Endovascular Treatment for Chronic Cerebrospinal Venous Insufficiency
in Multiple Sclerosis: A Longitudinal, Magnetic Resonance Imaging,
Blinded Pilot Study
P. Zamboni,a R. Galeotti,a B. Weinstock-Guttman,b G. Cutter,c
E. Menegatti,a A. M. Malagoni,a I. Bartolomei,d J. L. Cox,b F. Salvi,d and
R. Zivadinov,b Ferrara and Bologna, Italy; Buffalo, NY; and Birmingham,
From the University of Ferrara, Ferraraa; NY State University in Buffalo,
Buffalob; University of Alabama, Birminghamc; and Bellaria Neurosciences.d
Background: Chronic cerebrospinal venous insufficiency (CCSVI) is
characterized by stenoses of the internal jugular veins or the azygous vein, or
both. It has been recently reported that this condition contributes to severe
dis-regulation of the physiologic mechanisms of cerebral venous outflow in
patients with multiple sclerosis (MS). Endovascular treatment (EVT) was
demonstrated to be a safe and effective CCSVI treatment, but only in an
unblinded clinical evaluation.
Methods: We designed an open-label, magnetic resonance imaging
(MRI)-blinded, two-center, randomized, EVT intervention parallel-group,
12-month study (EVTMS) after an initial cross-sectional (CVIMS) study.
CIVMS enrolled 16 relapsing-remitting MS patients (8 from Ferrara, Italy
and 8 from Buffalo, NY). All 16 patients who completed the CVIMS study
and presented severe Doppler venous hemodynamic (VH) anomalies accepted
participation in the EVT intervention prospective study (EVTMS).
Half of the cohort, the early intervention group (4 from Buffalo and 4 from
Italy), was randomly selected to have the EVT procedure in Italy at 3
months, whereas 6 patients comprised the delayed control intervention
group (late group) at 6 months; 2 patients were followed-up without any
EVT. The EVT procedure consists of selective venography complemented
by balloon dilatation when significant stenoses are detected. All patients will
be prospectively evaluated at 3, 6, 9, and 12 months with ultrasound
imaging, MRI, and clinical examinations.
Results: For the CVIMS cross-sectional study, mean age at baseline
was 36.1 7.3 years, mean disease duration was 7.5 1.9 years, and median
Expanded Disability Status Scale (EDSS) was 2.5. The mean number of
gadolinium-active lesions at baseline was 0.38 1.5. The mean number of
T2 lesions was 27.1 10.5. Median of VH of CCSVI was 4 (range, 2-5).
The six MS patients investigated and none of the HCs met the VH criteria
for CCSVI (P .0001). MS patients showed significantly lower net cerebrospinal
fluid flow compared with the HC (P 0.038), which was
associated with the number of anomalous VH criteria present (r 0.79, P
.001; Fig, A) and confirmed by the strong relationship with the venous
hemodynamic insufficiency severity score (r 0.77, P .0007). 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;
Fig B). The 1-year blinded EVTMS longitudinal study will be concluded
next October and results analysis completed within the Fall.
Conclusions: CCSVI is associated with abnormal cerebrospinal fluid
flow dynamics and decreased brain volume. Finally, the EVTMS study
should provide valuable data on preliminary efficacy of EVT for CCSVI
associated with MS.