FISIOPATOLOGIA ED EMODINAMICA DELL’INSUFFICIENZA VENOSA CRONICA CEREBROSPINALE

According to the physic principles regulating the cerebrospinal venous drainage, a list of haemdoynamic parameters has been created and aimed to the sonographic evaluation of such venous district. All these values demonstrated to be physiology-related, easily reproducible and detectable by means of a new trans and extra-cranial echo-color Doppler protocol (ECD-TCCS) of evaluation. This assessment has been tested on 60 healthy volunteers. Experimental Part I: The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have not previously been investigated. Sixty-five patients affected by CDMS, and 235 controls composed, respectively, of healthy subjects, healthy subjects older than CDMS patients, patients affected by other neurological diseases and older controls not affected by neurological diseases but scheduled for venography (HAV-C) blindly underwent to ECD-TCCS aimed to detecting at least two of five parameters of anomalous venous outflow. According to the ECD-TCCS screening, patients and HAV-C further underwent selective venography of the azygous and jugular venous system with venous pressure measurement. CDMS and ECD-TCCS venous outflow anomalies were dramatically associated (OR 43, 95% CI 29 to 65, p<0.0001). Subsequently, venography demonstrated in CDMS, and not in controls, the presence of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments; this provides a picture of chronic cerebrospinal venous insufficiency (CCSVI) with four different patterns of distribution of stenosis and substitute circle. CDMS is strongly associated with CCSVI, a scenario that has not previously been described, characterized by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease Experimental Part II: It has been hypothesized the presence of the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics. For this reason 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001). This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS.