Cross-sectional area variations of internal jugular veins during supine head rotation in multiple sclerosis patients with chronic cerebrospinal venous insufficiency: a prospective diagnostic controlled study with duplex ultrasound investigation

Massimiliano Farina 0 Eugenio Novelli 2 Raffaello Pagani 1 0 Phlebolymphology Diseases Centre , Monza Polyclinic, Monza , Italy 1 Angiology Unit, Villa Cimarosa Medical Centre , Milan , Italy 2 Biostatistics Unit, San Gaudenzio Clinic (Monza Polyclinic Group) , Novara , Italy Background: Normally, chronic cerebrospinal venous insufficiency (CCSVI) has been studied using echo-colour Doppler (ECD). Subjects are examined in the supine and sitting positions, in accordance with a static protocol without rotation of the head. A dynamic approach, to assess venous sizes with different degrees of head rotation, has only been performed to improve jugular venous catheterisation. These echographic studies have suggested that head rotation to the contralateral side increases the cross-sectional area (CSA) of the internal jugular veins (IJVs) in supine subjects. Our goal was to evaluate the behaviour of CSA of the IJVs during supine head rotation in multiple sclerosis (MS) patients with CCSVI, compared to healthy controls (HCs). Methods: The IJVs of 313 MS patients with CCSVI (male 43.8%, male/female 137/176; mean age 45 years old, range 19-77 years) and 298 HCs, matched by gender (male 43.6%, male/female 130/168) and age (mean age 46 years old, range 20-79 years), were compared using ECD. Their CSAs were evaluated with the subjects seated in a tiltable chair, first in the supine position at the level of the cricoid cartilage, with the head in a neutral position, and then after contralateral rotation to 90 from midline. Results: Significant differences between the jugular CSAs before and after head rotation were observed only in the MS patients for the IJVs with wall collapse (F[6,1215] = 6414.57, p < 0.001), showing on longitudinal scans a typical hourglass aspect that we defined as miopragic. No significant difference was found in the distribution of these miopragic veins with regard to MS duration. There was a strong association between the CCSVI scores and the complexity of jugular morphological types (2 [9, N = 313] = 75.183, p < 0.001). Wall miopragia was mainly observed in MS patients with SP (59.3%) and PP (70.0%) clinical forms, compared to RR (48.3%) forms (p = 0.015). Conclusion: A dynamic ECD approach allowed us to detect IJVs with a significant increase in their CSAs during head rotation, but only in MS subjects. This feature, most likely the expression of congenital wall miopragia, could be secondary to dysregulation of collagen synthesis, but further histochemical studies will be needed to confirm this hypothesis. - Background Chronic cerebrospinal venous insufficiency (CCSVI) is a congenital syndrome affecting the extracranial vessels (internal jugular and azygos veins) that is characterised by different valve malformations, stenoses and segmental or global hypoplasia with impaired venous drainage, opening collateral circulation [1-3]. Several studies have demonstrated a strong association between multiple sclerosis (MS) and CCSVI, but subsequent clinical research has failed to support this hypothesis [4-13]. Thus, the debate currently continues over whether the relationship is real. In fact, some reports have claimed that the data in the literature have been insufficient to establish the importance of CCSVI as a major factor in MS pathogenesis. Echo-colour Doppler (ECD) studies of CCSVI are usually performed according to the five Zamboni criteria; the detection of at least two of these parameters indicates a diagnosis of CCSVI. Nevertheless, ECD investigation is still not currently standardised in many respects, and it is overly dependent on individual patients and operators, with high interobserver variability for untrained examiners [14,15]. However, different studies have reported that ECD is more sensitive than the magnetic resonance venography (MRV) in detecting intraluminal jugular defects, while MRV is more sensitive in showing collaterals [9,16]. Both techniques have proved effective in assessing the size and course of venous vessels of the neck, showing internal jugular vein (IJV) asymmetry in both normal subjects and MS patients. The left internal jugular vein is usually smaller than the right due to preferential intracranial venous drainage through one sigmoid sinus versus the other, with weak correlations with age and gender [17-21]. Venous size can vary depending on hydration status, position, cardiac status, thoracic pump, head position, and compression from adjacent structures [22-26]. Even dysfunction of the cardiovascular autonomic nervous system can reduce vascular tone, affecting jugular size [27]. More frequently, MS patients have shown a jugular cross-sectional area (CSA) 30 mm2 compared to healthy controls (HCs) (43.5% vs. 16.7%) [28]. These ultrasonographic findings were also confirmed by catheter venography (CV) and were mainly detected in the middle part of the IJV, at the level of the cricoid cartilage Age (years) (Mean [range]) Gender (% male -n male/female) Body weight (kg) (Mean SD) (range) EDSS (Mean [range]) Disease duration (years) (Mean [range]) 67.47 7.12 (4988) Table 1 Demographic and clinical characteristics of MS patients with CCSVI immediately below the sternocleidomastoid muscle (SCM) [29]. They have not been clearly correlated with intraluminal defects, although they have been explained by low values of internal pressure [30]. At this level, CV and ECD have shown a collapsed jugular vein with loss of its elliptical appearance under SCM imprinting [5,29]. Patients have usually been examined in the supine and sitting positions, in accordance with a static protocol without head rotation (0 from midline). A dynamic approach to assess venous sizes with different degrees of head rotation has only been applied to improve jugular venous catheterisation. These echographic studies have suggested that head rotation to the contralateral side increases the CSA of IJVs in supine subjects [25,31]. The aim of this study was to evaluate the behaviour of the CSA of the IJVs during supine head rotation in MS patients with CCSVI, compared to HCs. Methods Patients and controls Between June 2010 and November 2012, we studied 313 patients with clinically defined MS (according to the 2010 revised McDonald diagnostic criteria) and CCSVI, who were diagnosed with the presence of at least two of the five Zamboni criteria [1,32]. This group consisted of 172 patients with the relapsing-remitting (RR) clinical form, 91 with the secondary progressive (SP) form and 50 with the primary progressive (PP) form. An MS specialist evaluated all the patients, assigning disability scores according to the Kurtzke scale (EDSS). Table 1 shows the related demographic and clinical characteristics. We also studied 298 volunteers HCs (students and technical and administrative staff from our hospital) with a mean weight of 70.23 kg (standard deviation [SD] = 7.97; range: 4398), who were matched by gender (male 43.6%, male/female 130/168) and age (mean age 46 years ol (...truncated)