Neuroscience Letters 391 (2006) 131–135
Evaluation of extracranial blood flow in Parkinson disease Alpay Haktanir ∗ , Mehmet Yaman, Murat Acar, Omer Gecici, Reha Demirel, Ramazan Albayrak, Kemal Demirkirkan Afyon Kocatepe University, Faculty of Medicine, Department of Radiology, Mavi Hastane, 03120 Afyon, Turkey Received 30 April 2005; received in revised form 22 August 2005; accepted 22 August 2005
Abstract Decreased cerebral flow velocities in Parkinsonian patients were reported previously. Because of the limited data on vascular changes in Parkinson disease (PD), which may have a vascular etiology, we aimed to disclose any possible cerebral hemodynamic alteration in Parkinsonian patients. We prospectively evaluated 28 non-demented, idiopathic parkinsonian patients and 19 age and sex matched controls with Doppler sonography. Flow volumes, peak systolic flow velocities, and cross-sectional areas of vertebral and internal carotid arteries (ICA) were measured and compared between patients and controls. Correlation of patient age and disease duration with Doppler parameters was observed; and each Doppler parameter of patients within each Hoehn–Yahr scale was compared. There was no significant difference of measured parameters between groups. No correlation was found between disease duration and age with flow volume, cross-sectional area or peak systolic velocity. Hoehn–Yahr scale was not found having significant relation with Doppler parameters. Values of vertebral, internal carotid and cerebral blood flow volumes (CBF), peak systolic velocities, and cross-sectional areas were not significantly different between Parkinsonian patients and age and sex matched controls. Although regional blood flow decreases may be seen as reported previously, Parkinson disease is not associated with a flow volume or velocity alteration of extracranial cerebral arteries. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Parkinson disease; Cerebral blood flow volume; Doppler; Internal carotid artery; Vertebral artery
Parkinson disease (PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic nigrostriatal neurons. It is named after James Parkinson, the English physician who described the shaking palsy in 1817 [14]. PD is recognized as one of the most common neurological disorders, affecting approximately 1% of individuals older than 60 years [8]. Isotopic studies such as positron emission tomography, single-photon emission tomography, and imaging studies such as stable xenon computed tomography and magnetic resonance imaging-based technology have all proved to achieve reliable and accurate measurements of cerebral blood flow volume (CBF). All of these techniques, however, are cumbersome and expensive and imply the transfer of patients to the imaging or radionuclear facility. As such, these techniques cannot be repeated as clinically indicated and therefore, are of limited use in the clinical settings. Besides, only sonography and magnetic resonance phase-contrast flow quantification allow the assessment of individual vessels. Other techniques can only
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yield regional or total cerebral blood flow. The principal objective of cerebrovascular Doppler sonography is the analysis and characterization of cerebral hemodynamics under physiologic and pathologic circumstances. Applied to both internal carotid arteries (ICA) and vertebral arteries (VA), Doppler sonography measures CBF, which has been shown to be a precise and reliable approach [2,9,11,20,21]. While several observers showed unchanged regional CBF in Parkinsonian patients with single photon emission tomography [7,13,23,24,27], some authors reported decreasing regional CBF in various cerebral lobes [1,4,26]. In the other hand, Bornstein at al. [5], in their Doppler sonographic study, reported decreased flow velocities in the Parkinsonian patients when compared with healthy controls, although that decrease was statistically significant mainly in the vertebrobasilar arteries. Such a decrease, primary or secondary is expected to occur in the anterior cerebral circulation that supply the basal ganglia, and not in the vertebrobasilary system. These findings may raise further questions on the existence of vascular etiology of PD. Because of the limited data on vascular changes in PD, we planned to disclose any possible cerebral hemodynamic disruption in these patients via evaluating the flow volumes and flow
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velocities of vertebral and internal carotid arteries with Doppler sonography. A total of 28 idiopathic non-demented PD patients (21 men, 9 women; mean age 65.3 ± 8 years) and 19 (10 men, 9 women; mean age 60.8 ± 9 years) control subjects were examined. The clinical differentiation of atypical parkinsonian syndromes – such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration – from idiopathic PD and between each other is often difficult, leading to misdiagnosis even up to the time of death [12,16]. Although some observers reported various imaging methods differentiating PD and atypical parkinsonian syndromes [3,6,22], the definite clinical diagnosis have not been described yet. Therefore, the PD patients in our study were clinically diagnosed by the presence of at least two of the following characteristics: tremor, rigidity, and bradykinesia. The cases determined to be secondary Parkinsonism, such as drug-induced or vascular Parkinsonism, were excluded. Subjects with a history of vascular diseases before the diagnosis of PD and with two or more risk factors for vascular diseases including uncontrolled hypertension, uncontrolled diabetes mellitus, and hyperlipidemia, were also excluded from the study. None of the patients had pyramidal or other neurologic signs except from Parkinsonian signs. Severity of Parkinsonism was classified according to the Hoehn–Yahr scale [10]. Seven patients were classified as being in Hoehn–Yahr scale 2.5, eleven in 2, five in 1.5, and five in 1. The mean duration of PD was 4.6 ± 3 years (1–13 years). Descriptions of PD patients and subjects are presented in Table 1. None of the patients were taking any medication, except for antiparkinsonian drugs. The age and sex matched control group was selected randomly from the volunteers who were admitted for check-up. Controls with a known neurologic disease, and had a history or signs of cerebrovascular disease or cardiac insufficiency were excluded. Smoking, alcoholism, and alcohol or caffeine use in last two days was also included as exclusion criteria for all participants. All of the subjects were evaluated by the same neurologist (M.Y.). Doppler sonography was performed with 7.5 MHz transducer of a Toshiba Nemio 20 ultrasound system (Toshiba Corp., Tokyo, Japan) in a dimly lighted room with a comfortable temperature (22–24 ◦ C) after an adaptation period for at least 15 min rest in supine position. The ICAs and VAs of both sides were explored. Scans were performed by the same operator (A.H.). Before the measurements, a routine complete examination of the carotid and vertebral arteries was performed, and based on this examination, only subjects without sonographic evidence of VA occlusion or plaque formation in common and internal carotid arteries were included in this study. The patient’s head was turned slightly to the opposite side each time. Flow vol-
ume measurement of the internal carotid arteries was performed 1.5–2 cm distal to the carotid bifurcation. Measurement of vertebral arteries was done at the V2 segment, between the transverse processes of the C4 and C5 vertebrae. Visual control of the maximal luminal width and acoustic control of an optimum time frequency Doppler signal made certain that the sample volume passed through the center of the vessel. The sample volume was expanded over the entire vessel diameter, and the angle between the beam and the selected vessel was kept as low as possible (around 60◦ ). The diameter of each vessel was measured with Bmode imaging. The angle-corrected time averaged flow velocity (TAV) was determined as the integral of the mean flow velocities of all moving particles passing the sample volume over three to five complete cardiac cycles. In this way, the pulsatile parabolic flow is mathematically transformed into a continuous plug flow. The intravascular flow volume (FV) was calculated as the product of TAV and the cross-sectional area (A) of the circular vessel using the formula FV = TAV × A = TAV × ((diameter/2)2 π). The cross-sectional areas of the arteries were determined as the distance between the internal layers of the parallel walls (Fig. 1). Cerebral blood flow volume was calculated by the summation of net ICA and net VA flow volumes. All measurements were documented by black and white video printer. The complete
Table 1 Description of Parkinson disease (PD) patients and control subjects Subject type
N (M/F)
Age (mean ± S.D.)
Duration of PD (years)
Hoehn–Yahr
PD Control
28 (20/8) 19 (10/9)
65.3 ± 8 (45–80) 60.8 ± 9 (49–74)
4.4 ± 3 (1–13) –
1.8 ± 5 (1–2.5) –
Fig. 1. Flow volume measurements of internal carotid (above) and vertebral arteries (below).
A. Haktanir et al. / Neuroscience Letters 391 (2006) 131–135 13.8 ± 5.0 0.312 13.6 ± 4.1
LVA: left vertebral artery; RVA: right vertebral artery; LICA: left internal carotid artery; RICA: right internal carotid artery; PSV: peak systolic velocity; CSA: cross-sectional area. a p-values of the each Doppler parameter of PD patients within each Hoehn–Yahr scale found in one-way ANOVA.
13.9 ± 5.6 0.581 14.4 ± 4.7 4.7 ± 1.5 0.760 5.4 ± 2.1 5.6 ± 2.3 0.104 5.2 ± 2.1 62.6 ± 17.8 0.287 57.2 ± 17.4 63.9 ± 15.5 0.207 63.7 ± 20.1 44.7 ± 11.3 0.247 40.1 ± 10.9 43.5 ± 12.2 0.891 44.1 ± 10.8 683.9 ± 161.2 0.336 689.0 ± 162.9 538.7 ± 156.3 0.396 539.7 ± 136.1 145.2 ± 59.1 0.456 149.3 ± 42.7 264.3 ± 89.4 0.162 262.5 ± 76.3 65.4 ± 36.8 0.566 72.0 ± 43.4 PD pa Control
79.8 ± 47.0 0.494 77.3 ± 43.2
274.4 ± 91.9 0.624 277.2 ± 118.6
RICA CSA (cm2 ) LICA CSA (cm2 ) RVA CSA (cm2 ) LVA CSA (cm2 ) RICA PSV (cm/s) LICA PSV (cm/s) RVA PSV (cm/s) LVA PSV (cm/s) CBF (ml/s) Net ICA (ml/s) Net VA (ml/s) RICA (ml/s) LICA (ml/s) RVA (ml/s) LVA (ml/s)
Means of Doppler parameters
Subject type
Table 2 Mean values of Doppler parameters of PD patients and control subjects
examination took about 20 min for each case. Written informed consent was obtained from each subject. All parametric results were expressed as mean ± standard deviation for each group. χ2 and t-tests were performed comparing the gender and age between patients and controls. One sample Kolmogorov–Smirnov test was performed to check the normality of the data before running t-tests. Levene’s test was established for the equality of variances. Comparisons of the peak systolic flow velocity and flow volumes of each ICA, each VA, and sum of them as net VA, net ICA, and CBF between PD and control subjects were performed using the independent ttest. Correlation analyses between duration of PD with Doppler parameters and age with Doppler parameters were done by Pearson correlation analysis. Correlation of age was observed both with PD and control groups. Each Doppler parameter of PD patients within each Hoehn–Yahr scale was compared using the one-way ANOVA. A p-value less than 0.05 was considered to be statistically significant. Table 2 presents mean values of flow volumes, peak systolic velocities, and cross-sectional areas of vertebral and internal carotid arteries. There was no statistically significant difference for the flow volumes or peak systolic velocities of all measured individual vessels or any total (total VA, total ICA, and CBF) of them between patients and control subjects. In addition, crosssectional areas of vertebral and internal carotid arteries did not show a significant difference between patients and controls. All evaluated Doppler parameters were very close to each other between PD and control groups (Table 2). We could not find significant difference in the analysis of each Doppler parameter of PD patients within each Hoehn–Yahr scale. The p-values found in one-way ANOVA were presented in Table 2. In the Pearson correlation analysis, there was no significant correlation between Doppler parameters with age both in PD and control groups. There was also no correlation between disease duration with any of the Doppler parameters. Assessment of cerebral blood flow volume is required in clinical practice for the identification and quantification of focal or generalized perfusion disturbances in the course of cerebrovascular, traumatic, or neurodegenerative disorders. Nuclear medical techniques have been frequently established for the quantitative assessment of brain perfusion. Radiation exposure to the patient, expensiveness, and limited availability are the limitations of those modalities. In addition, the findings of regional CBF investigations with single photon emission tomography technique have been inconsistent. In the other hand, sonographic techniques have advanced the non-invasive diagnosis of cerebrovascular diseases. Estimation of global cerebral blood flow volume using Doppler sonography is a well established and reliable method which has been observed for some disease conditions as well as healthy people [2,9,20,21]. To the best of our knowledge, this is the first study assessing the global CBF with extracranial Doppler sonography in PD patients. In our study, there were not any significant differences in Doppler parameters of VA, ICA or CBF between patients and controls. This can be considered as consistent with some previ-
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ous reports, which established single photon emission tomography for the evaluation [23,27]. However, it must be kept in mind that extracranial estimation of CBF with Doppler sonography is not informative like nuclear medical techniques for the detailed functional knowledge. Thus, comparing these two modalities for CBF is not proper. Bornstein et al. [5] have found significant decrease of vertebral artery peak systolic velocity in PD patients when compared with non-PD controls in their extra- and transcranial Doppler study. Because the authors did not evaluate the flow volume of the vertebral artery which has greater importance for the cerebral perfusion, their findings appears to be not suitable to conclude on vascular predominance in PD. If the formula is considered, it can be seen that the cross-sectional area of the artery is the other factor affecting the blood flow volume: FV = TAV × A = TAV × ((diameter/2)2 π). The crosssectional area of a vessel can change under different physiologic or pathologic circumstances. Cerebral blood flow volume decrease with aging was reported previously [9,15,18,19]. Only few authors found that global CBF remains constant during healthy normal aging [25,17]. We also did not find any significant association of Doppler parameters with aging. However, selection of our study groups from middle or advanced aged subjects (mean age of patients: 65.3 ± 8 and controls: 60.8 ± 9) and their relatively narrow age range (45–80 years for patients and 49–75 years for controls) might have caused this result. In point of fact, the aim of our study was not to assess age related changes in patients or controls. Besides, we found very similar results in the correlation analysis of Doppler parameters with age in both Parkinsonians and age-matched controls. This may also imply that Doppler parameters do not change in aging PD patients. Our patients were diagnosed by the presence of at least two of the three cardinal characteristics (tremor, rigidity, and bradykinesia). This is a limitation of our study because that way of clinical diagnosis cannot discriminate PD from atypical parkinsonian syndromes including multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Several authors suggested various methods for correct diagnosis; however, to the best of our knowledge, there is not a described way for the definite clinical diagnosis of PD except from histopathologic examination [3,6,22]. In conclusion, we found very close values of vertebral, internal carotid and cerebral blood flow volumes and peak systolic velocities for Parkinsonian patients and age and sex matched controls. Regarding this, we suggest that although regional blood flow changes may be seen in PD as shown by single photon emission tomography in previous reports, this disease is not associated with a hemodynamic alteration of extracranial cerebral arteries. References [1] Y. Abe, T. Kachi, T. Kato, Y. Arahata, T. Yamada, Y. Washimi, K. Iwai, K. Ito, N. Yanagisawa, G. Sobue, Occipital hypoperfusion in Parkinson’s disease without dementia: correlation to impaired cortical visual processing, J. Neurol. Neurosurg. Psychiatry 74 (2003) 419–422.
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