Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis

Background:

The chronic cerebrospinal venous insufficiency theory proposes that altered cerebral venous hemodynamics play a role in the pathophysiology of multiple sclerosis. We aimed to explore the validity of this hypothesis by assessing the diagnostic criteria for chronic cerebrospinal venous insufficiency in persons with and without multiple sclerosis.

Methods:

We compared the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls using extracranial Doppler ultrasonography and gadolinium-enhanced magnetic resonance venography. Interpreting radiologists were blinded to the clinical status of participants.

Results:

We enrolled 120 patients with multiple sclerosis and 60 healthy controls. High proportions of both patients (67/115 58%]) and controls (38/60 63%]) met 1 or more of the proposed ultrasound criteria for diagnosis of chronic cerebrospinal venous insufficiency (p = 0.6). A minority of patients (23/115 20%]) and controls (6/60 10%]) fulfilled 2 or more of the proposed criteria (p = 0.1). There were no differences between patients and controls in the prevalence of each individual ultrasound criterion. Similarly, there were no differences in intracranial or extracranial venous patency between groups, as measured by magnetic resonance venography.

Interpretation:

We detected no differences in the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls. Moreover, our study revealed significant methodologic concerns regarding the proposed diagnostic criteria for chronic cerebrospinal venous insufficiency that challenge their validity.Multiple sclerosis is an inflammatory disease of the central nervous system, believed to arise from a dysfunctional immune-mediated response in a genetically susceptible host.¹ In 2009, “chronic cerebrospinal venous insufficiency” was proposed to play an etiologic role in multiple sclerosis.^2–4 Despite an abundance of published literature on this topic,^2–28 a causal link has not been established. Recent meta-analyses have suggested a strong association between an ultrasound-based diagnosis of chronic cerebrospinal venous insufficiency and multiple sclerosis,^26,28 yet there has been significant heterogeneity across studies.^26,27 A factor contributing to this heterogeneity appears to be the involvement of investigators who support endovascular procedures as a treatment for multiple sclerosis.²⁷ Furthermore, these meta-analyses have been predicated on the assumption that valid diagnostic criteria for chronic cerebrospinal venous insufficiency exist.We aimed to explore the validity of the chronic cerebrospinal venous insufficiency theory by using extracranial ultrasonography and gadolinium-enhanced magnetic resonance venography to compare the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy individuals. Our primary hypothesis was that if chronic cerebrospinal venous insufficiency is associated with multiple sclerosis, we would detect significant evidence of venous outflow obstruction in patients relative to controls.