http://registration.akm.ch/einsicht.php ... KEN_ID=900
MRI results of blinded chronic cerebrospinal venous insufficiency study in patients with multiple sclerosis, healthy controls and patients with other neurologic diseases
R. Zivadinov, G. Cutter, K. Marr, M. Ramanathan, R.H.B. Benedict, M. Elfadil, N. Bergsland, C. Morgan, E. Carl, D. Hojnacki, E. Yeh, L. Willis, M. Cherneva, S. Hussein, J. Durfee, C. Kennedy, M. Dwyer, B. Weinstock-Guttman (Buffalo, Birmingham, US)
Background: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by stenoses of the main extracranial veins with hampered cerebral venous outflow.
Objective: To determine the relationship of CCSVI and conventional MRI outcomes in a large cohort of patients with multiple sclerosis (MS), clinically isolated syndrome (CIS), other neurological diseases (OND) and healthy controls (HC).
Methods: A pre-planned examination of the first 499 consecutively enrolled subjects in the Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD) blinded study included 289 MS, 163 HC, 26 OND and 21 CIS subjects. All subjects received extracranial and transcranial Doppler evaluation according to the proposed criteria (Zamboni et al., JNNP 2009). Of these, 20 (95.2%) CIS, 243 (84.1%) MS, 73 (45.6%) HC, and 15 (42.3%) OND received MRI examinations using a standardized protocol. In total, 351 (70.3%) of 499 subjects obtained MRI examination. T2, T1 and gadolinium (Gad) lesion number and volume (LV) were calculated. Normalized measures of global and central brain atrophy were also assessed. Differences in group means were assessed using the Kruskal-Wallis test and all correlations are reported using Kendall's tau.
Results: The two venous scales' venous haemodynamic insufficiency severity score (VHISS) and number of venous haemodynamic criteria fulfilled (VH) were both significantly correlated with CCSVI diagnosis (Kendall's tau = .694 for VHISS, tau = .804 for VH, p < .001 for both scales). Subjects diagnosed with CCSVI (i.e. those who met at least 2 of the CCSVI criteria) had a significantly higher mean number of T2 lesions (x= 31.10, sd = 21.3, n = 173) than subjects classified as not having CCSVI (x= 24.96, sd = 22.7, n = 178; p < .001). Subjects diagnosed with CCSVI also had a significantly higher mean T2-LV (x= 20.69, sd = 8.9, n = 173) than those without CCSVI (x= 17.46, sd = 8.8, n = 173; p < .001). There was no significant difference between subjects with and without CCSVI for number or LV of either T1 or Gad lesions. Subjects diagnosed with CCSVI had significantly higher lateral ventricle volume (p < .001) than subjects without CCSVI. Subjects with CCSVI showed significantly lower gray matter volume (p = .023),
brain parenchymal volume (p = .025) and cortical volume (p = .023) than subjects without CCSVI.
Conclusions: Presence of CCSVI is significantly related to more severe lesion and brain atrophy MRI measures.
http://registration.akm.ch/einsicht.php ... KEN_ID=900
Associations of HLA DR*1501 status and chronic cerebrospinal venous insufficiency in multiple sclerosis
B. Weinstock-Guttman, R. Zivadinov, G. Cutter, M. Tamano-Blanco, D. Badgett , K. Marr, E. Carl, M. Elfadil, C. Kennedy, M. Ramanathan (Buffalo, Birmingham, US)
Background: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of veins outside the skull (Zamboni et al, JNNP, 2009). The Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD) study was designed to independently confirm whether the presence of CCSVI was associated with multiple sclerosis (MS).
Objectives: To evaluate the associations of HLA *1501 status and CCSVI correlates within the CTEVD study.
Results: The CTEVD study enrolled 499 subjects: 163 healthy controls (HC), 289 MS patients, 21 clinically isolated syndrome patients (CIS), 26 controls with other neurological disorders (OND's). Genotyping was obtained for 472 of 499 subjects. All subjects underwent a clinical examination and a combined transcranial and extracranial Doppler scan of the head and neck. The HLA DR*1501 status was obtained by genotyping DNA from peripheral blood for rs3135005, a SNP strongly correlated with DR*1501 status.
The controls group consisted of HC and OND's. The MS group was dichotomized into the non-progressive (relapsing remitting, CIS and Devic's disease) and progressive forms (secondary progressive and primary progressive). The frequency of CCSVI was higher (OR = 3.57, p < 0.001) in the MS group 54.8% vs. 25.4% in the controls group and also higher in the progressive MS group 69.6% vs. 48.6% in the non-progressive MS group. The frequency of HLA DR*1501 positivity (HLA+) in the MS group 49.5% was higher compared (OR = 2.15, p < 0.001) to 31.3% in the control group. The frequencies of HLA+ in the non-progressive and progressive MS groups were similar, 48.3% and 52.3% respectively.
In the controls group, 53.1% were negative for both HLA DR*1501 and CCSVI (denoted HLA' CCSVI'), 22.3% were HLA+ CCSVI', 15.6% were HLA' CCSVI+ and 8.9% were HLA+ CCSVI+.
In the non-progressive MS group, 27.1% were HLA' CCSVI', 23.7% were HLA+ CCSVI', 24.6% were HLA' CCSVI+ and 24.6% were HLA+ CCSVI+. In the progressive MS group, 18.6% were HLA' CCSVI', 11.6% were HLA+ CCSVI', 29.1% were HLA' CCSVI+ and 40.7% were HLA+ CCSVI+.
Conclusions: These cross sectional data support an association between CCSVI and MS progression separate from HLA*DR1501. This association could imply that CCSVI is a risk factor for the progression of disease or that it is a consequence of the progression. Longitudinal studies need to be conducted to decipher the meaning and implications of this association
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Endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis. A longitudinal pilot study
P. Zamboni, R. Galeotti, B. Weinstock-Guttman, G. Cutter, E. Menegatti, A.M. Malagoni, D. Hojnacki, M. Dwyer, N. Bergsland, M. Hiennen-Brown, A. Salter, C. Kennedy, I. Bartolomei, F. Salvi, R. Zamboni (Ferrara, IT; Buffalo, Birmingham, US; Bologna, IT)
Background: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture characterized by multiple strictures at the level of the main extracranial cerebrospinal venous outflow routes that may interfere with normal venous drainage.
Objective: To evaluate safety and tolerability of minimally invasive endovascular treatment (EVT) for CCSVI associated to MS using MRI, clinical and haemodynamic outcome measures.
Methods: We designed an open-label, MRI-blinded, two-center, randomized, EVT intervention parallel-group, 12 month study (EVTMS). Of 16 relapsing-remitting patients who were screened for hemodynamic venous anomalies, 15 (8 from Italy and 7 from the Buffalo) accepted participation in the EVT intervention prospective study (EVTMS). Additional 8 age- and sex-matched healthy controls (HC), 4 from Italy and 4 from Buffalo were followed. All enrolled patients presented with CCSVI and were on disease-modifying therapy. Half of the cohort (immediate treatment group [IEVT], 4 from Buffalo and 4 from Italy) were randomly selected to obtain the EVT procedure (in Italy) immediately after the screening, and half (delayed treatment group [DEVT]) at 6 months. The EVT procedure consisted of selective venography complemented by balloon dilatation (PTA) when significant stenoses were detected. All patients were prospectively evaluated at 0, 3, 6, 9 and 12 months with sonography, MRI (0, 6 and 12 months only), and clinical examinations.
Results: No serious adverse events occurred during the study except one transitory vaso-vagal syndrome approximately an hour after intervention.. One subject in DEVT group was lost from the study at 6 month follow-up. Three HC were lost to follow-up. Restenosis occurred in 29% of the study cohort after intervention (2 in DEVT arm at 3-month, 1 in the DEVT at 6-month and 1 in the IEVT arm at 12-month follow-up). There were no significant differences between the 2 groups at 6 months follow-up after the intervention for MRI and clinical outcomes. There was a significant decrease (p=0.0227) in T2 lesion number from the 6 month baseline time period to the 6 months following the intervention in DEVT arm. No significant worsening in mean change for other MRI and clinical metrics was observed in both groups over the follow-up.
Conclusions: Treatment with PTA was safe and well tolerated. Rate of restenosis was low, 0% in the AZY and 29% in the IJV. Further and larger studies are needed to determine the effect of EVT for CCSVI in MS.
http://registration.akm.ch/einsicht.php ... KEN_ID=900
No evidence of chronic cerebrospinal venous insufficiency in clinically isolated syndrome suggestive of multiple sclerosis
C. Baracchini, P. Perini, M. Calabrese, F. Causin, F. Farina, F. Rinaldi, P. Gallo (Padua, IT)
Background: A complex scenario of abnormalities of the cerebrospinal venous outflow termed "chronic cerebrospinal venous insufficiency" (CCSVI), has been reported in patients with multiple sclerosis (MS). Sonographic criteria of CCSVI include reflux in the deep cerebral veins and/or the internal jugular (IJVs) and vertebral veins (VVs), stenosis of the IJVs, missing flow in IJVs and VVs, and inverse postural response of the cerebral venous drainage. CCSVI has been suggested to be the cause of MS, however no data on the prevalence of CCSVI at MS clinical onset has been published up to this date. In order to demonstrate a possible causative relationship between CCSVI and MS, we performed extra- and transcranial color-coded venous sonography (ECCvS, TCCvS) in clinically isolated syndromes (CIS) suggestive of MS.
Materials and Methods: Fifty consecutive patients with CIS suggestive of MS and evidence of dissemination in space of lesions (i.e., possible MS, pMS) were enrolled into the study. All patients underwent a detailed diagnostic workup, including CSF examination, brain and spinal MRI with gadolinium, ECCvS and TCCvS. Patients with abnormal ultrasound findings underwent selective venography (VGF). Healthy individuals (HC) and patients with transient global amnesia (TGA) constituted our control groups.
Results: Mean age of pMS was 33.0+/-8.5 years, 35 (70%) were female, EDSS was 1.6+/-0.5. The onset was monosymptomatic in 27 (54%). Forty-two (81%) had IgGOB in the CSF. TCCvS was normal in all pMS patients. ECCvS abnormal findings were found in 26/50 (52.0%) pMS, in 32% of HC and in 68% of TGA patients. Eight out of 50 pMS patients (16.0%) met the CCSVI criteria: 6 were classified as Type C, one as Type B, one as type A, while none as Type D. VGF was completed in all these patients, except for one who developed a paroxysmal supraventricular tachycardia and the exam was stopped. Venography was normal in 6, while 1 patient had a hypoplasia of the right IJV.
Conclusions: Our findings do not support the hypothesis that cerebral venous congestion plays a causative role in the pathogenesis of MS.
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Safety and complications related to endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis patients
M. Simka, T. Ludyga, M. Kazibudzki, M. Hartel, M. Swierad, J. Piegza, P. Latacz, L. Sedlak, M. Tochowicz (Katowice, Zabrze, PL)
Purpose: The aim of this report is to assess the safety of endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI). Although balloon angioplasty and stenting in other vascular territories are already accepted and seem to be safe procedures, there are currently no data on such treatments of a large group of patients with compromised venous outflow in the internal jugular (IJV) and/or the azygous vein (AV).
Methods: A total of 587 endovascular procedures: 414 balloon angioplasties and 173 stent implantations were performed during 361 interventions in 347 CCSVI patients with associated multiple sclerosis.
Results: There were only few, rather minor and occasional complications or technical problems related to the procedures. These included: (i) life threatening complications: death - 0, major hemorrhage - 0; cerebral stroke - 0; stent migration - 0; (ii) major complications: early stent thrombosis - 2 (1.2%) (all two occlusions occurred after the stenting for severely hypoplastic internal jugular vein; there were no likely clinical consequences due to these thrombotic events because the veins were not patent before the procedures, and the hemodynamics did not worsen despite the unsuccessful stenting); postoperative false aneurysm in the groin - 2 (0.6%) (successfully treated with thrombin injection); surgical procedure (opening of femoral vein) to remove angioplastic balloon - 1 (0.3%); injury to the nerves - 0; (iii) minor complications: transient cardiac arrhythmia - 2 (0.6%); minor bleeding from the groin - 2 (0.6%); minor gastrointestinal bleeding - 1 (0.3%); postprocedural lymphatic cyst in the groin - 1 (0.3%); problems with the removal of angioplastic balloon or delivery system - 5 (0.9%); unsuccessful catheterization of the stenosed internal jugular vein - 4 (0.7%).
Conclusion: Regardless of the actual impact of the endovascular treatments for venous pathology on the clinical course of multiple sclerosis, which warrants more clinical studies and long term follow-ups, these procedures appeared to be safe and well tolerated by the patients.
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Use of magnetic resonance venography for visualisation of the internal jugular veins in patients with multiple sclerosis diagnosed with chronic cerebrospinal venous insufficiency and treated with percutaneous angioplasty
A. Lopez-Soriano, R. Zivadinov, R. Galeotti, D. Hojnacki, E. Menegatti, C. Schirda, A.M. Malagoni, K. Marr, C. Kennedy, I. Bartolomei, C. Magnano, F. Salvi, B. Weinstock-Guttman, P. Zamboni (Buffalo, US; Bologna, IT)
Background: Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in patients with multiple sclerosis (MS). CCSVI is diagnosed non-invasively by Doppler sonography (DS) and invasively by selective venography (SV). The role of magnetic resonance venography (MRV) in defining presence of CCSVI is not completely elucidated.
Objective: To assess the role of MRV for visualization of the internal jugular veins in patients with MS diagnosed with CCSVI and in healthy controls (HC) who obtained serial MRV and DS exams over the period of 12 months.
Methods: Ten MS patients diagnosed with CCSVI (as evidenced by DS and SV), and treated with percutaneous angioplasty as part of the endovascular venous treatment MS study (EVTMS), underwent a 2D-Time-Of-Flight venography (TOF), a 3D-Time Resolved Imaging of Contrast Kinetics angiography (TRICKS), DS and SV at baseline. They were re-evaluated 6 months post-treatment with MRV and DS. Four additional MS patients obtained exams post-treatment at 6 and 12 months respectively, without obtaining baseline MRV. Six HC underwent a baseline and a 6-month follow-up evaluation by DS and MRV. The internal jugular veins (IJVs) were examined and compared between MRV, DS and SV.
Results: The following observations were found at baseline in MS patients: 1) the overlap between DS and SV findings was 90%, 2) there was no overlap between TOF or TRICKS and DS findings in the IJVs in 85% of the examinations, 3) there was no overlap between TOF and SV in 80% and between TRICKS and SV in 70% of examinations, 4) there was no overlap between both MRV techniques in 22% of the exams. At 6-month follow-up, 20% of the patients showed changes on TOF from normal to abnormal; whereas on TRICKS, 50% of the patients showed changes, 4 of them from normal to abnormal and one from abnormal to normal. On TOF, 50% of the patients showed changes in the IJVs between the 6-month and the 12-month follow-up exams, whereas, 25% of the patients showed changes on TRICKS, being all these changes from normal IJVs to abnormal. Most of these changes did not overlap with DS findings at follow-up examinations. In HC, 50% of the TOF and 41% of the TRICKS showed no overlap with DS findings in IJVs at baseline. At 6-month follow-up, 33% of the HC showed changes from normal to abnormal IJVs and vice versa on TOF and 16% on TRICKS.
Conclusion: MRV has limited value to assess CCSVI for both diagnostic and follow-up purposes.
http://registration.akm.ch/einsicht.php ... KEN_ID=900
Clinical correlates of chronic cerebrospinal venous insufficiency in multiple sclerosis
B. Weinstock-Guttman, G. Cutter, K. Marr, D. Hojnacki, M. Ramanathan, R.H.B. Benedict, C. Morgan, E.A. Yeh, E. Carl, C. Kennedy, J. Reuther, C. Brooks, M. Elfadil, M. Andrews, R. Zivadinov (Buffalo, Birmingham, US)
Objectives: To evaluate the clinical correlates of chronic cerebrospinal venous insufficiency (CCSVI) in a large cohort of patients with multiple sclerosis (MS).
Background: CCSVI is a complex vascular condition characterized by anomalies of the primary veins outside the skull (Zamboni et al, JNNP, 2009). We previously showed in a pre-planned Combined Transcranial (TCD) and Extracranial Venous Doppler Evaluation (CTEVD) blinded study that the prevalence of CCSVI was significantly higher in the MS cohort vs. healthy controls (HC) (56.1% vs. 22.7%, p< 0.001).
Results: This study enrolled 499 subjects; 163 HC, 289 MS patients, 21 CIS patients, 26 subjects with other neurological disorders underwent a clinical examination and a combined Doppler and TCD scan of the head and neck. Thirty patients that were defined as borderline (technical limitation for criteria 2 and not meeting definition of CCSVI) were considered negative for this analysis.
CCSVI prevalence was significantly higher in more advanced MS disease subtypes: 89.5% in relapsing secondary-progressive (SP), 67.2% in non-relapsing SP, 54.5% in primary-progressive (PP), 49.2% in relapsing-remitting (RR) and 38.1% in CIS (p = 0.033). The mean venous haemodynamic insufficiency severity score (VHISS) was higher for subjects diagnosed with CCSVI (mean VHISS ± SD: 4.05 ± 1.4, n = 218) than for subjects without CCSVI (1.20 ± 1.0, n = 281; p < .001). Criteria 2, 4 and 5 showed significant associations with an EDSS >=4.0 (Criteria 2: OR of 2.25, p=0.005; criteria 4: OR: 3.28, p=0.004 and Criteria 5 OR: 2.67, p=0.008). MS subjects with CCSVI had significantly higher Pyramidal (p = 0.020), Cerebellar (p = 0.049), and Brain Stem (p = 0.010) EDSS sub-scale score than subjects without CCSVI. Subjects with CCSVI were significantly older than subjects without CCSVI (p = 0.04). However, the mean Multiple Sclerosis Severity Score (MSSS) trended higher for subjects with CCSVI (4.22 ± 2.6, n = 160) than for subjects without CCSVI (3.63 ± 2.4, n =127), but this difference was not significant (p = .073).
Conclusions: The presence of CCSVI in MS patients was associated with more advanced MS disease subtypes and more severe motor, cerebellar and brainstem involvement.
http://registration.akm.ch/einsicht.php ... KEN_ID=900
Correlation of localisation and severity of extracranial venous lesions with clinical status of multiple sclerosis
M. Simka, T. Ludyga, M. Kazibudzki, A. Adamczyk-Ludyga, J. Wrobel, P. Latacz, J. Piegza, M. Swierad (Katowice, PL)
Purpose: The discovery of chronic cerebrospinal venous insufficiency (CCSVI), which comprises stenoses in the extracranial veins that drain the central nervous system, has shed new light on the potential source of multiple sclerosis (MS). The aim of this report is to assess the correlations between patterns of CCSVI and clinical characteristics of MS.
Methods: Localization and degree of venous outflow blockages in the internal jugular veins (IJV) and the azygous vein (AV) in MS patients was assessed using standard venography. Analysis of clinical parameters of MS included: patients' age, duration of the disease, severity of disability using Multiple Sclerosis Impact Scale-29 (MSIS-29), evaluation of chronic fatigue using Fatigue Severity Scale (FSS), assessment of heat intolerance, and evaluation of the thickness of the ganglion cell complex (GCC) in optical coherence tomography (OCT).
Results: A total of 331 MS patients with previously diagnosed CCSVI, using color Doppler sonography and magnetic resonance venography, were evaluated. OCT was performed in 451 eyes. Severity of venous obstacles neither correlated with patients' age, nor did it with duration of the disease. It was also found that neither chronic fatigue, nor heat intolerance correlated with the localization or intensity of venous outflow blockages. On the contrary, more disabled MS patients, as revealed using MSIS-29 questionnaire, were found to suffer from bilateral and/or severe occlusions of the IJVs. Moreover, the patients with stenosed AV presented with the most aggressive clinical course of MS. Pathologic values of GCC were found in 61% of eyes, and this pathology was found more often in the cases with unilateral lesions in the IJV, interestingly: not necessarily at the diseased side. On the contrary, bilateral stenoses in the IJVs correlated with a less frequent pathology of the optic nerves. Stenoses in the AV had no impact on the frequency of pathologic GCC values.
Conclusion: It has been revealed that at least some elements of clinical characteristics of MS correlated with parameters of CCSVI. These findings indicate that most likely both pathologies are interconnected and CCSVI may play a role in the pathogenesis and progression of MS. Importantly, venous lesions in differently aged patients were comparable, and severity of venous lesions did not correlate with duration of MS. This finding favors the idea of congenital nature of those vascular malformations
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Chronic cerebrospinal venous insufficiency is an unlikely cause of multiple sclerosis
B. Yamout, A. Herlopian, Z. Issa, R.H. Habib, A. Fawaz, J. Salameh, H. Wadih, H. Awdeh, N. Muallem, R. Raad, A. Al-Kutoubi (Beirut, LB)
Introduction: A state of chronic cerebrospinal venous insufficiency (CCSVI) secondary to extracranial venous stenosis (EVS) was suggested as a possible cause of multiple sclerosis (MS).
Methods: In this study we performed selective extracranial venous angiography (SV) on 42 patents with early MS (EMS): clinically isolated syndrome (CIS) or relapsing remitting MS (RRMS) of less than 5 years duration, and late MS (LMS): RRMS of more than 10 years duration. We also reviewed available MRI and clinical relapse data in patients with documented EVS.
Results: EVS was present in 7/29 (24%) patients with EMS and 12/13(92%) patients with LMS, a highly significant statistical difference (p<0.0001). Only 3/42 (7%) patients (all in the LMS group) had 2 vessel stenosis, while the rest had only 1 vessel involved. The incidence of EVS in CIS was 9% compared to 33% in RRMS of less than 5 years duration. The most important factor in determining presence of EVS was disease duration: mean=9.4±6.8 years in 19 patients with EVS compared to 3.2±4.1 years in patients without (p<0.005), which stayed significant after controlling for age at disease onset and gender (p<0.002). Within the EMS group, patients with (n=7) and without (n=22) EVS had similar EDSS (1.43±2.13 and 0.8±0.008, p=0.85) and disease duration (mean =2.1 and 2.4 years, p=0.521), suggesting similar disease severity. The 7 EMS patients with stenosis had a total of 14 relapses since disease onset. No clear correlation could be found between site of EVS and relapse anatomical localization. A total of 97 spine and brain MRIs available since disease onset on all 19 patients with stenosis were reviewed. Again no clear correlation could be seen between the location of gadolinium enhancing (Gd+) lesions and site of EVS.
Conclusion: CCSVI is an unlikely cause of MS since it is not present in most cases early in the disease, and in only a minority of MS patients affects more than 1 extracranial vein. It is likely to be a late secondary phenomenon, possibly related to chronic central nervous system (CNS) disease and atrophy.
http://registration.akm.ch/einsicht.php ... KEN_ID=900
Multiple sclerosis patients with chronic cerebrospinal venous insufficiency present with increased iron concentration on susceptibility-weighted imaging in deep-grey matter
R. Zivadinov, M. Heininen-Brown, C. Schirda, C. Magnano, D. Hojnacki, C. Kennedy, E. Carl, N. Bergsland, S. Hussein, M. Cherneva, L. Willis, M. Dwyer, B. Weinstock-Guttman (Buffalo, US)
Background: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular phenomenon recently described in multiple sclerosis (MS) that is characterized by stenoses affecting the main extracranial venous outflow pathways that may lead to increased iron concentration (IC) in the brain parenchyma.
Objective: To investigate the relationship between presence of CCSVI and IC, measured on susceptibility-weighted imaging (SWI), in deep-gray matter (DGM) regions of MS patients and age- and sex-matched healthy controls (HC).
Methods: Ninety three (93) consecutive MS patients [66 relapsing-remitting (RR) and 27 secondary-progressive (SP], and 51 age- and sex-matched HC were imaged on a 3T GE scanner using SWI. Mean age in MS patients was 46.9 yrs, mean disease duration 14.6 yrs and median EDSS 2.5. The presence of CCSVI was determined by using extracranial and transcranial Doppler evaluation (Zamboni et al., JNNP 2009), with >=2 fulfilled criteria indicating diagnosis of CCSVI. High-iron tissue mean IC (HITMIC) was determined for the total DGM, caudate, putamen, globus pallidus, thalamus, pulvinar nucleus of the thalamus (PVNT), hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra regions by in-house developed software.
Results: CCSVI criteria were fulfilled in 62 (66.7%) of MS patients and 14 (27.5%) of HC (p< 0.001). The two venous scales - venous haemodynamic insufficiency severity score (VHISS) and number of venous haemodynamic criteria fulfilled (VH) - were both significantly correlated with CCSVI diagnosis (Spearman r = .89 for VHISS and r = .83 for VH, p < 0.001 for both scales). MS patients who presented with CCSVI showed significantly increased HITMIC in total DGM, thalamus and PVNT compared to patients without presence of CCSVI (p<0.05). No differences were found in HC with and without presence of CCSVI. Higher VH and VHISS were related to increased HITMIC in total DGM, PVNT, thalamus and caudate (p<0.05) in MS patients. The relationship between presence and severity of CCSVI and increased HITMIC in various DGM measures was stronger for SP than for RRMS patients.
Conclusion: This is the first large cohort study suggesting an important association between presence and severity of CCSVI and increased IC in DGM regions of MS patients.
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No evidence for cerebro-cervical venous congestion in patients with multiple sclerosis
F. Doepp, F. Paul, J.M. Valdueza, K. Schmierer, S.J. Schreiber (Berlin, Bad Segeberg, DE; London, UK)
Background: Multiple sclerosis (MS) is characterized by demyelination centered around cerebral veins. Recent studies suggested this topographic pattern may be caused by cerebral venous congestion, a condition termed 'chronic cerebro-spinal venous insufficiency' ('CCSVI'). In a recently published study we were unable to reproduce the reported findings of reflux in the deep cerebral veins and/or the internal jugular and vertebral veins (IJVs and VVs), stenosis of the IJVs, missing flow in IJVs and VVs, and inverse postural response of the cerebral venous drainage (Ann Neurol, in press).
Methods: We performed extra- and transcranial Doppler ultrasound studies including analysis of extracranial venous blood volume flow (BVF), cross-sectional areas, IJV flow analysis during valsalva manoever (VM) and 'CCSVI' criteria in 59 patients with MS (target: 80 patients) and 20 reference subjects.
Results: Except for one patient, blood flow direction in the IJVs and VVs was normal in all subjects. In none of the subjects was IJV stenosis detected. IJV and VV BVF in both groups were equal in the supine body position. The decrease of total jugular BVF upon turning into the upright position was less pronounced in patients (173 ± 235 vs 362 ± 150 ml/min; p<0.001), leading to higher BVF in the latter position (318 ml/min ± 242 vs 123 ± 109 ml/min; p<0.001). No difference between patients and controls was detected in intracranial veins and during VM. None of the subjects investigated in this study fulfilled more than one criterion for 'CCSVI'.
Conclusion: This data confirms in a larger cohort our recently published study challenging the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS. Future studies should elucidate the difference between patients and healthy subjects in BVF regulation.[/b]