Pubblicazioni Scientifiche

Objective: Chronic cerebrospinal venous insufficiency (CCSVI) is a recently discovered syndrome mainly due to stenoses of internal jugular (IJV) and/or azygos (AZ) veins. The present study retrospectively evaluates the feasibility and safety of endovascular treatment for CCSVI in a cohort of patients with multiple sclerosis (MS).
Methods: From September 2010 to October 2012, 1202 consecutive patients were admitted to undergo phlebograpy 6 endovascular treatment for CCSVI. All the patients had previously been found positive at color Doppler sonography (CDS) for at least two Zamboni criteria for CCSVI and had a neurologist-confirmed diagnosis of MS. Only symptomatic MS were considered for treatment. Percutaneous transluminal angioplasty was carried out as an outpatient procedure at two different institutes. Primary procedures, regarded as the first balloon angioplasty ever performed for CCSVI, and secondary (reintervention) procedures, regarded as interventions performed after venous disease recurrence, were carried out in 86.5% (1037 of 1199) and 13.5% (162 of 1199) of patients, respectively. Procedural success and complications within 30 days were recorded.
Results: Phlebography followed by endovascular recanalization was carried out in 1999 patients consisting of 1219 interventions. Balloon angioplasty alone was performed in 1205 out of 1219 (98.9%) procedures, whereas additional stent placement was required in the remaining 14 procedures (1.1%) following unsuccessful attempts at AZ dilatation. No stents were ever implanted in the IJV. The feasibility rate was as high as 99.2% (1209 interventions). Major complications included one (0.1%) AZ rupture occurring during balloon dilatation and requiring blood transfusion, one (0.1%) severe bleeding in the groin requiring open surgery, two (0.2%) surgical openings of the common femoral vein to remove balloon fragments, and three (0.2%) left IJV thromboses. The overall major and minor complication rates at 30 days were 0.6% and 2.5%, respectively.
Conclusions: Endovascular treatment for CCSVI appears feasible and safe. However, a proper learning curve can dramatically lower the rate of adverse events. In our experience, the vast majority of complications occurred in the first 400 cases performed. (J Vasc Surg 2013;58:1609-18.)

Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by stenoses of the internal jugular veins (IJVs) and/or azygos veins and formation of collateral venous channels. A case of a 57-year-old patient with CCSVI in whom the venous outflow from the left IJV to the right atrium occurred through a venous anomaly, the persistent left superior vena cava (PLSVC), is reported. PLSVC is caused by persistence of the left anterior cardinal vein that drains blood from the limb effluent from the left and the left side of head and neck into coronary sinus (Type a), or in the left atrium (Type b). PLSVC can be associated either with innominate vein hypoplasia or other congenital heart abnormalities. Because of evidence of left innominate vein hypoplasia, angioplasty was not performed using the ordinary route but passing with the balloon directly through the PLSVC up to the left IJV. Finally, angioplasty was carried out in a standard manner in the
right IJV as well as in the azygous vein. Confirmation angiogram revealed complete reopening of all treated vessels with no evidence of peri- and postoperative complications.
The patient was discharged home the following day in good general conditions. PLSVC is a rare congenital vein anomaly but in case of concomitant innominate vein hypoplasia may prove to be a valuable alternative to treat patients with IJV diseases

1.1. Objectives: Chronic Migraine (CM) is characterized by recurrent head pain often associated with electroencephalogram (EEG) abnormalities and asymmetry of intracranial venous circulation. Migraine is a symptom of the Chronic Cerebrospinal Venous Insufficiency (CCSVI).
1.2. Methods: Seven persons with CCSVI and CM, associated or not with other symptoms, underwent Percutaneous Transluminar Angioplasty (PTA) of Internal Jugular Veins (JVSs), performed an intracranial Magnetic Resonance Imaging venography and/or Echo-Colour Doppler (ECD) of IJVs, seven an EEG before and five after PTA. A Pain Scale Assessment for CM was sampled before and after PTA.
1.3. Results: Seven patients show a blood flow improvement of the JVs after PTA. Before PTA, seven persons showed EEG alterations, after PTA five also showed an improvement of the EEG and all seven showed an improvement in the pain score.
1.4. Conclusions: these preliminary observations suggest a strong association between CM, intra and extra cranial venous anomalies and EEG alterations.

Objective: Resting state electroencephalographic (EEG) rhythms are abnormal in multiple sclerosis (MS) patients, but it is unclear if they can reflect different neurophysiologic abnormalities in MS sub-types (phenotypes) such as relapsing–remitting (RR) and secondary progressive (SP).
Methods: We tested whether cortical sources of resting state EEG rhythms are abnormal in MS patients and differ between MS phenotypes. Resting state eyes-closed EEG activity was recorded in 36 RR, 23 SP, and 41 matched healthy subjects. EEG bands of interest were individually identified based on Transition frequency (TF), Individual alpha frequency (IAF), and Individual beta frequency (IBF). LORETA freeware estimated cortical EEG sources.
Results: Widespread TF 4 Hz (delta) and IAF (alpha) cortical sources were abnormal in the MS sub-groups compared to the control group. Furthermore, TF 4 Hz sources in central, parietal, and limbic regions were higher in amplitude in the SP compared to the RR sub-group.
Conclusion: Cortical sources of resting state EEG rhythms are abnormal in MS patients at group level and differ between RR and SP sub-groups.
Significance: Future studies should test the utility of these EEG markers in the diagnosis and management of MS clinical phenotypes and in the therapy evaluation.

Severe stenosis and/or thrombosis of the internal jugular vein could be managed through a novel technique herein reported. Recanalization can be achieved passing through the omolateral external jugular vein.

Purpose:
To investigate characteristics of cine phase contrast–calculated cerebrospinal fluid (CSF) flow and velocity measures in patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA).

Materials and Methods:
This case-controlled, magnetic resonance (MR) imaging–blinded study included 15 patients with RRMS who presented with significant stenoses (≥50% lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (case group), and seven had delayed PTA after 6 months of medical therapy alone (control group). CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle by a semiautomated method. Outcomes were compared between groups at baseline and at 6 and 12 months of the study by mixed-effect model analysis.

Results:
At baseline, no significant differences in CSF flow or velocity measures were detected between groups. At month 6, significant improvement in flow (P < .001) and velocity (P = .013) outcomes were detected in the immediate versus the delayed group, and persisted to month 12 (P = .001 and P = .021, respectively). Within-group flow comparisons from baseline to follow-up showed a significant increase in the immediate group (P = .033) but a decrease in the delayed group (P = .024). Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group.

Conclusions:
PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.

Balloon angioplasty (BA) is a treatment modality to correct vascular lesions in multiple sclerosis (MS) patients, who present with chronic cerebrospinal venous insufficiency (CCSVI). We hypothesized that BA clinical benefits stems in part from improvement in cardiovascular autonomic nervous system (ANS) function. We adopted the Transvascular Autonomic Modulation (TVAM), as a modified BA technique, with the objective of further enhancing ANS functional activities. TVAM involved dilation of multiple vascular beds, including IJVs, azygos and renal veins, and application of manual compression. Since the ANS regulates the function of the hypothalamus pituitary (HPA) axis, we examined TVAM effects on HPA axis in MS patients, and determined the relationship between ANS function and HPA activity. The adrenocorticotropic hormone (ACTH) and cortisol serum levels, systolic and diastolic blood pressure (BP), and heart rate variability (HRV) parameters were measured before and 24 h after TVAM procedure in 72 MS patients. Baseline ACTH and cortisol serum levels were lower than normal ranges in 18 % and 25 % MS patients respectively. The intervention resulted in significant reductions in both ACTH and cortisol (p < 0.001), with a more marked ACTH reduction in males compared to females (p < 0.001). Post-TVAM BP increased in patients who presented with baseline BP within lower limits of normal ranges, but decreased in patients with baseline BP above the normal ranges. In a univariate analysis, the changes (Δ) in ACTH serum levels correlated weakly, although significantly, with Δ in diastolic BP (r = − 0.265, p = 0.03), and Δ in cortisol serum levels correlated weakly, but significantly, with Δ in systolic BP (r = − 0.283, p = 0.01). The observed ACTH and cortisol reductions are counter to the stress-mediated increases in serum levels of these hormones, which are expected following an invasive procedure. The clinical implications of this unexpected response, warrants further investigations.

Objective: Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in patients with multiple sclerosis (MS). The hypothesis of the vascular aetiology provides a new approach in the investigation and treatment of MS.
Methods: Our open-label study included 94 MS patients who fulfilled ultrasound sonographic criteria required for CCSVI. The internal jugular and/or azygous veins by a catheter venography were dilated.
Results: In 34.8% of the patients unilateral, in 65.2% bilateral venous abnormalities and in 2.1% no luminal obstructions were demonstrated. The patient group with the higher disability score had a significantly higher number of venous lesions (P , 0.005). Significant improvement of clinical disability in relapsing-remitting patients was (P , 0.001) achieved. In our study no stents were used. Re-stenosis occurred in 21.7% of the patients.
Conclusion: The number of venous narrowings is higher in more disabled patients. A significant improvement in clinical disability in the relapsing-remitting group was observed.

Objectives
Multiple sclerosis (MS) patients frequently suffer from headaches and fatigue, and many reports have linked headaches with intracranial and/or extracranial venous obstruction. We therefore designed a study involving MS patients diagnosed with obstructive disease of internal jugular veins (IJVs), with the aim of evaluating the impact of percutaneous transluminal angioplasty (PTA) on headache and fatigue indicators.
Methods
286 MS patients (175 relapsing remitting (RR), 75 secondary progressive (SP), and 36 primary progressive (PP)), diagnosed with obstructive disease of IJVs, underwent PTA of IJVs during the period 2011±2015. This included 113 headache positive patients (82 RR, 22 SP, and 9 PP) and 277 fatigue positive patients (167 RR, 74 SP, and 36 PP). Migraine Disability Assessment (MIDAS), and the Fatigue Severity Scale (FSS) were evaluated: before PTA; 3-months after PTA; and at final follow-up in 2017. Patients were evaluated with Doppler sonography of the IJVs at 1, 6 and 12 months after PTA and yearly thereafter. Non-parametric statistical analysis was performed using a combination of the Friedman test and Spearman correlation analysis.
Results
With the exception of the PP patients there were significant reductions (all p < 0.001) in the MIDAS and FSS scores in the 3-month following PTA. The improvement in MIDAS score following PTA was maintained throughout the follow-up period in both the RR (p < 0.001; mean of 3.55 years) and SP (p = 0.002; mean of 3.52 years) MS cohorts. With FSS, significant improvement was only observed at 2017 follow-up in the RR patients (p < 0.001; mean of 3.37 years). In the headache-positive patients, post-PTA MIDAS score was significantly negatively correlated with the change in the blood flow score in the left (r = -0.238, p = 0.031) and right (r = -0.250, p = 0.023) IJVs in the RR patients and left IJV (r = -0.727, p = 0.026) in the PP patients. In the fatigue-positive cohort, post-PTA FSS score was also significantly negatively correlated with the change in blood flow in the right IJV in the PP patients (r = -0.423, p = 0.010). In addition, the pre and post-PTA FSS scores were significantly positively correlated in the fatigue-positive RR (r = 0.249, p = 0.001) and SP patients (r = 0.272, p = 0.019).
Conclusions
The intervention of PTA was associated with a large and sustained (>3 years) reduction in MIDAS score in both RR and SP MS patients. While a similar initial post-PTA reduction in FSS score was also observed, this was not maintained in the SP and PP patients, although
it remained significant at follow-up (>3 years) in the RR MS patients. This suggests that venoplasty might be a useful intervention for treating patients with persistent headaches and selected concomitant obstructive disease of the IJVs. 

Background: Multiple sclerosis (MS) is a disease of the nervous system that has profound effects on everyday functioning and quality of life of not only the person who is diagnosed, but also her/his family and acquaintances. Despite this, the uncertainties of the actual etiological basis of MS make it difficult to reach a conclusive statement about the optimal therapeutic management of the disease, which may differ depending on the given case and phase of illness. This has led to an interest in potential novel therapeutic avenues, including percutaneous transluminal angioplasty (PTA). Yet, evidence in support of PTA in the management of MS is scarce and
contradictory. The aim of the present study was to provide a preliminary assessment as to whether PTA may impact subjective quality of life and cognitive functioning in severe MS.
Method: Ninety-five MS outpatients were followed-up for 24 months on a scheduled basis using the Milan Overall Dementia Assessment and the short-form 36-item scales, and were clinically evaluated by an appointed neurologist and psychiatrist.
Results: At end point (month 24), only a minority of patients were still active in the study (n=33 or 34.74%). Among other measures, those who remained in the study until completion showed a significantly better Expanded Disability Status Scale and Milan Overall Dementia Assessment autonomy profile at study entrance compared to those patients who did not remain in the study until completion. Limitations were: a lack of any active control group; small sample size; Berkson’s bias; and selection by indication biases.
Conclusion: Given the burden of MS and its high attrition rate, additional studies, including bigger samples, active control groups, and Cox’s regression and survival analysis in case of randomization, should shed further light on the actual usefulness of PTA for the most severe cases of MS.

An open study was conducted with the aim of reporting long-term clinical outcome of endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS).
Twenty-nine patients with clinically definite relapsingremitting MS underwent percutaneous transluminal angioplasty for CCSVI, outside a clinical relapse. All the patients were regularly observed over at least two years before the first endovascular treatment and for at least two years after it (mean post-procedure follow up 30.6±6.1 months). The following clinical outcome measures were used: annual relapse rate and Expanded Disability Status Scale (EDSS) score. All the patients were observed intensively (mean 6 hours) on the day of the endovascular treatment to monitor for possible complications (bleeding, shock, heart attack, death).
We compared the annual relapse rate before and after treatment (in the two years before and the two years after the first endovascular treatment) and the EDSS score recorded two years before versus two years after the treatment.
Overall, 44 endovascular procedures were performed in the 29 patients, without complications. Thirteen of the 29 patients (45%) underwent more than one treatment session because of venous re-stenosis: 11 and two patients underwent two and three endovascular treatments respectively.
The annual relapse rate of MS was significantly lower post-procedure (0.45±0.62 vs 0.76±0.99; p=0.021), although it increased in four patients. The EDSS score two years after treatment was significantly lower compared to the EDSS score recorded at the examination two years before treatment (1.98±0.92 vs 2.27±0.93; p=0.037), although it was higher in four patients.
Endovascular treatment of concurrent CCSVI seems to be safe and repeatable and may reduce annual relapse rates and cumulative disability in patients with relapsing-remitting MS. Randomized controlled studies are needed to further assess the clinical effects of endovascular treatment of CCSVI in MS.

Purpose: To assess the safety of endovascular treatment of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS).
Materials and Methods: A total of 72 patients with CCSVI and MS (44 with relapsing remitting – RR, 4 with primary progressive, 20 with secondary progressive and 4 with benign MS) underwent percutaneous angioplasty. Outcome measures were colour Doppler ultrasonography parameters, gradient pressure at the vein abnormality level, postoperative complications, re-stenosis, disease severity scored by means of Expanded Disability Status Scale (EDSS) and patients’ assumption of disease status. Controls were done after one month on 72 patients, six months on 69 patients and one year on 61 patients, respectively (the average follow-up was 11 months).
Results: There were no postoperative complications. Colour Doppler ultrasonography showed significant improvement in cross-sectional area parameters (P<0.05) and significant decrease in confluence velocity values (P<0.05). Postoperative gradient pressure decreased, in internal jugular vein (IJV) significantly (P<0.05). Re-stenosis appeared in 5.3% of patients. EDSS score was significantly improved (P<0.01) and about half of patients reported significant or mild improvement in disease status and none of them worsening of symptoms.
Conclusion: Endovascular treatment of the IJV and azygous veins in patients with CCSVI and MS is a safe procedure with no post-procedural complications followed by significant improvement of IJV flow haemodynamic parameters and decrease in the EDSS score. Whether CCSVI percutaneous treatment might affect clinical improvement in patients suffering from MS is yet to be seen after completion of major multicentric clinical trials, still it seems like that this procedure is not negligible.

Introduction: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of the internal jugular veins (IJVs) and/or azygos veins with disturbed flow and formation of collateral venous channels. The presence of CCSVI has been associated with multiple sclerosis (MS). Percutaneous venous angioplasty (PVA) has been proposed to improve extracranial outflow; however, a non-invasive, post-procedural follow-up outcome measure has not been established.
Aim of the study: To evaluate the short-term hemodynamic follow-up of CCSVI after PVA using color Doppler ultrasound (CDU) and to investigate whether hemodynamic variation correlated with clinical variation.
Materials and methods: Forty-five patients affected by MS with confirmed CCSVI underwent IJVs PVA. Venous hemodynamic (VH) parameters indicative of CCSVI and the Venous Hemodynamic Insufficiency Severity Score (VHISS) were evaluated by CDU at baseline and 3 months post-PVA. Concurrently, the MS-related disability status (EDSS) was evaluated.
Results: The VH parameters and VHISS 3 months after IJVs PVA significantly decreased: the VH parameters 32.1% and the VHISS 33.8% (p<0.001). The EDSS score 3 months after IJVs PVA was significantly lower than the baseline (5.5%, p<0.001). Using the median value of the VHISS variation as the cut-off, we were able to identify two groups of patients: responders, group A; and non-responders, group B. The EDSS score variation at 3 months was 0.310 in group A and 0.275 in group B (p¼0.746).
Conclusions: CCSVI endovascular treatment can induce an improvement in VH parameters and the VHISS. The neurological disability score (EDSS) also improved after PVA; however, there was no correlation to the VHISS variation after PVA, MS type and duration.

Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome recently described in multiple sclerosis patients. It is characterized by abnormal venous hemodynamics resulting from numerous obstacles in the main veins draining the central nervous system, usually: the internal jugular veins and the azygous vein. Internal jugular vein is the most commonly vein affected. Most of the abnormalities in this vein are located at the level of jugular valve. The aim of this review is to give venographic and schematic descriptions of the most common valvular and perivalvular anomalies found in the lower part of internal jugular vein.

The aim of the study was to collect results from 366 chronic cerebrospinal venous insufficiency (CCSVI) affected patients that were regularly Duplex controlled after having received vein angioplasty following diagnosis for CCSVI. The procedures were all performed in the same Centre and same equipment. The patients were divided into three groups according to the attributed severity of the associated multiple sclerosis: 264 relapse-remitting (RR) (72%): 179 females (67.8%) and 85 (32.2%) males; 62 secondary progressive (17%): 37 (59.7%) females and 25 (40.3%) males; 40 primary progressive (11%): 22 (55%) females and 18 (45%) males. A data base revealed eleven most frequent disturbs and symptoms, together with working capacities, and was kept up-todate at every Duplex control aiming to establish a novel rapid CCSVI symptoms questionnaire assessment in 4 years follow up. The symptoms were: diplopia, fatigue, headache, upper limb numbness/mobility, lower limb numbness/mobility, thermic sensibility, bladder control, balance coordination, quality of sleep, vertigo, mind concentration.
Results, as follows, appear to be significantly good in the RR group, also the biggest one. Diplopia improved in 262/264 patients (99.2%) (P<0.0001); fatigue in 260/264 (98.5%) (P<0.0001); headache in 205/208 (98.6%) (P<0.0001); balance coordination in 23/26 (88.5%) (P<0.0001); quality of sleep in 55/59 (93.2%) (P<0.0001); vertigo in 30/33 (90.9%) (P<0.0001); mind concentration in 142/144 (98.6%) (P<0.0001). Other results regarded: upper limb numbness and mobility in 20/24 (83.3%) (P=0.0002); lower limb numbness and mobility 13/15 (86.7%) (P=0.0087); thermic sensibility 3/4 (75%) [P: not significant (n.s.)]; bladder control 2/3 (66.6%) (P: n.s.).
In contrast in the progressive cases results are quite different where, nevertheless, some useful considerations were collected and statistically significant, too.
In addition, venous angioplasty appears to be safe, side effects were observed only in seven patients (0.19%) that grew a monolateral Jugular thrombosis but still were regularly controlled and above all did not suffer worsening of the disease.
Finally, the overwhelming percutaneous transluminal angioplasty results in the RR group lead to say that the correct criteria should be the sooner the better.

Chronic cerebrospinal venous insufficiency (CCSVI) has been implicated as a contributing factor to multiple sclerosis (MS). This theory is strongly debated within the neurology and radiology communities. This report presents the case of a 45-year-old man with known MS and suspected CCSVI who had undergone previous internal jugular angioplasty and stenting. The patient reported dramatic improvement of symptoms after intervention. The stent thrombosed despite antithrombotic medication, and several endovascular interventions failed to restore long-term patency. Open venous reconstruction of the internal jugular vein was performed with a spiral graft from the saphenous vein. The patient’s symptoms improved for several weeks until the venous reconstruction occluded. This case is the first reported open venous reconstruction for suspected CCSVI.

Purpose: This study proposed to prospectively evaluate safety and clinical changes in outpatient endovascular treatment in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI).
Materials and Methods: Two hundred fifty-nine patients with MS were followed with the Multiple Sclerosis Impact Scale (MSIS-29) before and for 1and 6 months after treatment of extracranial internal jugular vein and azygos vein stenoses and occlusions using venous angioplasty, as well as stent placement in 2.5% of patients. Before treatment, the patients were tested with magnetic resonance (MR) venography and flow quantification.
Results: We found statistically significant improvements in the MSIS-29 scores (P  .01) at both 1 and 6 months. At 1 and 6 months, 67.9% and 53.6% were improved on the physical scale, respectively, and 53.0% and 44.4% were improved on the psychological scale, respectively. Women showed greater improvement than did men on the physical scale at 6 months (P  .01). Patients with primary progressive MS (PPMS) showed less improvement than did those with relapsing-remitting MS (RRMS) on the psychological scale at 1 month, and venoplasty treatment of more vein sites versus fewer vein sites showed greater improvement on the physical scale at both 1 and 6 months. Fifteen patients (6.3%) reported recurrent symptoms after clinical improvement and were treated again. There was one serious adverse event, a deep venous thrombosis at the catheter insertion site, which resolved with treatment.
Conclusions: Endovascular treatment of CCSVI in patients with MS appears to be a safe procedure resulting in significant clinical improvement.

Multiple sclerosis (MS) is a disorder characterized by damage to the myelin sheath insulation of nerve cells of the brain and spinal cord affecting nerve impulses which can lead to numerous physical and cognitive disabilities. The disease, which affects over 500,000 people in the United States alone, is widely believed to be an autoimmune condition potentially triggered by an antecedant event such as a viral infection, environmental factors, a genetic defect or a combination of each. Chronic cerebrospinal venous insufficiency (CCSVI) is a condition characterized by abnormal venous drainage from the central nervous system that has been theorized to have a possible role in the pathogenesis and symptomatology of MS (1). A significant amount of attention has been given to this theory as a possible explanation for the etiology of symptoms related to MS patients suffering from this disease. The work of Dr. Zamboni, et al, who reported that treating the venous stenoses causing CCSVI with angioplasty resulting in significant improvement in the symptoms and quality of life of patients with MS (2) has led to further interest in this theory and potential treatment. The article presented describes endovascular techniques employed to diagnose and treat patients with MS and CCSVI.

Multiple imaging modalities have been used for the evaluation of chronic cerebrospinal venous insufficiency (CCSVI). These include Doppler ultrasound, magnetic resonance venography, computed tomographic venography, and catheter venography. Although each of these tests is considered to contribute valuable information to the evaluation, each modality has deficiencies, which can impact treatment. Intravascular ultrasound (IVUS) has a role in this evaluation owing to its ability to accurately assess vessel circumference and cross-sectional area in real time. This can aid in identifying significant stenoses and optimizing balloon sizing during angioplasty. In addition, intraluminal abnormalities that may be difficult to see with venography can be identified with IVUS, which can further determine when angioplasty for CCSVI is indicated. Finally, IVUS can identify potential complications of angioplasty, including dissection and thrombus formation, allowing for rapid treatment. As a result, IVUS is an important part of an evaluation for CCSVI and, when available, should be used to identify patients who may benefit from endovascular treatment.

Background: The possible role of the venous system in the pathogenesis of chronic neurodegenerative diseases has been hypothesized for decades. Quite recently, the description of a venous condition defined as chronic cerebrospinal venous insufficiency (CCSVI) and its strong association with multiple sclerosis (MS) has brought back the attention of the scientific community to the hypothesis of an aetiological or concomitant role of an altered venous function in the occurrence of this pathology. CCSVI is identified by sonographic criteria, thus the indication for its possible treatment is based on ultrasound findings.
Method: We retrospectively examined 167 consecutive patients affected by clinically defined MS and CCSVI, identified by ultrasound assessment by the presence of at least two sonographic criteria. Ultrasonographic diagnosis of CCSVI was then integrated by venography and intravascular ultrasound examination (in 43 patients). Patients were all submitted to endovascular procedure (venoplasty).
Results: In 37% of cases there was no correspondence between the preoperative ultrasound assessment and the venographic findings. In the event of incongruity between venography and sonography, the intravascular ultrasound examination investigation, when performed, confirmed ultrasound findings in 42% of cases and venography results in 58%. At one month in 12% of cases ultrasound assessment showed the persistence of altered flux. In 67% of cases patients reported subjective amelioration, regarding non-specific symptoms.
Conclusion: The pathophysiology of CCSVI is yet to be defined. The superior cava venous system is highly complex in terms of anatomy and possible anomalies, as well as its haemodynamic mechanisms. Further studies are required to define the parameters of diagnosis and treatment of CCSVI.

Objective: Percutaneous transluminal angioplasty (PTA) of the internal jugular veins (IJVs) has been proposed in recent  years to treat chronic cerebrovascular venous insufficiency, with discordant results. Moreover, very little is known about the efficacy of PTA in restoring a normal cerebral venous outflow. The aim of this study was to investigate the anatomic factors and patient characteristics that might influence the efficacy of PTA of the IJV.
Methods: There were 797 consecutive patients with venous outflow anomalies who underwent standardized, operatorindependent catheter venography and PTA of the IJVs. Before and after PTA, morphologic and hemodynamic anomalies of the IJVs were documented. The primary end point of the study was to evaluate the morphologic factors influencing the efficacy of angioplasty in improving IJV outflow.
Results: PTA resulted in an increased outflow through the IJVs in most patients. However, younger individuals with transverse endoluminal defects and higher pre-PTA flows are more likely to respond well to PTA compared with those who exhibit hypoplasia, stenosis, or longitudinal endoluminal defects.
Conclusions: This study identified the factors that influence and could predict the efficacy of PTA in the treatment of IJV anomalies. (J Vasc Surg: Venous and Lym Dis 2017;5:777-88.)

Objective: Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by combined stenoses of the principal pathways of extracranial venous drainage, including the internal jugular veins (IJVs) and the azygous (AZY) vein, with development of collateral circles and insufficient drainage shown by increased mean transit time in cerebral magnetic resonance (MR) perfusion studies. CCSVI is strongly associated with multiple sclerosis (MS). This study evaluated the safety of CCSVI endovascular treatment and its influence on the clinical outcome of the associated MS.
Methods. Sixty-five consecutive patients with CCSVI, subdivided by MS clinical course into 35 with relapsing remitting (RR), 20 with secondary progressive (SP), and 10 with primary progressive (PP) MS, underwent percutaneous transluminal angioplasty (PTA). Mean follow-up was 18 months. Vascular outcome measures were postoperative complications, venous pressure, and patency rate. Neurologic outcome measures were cognitive and motor function assessment, rate of MS relapse, rate of MR active positive-enhanced gadolinium MS lesions (Gad), and quality of life (QOL) MS questionnaire.
Results: Outpatient endovascular treatment of CCSVI was feasible, with a minor and negligible complication rate. Postoperative venous pressure was significantly lower in the IJVs and AZY (P < .001). The risk of restenosis was higher in the IJVs compared with the AZY (patency rate: IJV, 53%; AZY, 96%; odds ratio, 16; 95% confidence interval, 3.5-72.5; P < .0001). CCSVI endovascular treatment significantly improved MS clinical outcome measures, especially in the RR group: the rate of relapse-free patients changed from 27% to 50% postoperatively (P < .001) and of MR Gad lesions from 50% to 12% (P < .0001). The Multiple Sclerosis Functional Composite at 1 year improved significantly in RR patients (P < .008) but not in PP or SP. Physical QOL improved significantly in RR (P < .01) and in PP patients (P < .03), with a positive trend in SP (P < .08). Mental QOL showed significant improvement in RR (P < .003) and in PP (P < .01), but not in SP.
Conclusions: PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment. Restenosis rates are elevated in the IJVs but very promising in the AZY, suggesting the need to improve endovascular techniques in the former. The results of this pilot study warrant a subsequent randomized control study. ( J Vasc Surg 2009;50:1348-58.)

Purpose: To evaluate if jugular vein flow restoration in various venographic defects indicative of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients can have positive effects on cerebral lesions identified using magnetic resonance imaging (MRI).
Materials and Methods: The Brave Dreams trial (ClinicalTrials.gov identifier NCT01371760) was a multicenter, randomized, parallel group, double-blind, sham-controlled trial to assess the efficacy of jugular venoplasty in MS patients with CCSVI. Between August 2012 and March 2016, 130 patients (mean age 39.9±10.6 years; 81 women) with relapsing/remitting (n=115) or secondary/progressive (n=15) MS were randomized 2:1 to venography plus angioplasty (n=86) or venography (sham; n=44). Patients and study personnel (except the interventionist) were masked to treatment assignment. MRI data acquired at 6 and 12 months after randomization were compared to the preoperative scan for new and/or >30% enlargement of T2 lesions plus new gadolinium enhancement of pre-existing lesions. The relative risks (RR) with 95% confidence interval (CI) were estimated and compared. In a secondary assessment, venograms of patients who underwent venous angioplasty were graded as “favorable” (n=38) or “unfavorable” (n=30) for dilation according to the Giaquinta grading system by 4 investigators blinded to outcomes. These subgroups were also compared.
Results: Of the 130 patients enrolled, 125 (96%) completed the 12-month MRI follow-up. Analysis showed that the likelihood of being free of new cerebral lesions at 1 year was significantly higher after venoplasty compared to the sham group (RR 1.42, 95% CI 1.00 to 2.01, p=0.032). Patients with favorable venograms had a significantly higher probability of being free of new cerebral lesions than patients with unfavorable venograms (RR 1.82, 95% CI 1.17 to 2.83, p=0.005) or patients in the sham arm (RR 1.66, 95% CI 1.16 to 2.37, p=0.005).
Conclusion: Expanded analysis of the Brave Dreams data that included secondary/progressive MS patients in addition to the relapsing/remitting patients analyzed previously showed that venoplasty decreases new cerebral lesions at 1 year. Secondary analysis confirmed the efficacy of the Giaquinta grading system in selecting patients appropriate for venoplasty who were more likely to be free from accumulation of new cerebral lesions at MRI.