Cerebral hemodynamics in patients with ankylosing spondylitis

1. Introduction

Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton that may be associated with the involvement of hip, shoulder or peripheral joints. Recently there has been considerable attention concerning the possible causal role of systemic inflammation in the development of atherosclerosis in patients with rheumatic diseases [1]. Increased risk of atherosclerosis regarding cardiovascular events such as myocardial infarction and stroke leads to a significantly increased mortality in patients with AS [2, 3]. The aim of this study was to assess the cerebral blood flow velocity as a marker of atherosclerosis by using transcranial Doppler (TCD) ultrasonography in patients with AS.

OPEN IN VIEWER

A total of 30 consecutively admitted patients aged 20 to 50 with a principal diagnosis of AS were enrolled in the AS group, who were in compliance with the modified New-York criteria for AS. The non-AS control group consisted of 30 age- and sex-matched, randomly selected patients who did not have any risk factors for atherosclerosis, such as diabetes, hypertension, and coronary artery disease. All patients with AS were under disease-modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor alpha inhibitor drugs. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels were measured to show the existence of inflammation. Consent was obtained from the local ethics committee (Kahramanmaras Sutcu Imam University, Faculty of Medicine), and all participants provided written informed consent.

TCD ultrasonography examination was performed with Multi-Dop X DWL, TCD machine after the subjects rested in a supine position for 10 min. The right and the left MCA were insonated from the temporal windows at 50–65 mm depth with 2 MHz pulsed Doppler probes. Bilateral MCA peak-systolic, end-diastolic, and mean blood flow velocities; pulsatility index values, and resistance index values were recorded (Fig. 1). The results of the AS group were compared with the results of non-AS control group.

In this study, male/female: 18/12, mean age: 37.4 ± 6.2 in the AS group and male/female: 18/12, mean age: 35.2 ± 4.9 in the non-AS control group. Clinical features of AS patients are given in Table 1. Mean value of CRP and ESR levels were 9.5 ± 6.2 mg/L (normal range: 0–5 mg/L) and 20.5 ± 11.6 mm/h respectively in the AS group. There was a statistically significant difference between the two groups for ESR (20.5 ± 11.6 mg/L vs. 13.5 ± 6.7 mg/L, p = 0.006) and CRP levels. ESR and CRP levels were higher in the AS group than the non-AS control group (9.5 ± 6.2 mg/L vs. 3.3 ± 0.25 mg/L, p = 0.00). Peak-systolic, end-diastolic, and mean blood flow velocities of bilateral MCA were significantly higher in the AS group than the control group (Table 2). The pulsatility index and resistance index values were not significantly different in each group.

4. Discussion

We know that AS patients show early features of atherosclerosis, such as an increase in intima media thickness in the carotid arteries and arterial stiffness [4, 5]. Inflammation plays an important role in the pathogenesis and progression of atherosclerosis in patients with AS [6, 7]. In the AS group we found that the mean values of ESR and CRP were higher than normal range. But what is the interaction between atherosclerosis and inflammation? Jänig reported that the autonomic nervous system is organized in the periphery in many functionally and anatomically separate pathways that transmit the centrally generated impulses faithfully to the effector cells. These autonomic pathways are connected to distinct neural circuits in the spinal cord, brain stem and hypothalamus [8, 9]. The sympatho-neural and sympatho-adrenal systems are important in the regulation of the protection of the body against injuries from both inside and outside of the body. They are thus involved in the regulation of the immune system, inflammation and nociceptor functions, i.e. pain and hyperalgesia. This is the neurobiological basis of autonomic regulations in which the sympathetic nervous system is involved [8, 9]. We attempted to evaluate the cerebral blood flow velocities by using TCD ultrasonography in patients with AS, because increased cerebral blood flow velocities indirectly indicate an increase in atherosclerosis.

Direct measurement of the blood flow in the brain arteries would be of value in all cases. With a TCD ultrasound probe, blood flow velocity can be measured in the main arteries of the base of the brain. In 10% of the patients, the transtemporal window is not feasible because of anatomical barriers. This was an exclusion criteria for our study. When cerebrovascular resistance increases, for example in vasospasm of the middle cerebral artery, systolic velocities increase [10].

We found that peak-systolic, end-diastolic and mean blood flow velocities were significantly higher in the AS group than in the non-AS control group. The pulsatility index and resistance index values were not significantly different in each group. However, the correct interpretation of the pulsatility index not only depends on cerebrovascular resistance but also on several systemic and cerebral variables [10]. The mechanisms that underlie this condition (increased velocity but normal PI values) are most likely to be due to mild diffuse atherosclerosis or low AS disease activity is not associated with accelerated atherosclerosis [11, 12]. The Rotterdam study reported that increased mild to moderate cerebral blood flow velocity is due to diffuse atherosclerosis or vasoconstriction [13].

Our study had methodological limitations, including inadequate sample size and an evaluation of activity and damage-like joint restriction. We also did not specify lung involvement.

This study suggests that persistent clinical and subclinical inflammation regarding atherosclerosis in patients with AS causes increased cerebral blood flow velocities. Our findings provide an insight to this association of AS with cerebrovascular diseases.