Claudio Baracchini

No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset.

An impaired cerebrospinal venous drainage, defined as chronic cerebrospinal venous insufficiency (CCSVI), has been recently hypothesized to be the possible cause of multiple sclerosis (MS). We investigated this hypothesis by studying the occurrence of CCSVI in clinically isolated syndromes (CISs) suggestive of MS.

Progressive multiple sclerosis is not associated with chronic cerebrospinal venous insufficiency.

Objective: Chronic cerebrospinal venous insufficiency (CCSVI) had been suggested to play a major pathogenetic role in multiple sclerosis (MS), but recent data on early stages of MS have not confirmed this theory. Nonetheless, CCSVI could represent a late phenomenon of MS or be associated with progression of disability. Thus, we studied CCSVI prevalence in primary progressive (PP) and secondary progressive (SP) MS, to clarify whether CCSVI characterizes the progressive forms of this disease. Methods: A total of 35 patients with SPMS, 25 patients with PPMS, and 60 age- and gender-matched normal controls (NC) were enrolled into a cross-sectional study. Extracranial and transcranial high-resolution venous echo color Doppler sonography (ECDS-TCDS) was performed in all patients and NC. Those patients having any abnormal ultrasound finding were asked to undergo selective venography (VGF). Results: Patients with PPMS (11 women, 14 men; mean age 47 ± 11 years) had a disease duration of 11 ± 7 years and Expanded Disability Status Scale (EDSS) score of 6.0 ± 0.5. Patients with SPMS (22 women, 13 men; mean age 45 ± 14.5 years) had a disease duration of 18 ± 14 years and EDSS score of 6.0 ± 0.8. TCDS was normal in all patients. ECDS showed one or more abnormal findings in 9/60 (15.0%) patients (7/35 [20.0%] SPMS, 2/25 [8.0%] PPMS) and in 14/60 (23.3%) NC (p not significant for all comparisons). CCSVI criteria were fulfilled in 0 NC and 4 (6.7%) patients with MS: 3 SPMS and 1 PPMS. VGF, performed in 6/9 patients, was abnormal only in one case who had bilateral internal jugular vein stenosis. Conclusion: Our findings indicate that CCSVI is not a late secondary phenomenon of MS and is not associated with disability.

The Quest for Early Predictors of Stroke Evolution Can TCD Be a Guiding Light

Background and Purpose The present study aimed at evaluating the prognostic value of transcranial Doppler ultrasonography (TCD) in the acute phase of ischemic stroke, when major therapeutic decisions must be made. Methods Seventy-three patients with a first-ever ischemic hemispheric stroke underwent neurological assessment according to the Unified Neurological Stroke Scale, clinical subgrouping according to the criteria of Bamford, CT scan, cervical duplex sonography, and TCD, all within 12 hours from stroke onset. TCD was repeated on days 2 and 7. Patients were followed for 90 days, during which we calculated the fatality rate and then assessed clinical outcome. Results Emergency TCD revealed middle cerebral artery (MCA) no-flow in 24 cases and MCA asymmetry in 30 subjects. Serial TCD showed early (<24 hours) MCA recanalization in 6 patients. After 90 days, no patient with MCA occlusion at admission was autonomous, while 17 of 19 patients (89.5%) with a normal baseline TCD were independent. The fatality rate at 3 months was 21% but was 46% in patients with MCA occlusion and 61% in patients without signs of early MCA recanalization. Total anterior circulation infarct and abnormal TCD were significantly correlated (P <0.001) with higher mortality rate and worse outcome (Barthel Index score ≤60), whereas early CT ischemic signs and severe carotid disease were not. Furthermore, TCD identified within the total anterior circulation infarct subgroup 2 prognostic clusters according to MCA patency at admission (P <0.001). Logistic regression selected normal baseline TCD as an independent predictor of good long-term outcome and MCA no-flow as an independent predictor of disability or death. Conclusions TCD findings play an important role in the early prognosis of anterior circulation stroke, providing possible guidance for therapeutic interventions.

A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion.

OBJECTIVE To compare the clinical outcome and restenosis incidence of patients who underwent carotid endarterectomy with patch closure (CEAP) on one side and carotid eversion endarterectomy (CEE) on the other. SUMMARY BACKGROUND DATA Although a few investigators have compared the results of CEAP versus CEE, no reports have compared the outcome of CEAP versus CEE in the same patient. METHODS Eighty-six patients were randomly selected for sequential surgical treatment involving either CEAP/CEE or CEE/CEAP. All patients underwent postoperative duplex ultrasound study and clinical follow-up at 1, 6, and 12 months and every year thereafter. Various factors were analyzed to ascertain any association with restenosis, and Kaplan-Meier analysis was used to estimate the risk of restenosis. RESULTS Demographic and clinical data were similar in the CEAP and CEE groups. The selective shunting rate was statistically higher in the CEAP group. There were no perioperative deaths. Although the incidence of perioperative ipsilateral stroke was not significant, CEAP patients had a rate of combined transient ischemic attacks and strokes that approached statistical significance. The mean follow-up was 40 months. CEAP patients had a significantly higher incidence of restenosis and combined occlusive events and restenoses. Kaplan-Meier analysis showed that CEE had a significantly better cumulative patency rate than CEAP and that freedom from restenoses at 24 and 36 months was 87% and 83% for CEAP and 98% and 98% for CEE, respectively. CONCLUSIONS CEE is less likely to cause perioperative neurologic complications and restenoses than CEAP. The significantly higher rate of unilateral recurrence suggests that local factors play a more important role than systemic factors in the occurrence of restenosis.

Neurosonographic monitoring of 105 spontaneous cervical artery dissections A prospective study

Objective: To monitor the sonographic course of spontaneous cervical artery dissections (sCADs) and investigate their recanalization and recurrence rates. Methods: All consecutive patients with an MRI-proven sCAD were prospectively evaluated by neurovascular ultrasound (nUS) daily while in hospital, then monthly for the first 6 months after discharge and every 6 months thereafter, for a mean follow-up period of 58 months (range, 28–96 months). Results: A total of 105 sCADs were detected in 76 patients: 61 (58.1%) involved the internal carotid artery and 44 (41.9%) the vertebral artery, while multiple sCADs were found in 4 patients (5.3%). Follow-up was obtained in 74 patients (97.3%, 103 vessels). The complete and hemodynamically significant (<50% stenosis) recanalization rates were 51.4% (53/103) and 20.4% (21/103). All but one complete recanalization occurred within the first 9 months. There were early recurrences (while in hospital) in 20 previously unaffected arteries (26.3%) and late recurrences in 2 arteries (2.7%), site of a previous sCAD. All patients (n = 6) with a family history of arterial dissection had a sCAD recurrence (4 early and 2 late) as opposed to 16 (22.8%) among those with no known familial disease (p < 0.001). Conclusions: These results suggest that most lumen changes occur within the first few months after the initial event, but recanalization may occur even after 1 year. Early recurrence is not uncommon and usually involves arteries previously unaffected by dissection, while the risk of late recurrence is low. A family history of arterial dissection is strongly associated with sCAD recurrence.

Carotid Endarterectomy within 2 weeks of minor ischemic stroke: A prospective study

OBJECTIVE Data from multicenter symptomatic trials have shown that benefit from carotid endarterectomy (CEA) was greatest in patients with carotid disease operated within 2 weeks of their last ischemic event. We prospectively analyzed the safety and benefit of CEA performed within 2 weeks of a stroke. METHODS The study involved patients with acute minor stroke admitted to two stroke units who underwent CEA within 2 weeks of their last ischemic event, once they were considered neurologically stable. Preoperative workup included scoring ischemia-related symptoms according to a modified ranking scale (mRS), carotid duplex scan, transcranial Doppler ultrasound, and head computed tomography or magnetic resonance imaging. All patients underwent neurological assessment on admission, 1 day before and 2 days after CEA, and at discharge. A complete neurological and ultrasound follow-up was performed at 1, 6, and 12 months after CEA, then yearly. All procedures were eversion CEA under deep general anesthesia, with selective shunting. Endpoints were perioperative (30-day) stroke/mortality rate or cerebral bleeding and long-term stroke recurrence or cerebral hemorrhage. RESULTS Between 2000 and 2005, 102 patients with a mRS </= 2 underwent CEA within a median 8 days of acute ischemic stroke. Shunting and contralateral carotid occlusion were found significantly correlated. There were no perioperative strokes or deaths, or cerebral hemorrhage. All patients were followed up for a mean 34 months (range 1-66) with no recurrent stroke or cerebral bleeding. CONCLUSIONS CEA can be performed within 2 weeks of carotid-related ischemic stroke with no perioperative stroke or cerebral bleeding, preventing the risk of stroke recurrence.

CCSVI and MS: a statement from the European Society of neurosonology and cerebral hemodynamics.

To systematically review the ultrasonographic criteria proposed for the diagnosis of chronic cerebrospinal venous insufficiency (CCSVI). The authors analyzed the five ultrasonographic criteria, four extracranial and one intracranial, suggested for the diagnosis of CCSVI in multiple sclerosis (MS), together with the references from which these criteria were derived and the main studies that explored the physiology of cerebrospinal drainage. The proposed CCSVI criteria are questionable due to both methodological and technical errors: criteria 1 and 3 are based on a scientifically incorrect application of data obtained in a different setting; criteria 2 and 4 have never been validated before; criterion 2 is technically incorrect; criteria 3 and 5 are susceptible to so many external factors that it is difficult to state whether the data collected are pathological or a variation from the normal. It is also unclear how it was decided that two or more of these five ultrasound criteria may be used to diagnose CCSVI, since no validation of these criteria was performed by different and independent observers nor were they blindly compared with a validated gold-standard investigation. The European Society of Neurosonology and Cerebral Hemodynamics (ESNCH) has considerable concerns regarding the accuracy of the proposed criteria for CCSVI in MS. Therefore, any potentially harmful interventional treatment such as transluminal angioplasty and/or stenting should be strongly discouraged.

Heritability of central blood pressure and arterial stiffness: a twin study.

Objective: Central blood pressure and aortic stiffness have been consistently reported as strong cardiovascular risk factors. Twin studies by comparing identical with nonidentical twins produce information on the relative contribution of genes and environment. Methods: One hundred and fifty-four monozygotic (MZ) and 42 dizygotic (DZ) twin pairs (age 43 ± 17 years) from Hungary and the United States underwent brachial and central augmentation index (AIx), brachial and central pressure, and aortic pulse wave velocity (PWV) measurements with the invasively validated Arteriograph device. Bivariate Cholesky decomposition models were applied. Results: Age-adjusted, sex-adjusted and country-adjusted heritability was 60.0% for central SBP [95% confidence interval (CI), 44.8–69.6%], 50.1% for aortic PWV (95%CI, 26.0–66.8%), 48.7% for aortic AIx (95%CI, 1.7–74.0%), 46.8% for brachial AIx (95%CI, 1.1–73.8%), 46.7% for central pulse pressure (PP) (95%CI, 12.4–61.4%), and 30.0% for brachial PP (95%CI, 0.0–53.4%). Central SBP and PP had strong bivariate correlations with brachial (r = 0.461 and 0.425) and central AIx (r = 0.457 and 0.419), as well as with aortic PWV (r = 0.341 and 0.292, all P < 0.001). Brachial PP had a weak correlation with brachial AIx (r = −0.118, P < 0.05), central AIx (r = −0.122, P < 0.05), and none with aortic PWV (r = 0.08, P = n.s.). Genetic factors explained a moderate phenotypic correlation between central PP, SBP, brachial SBP and aortic PWV. Conclusions: Central systolic and PPs, brachial PP, AIx, aortic PWV are moderately heritable. A moderate genetic covariance among aortic PWV and central PP, central SBP and brachial SBP was found.

Age‐adjusted reference limits for carotid intima‐media thickness as better indicator of vascular risk: population‐based estimates from the VITA project

Summary.  Background: An increase of carotid intima‐media thickness (CIMT) has been demonstrated to be associated in many studies with the subsequent risk of cardio‐ and cerebrovascular events, but the threshold level of CIMT for an increased risk at different ages remains uncertain. Objectives: We aimed at establishing optimal reference limits associated with a definite increased vascular risk in the general population. Methods: A cohort of 2580 subjects was enrolled in a population‐based cross‐sectional survey. CIMT was measured on both left and right common carotid arteries, and age‐specific, percentile‐based reference ranges for CIMT were computed together with the Framingham risk score. Results: A significant, steady increase of CIMT reference ranges was observed within different age strata. CIMT levels were linearly related with an increase of the Framingham risk score, but after age‐adjustment only the upper CIMT quintile was associated with a higher Framingham risk score. Conclusions: Age‐specific reference limits provide better estimate of vascular risk in the population and correlation with established risk factors.

Jugular veins in transient global amnesia: innocent bystanders.

Background and Purpose— Transient global amnesia (TGA) has been associated with an increased prevalence of internal jugular valve insufficiency and many patients report Valsalva-associated maneuvers before TGA onset. These findings have led to the assumption of hemodynamic alterations in intracranial veins inducing focal hippocampal ischemia. We investigated this hypothesis in patients with TGA and control subjects. Methods— Seventy-five patients with TGA and 75 age- and sex-matched healthy subjects were enrolled into a cross-sectional study. Extracranial and transcranial high-resolution venous echo-color-Doppler sonography was performed blindly in all patients and control subjects. Blood flow direction and velocities were recorded at the internal jugular veins, basal veins of Rosenthal, and vein of Galen, both at rest and during Valsalva-associated maneuvers. Results— Mean age of patients with TGA was 60.3±8.0 years (median, 60 years; range, 44–78 years); 44 (59%) were female (female/male ratio: 1.42). Internal jugular valve insufficiency (left, right, or bilateral) was found to be more frequent in patients with TGA than in control subjects: 53 (70.7%) versus 22 (29.3%; P<0.05). Blood flow velocities in the deep cerebral veins of patients with TGA did not differ from control subjects both at rest and during Valsalva-associated maneuvers. Intracranial venous reflux was neither observed in patients with TGA nor in control subjects despite unilateral or bilateral internal jugular valve insufficiency during prolonged and maximal Valsalva-associated maneuvers. Conclusions— This study, although confirming the association between TGA and internal jugular valve insufficiency, challenges the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of TGA.