Massimiliano Farina

Blood flow variations in internal carotid and middle cerebral arteries induced by postmenopausal hormone replacement therapy

OBJECTIVE Our purpose was to clarify the mechanisms by which postmenopausal estrogen replacement therapy exerts its protective effect on cardiovascular risk. STUDY DESIGN By means of a bidirectional Doppler ultrasonographic system we measured pulsatility index variations the internal carotid artery and middle cerebral artery in 25 early postmenopausal women during a 6-month period of hormone replacement therapy. Transdermal estradiol (50 micrograms/day) was continuously administered. A 12-day course of medroxyprogesterone acetate (10 mg/day) was added every second month. RESULTS The pulsatility index showed a significant (p = 0.0001) reduction in both arteries after 6 weeks. At 22 weeks a 25% reduction was measured. No variation of the estrogen-induced pulsatility index reduction was observed at the end of every cyclic progestogen supplementation. CONCLUSIONS In early postmenopausal women hormone replacement therapy causes a rapid reduction of pulsatility index in brain arteries. Cyclical progestational supplementation does not modify this positive effect on reactivity of the blood vessels.

Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study

BackgroundChronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated.MethodWe analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian). All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al.ResultsOverall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS.ConclusionThe methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity.

Cerebral artery blood flow in relation to age and menopausal status

Objective To investigate vascular reactivity in womens cerebral arteries from reproductive age to postmenopause. Methods The pulsatility index (PI) was measured cross-sectionally in the internal carotid and middle cerebral arteries of 120 women, using a Doppler ultrasound system. Fifteen women were enrolled in each of eight 5-year intervals, spanning ages 20–59 years. Results In the population as a whole, there was a slight but statistically significant correlation between age and the PI in both arteries, but not after excluding postmenopausal subjects. A significant correlation was found between PI and months since menopause (but not chronologic age) in the postmenopausal women. There was also a statistically significant difference in the PI values for both arteries between pre- and postmenopausal women of similar age. Conclusion Menopause causes a significant increase in the PI of womens cerebral arteries. In postmenopausal women, there is a significant correlation between the PI of the internal carotid and middle cerebral arteries and menopausal but not chronologic age. This effect may be one of the mechanisms by which menopause is associated with the known higher risk for coronary heart disease observed in women.

The effect of tamoxifen and transdermal 17β-estradiol on cerebral arterial vessels: A randomized controlled study

OBJECTIVES Our objective was to study the effects of tamoxifen on cerebral arterial reactivity. STUDY DESIGN We studied the reactivity of both the internal carotid artery and the middle cerebral artery during a 12-month period of administration of either oral tamoxifen or transdermal estradiol or no treatment. A total of 45 healthy postmenopausal women who had undergone hysterectomy were followed up. Patients were randomly allocated to treatment with either oral tamoxifen 20 mg/day or transdermal estradiol 50 microg/day or nothing (15 patients in each group). They all underwent Doppler examinations of the internal carotid artery and middle cerebral artery at the beginning of the study and after 2, 6, and 12 months of treatment. The pulsatility index was measured. RESULTS In the women given transdermal estradiol the pulsatility index of both the internal carotid artery and the middle cerebral artery was significantly reduced compared with that in the controls. Tamoxifen did not induce variations of pulsatility index in either artery during all the study period. The difference between the effect of the two drugs on the pulsatility index of both arteries was highly significant. CONCLUSIONS Our findings demonstrate that tamoxifen does not cause any variation in the pulsatility index of cerebral arteries. The action of transdermal estradiol on the pulsatility index of cerebral arteries in postmenopausal women is the expression of a generalized action of estrogens on arterial vessels, and if this expression plays a role in the protective effect of hormone replacement therapy on risk of cardiovascular disease, tamoxifen treatment in healthy postmenopausal women should be considered with renewed caution.

Assessment of jugular endovascular malformations in chronic cerebrospinal venous insufficiency: colour-Doppler scanning and catheter venography compared with intravascular ultrasound.

Objectives Chronic cerebrospinal venous insufficiency (CCSVI) is a malformative condition characterized by several anomalies of the azygos and/or internal jugular veins (IJVs). Recommended diagnosis of CCSVI is performed with colour-Doppler (CD) sonography. Though catheter venography (CV) is considered as the gold standard for determining vascular anatomy, its uniplanar point of view does not allow an overall evaluation of endoluminal structures. This limit could be addressed by intravascular ultrasound (IVUS). The aim of this report is to evaluate, in patients with multiple sclerosis (MS), the accuracy of CD sonography and CV versus IVUS in estimating the diameter and the cross-sectional area (CSA) of the IJVs and in detecting jugular endoluminal malformations (JEM). Method Forty-five MS patients with CCSVI, diagnosed by CD sonography, were submitted to CV during IJVs angioplasty. Twenty-five subjects were also examined with IVUS. The IJVs maximum diameter (MAXD) and CSA were estimated. CD and CV data were compared with IVUS data with the Bland-Altman method. Results The mean difference in IJV MAXD recorded by CD and IVUS was —0.5 mm. The mean difference in IJV MAXD recorded by CV and IVUS was 3.36 mm. The mean difference in IJV CSA recorded by CD and IVUS was —11.2 mm2. JEM recorded by IVUS were detected by CD sonography and CV with 88% and 32% accuracy, respectively. Conclusions CV was significantly inferior to CD sonography and IVUS in detecting JEM. Differences between IVUS and CD sonography in detecting JEM and in quantifying jugular diameters were not significant. The IJV CSA was underestimated by CD sonography compared with IVUS. CD sonography was proven to be important in the anatomical characterization of CCSVI, providing useful information for correct intravascular treatment.

Gonadotropin-releasing hormone agonist-induced hypoestrogenism and blood flows in cerebral arteries *

OBJECTIVE To evaluate the effect of the hypoestrogenism induced by GnRH agonist (GNRH-a) therapy on cerebral vessel blood flow. DESIGN Open, controlled study. SETTING Tertiary care units of the University of Milan, Italy. PATIENTS Young women scheduled to undergo 6 months of therapy with a GnRH-a; a control group was also enrolled. INTERVENTIONS In both groups, the pulsatility index of both the internal carotid artery (ICA) and middle cerebral artery (MCA) was measured by means of Doppler ultrasound over a period of 6 months. MAIN OUTCOME MEASURE The ICA and MCA pulsatility index. RESULTS No variation in the pulsatility index of either artery was found in either group. CONCLUSIONS A 6-month period of GnRH-a-induced hypoestrogenism in young women does not lead to any variation in the blood flow of cerebral vessels. This provides some reassurance as to the safety of these drugs in relation to the role that the reactivity of peripheral arteries may play in determining risk of cardiovascular disease. Furthermore, our results show that blood flow in the cerebral vessels of young subjects is under extraestrogenic control and that this may counterbalance estrogen deprivation through mechanisms that probably are no longer active in the perimenopausal years.

Venous Hemodynamic Insufficiency Severity Score variation after endovascular treatment of chronic cerebrospinal venous insufficiency

Introduction Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of the internal jugular veins (IJVs) and/or azygos veins with disturbed flow and formation of collateral venous channels. The presence of CCSVI has been associated with multiple sclerosis (MS). Percutaneous venous angioplasty (PVA) has been proposed to improve extracranial outflow; however, a non-invasive, post-procedural follow-up outcome measure has not been established. Aim of the study To evaluate the short-term hemodynamic follow-up of CCSVI after PVA using color Doppler ultrasound (CDU) and to investigate whether hemodynamic variation correlated with clinical variation. Materials and methods Forty-five patients affected by MS with confirmed CCSVI underwent IJVs PVA. Venous hemodynamic (VH) parameters indicative of CCSVI and the Venous Hemodynamic Insufficiency Severity Score (VHISS) were evaluated by CDU at baseline and 3 months post-PVA. Concurrently, the MS-related disability status (EDSS) was evaluated. Results The VH parameters and VHISS 3 months after IJVs PVA significantly decreased: the VH parameters −32.1% and the VHISS −33.8% (p < 0.001). The EDSS score 3 months after IJVs PVA was significantly lower than the baseline (−5.5%, p < 0.001). Using the median value of the VHISS variation as the cut-off, we were able to identify two groups of patients: responders, group A; and non-responders, group B. The EDSS score variation at 3 months was 0.310 in group A and 0.275 in group B (p = 0.746). Conclusions CCSVI endovascular treatment can induce an improvement in VH parameters and the VHISS. The neurological disability score (EDSS) also improved after PVA; however, there was no correlation to the VHISS variation after PVA, MS type and duration.

New Criteria Reduce Inter-Observer Variability in Chronic Cerebrospinal Venous Insufficiency: A Case Control Study

1Director of Phlebolymphologic Diseases Centre, Monza Polyclinic, Via Amati 111, Monza 20900, Italy 2Biostatistics Unit, San Gaudenzio Clinic (Monza Polyclinic Group), Novara 28100, Italy 3Angiology Unit, Villa Cimarosa Medical Centre, Milan 20144, Italy *Corresponding author Massimiliano Farina, MD Director of Phlebolymphologic Diseases Centre Monza Polyclinic Via Amati 111 Monza (MB) 20900, Italy Tel. +393356055219 Fax: +390396188077 E-mail: massimiliano.farina@angiologiamonza.com

Blood Flows in Cerebral Arteries After Suspension of Postmenopausal Hormone Replacement Therapy. A Randomized Crossover Study

To investigate the effects of the suspension of hormone replacement therapy (HRT) on cerebral blood flow, we evaluated 23 postmenopausal women who were on continuous administration of transdermal estradiol and cyclical supplementation of medroxyprogesterone acetate (MPA) for 12 days every second month. The duration of the study was 12 months.