Intra- and Extraluminal Structural and Functional Venous Anomalies in Multiple Sclerosis, as Evidenced by 2 Noninvasive Imaging Techniques

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Fig 1.
Intraluminal (septum, A) structural abnormality in the right IJV causing significant reflux/bidirectional flow directed toward the brain for a duration of >0.88 seconds in both the supine and sitting positions (B), as detected by using DS, in a 33-year-old woman with RRMS with 2 years of disease duration and minimal disability (EDSS score, 1.0). 2D TOF (C) and enhanced 3D TRICKS (D and E) sequences show normal flow morphology.
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Fig 2.
Examples of intraluminal structural abnormalities in the IJVs causing hemodynamic abnormality in HCs and patients with MS, 22 and 47 years of age. A, septum. B, Flap. C, Single leaflet valve. D, Web.
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Fig 3.
Extraluminal structural abnormality in the left IJV causing significantly reduced flow in both the supine and sitting positions, as detected by using DS (A) and MRV (B–D) in a 46-year-old woman with SPMS with 20 years of disease duration and advanced disability (EDSS score, 5.0). 2D TOF (B) and enhanced 3D TRICKS (C and D) sequences show pinpoint flow morphology.

Table 1:

Proposed classification of IJV abnormalities on DS

DS Classification	Types/Examples
Intraluminal structural venous abnormality; this is an echogenic structure extending from the endothelial lining of the vein wall with/without presence of functional abnormality; these abnormalities include web, flap, septum, membrane, and malformed valve	Web: multiple septa and/or flaps located in a cluster
	Flap: thin linear echogenic structure extending from endothelial lining of vein wall
	Septum: thin linear echogenic structure extending from endothelial lining of vein wall, and attached to it at both ends; septum may extend across a vein to attach on opposing sides or attach on same side
	Membrane: membranous structure almost occluding the entire diameter of the vein
	Malformed valve: dysdynamic or fibrous valve
Extraluminal structural venous abnormality; this is a restriction of the venous wall or stenosis; these abnormalities include stenosis and annulus	Stenosis: CSA measurement of ≤3 mm²
	Annulus: circumferential thickened vein wall that is restricting the vein from fully expanding with respiratory or positional changes
Functional venous abnormality; this is an abnormal cerebral venous outflow in the presence of a structural venous anomaly; these abnormalities include reflux/bidirectional flow, paradox, and no flow	Reflux/bidirectional flow: present in the IJV for >0.88 seconds with the head at 90° and 0°
	Paradox: vein wall not reacting to respiratory phase; noncompliant
	No flow: no color flow noted in vein, despite deep breaths

Table 2:

Demographic and clinical characteristics in patients with MS and HCs^a

	MS (n = 150)	HC (n = 63)	P	NPRMS (n = 104)	PRMS (n = 46)	P
Female sex (No.) (%)	102 (68)	36 (57.1)	NS	73 (70.2)	29 (63)	NS
Age (yr) (mean) (SD)	43.2 (10.6)	42 (15)	NS	40.7 (10.7)	48.6 (8.2)	<.001
Age at onset, mean (SD)	31.3 (10)	–	–	31.9 (9.9)	30 (10.3)	NS
Disease duration (mean) (SD)	12.1 (9.1)	–	–	9.2 (7)	18.6 (9.9)	<.001
Disease course (No.) (%)		–
RR	104 (70.4)			104 (100)
SP	38 (25.3)				38 (82.6)
PP	8 (5.3)				8 (17.4)
EDSS (mean) (SD) (median)	3.4 (9.1) 2.5	–	–	2.5 (1.4) 2.0	5.8 (1.7) 6.0	<.001

Note:—NS indicates nonsignificant; NPR, nonprogressive; PR, progressive; –, not available.
↵a The differences between the study groups were tested using the χ² test, Student's t test, and Mann-Whitney U test.

Table 3:

Intraluminal and extraluminal structural and functional venous abnormalities in IJVs in patients with MS and HCs on DS^a

Individual Frequency of Venous Abnormalities	HC (n = 63)	MS (n = 150)	P Value^b	NPRMS (n = 104)	PRMS (n = 46)	P Value^c
Total structural (No.) (%)	34 (54)	111 (74)	.004	72 (69.2)	39 (84.8)	.033
Intraluminal structural (No.) (%)	31 (49.2)	102 (68)	.008	67 (64.4)	35 (76.1)	.110
Web	0	6 (4)		5 (4.8)	1 (2.2)
Flap	17 (27)	51 (34)		36 (34.6)	15 (32.6)
Septum	9 (14.3)	43 (28.7)		34 (32.7)	9 (19.6)
Membrane	0	0		0	0
Malformed valve	18 (28.6)	40 (26.7)		25 (24)	15 (32.6)
Extraluminal structural (No.) (%)	7 (11.1)	33 (22)	.044	17 (16.3)	16 (34.8)	.01
Stenosis	7 (11.1)	33 (22)		17 (16.3)	16 (34.8)
Annulus	0	0		0	0
Total functional (No.) (%)	21 (33.3)	82 (54.7)	.003	55 (52.9)	27 (58.7)	.316
Reflux	20 (31.7)	74 (49.3)		49 (47.1)	25 (54.3)
Paradox	0	2 (1.3)		1 (1)	1 (2.2)
No flow	2 (3.2)	16 (10.7)		8 (7.7)	8 (17.4)
No. of venous abnormalities
Total structural (mean) (SD)	1.05 (1.3)	1.85 (1.8)	.001	1.75 (1.7)	2.04 (1)	.384
Intraluminal structural (mean) (SD)	0.9 (1.2)	1.53 (1.7)	.005	1.5 (1.6)	1.61 (1.9)	.805
Web	0	0.07 (0.4)		0.07 (0.3)	0.09 (0.6)
Flap	0.33 (0.6)	0.56 (1)		0.56 (1)	0.57 (1)
Septum	0.24 (0.7)	0.55 (1)		0.57 (1)	0.5 (1.2)
Membrane	0	0		0	0
Malformed valve	0.35 (0.6)	0.37 (0.7)		0.33 (0.6)	0.5 (0.8)
Extraluminal structural, (mean) (SD)	0.13 (0.5)	0.31 (0.7)	.023	0.25 (0.7)	0.43 (0.7)	.01
Stenosis	0.13 (.5)	0.31 (0.7)		0.25 (0.7)	0.43 (0.7)
Annulus	0	0		0	0
Total functional (mean) (SD)	0.51 (0.9)	1.13 (1.2)	<.0001	1.02 (1.2)	1.4 (1.3)	.096
Reflux	0.44 (0.8)	0.88 (1.1)		0.85 (1.1)	0.96 (1.2)
Paradox	0	0.02 (0.2)		0.02 (0.2)	0.02 (0.1)
No flow	0.06 (0.6)	0.17 (0.5)		0.13 (0.5)	0.26 (0.6)

Note:—NPR indicates nonprogressive; PR, progressive.
↵a The frequency differences of the structural and functional venous abnormalities between the study groups were tested using the Fisher exact test, whereas the number of venous abnormalities differences was tested using Mann-Whitney U test.
↵b P value represents comparison between HC and MS.
↵c P value represents comparison between patients with NPR- and PRMS.

Table 4:

Flow morphology of IJVs in patients with MS and HCs 2D-TOF using venography and 3D-TRICKS^a

Note:—NPR indicates nonprogressive; PR, progressive.
↵a The differences on the ordinal morphologic flow scale between the study groups were evaluated using the Mann-Whitney U test. Only absent and pinpoint flows in the IJVs were considered abnormal.