To the best of our knowledge, this is the first investigation of neuropsychological status in MS patients in relation to CCSVI. In this sample of 109 MS patients, we find no evidence of an association between CCSVI and cognitive impairment. Moreover, no relationship between cognitive performance and the severity of CCSVI criteria, as determined by DS, was detected in linear regression analysis. When patients were categorized by their CCSVI status (positive/negative), significant group differences emerged for only one test, in a direction contrary to the hypothesis that CCSVI is a risk factor for cognitive impairment in MS. Similarly, there was no relationship between CCSVI and depression in this cohort.
The CCSVI hypothesis has provoked great controversy and debate in the MS research community since it was first presented [11, 13]. The hypothesis gained popularity among MS patients because of the postulated possibility of venous insufficiency correction using endovascular procedures. While the diagnosis of CCSVI can be established using noninvasive and invasive imaging techniques , the validity of DS to establish the diagnosis of CCSVI remains controversial. We showed previously that DS, in properly trained hands, has high sensitivity and specificity for CCSVI diagnosis, when compared to invasive imaging methods [48, 49]. This was the same method as used in this study, and thus we are confident in the validity of the CCSVI categorization in our analysis.
The true prevalence of CCSVI in MS patients is unknown, and there is good evidence that the condition is also found in patients with other neurologic diseases . In this study, 64% of the participating MS subjects presented with CCSVI, which is similar to our previous study . The difference between the prevalence rates of CCSVI-positive versus -negative MS patients in this study is modest, and of uncertain meaning with respect to MS pathology. Indeed, emerging studies point against CCSVI having a primary causative role in the development of MS [11, 13]. A multimodal approach will likely be needed to determine the extent to which CCSVI is present in various healthy and disease groups and MS subtypes .
Cognitive impairment is common in MS and can be reliably quantified using neuropsychological tests emphasizing episodic memory, mental processing speed and some aspects of executive function . Neuropsychological deficits are also robustly correlated with brain MRI measures, especially global and regional brain atrophy . The heterogeneity of neuropsychological presentation among MS patients is influenced by many factors, including genetics, gender, intelligence, disease course, comorbid neuropsychiatric illness and health behaviors. The present study employed consensus standard tests emphasizing multiple domains of cognitive function, allowing us to test, in a comprehensive way, whether the presence and severity of CCSVI can influence this important sphere of disability in MS patients. No association between cognitive impairment and the presence and severity of CCSVI was found. This is consistent with our previous findings of a lack of association between the presence of CCSVI and severity of lesion burden and brain atrophy outcomes in MS patients .
There are a number of potential limitations in this study. Selection of participants was based on the inclusion or exclusion criteria in patients agreeing to undergo cognitive testing. However, it may be that the most severe patients presenting in our Center were not included in the study. Another potential limit is not including a control group. However, the aim of this study was not to assess CCSVI prevalence, but rather an association with cognitive impairment. Finally, the diagnosis of CCSVI was not confirmed by the use of other invasive diagnostic methods.