = .044). CSF HVA and DOPAC were decreased in PD (p < .0001 each) and MSA (p < .0001 each) but not in PAF. The three synucleinopathies therefore have in common in vivo evidence of central noradrenergic deficiency but differ in the extents of central dopaminergic deficiency—prominent in PD and MSA, less apparent in PAF. Data from putamen ¹⁸F‐DOPA and cardiac ¹⁸F‐dopamine neuroimaging in the same patients, post‐mortem tissue catecholamines in largely separate cohorts, and review of the neuropathology literature fit with these distinctions. The results suggest a ‘norepinephrine first’ ascending pathogenetic sequence in synucleinopathies, with degeneration of pontine locus ceruleus noradrenergic neurons preceding the loss of midbrain substantia nigra dopaminergic neurons.
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... Droxidopa also may be up-taken in non-neuronal tissues or organs, and there converted to norepinephrine by nonneuronal L-aromatic amino acid decarboxylase and released into the blood-stream inducing a pressor effect at neurovascular junctions [97,114]. Also, in non-neuronal tissues or organs, the conversion of droxidopa into norepinephrine occurs even in conditions where postganglionic sympathetic nerves degenerate [115]. ...
Purpose of Review
The aim of this review article was to summarize the cardiovascular and blood pressure profile regarding Parkinson disease patients and to provide an update on the recent advancements in the field of the diagnosis and management of blood pressure abnormalities in these patients. Our goal was to guide physicians to avoid pitfalls in current practice while treating patients with Parkinson disease and blood pressure abnormalities. For this purpose, we searched bibliographic databases (PubMed, Google Scholar) for all publications published on blood pressure effects in Parkinson disease until May 2020. Furthermore, we highlight some thoughts and potential perspectives for the next possible steps in the field.
Recent findings
Blood pressure dysregulation in patients with Parkinson’s disease has several implications in clinical practice and presents an ongoing concern. Compared with chronic essential hypertension, the syndrome of combined neurogenic orthostatic hypotension and supine hypertension in Parkinson’s disease has received little attention. If left untreated, hypertension may lead to cardiovascular disease whereas hypotension may lead to fall-related complications, with tremendous impact on the quality of life of affected individuals.
Summary
The effect of blood Epressure control and the risk of death from cardiovascular disease in Parkinson disease are largely unexplored. Blood pressure abnormalities in Parkinson disease present bidirectional relationship and the rationale for treating and controlling hypertension in persons with Parkinson disease and concurrent neurogenic orthostatic hypotension and/or supine hypertension is compelling. Further research is warranted in order to clarify the mechanisms, clinical implications, and potential reversibility of compromised cardiovascular function, in persons with Parkinson disease.
