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Changes in cerebral and ocular hemodynamics in Behçet's disease assessed by color-coded duplex sonography
European Journal of Radiology 58 (2006) 102–109
Changes in cerebral and ocular hemodynamics in Behc¸et’s disease assessed by color-coded duplex sonography Sevda Yilmaz a,∗ , Cengiz Akarsu b b
a Department of Radiology, School of Medicine, University of Kirikkale, Kirikkale, Turkey Department of Ophthalmology, School of Medicine, University of Kirikkale, Kirikkale, Turkezy
Received 25 July 2005; received in revised form 28 November 2005; accepted 3 January 2006
Abstract Aim: To quantify the cerebral and retrobulbar hemodynamics in Behc¸et’s disease with and without ocular involvement and compared with that of healthy controls. Materials and methods: Of 51 people studied, 17 had Behc¸et’s disease with ocular involvement, 17 had Behc¸et’s disease without ocular involvement, and 17 were healthy controls. A single eye was examined in each patient. Peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged maximum velocity (Tamax), and resistance index (RI) were evaluated in the ophthalmic (OA), posterior ciliary (PCA), central retinal (CRA) and middle cerebral artery (MCA). Additionally, the average blood flow velocities in the central retinal vein (CRV), and acceleration time (AT) and pulsatility index (PI) in the MCA were calculated. Results: The mean EDV in the PCA was 25% lower and RI was higher in patients with ocular involvement of BD than in patients without involvement (p = 0.006 and p = 0.005, respectively) and in healthy controls (p = 0.003 and p = 0.004, respectively). Differences were smaller in comparisons of the CRA and absent on comparisons of the OA and MCA. The acceleration time of the MCA was significantly higher in patients with Behc¸et’s disease than in healthy controls (p = 0.03). Conclusion: This study suggests that the flow hemodynamics in retrobulbar circulation has more altered Behc¸et’s disease with ocular involvement than without ocular involvement and healthy control. Additionally, the cerebral hemodynamic might be affected in patients with Behc¸et’s disease compared with healthy controls. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Behc¸et’s disease; Color Doppler imaging; Transcranial Doppler sonography; Retrobulbar hemodynamic; Cerebral hemodynamic; Acceleration time
1. Introduction Behc¸et’s disease (BD) was firstly defined by Professor Hulusi Behc¸et in 1937 as an illness characterized by recurrent oral and genital ulcers and uveitis [1]. BD has been observed all over the world, but the largest numbers of cases have been reported from Japan, the Middle East, and Mediterranean countries [2,3]. It is considered as a chronic multisystem disorder with vasculitis, which is probably caused by abnormal circulating immune complexes [4]. Nonspecific vasculitis ∗ Corresponding author at: ˙Ivedik cad. Umit ¨ sok. 100, Yıl sitesi, A Blok 8/38, Yenimahalle-Ankara O6170, Turkey. Tel.: +90 312 3442833; fax: +90 318 2252819. E-mail address: [email protected] (S. Yilmaz).
0720-048X/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2006.01.001
may affect any arteries or veins [5,6]. The most frequent and serious complication of BD is ocular involvement that has been reported as 60–90% [7,8]. BD is also associated with other systemic manifestations such as central nervous system (CNS), cardiovascular system, pulmonary and gastrointestinal tract, large vessels, joints, ear, and vestibular involvement due to large and small vessel involvement both in the arterial and venous sides [9–11]. CNS involvement, neuro-Behcet syndrome, is one of the most serious manifestations of BD and occurs in about 10–25% of patients [12,13]. Cerebral angio-Behc¸et’s syndrome is rare but important complication of BD characterized by occlusive panarteritis of some medium-sized pial branches of the middle cerebral artery (MCA), small infarctions, and patchy or confluent demyelinated foci in the brain [14]. Although vascular lesions are
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not listed among the criteria for the diagnosis of BD, up to 25–30% of patients develop complications during follow-up in large vessels [15]. Both transcranial color-coded duplex sonography (TCCS) for the measurement of intracranial arterial blood flow velocities and color Doppler imaging (CDI) for the evaluation of retrobulbar hemodynamics are noninvasive, painless and highly reproducible imaging techniques [16–18]. CDI has been used to detect vascular disorders of the orbit and optic nerve in different diseases such as diabetes mellitus [21], glaucoma [22], tumors [23], and cigarette smokers [24]. TCCS permits visualization of intracranial blood vessels and direction of blood flow detecting intracranial vascular pathology [10,19,20]. Transcranial Doppler ultrasonography has been used in many central nervous system disorders to allow insight into cerebrovascular function. A limited number of CDI investigations of ocular hemodynamics in BD have been studied [25–32], but to the best of our knowledge, TCCS of cerebral hemodynamic changes has not been research previously in the literature. Although vascular involvement is a well-known manifestation of BD and may affect systemic and regional circulation, little information is available for the extent of vascular involvement in patients with BD who are free of vascular sign and symptoms. Thus, we examined the retrobulbar blood flow velocities in patients with or without ocular involvement. As well as, we evaluated the cerebral hemodynamic alterations occurred in patients with Behc¸et’s disease who are free of cerebrovascular symptoms and neurological involvement.
2. Patients and methods 2.1. Patients Forty-one patients with known Behc¸et’s disease and 17 healthy volunteers were enrolled in this prospective study. All participants gave informed consent to the study and the tenets of the Declaration of Helsinki were followed. According to the ethical standards of our institution, written informed consent was obtained from each patient and healthy control before they enrolled in present study. The diagnosis of BD was based on the previously published diagnostic criteria of the International Study Group for Behc¸et’s disease [33]. Each subject underwent a complete ophthalmologic, neurological and general physical examination. All healthy controls had a visual acuity of 20/20 or better and had normal ophthalmologic examination findings. The patients with Behc¸et’s disease had no signs or symptoms of cerebrovascular and neurological involvement. All subjects had no history of neurological disorders, arterial hypertension, hypercholesterolemia, ischemic heart disease, atrial fibrillation, cardiac valve prosthesis, cigarette smoking, diabetes mellitus, polistemia, and migraine. Excluded from this study were subjects with a his-
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tory of incisional ocular surgery, acute ocular aggravation of Behc¸et’s disease within last 3 months, oral contraceptive usage, and hormonal therapy. The ocular involvement was diagnosed on the basis of the presence of one or more following findings: keratic precipitates, posterior synechiae, retinal vascular sheathing and attenuation, retinal neovascularization, retinal hemorrhages, cells in the vitreous, chorioretinal scarring, optic nerve or macular edema, and optic atrophy. Of 41 patients, 22 had previous ocular involvement at least in one eye and 19 had no signs or symptoms of ocular involvement. In Behc¸et’s disease with ocular involvement group, two patients had arterial hypertension, two patients had ocular aggravation within 3 months and one patient was heavy smoker. Similarly, in Behc¸et’s disease without ocular involvement group, one patient had arterial hypertension and one patient was heavy smoker. Therefore, they were excluded from the study. If both eyes of each subject were eligible, we randomly selected one eye of each subjects. So, 17 eyes of 17 patients with Behc¸et’s disease with ocular involvement, 17 eyes of 17 patients with Behc¸et’s without ocular involvement, and 17 eyes of 17 healthy controls were enrolled. Participants were instructed not to drink caffeine-containing beverage during the day of test. Intraocular pressure (IOP) by a Goldmann applanation tonometer, blood pressure (BP) by sphygmomanometer, and heart rate by palpation of radial pulse were measured in a masked manner after a 15-min rest. 2.2. Color-coded duplex sonography examination We used a color Doppler unit (Logiq 9; GE Healthcare, Milwaukee, WI) with a 9–14-MHz linear transducer for the retrobulbar vessels, and a 2–4-MHz sector transducer for the MCA. First ocular and then MCA color Doppler examination were performed in a thermally controlled room by the same radiologist after a 20-min rest. To minimize the effects of diurnal variation, all measurements were recorded at about the same time of day (between 9:00 and 10:00 a.m.). During CDI, transmission gel was applied to the external surface of the eyelids, in a supine position. Care was taken to apply as little pressure as possible on the eye. First, a preliminary gray-scale ultrasonographic examination of the eyes was performed to identify any abnormalities. Then, CDI measurements were performed. The central retinal artery (CRA) and central retinal vein (CRV) were depicted within the optic nerve, approximately 2–4 mm posterior to the optic disc (Fig. 1). The spectrum of the CRA showed a venous overlap from the CRV. The ophthalmic artery (OA) was examined in the deeper part of the orbit, near the optic nerve medially, 10–15 mm behind the globe (Fig. 2). The network of posterior ciliary artery (PCA) was examined where its branches surrounding the globe, near the optic nerve laterally (Fig. 3). The axial or oblique scans were used according to parallel to the long axis of each vessel and to identify the precise direction of the orbital vessels. Examinations were performed in a low or medium flow setting to permit for optimal detection of Doppler frequency shifts of the slow-flowing blood
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Fig. 1. Color Doppler ultrasonography showing the central retinal artery waveform.
Fig. 3. Color Doppler ultrasonography showing the posterior ciliary artery waveform.
in the small orbital vessels. Only for the OA, medium to high flow settings were applied, because flow in this vessel is faster. Vessels were seen on axial and oblique scans. Finally, both M1-segments of the middle cerebral arteries (MCA) of all subjects were examined with sector transducer through the transtemporal acoustic window (at the point where the best signal-to-noise ratio was obtained) at an examination depth approximately 50–65 mm (Fig. 4). During TCCS the patients were positioned in dorsal decubitus in a semisitting position at an angle of 15–20◦ between the subject and the examination table. The transducer was angled until the highest measurements were obtained. Doppler color gain was first turned down completely and then increased very gradually until the static background noise barely appeared. The
Doppler sample volume was placed over the investigated vessel. Angle-corrected velocity waveform measurements were obtained, the optimum insonation angles were maintained at or lower than 20◦ and 45◦ for the retrobulbar vessels and MCA, respectively, and when the highest velocity measurements were obtained, spectral waveforms were recorded. The flow velocities were measured automatically by the color Doppler unit for the retrobulbar vessels and MCA. The peak systolic velocity (PSV), end-diastolic velocity (EDV) and time-averaged maximum velocity (Tamax) were measured for the OA, PCA, CRA, and MCA. From these values, resistance index (RI = [PSV − EDV]/PSV) and pulsatility index (PI = [PSV − EDV]/mean velocity), were calculated by the machine. Additionally, the acceleration time (AT) was measured for the MCA and the averaged blood flow velocity in the central retinal vein (CRV) was calculated. Only one waveform tracing from each examination was chosen for analysis. Because multiple measurements were obtained, the tracing with the most normal waveform was selected for analysis. The entire examination of a subject lasted about 15–20 min.
Fig. 2. Color Doppler ultrasonography showing the ophthalmic artery waveform.
Fig. 4. Transcranial color Doppler ultrasonography showing the middle cerebral artery (MCA) and anterior cerebral artery (ACA).
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2.3. Statistical analysis
3. Results
The results were expressed as the mean ± S.D. (standard deviation). A sample size 17 provides 90% power to detect a 15% change in flow velocity in the ophthalmic artery [34]. The sample size also, provides 90% power to detect a 15% change in the posterior ciliary artery and a 20% change in the central retinal artery. Data were analyzed using the Statistical Package for Social Sciences (SPSS for windows, 9.0, Chicago, IL.). Differences in retrobulbar hemodynamic between groups were evaluated using one-way analysis of variance (ANOVA). If a significant difference was detected using ANOVA, Tukey HSD was conducted for post hoc test. Statistical analysis was performed with an unpaired Student’s t-test to compare the differences in cerebral hemodynamic between patients with BD and controls. The χ2 -test was used for categorical data. Statistical significance was set at p < 0.05.
The general characteristics of the subjects are summarized in Table 1. There was no significant difference in the mean age (p = 0.27), gender (p = 0.78) mean blood pressure (p = 0.38 for systolic blood pressure and p = 0.64 for diastolic blood pressure), mean pulse rate (p = 0.98), and mean IOP (p = 0.47) between the groups. The Doppler parameters of the OA, PCA, and CRA are shown in Table 2. The PSV and Tamax were lower in patients with BD with ocular involvement than in patients with BD without ocular involvement and normal subjects in all retrobulbar arteries, but did not reach statistical significance (p > 0.05). Patients with BD with ocular involvement had significantly lower EDV and higher RI than did BD without ocular involvement (p = 0.006 and p = 0.005, respectively) and controls (p = 0.003 and p = 0.004, respectively) in their PCA. The EDV in the CRA were significantly lower in BD with ocular involvement than in BD without ocular
Table 1 Subjects’ age, blood pressure (BP), heart rate, and intraocular pressure (IOP) for the patients with Behc¸et’s disease and healthy controls Variables
Behc¸et’s disease with ocular involvement
Behc¸et’s disease without ocular involvement
Age (years)
35.8 ± 10.6
31.1 ± 7.6
Gender Male Female
7 10
6 11
Systolic BP (mmHg) Diastolic BP (mmHg) Heart rate (beats/min) IOP (mmHg)
106.5 ± 17.3 65.9 ± 11.2 70.4 ± 6.2 17.0 ± 1.8
Healthy controls 33.6 ± 7.8 8 9
108.8 ± 16.2 65.3 ± 10.1 71.6 ± 8.2 16.6 ± 1.4
104.1 ± 15.4 68.8 ± 13.2 69.7 ± 8.6 17.4 ± 1.8
Table 2 Hemodynamic values measured in the retrobulbar vessels for the patients with Behc¸et’s disease and healthy controls Parameters
Behc¸et’s disease with ocular involvement
Behc¸et’s disease without ocular involvement
Healthy controls
Ophthalmic artery PSV (cm/s) EDV (cm/s) RI Tamax (cm/s)
34.53 9.32 0.73 16.79
± ± ± ±
10.44 3.88 0.06 5.98
36.93 9.93 0.73 16.87
± ± ± ±
8.30 3.58 0.07 4.28
37.04 10.44 0.72 18.03
± ± ± ±
11.31 4.05 0.05 6.09
Posterior ciliary artery PSV (cm/s) EDV* (cm/s) RI† Tamax (cm/s)
12.62 3.97 0.67 7.95
± ± ± ±
1.12 1.17 0.04 1.24
13.84 5.42 0.61 8.82
± ± ± ±
3.15 1.36 0.05 2.30
14.20 5.54 0.61 9.08
± ± ± ±
3.90 1.37 0.06 1.75
Central retinal artery PSV (cm/s) EDV‡ (cm/s) RI Tamax (cm/s)
10.74 3.42 0.68 5.99
± ± ± ±
2.09 0.82 0.06 1.42
11.69 4.24 0.65 7.00
± ± ± ±
2.92 1.15 0.06 1.94
12.13 4.20 0.65 6.88
± ± ± ±
2.99 0.79 0.05 1.48
PSV, peak systolic velocity; EDV, end-diastolic velocity; RI, resistivity index; PI, pulsatility index; Tamax, time-averaged maximum velocity. * There was statistically significant difference between Behc ¸ et’s disease with ocular involvement and without ocular involvement (p = 0.006) and healthy controls (p = 0.003). † There was statistically significant difference between Behc ¸ et’s disease with ocular involvement and without ocular involvement (p = 0.005) and healthy controls (p = 0.004). ‡ There was statistically significant difference between Behc ¸ et’s disease with ocular involvement and without ocular involvement (p = 0.037) and healthy controls (p = 0.045).
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Table 3 Hemodynamic parameters measured in the middle cerebral artery for the patients with Behc¸et’s disease and healthy controls Parameters
Behc¸et’s disease
PSV (cm/s) EDV (cm/s) RI PI Tamax (cm/s) AT* (s)
106.66 49.62 0.54 0.85 70.25 0.06
± ± ± ± ± ±
18.29 10.71 0.06 0.17 14.72 0.04
Healthy controls 104.53 51.56 0.50 0.79 69.83 0.04
± ± ± ± ± ±
15.61 8.51 0.04 0.13 9.85 0.02
PSV, peak systolic velocity; EDV, end-diastolic velocity; RI, resistivity index; PI, pulsatility index; Tamax, time-averaged maximum velocity; AT, acceleration time; s, second. * p = 0.03.
Fig. 5. Transcranial color-coded duplex sonography showing the middle cerebral artery waveform including prolonged acceleration time.
involvement and controls (p = 0.037 and p = 0.045, respectively). The EDV were lower in the OA and the RI was higher in the OA and CRA in BD with ocular involvement than in BD without ocular involvement and controls, but did not achieve statistical significance (p > 0.05). There was no significant difference in the average velocity measurement in the CRV among the groups. The Doppler parameters of the MCA are represented in Table 3. No statistically significant differences were observed in the PSV, EDV, Tamax, RI and PI of the MCA between the patients with BD regardless of ocular involvement and healthy controls (p > 0.05). On the other hand, acceleration time of the MCA was significantly prolonged in the patients with BD than in healthy controls (p = 0.03) (Fig. 5).
4. Discussion In this prospective study, we showed that mean EDV was lower and RI was higher in BD with ocular involvement than in BD without ocular involvement and healthy controls in the PCA. Additionally, EDV in the CRA of BD with ocular involvement was lower than BD without ocular involvement and healthy controls. However, there was no significantly difference between BD without ocular involvement and healthy
controls. This suggests that BD with ocular involvement has significantly altered retrobulbar circulation and the hemodynamic changes occurred in patients with BD with ocular involvement was more evident in the PCA than in the other retrobulbar vessels. These differences suggest that nonspecific occlusive vasculitis of PCA is more specific to BD and occurs inactive course of the disease. The current study confirmed the previous studies, which showed alteration in the retrobulbar hemodynamics in BD with ocular involvement than in BD without ocular involvement and control subjects [26,28]. A previous study revealed that blood flow velocities in the CRA of patients with severe retinal involvement were significantly lower than those with mild to moderate vasculitis and control groups [31]. Lower EDV and higher RI and PI were observed in all retrobulbar arteries in BD with ocular involvement compared with BD without ocular involvement and healthy volunteers [27]. In addition, the blood flow velocities were evaluated in the OA and CRA, and found that mean ophthalmic and central retinal artery flow velocities were lower in patients with BD than in healthy controls [29]. Similarly, Soylu et al. [30] found significantly lower EDV in the PCA and CRA in patients with BD regardless of the ocular activation compared with controls. On the other hand, they found no significant differences in the retrobulbar blood flow velocities between active and inactive eyes of BD. Duranoglu et al. [27] observed no significant difference in blood flow velocity of the CRV in three groups. Similarly, we also observed no significant difference in blood flow velocity of the CRV among three groups. On the other hand, Ucakhan et al. [31] showed that the average blood flow velocities in the CRV of patients with severe vasculitis were significantly lower than in mild to moderate vasculitis and control subjects. There are some differences between our study and above mentioned studies. These may be resulted from the definition or severity of ocular involvement, duration of BD and ocular involvement, the time between ocular involvement and examination, patients’ characteristics, level of CDI measurement, and use of medications. The involvement of the brain is one of the most devastating complications of Behc¸et’s disease. In the course of the BD, neurologic involvement may occur by primary neural parenchymal lesions, or be secondary to major vascular involvement [12,35]. In patients with vascular BD, the visible lesions and clinical features usually correspond to main vascular territories. The histopathologic changes may effect the tissue perfusion, leading to tissue destruction. Although vasculitis is common and may account for much of the pathologic process in BD, the pathological process in the vascular system is not very clear and knowledge is limited by data derived from pathological and angiographic studies. Some cases have been reported with typical appearance of arteritis with multiple segments of stenosis, occlusion [36,37] and an autopsy study of patients with vascular BD showed inflammation and destruction occurring in the media and adventitia [38] but, lymphocytic infiltration progressing from the adventitia
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toward the intima, possibly leading the thrombus formation was also reported by pathological examination [39]. The vascular injuries are superimposed on the hypercoagulability that is also characteristic of BD and that may be due in part to activated endothelial cells and activated platelets. Occlusion of major veins and arteries often causes bleeding, infarction and organ failure. It is probable that in some patients with BD immunological mechanism propagates the formation of microthrombus, and thereafter leads to embolisation of distal vascular system. BD with the involvement of large or medium-sized vessels leads to neurological abnormalities such as transient ischemic attacks, vascular thrombosis, cerebral artery occlusion, stroke, pseudotumor cerebri and death [40,41]. CNS involvement in BD is reported in 4–49% of all patients [42]. To the best of our knowledge, no studies have been published on cerebral artery blood flow hemodynamics in patients having BD with or without cerebrovascular symptoms. In this prospective study, we demonstrated that there were no significant differences in PSV, EDV, Tamax, PI and RI of the MCA between the patients with BD and healthy controls. However, the AT value was significantly prolonged in patients with BD who are free of cerebrovascular symptoms and neurological involvement than in healthy controls. Several parameters derived from the Doppler waveform related to the duration of systole such as AT that may demonstrate better predictive discrimination than traditional measurements in the detection of vascular resistance. AT is one of the reliable hemodynamic parameters for arterial vascular function and a diagnostic parameter that is occasionally used for the diagnosis of vascular and circulatory diseases. AT is measured from the beginning of the systolic upstroke to the highest systolic peak in the waveform. The waveform is shaped not only by downstream organ resistance, but also by compliance that is related to the elasticity of the vessel wall and fluid inductance. AT is not influenced by sympathetic tone [43]. It may allow detection of abnormalities not found with peak velocity and no-flow parameters. In the previous reports, AT was used in different artery related disease in the body as a measure of stream resistance as follows; the usefulness of the AT in the evaluation of possible substantial upstream stenosis and possible acute allograft rejection was suggested in many studies [44–46]. AT was examined in renal arteries in the patients with pregnancy-induced hypertension (PIH) and found that it was significantly prolonged in the women with PIH than healthy pregnant women [47]. AT was also been used to detect vascular disorders such as nonvasculogenic male erectile dysfunction [48], assessment of vascular patterns of small liver mass lesions [49] and thyroid blood flow parameters in healthy women [50]. Although no significant impairment was found in the left and right ventricular diastolic functions by either conventional or tissue Doppler echocardiography in the patients with BD, decreased aortic elasticity and increased aortic stiffness were found, suggesting vasculitic involvement of aorta [51].
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To our knowledge, there are only a few studies related to AT on cerebrovascular circulation. Acceleration time was measured in the pericallosal, internal carotid, and basilar arteries with two-dimensional/pulsed Doppler ultrasonography in nondistressed preterm and term infants between 24 and 48 h after birth. In all three arteries it was found a linear relationship between the AT and menstrual age or birth weight. It was speculated that there was an important role for cerebral autoregulation in the AT variations between newborn infants of differing menstrual ages and birth weights [52]. Chang et al. [53] investigated the parameters of fetal circulation of normal pregnancies and their relationship to fetal cardiac output and they found that the AT in MCA positively correlated with the gestational age and cardiac output but not related to fetal heart rate. However, a significant correlation was found between the AT in MCA and the heart rate in preterm infants [52]. In a previous study, AT in the fetal MCA and its relationship with fetal cardiac output were investigated in normal pregnancies and reported that there was a significant positive correlation between gestational age (only between the 26th and 30th week of gestation) and AT values of the MCA, whereas, an increase was observed between 34 and 38 weeks of gestation, this difference was not statistically significant [54]. TCCS allows the investigator to measure the angle of insonation and to obtain flow velocities closer to the true value. It is widely used to screen patients with suspected intracranial hemodynamic disturbances and useful for detecting abnormalities of cerebral hemodynamics among patients with risk factors for cerebrovascular disease. Cerebral blood flow may be affected if cardiac manifestations of BD, including myocarditis, intracardiac thrombi, arrhythmias, tachycardia, bradycardia or depressed cardiac output, are present. Therefore, we tried to exclude the possibility of cardiac and aortic disease in our patients. AT in the patient group may have provided more information than cerebral blood flow measurements in the presence of inflammation, especially because the radiologic methods were unable to localize the sites of involvement. Important complication of BD characterized by occlusive panarteritis of some medium-sized pial branches of the MCA and small infarctions in the brain were reported [14]. The spectral changes of affected MCA, which appeared as the prolonged AT, were thought to be more obvious and useful than overall quantitative evaluation. In the present study, prolonged AT in the patients was probably due to vasculitis because there were no other risk factors or findings of large- or small-artery disease. Furthermore, it may postulated that prolonged AT in the MCA may mostly due to reduction in compliance of the MCA and/or in the vessels distal to the MCA caused by vasculitic processes in patients with BD. The profile of the TCCS waveform depends on many factors including cardiac function and vascular compliance in addition to resistance in the distal arterial bed. Cerebrovascular autoregulation functions to maintain steady cerebral blood flow. If the resistance is increased in the distal cerebral vascular bed an increase will occur in the duration
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time spent in systole in order to maintain normal cerebral blood flow. Therefore, the patients with BD may have inadequate cerebral blood flow, even in the presence of cerebral autoregulation. Because we did not measure MCA area, no information is available on volume flow. Prolonged AT may be an unknown protective effect on the cerebral circulation in BD. In summary, Behc¸et’s disease with ocular involvement has altered retrobulbar circulation compared with BD without ocular involvement and healthy controls. However, Behc¸et’s disease without ocular involvement has more normal retrobulbar blood flow velocities and resistivity indices in any of the retrobulbar vessels compared with healthy controls. Furthermore, it seems that cerebral circulation is affected in Behc¸et’s disease when compared with healthy controls. AT is an index that, like other already described parameters, can contribute to cerebral hemodynamic assessment. It also may be used to in the assessment of cerebral hemodynamics in the patients with Behc¸et’s disease alongside other established parameters. Although our study is preliminary and further prospective studies are needed in order to clarify the effect of altered cerebral circulation on the progression of BD and, required to define the true sensitivity and specificity of TCCS in these patients, our results suggest that TCCS may play a major part in the assessment of patients with Behc¸et’s disease in the early detection.
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Changes in cerebral and ocular hemodynamics in Behc¸et’s disease assessed by color-coded duplex sonography Sevda Yilmaz a,∗ , Cengiz Akarsu b b
a Department of Radiology, School of Medicine, University of Kirikkale, Kirikkale, Turkey Department of Ophthalmology, School of Medicine, University of Kirikkale, Kirikkale, Turkezy
Received 25 July 2005; received in revised form 28 November 2005; accepted 3 January 2006
Abstract Aim: To quantify the cerebral and retrobulbar hemodynamics in Behc¸et’s disease with and without ocular involvement and compared with that of healthy controls. Materials and methods: Of 51 people studied, 17 had Behc¸et’s disease with ocular involvement, 17 had Behc¸et’s disease without ocular involvement, and 17 were healthy controls. A single eye was examined in each patient. Peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged maximum velocity (Tamax), and resistance index (RI) were evaluated in the ophthalmic (OA), posterior ciliary (PCA), central retinal (CRA) and middle cerebral artery (MCA). Additionally, the average blood flow velocities in the central retinal vein (CRV), and acceleration time (AT) and pulsatility index (PI) in the MCA were calculated. Results: The mean EDV in the PCA was 25% lower and RI was higher in patients with ocular involvement of BD than in patients without involvement (p = 0.006 and p = 0.005, respectively) and in healthy controls (p = 0.003 and p = 0.004, respectively). Differences were smaller in comparisons of the CRA and absent on comparisons of the OA and MCA. The acceleration time of the MCA was significantly higher in patients with Behc¸et’s disease than in healthy controls (p = 0.03). Conclusion: This study suggests that the flow hemodynamics in retrobulbar circulation has more altered Behc¸et’s disease with ocular involvement than without ocular involvement and healthy control. Additionally, the cerebral hemodynamic might be affected in patients with Behc¸et’s disease compared with healthy controls. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Behc¸et’s disease; Color Doppler imaging; Transcranial Doppler sonography; Retrobulbar hemodynamic; Cerebral hemodynamic; Acceleration time
1. Introduction Behc¸et’s disease (BD) was firstly defined by Professor Hulusi Behc¸et in 1937 as an illness characterized by recurrent oral and genital ulcers and uveitis [1]. BD has been observed all over the world, but the largest numbers of cases have been reported from Japan, the Middle East, and Mediterranean countries [2,3]. It is considered as a chronic multisystem disorder with vasculitis, which is probably caused by abnormal circulating immune complexes [4]. Nonspecific vasculitis ∗ Corresponding author at: ˙Ivedik cad. Umit ¨ sok. 100, Yıl sitesi, A Blok 8/38, Yenimahalle-Ankara O6170, Turkey. Tel.: +90 312 3442833; fax: +90 318 2252819. E-mail address: [email protected] (S. Yilmaz).
0720-048X/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2006.01.001
may affect any arteries or veins [5,6]. The most frequent and serious complication of BD is ocular involvement that has been reported as 60–90% [7,8]. BD is also associated with other systemic manifestations such as central nervous system (CNS), cardiovascular system, pulmonary and gastrointestinal tract, large vessels, joints, ear, and vestibular involvement due to large and small vessel involvement both in the arterial and venous sides [9–11]. CNS involvement, neuro-Behcet syndrome, is one of the most serious manifestations of BD and occurs in about 10–25% of patients [12,13]. Cerebral angio-Behc¸et’s syndrome is rare but important complication of BD characterized by occlusive panarteritis of some medium-sized pial branches of the middle cerebral artery (MCA), small infarctions, and patchy or confluent demyelinated foci in the brain [14]. Although vascular lesions are
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not listed among the criteria for the diagnosis of BD, up to 25–30% of patients develop complications during follow-up in large vessels [15]. Both transcranial color-coded duplex sonography (TCCS) for the measurement of intracranial arterial blood flow velocities and color Doppler imaging (CDI) for the evaluation of retrobulbar hemodynamics are noninvasive, painless and highly reproducible imaging techniques [16–18]. CDI has been used to detect vascular disorders of the orbit and optic nerve in different diseases such as diabetes mellitus [21], glaucoma [22], tumors [23], and cigarette smokers [24]. TCCS permits visualization of intracranial blood vessels and direction of blood flow detecting intracranial vascular pathology [10,19,20]. Transcranial Doppler ultrasonography has been used in many central nervous system disorders to allow insight into cerebrovascular function. A limited number of CDI investigations of ocular hemodynamics in BD have been studied [25–32], but to the best of our knowledge, TCCS of cerebral hemodynamic changes has not been research previously in the literature. Although vascular involvement is a well-known manifestation of BD and may affect systemic and regional circulation, little information is available for the extent of vascular involvement in patients with BD who are free of vascular sign and symptoms. Thus, we examined the retrobulbar blood flow velocities in patients with or without ocular involvement. As well as, we evaluated the cerebral hemodynamic alterations occurred in patients with Behc¸et’s disease who are free of cerebrovascular symptoms and neurological involvement.
2. Patients and methods 2.1. Patients Forty-one patients with known Behc¸et’s disease and 17 healthy volunteers were enrolled in this prospective study. All participants gave informed consent to the study and the tenets of the Declaration of Helsinki were followed. According to the ethical standards of our institution, written informed consent was obtained from each patient and healthy control before they enrolled in present study. The diagnosis of BD was based on the previously published diagnostic criteria of the International Study Group for Behc¸et’s disease [33]. Each subject underwent a complete ophthalmologic, neurological and general physical examination. All healthy controls had a visual acuity of 20/20 or better and had normal ophthalmologic examination findings. The patients with Behc¸et’s disease had no signs or symptoms of cerebrovascular and neurological involvement. All subjects had no history of neurological disorders, arterial hypertension, hypercholesterolemia, ischemic heart disease, atrial fibrillation, cardiac valve prosthesis, cigarette smoking, diabetes mellitus, polistemia, and migraine. Excluded from this study were subjects with a his-
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tory of incisional ocular surgery, acute ocular aggravation of Behc¸et’s disease within last 3 months, oral contraceptive usage, and hormonal therapy. The ocular involvement was diagnosed on the basis of the presence of one or more following findings: keratic precipitates, posterior synechiae, retinal vascular sheathing and attenuation, retinal neovascularization, retinal hemorrhages, cells in the vitreous, chorioretinal scarring, optic nerve or macular edema, and optic atrophy. Of 41 patients, 22 had previous ocular involvement at least in one eye and 19 had no signs or symptoms of ocular involvement. In Behc¸et’s disease with ocular involvement group, two patients had arterial hypertension, two patients had ocular aggravation within 3 months and one patient was heavy smoker. Similarly, in Behc¸et’s disease without ocular involvement group, one patient had arterial hypertension and one patient was heavy smoker. Therefore, they were excluded from the study. If both eyes of each subject were eligible, we randomly selected one eye of each subjects. So, 17 eyes of 17 patients with Behc¸et’s disease with ocular involvement, 17 eyes of 17 patients with Behc¸et’s without ocular involvement, and 17 eyes of 17 healthy controls were enrolled. Participants were instructed not to drink caffeine-containing beverage during the day of test. Intraocular pressure (IOP) by a Goldmann applanation tonometer, blood pressure (BP) by sphygmomanometer, and heart rate by palpation of radial pulse were measured in a masked manner after a 15-min rest. 2.2. Color-coded duplex sonography examination We used a color Doppler unit (Logiq 9; GE Healthcare, Milwaukee, WI) with a 9–14-MHz linear transducer for the retrobulbar vessels, and a 2–4-MHz sector transducer for the MCA. First ocular and then MCA color Doppler examination were performed in a thermally controlled room by the same radiologist after a 20-min rest. To minimize the effects of diurnal variation, all measurements were recorded at about the same time of day (between 9:00 and 10:00 a.m.). During CDI, transmission gel was applied to the external surface of the eyelids, in a supine position. Care was taken to apply as little pressure as possible on the eye. First, a preliminary gray-scale ultrasonographic examination of the eyes was performed to identify any abnormalities. Then, CDI measurements were performed. The central retinal artery (CRA) and central retinal vein (CRV) were depicted within the optic nerve, approximately 2–4 mm posterior to the optic disc (Fig. 1). The spectrum of the CRA showed a venous overlap from the CRV. The ophthalmic artery (OA) was examined in the deeper part of the orbit, near the optic nerve medially, 10–15 mm behind the globe (Fig. 2). The network of posterior ciliary artery (PCA) was examined where its branches surrounding the globe, near the optic nerve laterally (Fig. 3). The axial or oblique scans were used according to parallel to the long axis of each vessel and to identify the precise direction of the orbital vessels. Examinations were performed in a low or medium flow setting to permit for optimal detection of Doppler frequency shifts of the slow-flowing blood
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Fig. 1. Color Doppler ultrasonography showing the central retinal artery waveform.
Fig. 3. Color Doppler ultrasonography showing the posterior ciliary artery waveform.
in the small orbital vessels. Only for the OA, medium to high flow settings were applied, because flow in this vessel is faster. Vessels were seen on axial and oblique scans. Finally, both M1-segments of the middle cerebral arteries (MCA) of all subjects were examined with sector transducer through the transtemporal acoustic window (at the point where the best signal-to-noise ratio was obtained) at an examination depth approximately 50–65 mm (Fig. 4). During TCCS the patients were positioned in dorsal decubitus in a semisitting position at an angle of 15–20◦ between the subject and the examination table. The transducer was angled until the highest measurements were obtained. Doppler color gain was first turned down completely and then increased very gradually until the static background noise barely appeared. The
Doppler sample volume was placed over the investigated vessel. Angle-corrected velocity waveform measurements were obtained, the optimum insonation angles were maintained at or lower than 20◦ and 45◦ for the retrobulbar vessels and MCA, respectively, and when the highest velocity measurements were obtained, spectral waveforms were recorded. The flow velocities were measured automatically by the color Doppler unit for the retrobulbar vessels and MCA. The peak systolic velocity (PSV), end-diastolic velocity (EDV) and time-averaged maximum velocity (Tamax) were measured for the OA, PCA, CRA, and MCA. From these values, resistance index (RI = [PSV − EDV]/PSV) and pulsatility index (PI = [PSV − EDV]/mean velocity), were calculated by the machine. Additionally, the acceleration time (AT) was measured for the MCA and the averaged blood flow velocity in the central retinal vein (CRV) was calculated. Only one waveform tracing from each examination was chosen for analysis. Because multiple measurements were obtained, the tracing with the most normal waveform was selected for analysis. The entire examination of a subject lasted about 15–20 min.
Fig. 2. Color Doppler ultrasonography showing the ophthalmic artery waveform.
Fig. 4. Transcranial color Doppler ultrasonography showing the middle cerebral artery (MCA) and anterior cerebral artery (ACA).
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2.3. Statistical analysis
3. Results
The results were expressed as the mean ± S.D. (standard deviation). A sample size 17 provides 90% power to detect a 15% change in flow velocity in the ophthalmic artery [34]. The sample size also, provides 90% power to detect a 15% change in the posterior ciliary artery and a 20% change in the central retinal artery. Data were analyzed using the Statistical Package for Social Sciences (SPSS for windows, 9.0, Chicago, IL.). Differences in retrobulbar hemodynamic between groups were evaluated using one-way analysis of variance (ANOVA). If a significant difference was detected using ANOVA, Tukey HSD was conducted for post hoc test. Statistical analysis was performed with an unpaired Student’s t-test to compare the differences in cerebral hemodynamic between patients with BD and controls. The χ2 -test was used for categorical data. Statistical significance was set at p < 0.05.
The general characteristics of the subjects are summarized in Table 1. There was no significant difference in the mean age (p = 0.27), gender (p = 0.78) mean blood pressure (p = 0.38 for systolic blood pressure and p = 0.64 for diastolic blood pressure), mean pulse rate (p = 0.98), and mean IOP (p = 0.47) between the groups. The Doppler parameters of the OA, PCA, and CRA are shown in Table 2. The PSV and Tamax were lower in patients with BD with ocular involvement than in patients with BD without ocular involvement and normal subjects in all retrobulbar arteries, but did not reach statistical significance (p > 0.05). Patients with BD with ocular involvement had significantly lower EDV and higher RI than did BD without ocular involvement (p = 0.006 and p = 0.005, respectively) and controls (p = 0.003 and p = 0.004, respectively) in their PCA. The EDV in the CRA were significantly lower in BD with ocular involvement than in BD without ocular
Table 1 Subjects’ age, blood pressure (BP), heart rate, and intraocular pressure (IOP) for the patients with Behc¸et’s disease and healthy controls Variables
Behc¸et’s disease with ocular involvement
Behc¸et’s disease without ocular involvement
Age (years)
35.8 ± 10.6
31.1 ± 7.6
Gender Male Female
7 10
6 11
Systolic BP (mmHg) Diastolic BP (mmHg) Heart rate (beats/min) IOP (mmHg)
106.5 ± 17.3 65.9 ± 11.2 70.4 ± 6.2 17.0 ± 1.8
Healthy controls 33.6 ± 7.8 8 9
108.8 ± 16.2 65.3 ± 10.1 71.6 ± 8.2 16.6 ± 1.4
104.1 ± 15.4 68.8 ± 13.2 69.7 ± 8.6 17.4 ± 1.8
Table 2 Hemodynamic values measured in the retrobulbar vessels for the patients with Behc¸et’s disease and healthy controls Parameters
Behc¸et’s disease with ocular involvement
Behc¸et’s disease without ocular involvement
Healthy controls
Ophthalmic artery PSV (cm/s) EDV (cm/s) RI Tamax (cm/s)
34.53 9.32 0.73 16.79
± ± ± ±
10.44 3.88 0.06 5.98
36.93 9.93 0.73 16.87
± ± ± ±
8.30 3.58 0.07 4.28
37.04 10.44 0.72 18.03
± ± ± ±
11.31 4.05 0.05 6.09
Posterior ciliary artery PSV (cm/s) EDV* (cm/s) RI† Tamax (cm/s)
12.62 3.97 0.67 7.95
± ± ± ±
1.12 1.17 0.04 1.24
13.84 5.42 0.61 8.82
± ± ± ±
3.15 1.36 0.05 2.30
14.20 5.54 0.61 9.08
± ± ± ±
3.90 1.37 0.06 1.75
Central retinal artery PSV (cm/s) EDV‡ (cm/s) RI Tamax (cm/s)
10.74 3.42 0.68 5.99
± ± ± ±
2.09 0.82 0.06 1.42
11.69 4.24 0.65 7.00
± ± ± ±
2.92 1.15 0.06 1.94
12.13 4.20 0.65 6.88
± ± ± ±
2.99 0.79 0.05 1.48
PSV, peak systolic velocity; EDV, end-diastolic velocity; RI, resistivity index; PI, pulsatility index; Tamax, time-averaged maximum velocity. * There was statistically significant difference between Behc ¸ et’s disease with ocular involvement and without ocular involvement (p = 0.006) and healthy controls (p = 0.003). † There was statistically significant difference between Behc ¸ et’s disease with ocular involvement and without ocular involvement (p = 0.005) and healthy controls (p = 0.004). ‡ There was statistically significant difference between Behc ¸ et’s disease with ocular involvement and without ocular involvement (p = 0.037) and healthy controls (p = 0.045).
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Table 3 Hemodynamic parameters measured in the middle cerebral artery for the patients with Behc¸et’s disease and healthy controls Parameters
Behc¸et’s disease
PSV (cm/s) EDV (cm/s) RI PI Tamax (cm/s) AT* (s)
106.66 49.62 0.54 0.85 70.25 0.06
± ± ± ± ± ±
18.29 10.71 0.06 0.17 14.72 0.04
Healthy controls 104.53 51.56 0.50 0.79 69.83 0.04
± ± ± ± ± ±
15.61 8.51 0.04 0.13 9.85 0.02
PSV, peak systolic velocity; EDV, end-diastolic velocity; RI, resistivity index; PI, pulsatility index; Tamax, time-averaged maximum velocity; AT, acceleration time; s, second. * p = 0.03.
Fig. 5. Transcranial color-coded duplex sonography showing the middle cerebral artery waveform including prolonged acceleration time.
involvement and controls (p = 0.037 and p = 0.045, respectively). The EDV were lower in the OA and the RI was higher in the OA and CRA in BD with ocular involvement than in BD without ocular involvement and controls, but did not achieve statistical significance (p > 0.05). There was no significant difference in the average velocity measurement in the CRV among the groups. The Doppler parameters of the MCA are represented in Table 3. No statistically significant differences were observed in the PSV, EDV, Tamax, RI and PI of the MCA between the patients with BD regardless of ocular involvement and healthy controls (p > 0.05). On the other hand, acceleration time of the MCA was significantly prolonged in the patients with BD than in healthy controls (p = 0.03) (Fig. 5).
4. Discussion In this prospective study, we showed that mean EDV was lower and RI was higher in BD with ocular involvement than in BD without ocular involvement and healthy controls in the PCA. Additionally, EDV in the CRA of BD with ocular involvement was lower than BD without ocular involvement and healthy controls. However, there was no significantly difference between BD without ocular involvement and healthy
controls. This suggests that BD with ocular involvement has significantly altered retrobulbar circulation and the hemodynamic changes occurred in patients with BD with ocular involvement was more evident in the PCA than in the other retrobulbar vessels. These differences suggest that nonspecific occlusive vasculitis of PCA is more specific to BD and occurs inactive course of the disease. The current study confirmed the previous studies, which showed alteration in the retrobulbar hemodynamics in BD with ocular involvement than in BD without ocular involvement and control subjects [26,28]. A previous study revealed that blood flow velocities in the CRA of patients with severe retinal involvement were significantly lower than those with mild to moderate vasculitis and control groups [31]. Lower EDV and higher RI and PI were observed in all retrobulbar arteries in BD with ocular involvement compared with BD without ocular involvement and healthy volunteers [27]. In addition, the blood flow velocities were evaluated in the OA and CRA, and found that mean ophthalmic and central retinal artery flow velocities were lower in patients with BD than in healthy controls [29]. Similarly, Soylu et al. [30] found significantly lower EDV in the PCA and CRA in patients with BD regardless of the ocular activation compared with controls. On the other hand, they found no significant differences in the retrobulbar blood flow velocities between active and inactive eyes of BD. Duranoglu et al. [27] observed no significant difference in blood flow velocity of the CRV in three groups. Similarly, we also observed no significant difference in blood flow velocity of the CRV among three groups. On the other hand, Ucakhan et al. [31] showed that the average blood flow velocities in the CRV of patients with severe vasculitis were significantly lower than in mild to moderate vasculitis and control subjects. There are some differences between our study and above mentioned studies. These may be resulted from the definition or severity of ocular involvement, duration of BD and ocular involvement, the time between ocular involvement and examination, patients’ characteristics, level of CDI measurement, and use of medications. The involvement of the brain is one of the most devastating complications of Behc¸et’s disease. In the course of the BD, neurologic involvement may occur by primary neural parenchymal lesions, or be secondary to major vascular involvement [12,35]. In patients with vascular BD, the visible lesions and clinical features usually correspond to main vascular territories. The histopathologic changes may effect the tissue perfusion, leading to tissue destruction. Although vasculitis is common and may account for much of the pathologic process in BD, the pathological process in the vascular system is not very clear and knowledge is limited by data derived from pathological and angiographic studies. Some cases have been reported with typical appearance of arteritis with multiple segments of stenosis, occlusion [36,37] and an autopsy study of patients with vascular BD showed inflammation and destruction occurring in the media and adventitia [38] but, lymphocytic infiltration progressing from the adventitia
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toward the intima, possibly leading the thrombus formation was also reported by pathological examination [39]. The vascular injuries are superimposed on the hypercoagulability that is also characteristic of BD and that may be due in part to activated endothelial cells and activated platelets. Occlusion of major veins and arteries often causes bleeding, infarction and organ failure. It is probable that in some patients with BD immunological mechanism propagates the formation of microthrombus, and thereafter leads to embolisation of distal vascular system. BD with the involvement of large or medium-sized vessels leads to neurological abnormalities such as transient ischemic attacks, vascular thrombosis, cerebral artery occlusion, stroke, pseudotumor cerebri and death [40,41]. CNS involvement in BD is reported in 4–49% of all patients [42]. To the best of our knowledge, no studies have been published on cerebral artery blood flow hemodynamics in patients having BD with or without cerebrovascular symptoms. In this prospective study, we demonstrated that there were no significant differences in PSV, EDV, Tamax, PI and RI of the MCA between the patients with BD and healthy controls. However, the AT value was significantly prolonged in patients with BD who are free of cerebrovascular symptoms and neurological involvement than in healthy controls. Several parameters derived from the Doppler waveform related to the duration of systole such as AT that may demonstrate better predictive discrimination than traditional measurements in the detection of vascular resistance. AT is one of the reliable hemodynamic parameters for arterial vascular function and a diagnostic parameter that is occasionally used for the diagnosis of vascular and circulatory diseases. AT is measured from the beginning of the systolic upstroke to the highest systolic peak in the waveform. The waveform is shaped not only by downstream organ resistance, but also by compliance that is related to the elasticity of the vessel wall and fluid inductance. AT is not influenced by sympathetic tone [43]. It may allow detection of abnormalities not found with peak velocity and no-flow parameters. In the previous reports, AT was used in different artery related disease in the body as a measure of stream resistance as follows; the usefulness of the AT in the evaluation of possible substantial upstream stenosis and possible acute allograft rejection was suggested in many studies [44–46]. AT was examined in renal arteries in the patients with pregnancy-induced hypertension (PIH) and found that it was significantly prolonged in the women with PIH than healthy pregnant women [47]. AT was also been used to detect vascular disorders such as nonvasculogenic male erectile dysfunction [48], assessment of vascular patterns of small liver mass lesions [49] and thyroid blood flow parameters in healthy women [50]. Although no significant impairment was found in the left and right ventricular diastolic functions by either conventional or tissue Doppler echocardiography in the patients with BD, decreased aortic elasticity and increased aortic stiffness were found, suggesting vasculitic involvement of aorta [51].
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To our knowledge, there are only a few studies related to AT on cerebrovascular circulation. Acceleration time was measured in the pericallosal, internal carotid, and basilar arteries with two-dimensional/pulsed Doppler ultrasonography in nondistressed preterm and term infants between 24 and 48 h after birth. In all three arteries it was found a linear relationship between the AT and menstrual age or birth weight. It was speculated that there was an important role for cerebral autoregulation in the AT variations between newborn infants of differing menstrual ages and birth weights [52]. Chang et al. [53] investigated the parameters of fetal circulation of normal pregnancies and their relationship to fetal cardiac output and they found that the AT in MCA positively correlated with the gestational age and cardiac output but not related to fetal heart rate. However, a significant correlation was found between the AT in MCA and the heart rate in preterm infants [52]. In a previous study, AT in the fetal MCA and its relationship with fetal cardiac output were investigated in normal pregnancies and reported that there was a significant positive correlation between gestational age (only between the 26th and 30th week of gestation) and AT values of the MCA, whereas, an increase was observed between 34 and 38 weeks of gestation, this difference was not statistically significant [54]. TCCS allows the investigator to measure the angle of insonation and to obtain flow velocities closer to the true value. It is widely used to screen patients with suspected intracranial hemodynamic disturbances and useful for detecting abnormalities of cerebral hemodynamics among patients with risk factors for cerebrovascular disease. Cerebral blood flow may be affected if cardiac manifestations of BD, including myocarditis, intracardiac thrombi, arrhythmias, tachycardia, bradycardia or depressed cardiac output, are present. Therefore, we tried to exclude the possibility of cardiac and aortic disease in our patients. AT in the patient group may have provided more information than cerebral blood flow measurements in the presence of inflammation, especially because the radiologic methods were unable to localize the sites of involvement. Important complication of BD characterized by occlusive panarteritis of some medium-sized pial branches of the MCA and small infarctions in the brain were reported [14]. The spectral changes of affected MCA, which appeared as the prolonged AT, were thought to be more obvious and useful than overall quantitative evaluation. In the present study, prolonged AT in the patients was probably due to vasculitis because there were no other risk factors or findings of large- or small-artery disease. Furthermore, it may postulated that prolonged AT in the MCA may mostly due to reduction in compliance of the MCA and/or in the vessels distal to the MCA caused by vasculitic processes in patients with BD. The profile of the TCCS waveform depends on many factors including cardiac function and vascular compliance in addition to resistance in the distal arterial bed. Cerebrovascular autoregulation functions to maintain steady cerebral blood flow. If the resistance is increased in the distal cerebral vascular bed an increase will occur in the duration
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time spent in systole in order to maintain normal cerebral blood flow. Therefore, the patients with BD may have inadequate cerebral blood flow, even in the presence of cerebral autoregulation. Because we did not measure MCA area, no information is available on volume flow. Prolonged AT may be an unknown protective effect on the cerebral circulation in BD. In summary, Behc¸et’s disease with ocular involvement has altered retrobulbar circulation compared with BD without ocular involvement and healthy controls. However, Behc¸et’s disease without ocular involvement has more normal retrobulbar blood flow velocities and resistivity indices in any of the retrobulbar vessels compared with healthy controls. Furthermore, it seems that cerebral circulation is affected in Behc¸et’s disease when compared with healthy controls. AT is an index that, like other already described parameters, can contribute to cerebral hemodynamic assessment. It also may be used to in the assessment of cerebral hemodynamics in the patients with Behc¸et’s disease alongside other established parameters. Although our study is preliminary and further prospective studies are needed in order to clarify the effect of altered cerebral circulation on the progression of BD and, required to define the true sensitivity and specificity of TCCS in these patients, our results suggest that TCCS may play a major part in the assessment of patients with Behc¸et’s disease in the early detection.
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