ABSTRACT
BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been introduced as a chronic state of impaired cerebral or cervical venous drainage that may be causally implicated in multiple sclerosis (MS) pathogenesis. Moreover, percutaneous transluminal angioplasty of extracranial veins termed "Liberation treatment" has been proposed (based on nonrandomized data) as an alternative therapy for MS. METHODS: A comprehensive literature search was conducted to identify available published, peer-reviewed, clinical studies evaluating (1) the association of CCSVI with MS, (2) the reproducibility of proposed ultrasound criteria for CCSVI detection (3) the safety and efficacy of "Liberation treatment" in open-label and randomized-controlled trial (RCT) settings. RESULTS: There is substantial heterogeneity between ultrasound case-control studies investigating the association of CCSVI and MS. The majority of independent investigators failed to reproduce the initially reported high prevalence rates of CCSVI in MS. The prevalence of extracranial venous stenoses evaluated by other neuroimaging modalities (contrast or MR venography) is similarly low in MS patients and healthy individuals. One small RCT failed to document any benefit in MS patients with CCSVI receiving "Liberation treatment", while an exacerbation of disease activity was observed. "Liberation treatment" has been complicated by serious adverse events (SAEs) in open-label studies (e.g., stroke, internal jugular vein thrombosis, stent migration, hydrocephalus). CONCLUSION: CCSVI appears to be a poorly reproducible and clinically irrelevant sonographic construct. "Liberation treatment" has no proven efficacy, may exacerbate underlying disease activity and has been complicated with SAEs. "Liberation treatment" should stop being offered to MS patients even in the settings of RCTs.
Subject(s)
Angioplasty , Multiple Sclerosis/complications , Venous Insufficiency/complications , Venous Insufficiency/therapy , Chronic Disease , Humans , Multiple Sclerosis/cerebrospinal fluid , Randomized Controlled Trials as Topic , Reproducibility of Results , Treatment Outcome , Ultrasonography , Venous Insufficiency/cerebrospinal fluid , Venous Insufficiency/diagnostic imagingSubject(s)
Ferritins/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/etiology , Venous Insufficiency/cerebrospinal fluid , Venous Insufficiency/complications , Autoantibodies/immunology , Blood Pressure , Blood-Brain Barrier/pathology , Blood-Brain Barrier/physiology , Cerebrovascular Circulation/physiology , Chronic Disease , Humans , Multiple Sclerosis/immunology , Retinal Vein/anatomy & histology , Retinal Vein/physiologySubject(s)
Ferritins/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/etiology , Venous Insufficiency/cerebrospinal fluid , Venous Insufficiency/complications , Autoantibodies/immunology , Blood Pressure , Blood-Brain Barrier/pathology , Blood-Brain Barrier/physiology , Cerebrovascular Circulation/physiology , Chronic Disease , Humans , Multiple Sclerosis/immunologySubject(s)
Ferritins/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/etiology , Venous Insufficiency/cerebrospinal fluid , Venous Insufficiency/complications , Adult , Aged , Autoantibodies/immunology , Blood Pressure , Blood-Brain Barrier/pathology , Blood-Brain Barrier/physiology , Cerebrovascular Circulation/physiology , Chronic Disease , Humans , Middle Aged , Multiple Sclerosis/immunologyABSTRACT
Cerebrospinal fluid (CSF) flow dynamics, which supposedly have a strong relationship with chronic cerebrospinal venous insufficiency (CCSVI), might be expected to be affected in multiple sclerosis (MS) patients. In this study, CSF flow at the level of the cerebral aqueduct was evaluated quantitatively by phase contrast magnetic resonance imaging (PC-MRI) to determine whether CSF flow dynamics are affected in MS patients. We studied 40 MS patients and 40 healthy controls using PC-MRI. We found significantly higher caudocranial (p=0.010) and craniocaudal CSF flow volumes (p=0.015) and stroke volume (p=0.010) in the MS patients compared with the controls. These findings may support the venous occlusion theory, but may also be explained by atrophy-dependent ventricular dilatation independent of the venous theory in MS patients.
Subject(s)
Cerebrospinal Fluid/physiology , Magnetic Resonance Imaging/methods , Multiple Sclerosis, Chronic Progressive/physiopathology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Venous Insufficiency/physiopathology , Adult , Cerebral Veins/physiopathology , Cerebrovascular Disorders/cerebrospinal fluid , Cerebrovascular Disorders/physiopathology , Chronic Disease , Contrast Media , Female , Humans , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/cerebrospinal fluid , Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid , Stroke Volume/physiology , Venous Insufficiency/cerebrospinal fluidABSTRACT
AIM: We previously reported unexpectedly robust associations between vascular haemodynamic (VH) anomalies in the principal extracranial cerebral veins, causing chronic cerebrospinal venous insufficiency (CCSVI), and multiple sclerosis (MS). Aim of this study was to investigate the relationship between the VH changes and MRI measures of MS disease severity in a cross sectional survey. METHODS: The number of anomalous VH criteria were measured using an echo-color Doppler, whereas CSF flow, atrophy and lesion measures were obtained from quantitative magnetic resonance imaging (MRI) analysis in sixteen consecutive relapsing-remitting MS patients, (mean age: 36.1+/-SD 7.3 years, disease duration: 7.5+/-1.9 years and median EDSS: 2.5) and in 8 healthy controls (HC) with similar age and sex distributions. RESULTS: All 16 MS patients investigated and none of the HCs met the VH criteria for CCSVI (P<0.0001). MS patients showed significantly lower net CSF flow compared to the HC (P=0.038) that was associated with number of anomalous VH criteria present (r=0.79, P<0.001). Moreover, increases in the number of anomalous VH criteria present were negatively associated with lower whole brain volume (Spearman R=-0.5, P=0.05). CONCLUSION: VH changes occur more frequently in MS patients than controls. Altered VH is associated with abnormal CSF flow dynamics and decreased brain volume.
Subject(s)
Azygos Vein , Brain/pathology , Jugular Veins , Magnetic Resonance Imaging , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Spinal Cord/blood supply , Ultrasonography, Doppler, Color , Venous Insufficiency/diagnosis , Adult , Atrophy , Azygos Vein/abnormalities , Azygos Vein/diagnostic imaging , Azygos Vein/physiopathology , Cerebral Veins/abnormalities , Cerebral Veins/diagnostic imaging , Cerebral Veins/physiopathology , Cerebrovascular Circulation , Constriction, Pathologic , Cross-Sectional Studies , Humans , Jugular Veins/abnormalities , Jugular Veins/diagnostic imaging , Jugular Veins/physiopathology , Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Organ Size , Pilot Projects , Regional Blood Flow , Venous Insufficiency/cerebrospinal fluid , Venous Insufficiency/physiopathologyABSTRACT
Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture that shows a strong association with multiple sclerosis (MS). The aim of this study was to investigate the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics in 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs). The two groups (patients and controls) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001). This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS.
Subject(s)
Cerebrospinal Fluid/physiology , Cerebrovascular Circulation/physiology , Cerebrovascular Disorders/complications , Hemodynamics , Multiple Sclerosis, Relapsing-Remitting/complications , Venous Insufficiency/complications , Adult , Brain/blood supply , Case-Control Studies , Cerebrospinal Fluid Pressure , Cerebrovascular Disorders/cerebrospinal fluid , Chronic Disease , Female , Humans , Magnetic Resonance Imaging , Male , Matched-Pair Analysis , Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid , Pilot Projects , Reference Values , Regional Blood Flow , Severity of Illness Index , Single-Blind Method , Spinal Cord/blood supply , Ultrasonography, Doppler, Color , Ultrasonography, Doppler, Transcranial , Venous Insufficiency/cerebrospinal fluidABSTRACT
In order to study the effect of jugular venous outflow obstruction on intracranial pressure and cerebrospinal fluid (CSF) reabsorption capability, changes in epidural pressure (EDP) and CSF outflow resistance (Ro) were examined following bilateral jugular vein ligation in cats. EDP increased significantly (P less than 0.01) immediately after ligation from the control value of 4.9 +/- 0.5 mmHg (mean +/- SEM) to 15.9 +/- 0.9 mmHg. Thereafter, EDP gradually decreased back toward the control value. The pressure level had decreased to 6.7 +/- 0.5 mmHg by 20 minutes after ligation. The mean Ro was significantly (P less than 0.01) higher in the ligation group (200.4 +/- 9.7 mmHg/ml/min) that in the non-ligation group (120.0 +/- 9.9 mmHg/ml/min). These results suggest that bilateral jugular vein ligation impairs CSF reabsorption.
