Concept: Chronic cerebrospinal venous insufficiency
Recent evidence has indicated an association between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis. Small internal jugular veins (IJVs) (with a cross-sectional area of less than 0.4 cm2) have been previously described as difficult to catheterize, and their presence may potentially affect cerebrospinal venous drainage. In this blinded extracranial color-Doppler study we had two principal aims: first, to assess prevalence of CCSVI among Serbian MS patients compared to healthy controls; and second, to assess prevalence of small IJVs (with a CSA <= 0.4 cm2) among MS patients and controls.
Multiple sclerosis (MS) is a chronic neurodegenerative disease of the CNS. Recently a controversial vascular hypothesis for MS, termed chronic cerebrospinal venous insufficiency (CCSVI), has been advanced. The objective of this study was to evaluate the relative prevalence of the venous abnormalities that define CCSVI.
Abstract Background: Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) has been proposed to be associated with Multiple Sclerosis (MS). Zamboni et al reported significant improvement in neurological outcomes in MS patients who underwent Percutaneous Transluminal Angioplasty (PTA). Objectives: To retrospectively evaluate the neurological outcomes in MS patients who underwent PTA. Method: Relapsing remitting MS patients who underwent PTA and completed at least one year post PTA were assessed. Patients with clinically isolated syndrome or progressive forms of MS were excluded. Primary endpoint was the proportion of relapse-free patients at one year. Secondary endpoints were change in mean EDSS score and proportion of patients with new MRI activity (defined as either Gadolinium-enhancing or new T2 lesions) at one year. Results: 45 patients satisfied the inclusion criteria. Females constituted 71.1%. The mean age and mean disease duration were 33.76 and 7.16 years respectively. At one-year post-PTA, the proportion of relapse-free patients decreased from 84.44% to 66.67% (p = 0.085) whereas the mean EDSS score increased (p = 0.017). The proportion of patients with new MRI activity increased significantly from 17.78% to 44.44% (p = 0.012). 35.6% of patients stopped their DMTs. There was no difference among the patients who stopped their DMTs with respect to relapses, EDSS score or new MRI activity. Conclusion: The study revealed that PTA in relapsing remitting MS patients was not associated with any neurological improvement. However, there was an increase in disease activity irrespective of the adherence to DMTs. Further evidence of the association between CCSVI and MS is required.
Occurrence of CCSVI in patients with MS and its relationship with iron metabolism and varicose veins.
- European journal of neurology : the official journal of the European Federation of Neurological Societies
- Published over 7 years ago
BACKGROUND: A new treatable venous disorder, chronic cerebrospinal venous insufficiency (CCSVI), has been proposed in patients with multiple sclerosis (MS). Its relationship with iron metabolism is suggested, but has not been examined prospectively. METHODS: We performed extra- and transcranial echo colour Doppler (ECD) in 90 patients with MS and 41 healthy controls (HC). Indices of iron metabolism and the presence of peripheral signs of impaired venous flow were also examined. RESULTS: The ECD examination showed CCSVI in 8 (9%) of the 90 patients with MS and 0 HC (P = 0.11). The 8 CCSVI-positive MS patients were older (P = 0.02), had less often RR-MS (P = 0.02) and had more neurological disability assessed by expanded disability status scale (EDSS, P = 0.001) and longer duration of disease (P = 0.02) in comparison with the 82 CCSVI-negative MS patients. Multivariate analysis revealed that EDSS remained an independent factor associated with CCSVI (odds ratio 1.89, 95%CI 1.17-3.05, P-value = 0.009). CCSVI MS patients more often had bilateral telangiectasia at the legs (P = 0.008), reticular veins (P = 0.006) and venous stasis dermatitis (P = 0.004). No relationship was found between CCSVI and impaired iron metabolism in patients with MS. CONCLUSIONS: CCSVI is uncommon and is a secondary epiphenomenon in MS and related to more neurological disability and the presence of varicose veins at the legs.
BACKGROUND: In 2009, Dr. Paolo Zamboni proposed chronic cerebrospinal venous insufficiency (CCSVI) as a possible cause of multiple sclerosis (MS). Although his theory and the associated treatment (“liberation therapy”) received little more than passing interest in the international scientific and medical communities, his ideas became the source of tremendous public and political tension in Canada. The story moved rapidly from mainstream media to social networking sites. CCSVI and liberation therapy swiftly garnered support among patients and triggered remarkable and relentless advocacy efforts. Policy makers have responded in a variety of ways to the public’s call for action. DISCUSSION: We present three different perspectives on this evolving story, that of a health journalist who played a key role in the media coverage of this issue, that of a health law and policy scholar who has closely observed the unfolding public policy developments across the country, and that of a medical ethicist who sits on an expert panel convened by the MS Society of Canada and the Canadian Institutes of Health Research to assess the evidence as it emerges. SUMMARY: This story raises important questions about resource allocation and priority setting in scientific research and science policy. The growing power of social media represents a new level of citizen engagement and advocacy, and emphasizes the importance of open debate about the basis on which such policy choices are made. It also highlights the different ways evidence may be understood, valued and utilized by various stakeholders and further emphasizes calls to improve science communication so as to support balanced and informed decision-making.
There is no established noninvasive or invasive diagnostic imaging modality at present that can serve as a ‘gold standard’ or “benchmark” for the detection of the venous anomalies, indicative of chronic cerebrospinal venous insufficiency (CCSVI). We investigated teh sensitivity and specificity of 2 invasive vs. 2 noninvasive imaging techniques for the detection of extracranial venous anomalies in the internal jugular veins (IJVs) and azygos vein/vertebral veins (VVs) in patients with multiple sclerosis (MS).
- Phlebology / Venous Forum of the Royal Society of Medicine
- Published over 6 years ago
This study is the first in a series investigating the relationship between autonomic nervous system dysfunction and chronic cerebrospinal venous insufficiency in multiple sclerosis patients. We screened patients for the combined presence of the narrowing of the internal jugular veins and symptoms of autonomic nervous system dysfunction (fatigue, cognitive dysfunction, sleeping disorders, headache, thermal intolerance, bowel/bladder dysfunction) and determined systolic and diastolic blood pressure responses to balloon angioplasty.
BACKGROUND: This study aimed to investigate the prevalence and clinical relevance of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients and healthy controls using extra- and intracranial colour Doppler sonography. METHODS: We examined 146 MS patients, presenting with a clinically isolated syndrome, relapsing-remitting, secondary progressive, or primary progressive MS, and 38 healthy controls. Sonographic examination was performed according to Zamboni’s protocol and was performed by three independent sonographers. The results of sonographic examination were compared with clinical and demographic characteristics of the patients. RESULTS: CCSVI, defined as the presence of at least two positive Zamboni’s criteria, was found in 76% of MS patients and 16% of control subjects. B-mode anomalies of internal jugular veins, such as stenosis, malformed valves, annuli, and septa were the most common lesions detected in MS patients (80.8%) and controls (47.4%). We observed a positive correlation between sonographic diagnosis of CCSVI and the patients' age (p=0.003). However, such a correlation was not found in controls (p=0.635). Notably, no significant correlations were found between sonographic signs of CCSVI and clinical characteristics of MS, except for absent flow in the jugular veins, which was found more often in primary (p<0.005) and secondary (p<0.05) progressive patients compared with non-progressive patients. Absent flow in jugular veins was significantly correlated with patients' age (p<0.0001). CONCLUSIONS: Sonographically defined CCSVI is common in MS patients. However, CCSVI appears to be primarily associated with the patient's age, and poorly correlated with the clinical course of the disease.
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a disabling progressive course. Chronic cerebrospinal venous insufficiency (CCSVI) has recently been described as a vascular condition characterized by restricted venous outflow from the brain, mainly due to blockages of the internal jugular and azygos veins. Despite a wide variability among studies, it has been found to be associated with MS. Data from a few small case series suggest possible improvement of the clinical course and quality of life by performing percutaneous balloon angioplasty (PTA) of the stenotic veins.Study design and methodsThis is a multicenter, randomized, parallel group, blinded, sham-controlled trial to assess the efficacy and safety of PTA. Participants with relapsing remitting MS or secondary progressive MS and a sonographic diagnosis of CCSVI will be enrolled after providing their informed consent. Each participant will be centrally randomized to receive catheter venography and PTA or catheter venography and sham PTA. Two primary end points with respect to efficacy at 12 months are (1) a combined end point obtained through the integration of five functional indicators, walking, balance, manual dexterity, bladder control, and visual acuity, objectively measured by instruments; and (2) number of new brain lesions measured by T2-weighted MRI sequences. Secondary end points include annual relapse rate, change in Expanded Disability Status Scale score, proportion of patients with zero, one or two, or more than two relapses; fatigue; anxiety and depression; general cognitive state; memory/attention/calculus; impact of bladder incontinence; and adverse events. Six hundred seventy-nine patients will be recruited. The follow-up is scheduled at 12 months. Patients, treating neurologists, trained outcome assessors, and the statistician in charge of data analysis will be masked to the assigned treatment. DISCUSSION: The study will provide an answer regarding the efficacy of PTA on patients' functional disability in balance, motor, sensory, visual and bladder function, cognitive status, and emotional status, which are meaningful clinical outcomes, beyond investigating the effects on inflammation. In fact, an important part of patients' expectations, sustained and amplified by anecdotal data, has to do precisely with these functional aspects.Trial registrationClinicaltrials.gov NCT01371760.
The vascular hypothesis of multiple sclerosis (MS), called chronic cerebrospinal venous insufficiency (CCSVI), and its treatment (known as liberation therapy) was immediately rejected by experts but enthusiastically gripped by patients who shared their experiences with other patients worldwide by use of social media, such as patient online forums. Contradictions between scientific information and lay experiences may be a source of distress for MS patients, but we do not know how patients perceive and deal with these contradictions.