Home Archive Vol.39, No.1, 2013 Original Papers The value of Doppler cerebral parameters to assess a group of patients with multiple sclerosis

The value of Doppler cerebral parameters to assess a group of patients with multiple sclerosis

 AURA COTEANU(1), SIMONA GUSTI(2), CATALINA COTEANU(3)

(1)Departament of Neurology, Unimed Clinic, Slatina;

(2)Department of Physiology, University of Medicine and Pharmacy of Craiova;

(3)Department of Clinical Laboratory, Clinical Municipal Hospital, Craiova.

ABSTRACT: Background: The current definition of multiple sclerosis is an inflammatory/degenerative disease of central nervous system with focal demyelination around cerebral veins. In 2007 a theory was proposed that demonstrates an alteration of cerebral venous flow in patients with multiple sclerosis. Our study wants to see if there is a statistically significant differences between cerebral venous hemodynamics in multiple sclerosis patients and healthy people. Methods: We admitted in the study twenty-seven patients with multiple sclerois possible or defined, and thirty clinically healthy persons.  All subjects underwent neurological assessment and extra-cranial Doppler examination. We calculated for each internal jugular vein a parameter called ΔCSA. The sum of all the venous flows was then calculated in clinostatism and in seated position and the difference between the two parameters has been named ΔCVF. We assess the eventual presence of reflux in the internal jugular vein after a short period of apnea. Results:  Between results of ΔCSA parameter were differences with very high statistical significance. Similarly a negative ΔCVF is significantly associated with multiple sclerosis. The persisting presence of reflux in internal jugular vein was observed  in 60%  multiple sclerosis patients.  Conclusions: Studied parameters have revealed that there is a hemodynamic significance in the pathology of multiple sclerosis. Thus data obtained led us to the conclusion that the presence of reflux in the internal jugular vein correlated with a negative ΔCVF is statistically significant in patients with multiple sclerosis.

KEYWORDS: multiple sclerosis, extra-cranial Doppler, cerebral venous hemodynamics.

Introduction

The current definition of multiple sclerosis (MS) is an inflammatory/degenerative disease of central nervous system with focal demyelination around cerebral veins. This topographic pattern might be correlated to venous congestion. [1,2]

Since almost a century ago appears in the works of renowned authors idea that venous thrombosis as the primary alteration in the production of demyelinating lesions. The effect of venous obstruction in the central nervous system have been studied by T. J. Putnam, in an article publised in JAMA the autor reported that the commonest lesion consists of a swelling and disintegration of myelin upstream along the vein, accompanied in the severer lesion by some swelling and fragmentation  of axis cylinders.[3]

This problem continued to be studied by numerous researchers, and in 2007 an Italian group headed by P. Zamboni launched a theory that demonstrates an alteration of cerebral venous flow in patients with multiple sclerosis.[4]

So they define five parameters that-if at least two are present-allow diagnosis of chronic cerebrospinal venous insufficiency (CCSVI). These parameters are: reflux in the internal jugular and/or vertebral veins; reflux in the deep cerebral veins; B-mode evidence of internal jugular vein stenosis; flow not Doppler-detectable in the internal jugular and/or vertebral veins; reverted postural control of the main cerebral venous outflow pathways.[5]

Our study does not analyse the ultrasonographic parameters reported by Zamboni but wants to see if there is a role for venous congestion in the pathogenesis of MS.

Material and methods

Aim of this study was to evaluate whether there is a statistically significant differences between cerebral venous hemodynamics in multiple sclerosis patients and healthy people.

We admitted in the study 27 patients with multiple sclerois possible or defined, including both Clinically Isolated Syndrome (CIS) and Relapsing/Remitting Multiple Sclerosis (RR-MS). Also we used a control group of 30 clinically healthy individuals with similar demographic characteristics.

The term „clinically isolated syndrome” (CIS) means the onset of a neurological episode (symptom or sign) lasting at least 24 hours caused by inflammation/ demyelination in one or more places in the central nervous system. An individual affected by CIS can have just a single neurological symptom (e.g., retrobulbar neuritis or a lack of strength on the left half of the body), due to a single lesion, or several neurological signs or symptoms at the same time due to several brain lesions. The former case is defined monofocal CIS, the latter multifocal CIS. [6]

RR-MS was defined according to 2010 Revisions to the McDonald Criteria for diagnosis of multiple sclerosis.[7]

The degree of patients „disability” was assessed using the Expanded Disability Status Scale (EDSS).[8]

Patients and healthy subjects underwent neurological assessment and Extra-Cranial Doppler (ECD) examination. The patients were divided into the three subgroups:  Group 1 included clinically isolated syndrome (n:7), Group 2 included relapsing remitting MS (n: 20), Group 3 included controls (n:30).

We used a Full Digital Ultrasound System Fukuda Denshi UF 850-XTD equipped with a linear probe FUT-LG-386-9A for cervical vessels with selectable frequency 6.0/7,5/9,0 MHz.

Postural dependency of the cerebral venous outflow (CVF) has been demonstrated in healthy subjects by Extra-Cranial Doppler. According to findings internal jugular vein (IJVs) are the main outflow system in the supine position, confirmed by an increased cross-section area of the internal jugular vein  related to increased blood volume in said posture; IJVs collapse in the seated position, while vertebral vein (VVs) increase the venous outflow and partially compensate the venous drainage.[9,10]

Calculating the flow of the distal tract of each of these veins it is possible to obtain the majority of CVF in clinostatism and seated position.

The cross-sectional area (CSA) of IJVs and VVs were measured in horizontal plane, avoiding any vessel compression. The CSA of right and left IJVs were measured at their middle tract, and under valve plane in both clinostatism and seated position. The CSA of right and left VVs were measured under the valve plane in both clinostatism and seated position. Exact angle correction of Doppler frequencies was achieved by adjusting the angle between the Doppler bean and the longitudinal axis of the vessel.

CVF of IJVs and VVs was calculated from the time average velocity (TAV) and the CSA of the vessel (CVF = CSA x TAV).

TAV was measured over a minimum of the three cardiac cycles at the end of the expiratory phase. CVF of each vein was calculated in both clinostatism and seated position. The sum of all the venous flows was then calculated in clinostatism (CVFc) and in seated position (CVFs). The difference between the CVFc and CVFs has been named ΔCVF.

Also we calculated for each IJVs (right and left) a parameter called ΔCSA resulted from the difference between CSA in clinostatism (CSAc) and CSA in seated position (CSAs).

We assess the eventual presence of reflux in the IJVs after a short period of apnea following a normal exhalation, as previously reported, with the head positioned at 0°, and 90°. According to a recent study on reflux time cut-off values, we considered reflux a flow directed toward the brain for a duration > 0.88 second.[11]

The statistical analysis was performed by means of non parametric tests, namely Fisher’s exact test for assessing the significance of differences in contingency tables, Mann-Whitney test and ANOVA Kruskal-Wallis test for comparing the medians of two or more groups, respectively.

Demographic characteristics are expressed as mean ± SD. EDSS are expressed as median and 25th–75th percentile. Differences among groups were tested for significance with the one-way ANOVA analysis of variance; p-values up to 0.05 were considered statistically significant.

Results:

The demographic characteristics of the groups are presented in table 1.

  

Table 1 Demographic caracteristics of the studied groups

 

Group 1 (CIS)

Group 2 (RR-MS)

Group 3 (control)

Age

29.6 ± 9.2

40.6 ± 12.1

38.7 ± 11.2

Sex ratio (female/male)

5/2

14/6

20/10

EDSS median (IQR)

1 (0.5)

2.5 (1)

0

 

As shown in table 2, between the results for DCSA parameter for the IJVs (left and right) on both groups of patients and results in the control group there were differences with very high statistical significance (p<0.001). The highest differences occurred in the group of patients with relapsing-remitting multiple sclerosis. Related to comparing group 1 with group 2 we did not obtain statistically significant differences.

 

Table 2 Results of DCSA parameter for the IJVs left and IJVs right

 

IJVs left

IJVs right

 

DCSA positive

DCSA negative

DCSA positive

DCSA negative

Group 1 (CIS)

4

3

4

3

Group 2 (RR-MS)

9

11

8

12

Group 3 (control)

27

3

28

2

p - ANOVA

p<0.001

p<0.001

p<0.001

p<0.001

 

 

Simmilary a negative ΔCVF is significantly associated with MS (p<0.001), while a positive ΔCVF is correlated to normal physiological condition. (table 3)

Evaluation which showed a significant difference between Group 1 vs Group 3 (p<0.001), and Group 2 vs Group 3 (p<0.0001), while there was no difference between Group 1 and Group 2. The negative ΔCVF was 57.1% in Group 1 and 65% in Group 2, these differences were not significant (p= 0.19).


Table 3 Results of DCVF parameter for the IJVs left and IJVs right

 

DCVF positive

DCVF negative

 

p*

Group 1 (CIS)

3

4

57.1%

p<0.001

Group 2 (RR-MS)

7

13

65%

p<0.0001

Group 3 (control)

28

2

6.6%

-

p - ANOVA

p<0.001

p<0.001

-

-

p* = group 1 vs group 3 and group 2 vs group 3

 


The persisting presence of reflux with the head positioned at 0° and +90° (supine and sitting posture), in at least one IJVs was observed just in one subject among the group control populations. This finding was observed in 12 MS patients (60%), respectively in 3 (42.8%) in CIS group(Table 4)

Table 4 Presence of reflux in at least one IJVs

 

Reflux present

Reflux absent

 

p*

Group 1 (CIS)

3

4

42.8%

p<0.0001

Group 2 (RR-MS)

12

8

60%

p<0.0001

Group 3 (control)

1

29

3.3%

-

p - ANOVA

p<0.001

p<0.001

-

-

p* = group 1 vs group 3 and group 2 vs group 3

 

 

Analyzing the association between studied parameters using chi square test we found that there are several results with statistical significance. Thus there is a correlation between the presence of reflux and a negative DCVF in the group of patients with RR-MS. (table 5)

 

 Table 5 Association between DCVF and presence of reflux using chi-square test

Group 2 (RR-MS)

Reflux present

Reflux absent

Total

DCVF negative

11

2

13

DCVF positive

1

6

7

Total

12

8

20

chi-square: 6.68

 

Conclusions:

Studied parameters have revealed that there is a hemodynamic significance in the pathology of multiple sclerosis.

Thus data obtained led us to the conclusion that the presence of reflux in the internal jugular vein correlated with a negative DCVF is statistically significant in patients with RR-MS.

In the patient group with CIS there are also changes in venous Doppler parameters but the lack of a statistical significance compared to the the group with MS does not help us to identify clear diagnosis algorithms.

The aim of our study was not to verify the ultrasonographic parameters reported by Zamboni, but to demonstrate if there is a role for venous congestion in the pathogenesis of MS.

Although the materiality level obtained in this study have low or medium value must not be neglected human results. Thus, the results are statistically significant (p <0.05), significant in practice and significant in clinical perspective.

References:

1.   Lassmann H. Multiple sclerosis pathology: evolution of pathogenetic concepts. Brain pathol 2005; 15: 217–222. .

2.   D’haeseleer M, Cambron M, Vanopdenbosch L, et al. Vascular aspects of multiple sclerosis. Lancet Neurol 2011; 10: 657–666.

3.   Putnam TJ. Lesions of ‘encephalomyelitis’ and multiple sclerosis. Venous thrombosis as the primary alteration. JAMA 1937; 1477.

4.   Zamboni P, Menegatti E, Bartolomei I, et al. Intracranial venous haemodynamics in multiple sclerosis. Curr Neurovasc Res 2007; 4:252-258

5.   Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009; 80:392-399.

6.   Miller DH, Chard DT, Ciccarelli O. Clinically isolated syndromes. Lancet Neurol. 2012 Feb;11(2):157-169.

7.   Polman CH, Reingold SC, Banwell B, et al.  Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb; 69(2):292-302.

8.   Kurtzke JF. "Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)". Neurology 1983; 33 (11): 1444–1452. 

9.   Valdueza JM, von Mu¨nster T, Hoffman O, et al. Postural dependency of the cerebral venous outflow. Lancet 2000; 355: 200–201.

10. Gisolf J, van Lieshout JJ, van Heusden K, et al. Human Cerebral venous outflow pathway depends on posture and central venous pressure. J Physiol 2004; 560: 317–327

11. Nedelmann, M, Eicke, BM, Dieterich, M. Functional and morphological criteria of internal jugular valve insufficiency as assessed by ultrasound. J Neuroimaging 2005; 15: 70-75

 

Correspondence Address: Aura Coteanu, M.D., Department of Neurology, Unimed Clinic, Slatina, Olt, Romania,Str. Basarabilor, no.16A; e-mail: auracoteanu@yahoo.com

 


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