• Age 18-55 years;
• Unisex patients diagnosed with MS according to McDonald criteria and successive relapse (38, 39), and subjects with CIS;
• Course of the disease: RR-SP-PP-CIS;
• Disease duration (starting from diagnosis): from 1 month to 25 years for subjects with RR, SP, and PP; a maximum of 5 years for subjects with CIS;
• Not in clinical relapse (at least 30 days after the last clinical relapse);
• Subjects treated or non-treated with immunomodulatory and immunosupressive drugs;
• Signature of the informed consent.

• Age 18-55 years;
• Absence of significant diseases and lack of familiarity with MS, ie health check-ups (HC);
• Signature of the informed consent.

The subjects included in this group could be, for example, unrelated relatives or spouses of those affected by MS or other diseases in the study, or linked to these by affinity restrictions (such as, the father-in-law with the son-in-law, the husband with his wife's brother, etc.) or accompanying persons or operators of other centres.

• Aged 18-55 years;
• Subjects with other non-inflammatory neurodegenerative disease (OND), for example Parkinson, ALS, ataxy.
• Signature of the informed consent.

• Age 18-55 years;
• subjects suffering of other inflammatory neurodegenerative diseases (ONDi), for example optical neuromielitys, ADEM, encephalitis, neuro lupus, neurological complications of systemic autoimmune diseases;
• Signature of the informed consent.

For the subjects diagnosed with MS (group A), who did not need to be in a period of clinical relapse of the disease (at least 30 days from the last clinical relapse), the duration and the form of the disease was indicated (CIS, RR, SP or PP). The Investigator has submitted these subjects to a neurological examination which included the standard neurological examination, the Kurtzke EDSS (Kurtzke Expanded Disability Status Scale) comprising the functional systems of Kurtzke and the Barthel scale. After completing the selection phase following the previous examinations, the subjects were directed towards the qualified practitioner for the ecocolor-Doppler examination which was performed in blind.

The protocol provided that the presence of CCSVI was evaluated according to the Zamboni criteria at local level. Therefore, the ecocolor-Doppler images were sent in a randomized process to a central assessor who performed the first centralized reading. In case of disagreement with the local reading, the same images were to be sent to other two central readers, preserving the anonymity, in order to obtain a final evaluation in regards to the CCSVI presence.