The value of cerebral Doppler venous haemodynamics in the assessment of multiple sclerosis

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Abstract

Iron stores in the white and deep grey matter in course of multiple sclerosis (MS) have never been explained and could be related to abnormalities in venous drainage, but this possibility has never before been investigated.

From an initial cohort of 320 subjects, after application of exclusion criteria, we selected 109 patients affected by MS, and 177 controls respectively composed by age- and sex-matched, healthy aged, and patients affected by other neurological diseases. They blindly underwent transcranial and extracranial Color–Doppler sonographic examination (TCCS-ECD), aimed at investigating five parameters related to normal cerebral venous outflow haemodynamics.

Overall we analyzed 1430 TCSS-ECD parameters. In controls we found 861 normal parameters of cerebral venous return vs. 24 anomalous, whereas in MS 288 parameters were normal and 257 anomalous, respectively. Consequently, each of the considered Doppler haemodynamic parameters, when compared to revised McDonald criteria as a gold standard of MS diagnosis, showed separately a highly significant sensitivity and a noteworthy specificity. However, the detection ≥ 2 parameters in the same subject, never observed in controls, perfectly overlapped the diagnosis of MS (value, 95%CI: sensitivity 100%, 97–100; specificity 100%, 98–100; positive predictive value 100%, 97–100, negative predictive value 100%, 98–100; p < 0.0001). Moreover, this study demonstrates a significant impairment of cerebral venous drainage in patients affected by MS, a mechanism potentially related to increased iron stores.

Section snippets

Patients and controls

We admitted to the first part of the study 120 patients affected by clinically defined MS (CDMS), diagnosed according to the recommended criteria [22]. We also recruited 200 controls subdivided into three groups: i) 60 healthy subjects homogeneous for age and gender with MS patients (HM-C); ii) 80 healthy subjects older than the median age of the European MS population (HA-C) [23]; and iii) 60 patients affected by other neurological diseases (OND).

Patients and controls

Table 2a, Table 2b show clinical and demographic characteristics for the entire group of MS patients, as well as for the subgroups. Significant differences were found, as expected, in the followings:

  • Age: SP vs RR, p < 0.01. PP vs RR, p < 0.01 (ANOVA).

  • EDSS: SP vs RR, p < 0.01. PP vs RR, p < 0.01 (ANOVA).

  • Disease duration: SP vs RR, p < 0.01 (ANOVA).

Physiologic flow direction in the IJVs and\or VVs with the head in any position

Venous flow direction was consistently directed toward the heart with the head in any position, and increased by inspiration in all controls. Bidirectional flow

Discussion

The principal result of our study is the original description of the overturning of the physiologic regulation of venous return assessed in our CDMS population, with parameters that are significantly different from those of all control groups (Table 3, Fig. 1, Fig. 2, Fig. 3, Fig. 4). The latter include also older subject (Tables 2a) and OND patients (Tables 2b). Had Doppler hemodynamic anomalies been present in the healthy aged control group, we would not have been able to maintain that they

Competing financial interests

None.

Funding

Research supported by the Italian Ministry for University and Scientific Research and by the Foundation Cassa di Risparmio di Ferrara.

Acknowledgments

We wish to thank Mrs Francesca Pancaldi for her help in organising this study and in preparing the manuscript. Many thanks to Roberto Manfredini, MD, Head of the Department of Internal Medicine of the Delta Hospital Lagosanto, Ferrara, Italy, and his staff for the valuable selection of control subjects.

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    Center for Rare and Neuroimmunitary Diseases, Bellaria Hospital, Bologna, Italy

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