Thursday, September 10, 2009, 15:30 - 17:00
Endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis. A longitudinal pilot studyP. Zamboni, R. Galeotti, B. Weinstock-Guttman, G. Cutter, E. Menegatti, A. Malagoni, D. Hojnacki, J. Cox, C. Kennedy, I. Bartolomei, F. Salvi, R. Zivadinov (Ferrara, IT; Buffalo, Birmingham, US; Bologna, IT)
Objective: To evaluate safety of minimally invasive endovascular treatment (EVT) for chronic cerebrospinal venous insufficiency (CCSVI) associated to multiple sclerosis (MS) using MRI, clinical and haemodynamic outcome measures.
Background: CCSVI is a vascular picture characterized by multiple strictures at the level of the main extracranial cerebrospinal venous outflow routes including the internal jugular and the azygous venous systems. It is strongly associated to MS (JNNP 2009 Apr;80(4):392-9).
Design/Methods: We designed an open-label, MRI-blinded, two-center, randomized, EVT intervention parallel-group, 12 month study (EVTMS) following an initial cross-sectional (CVIMS) study. Sixteen relapsing-remitting (RR) MS patients, 8 from Bologna, Italy and 8 from Buffalo, NY were enrolled in CVIMS. All 16 patients who completed the CVIMS study and presented severe hemodynamic venous anomalies accepted participation in the EVT intervention prospective study (EVTMS). Half of the cohort (early intervention group, 4 from Buffalo and 4 from Italy) were randomly selected to have the EVT procedure (in Italy) at 3 months and half (delayed control intervention group, late group) at 6 months. The EVT procedure consists of selective venography complemented by balloon dilatation when significant stenosies are detected. All patients will be prospectively evaluated at 3, 6, 9 and 12 months with sonography, MRI, and clinical examinations, or in case of MS relapse only with sonography and clinical examinations.
Outcome measures: Safety, and preliminary efficacy will be monitored using MRI (T2 and Gd lesions measures), Doppler haemodynamic parameters of CCSVI and clinical measures (relapse rate, EDSS, MS functional composite). In addition, a variety of vascular and other MRI measures (including susceptibility-weighted imaging and CSF flow) assessments will be performed and compared to the 1-year outcome in all cohort as well as in between the 2 groups (early and delayed EVT intervention).
Preliminary Results: Mean age at baseline was 36.1±7.3 yrs, mean disease duration 7.5 ±1.9 yrs and median EDSS 2.5. Mean number of gadolinium (Gd) active lesions at baseline was 0.38±1.5 and mean number of T2 lesions 27.1±10.5. Median of Doppler parameters of CCSVI was 4 (2-5). Mean follow up at the time of abstract presentation will be 11 months.
Conclusion/Relevance: This study should provide valuable data on safety, tolerability and preliminary efficacy of EVT for CCSVI associated to MS.
Friday, September 11, 2009, 15:30 - 17:30
Chronic cerebrospinal venous insufficiency is related to inverted and decreased cerebrospinal fluid flow and greater brain atrophy in patients with multiple sclerosis
P. Zamboni, E. Menegatti, B. Weinstock-Guttman, J. Cox, C. Schirda, A. Malagoni, D. Hojnacki, C. Kennedy, E. Carl, M. Dwyer, N. Bergsland, R. Galeotti, S. Hussein, I. Bartolomei, F. Salvi, R. Zivadinov (Ferrara, IT; Buffalo, US; Bologna, IT)
Objective: To investigate the cerebral Doppler venous outflow haemodynamics (VH) in multiple sclerosis (MS) patients vs healthy controls (HC) and to correlate VH parameters with MRI measures of disease severity.
Background: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture characterized by stenosies affecting the main extracranial venous outflow pathways. This picture is strongly and constantly associated to MS
and determines significant alterations of five specific VH criteria (JNNP doi:10.1136/jnnp.2008.157164). CCSVI diagnosis needs to fulfill at least 2 out of 5 VH criteria. VH in CCSVI is characterized by blocked outflow and a high rate of cerebral venous reflux, but the relationship with MRI disease outcome has never been investigated.
Methods: Sixteen (16) consecutive relapsing-remitting MS patients (mean age 36.1±7.3 yrs, mean disease duration 7.5 ±1.9 yrs and median EDSS 2.5) and 8 age- and sex-matched HC were scanned on a GE 3T scanner. CSF flow and velocity measures, as well as lesion volume (LV), atrophy and perfusion MRI outcomes were assessed. VH was obtained in MS and HC by means of the detection of the 5 above mentioned criteria.
Results: All MS patients and none of the HC presented severe CCSVI. Particularly, HC presented 1/40 pathologic VH criteria, whereas MS patients 61/80 (median 0 vs 4, p< 0.0001). MS patients showed a higher antegrade and retrograde peak velocities and higher antegrade and retrograde CSF flow than HC. The net CSF flow was inverted and significantly lower in MS patients than in HC (p=0.038). Both in correlation and regression analyses the number of VH criteria was highly related to decreased mean net CSF flow (r=0.8, p<0.0001, R2=0.6, p<0.0001, respectively). In addition the number of pathologic VH criteria was related significantly to greater whole brain atrophy(r= -0.5, p=0.05), and there was a trend for increased gray matter atrophy (r=0.46, p=0.079). Finally, the relationship with LV and perfusion measures did not reach statistical significance.
Conclusion: Inverted direction and decreased CSF flow in MS suggest the activation of patho-physiological mechanisms in CCSVI in response to impaired venous drainage of brain tissue. In addition, the relationship between brain atrophy and VH measures on one side, and the strong correlation between VH and net CSF flow on the other, clearly suggest a pivotal role of CCSVI in MS pathogenesis.