COVID-19 is a complex, multi-organ disease where lungs are primarily affected, resulting in a form of ARDS in the later stages. In fact, a relevant role has been attributed to iron dysmetabolism and series of literature data highlight a clear-cut alteration in a few related parameters; significantly high figures of ferritin, hepcidin, red blood cell width distribution, lactate dehydrogenase and lactate, in combination with low levels of serum iron and transferrin, have been repeatedly reported in patients affected by Sars-Cov-2 infection at later stages. Overall, these alterations have a negative prognostic value, indicating a pattern of ferroptosis and of a possible dysfunctional hemoglobin, with pro-coagulant and pro-inflammatory repercussions. Different pathomechanisms have been proposed, from erythrocyte attack and an hepcidin-mimetic action of the viral spike proteins, to a more general iron and calcium deregulated intracellular accumulation. Iron chelation has been advocated as one of the possible treatments of COVID-19 and CaNa2ethylendiaminetetraacetic acid (EDTA) is known as a safe and effective mineral-chelator. In this review the authors propose an EDTA-based therapeutic protocol for those patients in most critical stages and admitted to intensive care unit, with the aim to reduce intracellular and blood ferritin overload. Bloodletting and blood transfusion have proved to be beneficial in patients with viral disease-associated iron accumulation. The inclusion of these two procedures in the proposed protocol aims at improving oxygenation by new normo-functioning hemoglobin, while decreasing toxic hyperferritinemia and interleukins. Lastly, a few specific compounds are also taken into consideration to synergistically complement EDTA infusion. A series of technical details are provided for the possible use of the protocol in clinical practice.

The aim of the present study was to assess the size of the third ventricle in a sample of patients with multiple sclerosis (MS) affected by chronic cerebrospinal venous insufficiency (CCSVI), versus size of the third ventricle in a healthy control group. Background: CCSVI, a new nosological vascular pattern, has recently been associated with MS. Methods: We enrolled 33 patients affected by MS (three in the primary progressive clinical course, 23 in the relapsing-remitting clinical course, and seven in the secondary-progressive clinical course). All patients had been affected by CCSVI and were tested using an echo color Doppler (ECD) imaging unit. The group of 33 affected by both MS and CCSVI (MS-CCSVI) was composed of 19 females and 14 males with a mean age of 40±10 years, from a minimum age of 20 years to a maximum age of 66 years, with a median of 40 years and a mode of 32 years. We compared the 33 MS-CCSVI patients with 33 healthy control subjects of similar sex and age. In the MS-CCSVI group, the MS clinical severity was expressed by expanded disability status scale (EDSS) score: light (19 patients, scoring 1, 2, or 3); medium (ten patients with a score of 4, 5, or 6), and severe (four patients with a score of 7, 8, or 9). The average duration of the MS was 10±7 years (from a minimum of 1 to a maximum of 26 years, with a median of 10 years and a mode of 1 year). Results: In the MS-CCSVI group, the third ventricle diameter was 6.2±1.7 mm (from a minimum of 2.5 mm to a maximum of 9.2 mm, with a median of 6.3 mm, and a mode of 6.0 mm). Our data showed that 29 patients (88%) had an increase in third ventricle diameter, whereas only four patients (12%) had physiological size (less than 4 mm) comparable to all healthy control group subjects (27.28%). These results show that the increase in the third ventricle diameter could represent a criterion of positivity of neurological disease in patients with CCSVI.

The aim of our work is to describe the Memnet program’s use and potential and to show the data of Italian Chronic Cerebrospinal Venous Insufficiency (CCSVI)-National Epidemiological Observatory (NEO) activity in the first three years (http://www.osservatorioccsvi. org). From 2011 to 2014, all echo-color- Doppler (ECD) assessments were stored by Mem-net program into CCSVI-NEO web site (http://www.mem-net.it). Mem-net is a tool for multicenter data collection based on the International Society for Neurovascular Disease consensus and position statement, where we can insert patients (pts) history, neurological visits, ECD assessments, different examinations, therapies and surgical procedures. The website provides an epidemiological and statistical program for data analysis in real time. At present, 7 medical centers, affiliated to CCSVI-NEO, input their symptomatic and asymptomatic subjects with CCSVI. Data were storage using the Mem-net program. We analyzed data of only four centers on seven (Rome, Bari, Cagliari and Benevento). Total pts number with multiple sclerosis (MS) was 1109, mean age 46.0±13.4 [male 422 (38.05%); female 687 (61.95%)]. CCSVI positive pts were 937 (84.49%), CCSVI negative pts were 172 (15.51%). The CCSVI type 1 subjects were 530 (56.56%), CCSVI type 2 subjects were 20 (2.13%), CCSVI type 3 subjects were 387 (41.30%). We found 800 (85.38%) pts with criterion 1; 725 (77.37%) with criterion 2; 519 (55.39%) with criterion 3; 483 (51.55%) with criterion 4; 88 (9.39%) with criterion 5. The venous hemodynamic insufficiency severity score mean score was 3.8; the CCSVI mean score was 2.8; the MEM mean score was 34.7; the expanded disability status scale mean score was 4.5; the disease mean duration was 12.5±5.7 years. MS clinical types were divided as follows: relapsing-remitting pts were 449 (47.92%), Secondary progressive pts were 144 (15.37%), primary progressive pts were 72 (7.68%). The CCSVI-NEO database and Memnet software may be useful medical and researching tools for recording, storing, analyzing and studying ECD and vascular data. Preliminary data of NEO show an elevated prevalence of CCSVI in MS.

Journal of Vascular Diagnostics Dovepress submit your manuscript | www.dovepress.com Dovepress 59 S t u Dy P r o t o c o l open access to scientific and medical research open Access Full text ArticleIntroduction: Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by multiple stenosis/obstructions affecting the principal extracranial outflow pathways of the cerebrospinal venous system. Using EchoColorDoppler (ECD) to assess chronic CCSVI is a very difficult and long examination. It takes about an hour even for an expert sonographer. Methods: Hemodynamic morphological map (MEM-Net) is a program that works on the Internet. All the morphological and hemodynamic data of the patient can be entered into the program's anatomical scheme to create a map of the ECD report. The program also allows us to collect all the data during the ECD assessment and, using its algorithm, make the report uniform. Conclusion: Reporting on the map by using MEM-net shortens the time of ECD written reporting that is done automatically. The program also makes a blind control of the report and enables the use of it for scientific research. We hope that in the future everyone will use this data collection tool for all scientific work on this topic.

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The aims of this study were: i) analysis of clinical severity evolution in multiple sclerosis patients; ii) identification of temporal indicators for clinical worsening. We investigated by echo-color-Doppler (ECD) 789 patients (490 female plus 299 male), aged 45.4 years, with chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis (MS). All patients tested positive for CCSVI by ECD assessment were divided into three groups, namely: type 1 CCSVI (371) presenting an endo-vascular obstacle to the venous drainage; type 2 CCSVI (40) presenting an extra-vascular obstacle to the venous drainage, for external compression of the vessel; type 3 CCSVI (315) presenting both venous endo-vascular and extra-vascular obstructed drains. We analyzed the morphological and hemodynamic data recorded on computerized map (MEM-net). All data were collected by respecting the Italian Privacy Laws and they are available on the National Epidemiological Observatory on CCSVI website (www.osservatorioccsvi.org). We focused in the three main parameters in all studied patients. First parameter was expanded disability status scale (EDSS) score; second parameter was illness duration; third parameter was CCSVI type. The MS duration values stratified by EDSS grouped values in CCSVItype- 1 and CCSVI-type-3 patients shows that the differences were statistical significant by Kruskal-Wallis test: H=44.2829; degree of freedom= 1 for CCSVI-type-1 (P<0.001); and H=37.3036; degree of freedom=1 for CCSVItype- 3 (P<0.001). The present study confirmed and completed scientific literature about relation between CCSVI and MS. On the same time, we found a strong correlation between MS illness duration and severity of EDSS score. In fact there is a clinical severity worsening after 11 years of illness in MS patients with CCSVI type-1 or type-3 (P<0.001). These data may suggest the influence of chronic vascular disease on MS. Further searches need in order to learn more about this new aspect in MS etiology.

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