The Central Vein Sign and Paramagnetic Rim Sign in White Matter - - PowerPoint PPT Presentation

The Central Vein Sign and Paramagnetic Rim Sign in White Matter Lesions of Radiologically Isolated Syndrome

Suradech Suthiphosuwan1,2, Pascal Sati3, Melanie Guenette2, Martina Absinta3, Daniel Reich3, Aditya Bharatha1,4, Jiwon Oh2,5

1 .Division of Neuroradiology, Department of Medical Imaging, St. Michael’s Hospital, University of Toronto 2 .Division of Neurology, Department of Medicine, St. Michael’s Hospital, University of Toronto 3 . Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, NIH

• 4. Division of Neurosurgery, Department of Surgery, St. Michael’s Hospital, University of Toronto
• 5. Department of Neurology, Johns Hopkins University

• No disclosures

Disclosures

Background: Multiple Sclerosis (MS)

Tallantyre et al, Neurology 2011

MS lesions: perivenular inflammatory infiltrates MRI: Central vein inside white matter lesion (WML) = “Central Vein Sign” (CVS)

MS: A high proportion of WML with CVS+ A cut-off threshold of 40% has been propose to distinguish MS vs. non-MS

Mistry et al, MSJ 2015 Popescu et al, Multiple sclerosis, Elsevier 2016

Background: Multiple Sclerosis (MS)

MRI: “Paramagnetic rim sign (PRS)” = Chronic active inflammation attributed to paramagnetic effects from iron-laden microglia macrophages at the lesions edge.

Absinta M, JCI 2016

Background: Radiologically Isolated Syndrome (RIS)

• RIS cases are at increased risk
• f developing MS.
• One-third of RIS cases

developed clinical definite MS within 5 years.

• Risk factors of developing MS
• Young age (<37 years)
• Being Male
• Presence of Spinal cord lesion

Asymptomatic cases with incidental MRI findings suggestive

• f MS

Objective

To assess for the presence of the CVS and PRS in WMLs of RIS.

Methods: Subjects

• IRB Approved
• RIS cases were prospectively

recruited from the St Michael’s Hospital MS clinic from July 2017 to December 2017.

• Inclusion criteria: adult subjects

meeting previously published clinical and MRI criteria for RIS

(Okuda et al, Neurology 2009)

Barkhof’s criteria (at least 3 out of 4) Number of T2 lesions ≥ 9 T2 hyperintense

• r ≥ 1 Gd enhancing

Infratentorial or cord lesions ≥ 1 Juxtacortical lesions ≥ 1 Periventricular lesions ≥ 3

Methods: MRI Protocol

• 3.0T MRI scanner: Siemens

Skyra, Erlangen, Germany.

• 20-channel head-neck

coil

• 3D FLAIR: lesion

detections, lesion count, and location

• 3D T2* EPI:
• Magnitude: CVS

assessment

• Phase: PRS assessment

3D T2* EPI Magnitude 3D FLAIR 3D T2* EPI Phase

Methods: CVS assessment

Central Vein Sign on 3D T2* EPI

(Sati et al, Nrneurol, 2016)

• Thin hypointense line or small dot
• Visualized in at least two

perpendicular planes, and appears as a thin line in at least one plane

• Small apparent vein diameter
• Runs through the lesion
• Positioned centrally in the lesion

Ax Cor Sg

Methods: CVS assessment

Exclusion criteria for lesions

(Sati et al, Nrneurol, 2016)

• Lesion is <3 mm in diameter
• Confluent lesions
• Lesion has multiple veins
• Lesion is poorly visible

FLAIR T2* EPI

PRS positive lesion

• WML >3 mm in size
• Presence complete/incomplete

hypointense rim on Phase image

Exclusion

• WML <3 mm in size
• Poorly visible lesion due to artifact

Methods: PRS assessment

3D T2* EPI Magnitude 3D T2* EPI Phase

Demographics Participants, n 15 Age, mean (SD) 45 (11.5) Female, n (%) 11 (73%) Reasons for Performing Initial Brain MRI Headaches 7 (46%) Transient paraphasic symptoms atypical for demyelinating disease 2 (13%) Intermittent subjective cognitive symptoms 1 (7%) Intermittent nocturnal tremor 1 (7%) Pars planitis 1 (7%) Back pain 1 (7%) Dental pain 1 (7%) Tinnitus 1 (7%)

Radiological Characteristics Total brain lesion count, n 680

• No. brain lesion per subject, meadian (range)

31 (9-165)

• No. Brain lesion per location

Cortical/Juxtacortical 147 (22%) Subcortical/Deep white matter 342 (50%) Periventricular white matter 160 (23%) Infratentorial 31 (5%) Cervical spinal cord lesion

• No. of Participants with cervical spinal cord lesions

10 Total cervical spinal cord lesions 22

• No. of Cervical spinal cord lesions per subjects, median (range)

1 (0-4)

Clinical and MRI Characteristics of RIS subjects

Results:

Results:

Total WML 680 Exclusion 424 (62%) Inclusion 256 (38%) CVS- 39 (15%) CVS+ 217 (85%)

Proportion of WML with CVS + per Subject

Median %CVS+ per RIS case 83% (range 31% – 100%)

%CVS+ >40% 14 cases (93%) %CVS+ < 40% 1 cases (7%)

Results:

Total WML 680 Exclusion 231 (34%) Inclusion 449 (66%) PRS - 368 (82%) PRS + 81 (18%)

• The PRS was present in 11 cases

(73%)

• The mean proportion of PRS

+ WMLs per case was 19% (range:8-44%).

• PRS were absent in 4 cases

(27%):

• 3 had low total lesion loads

(9-25 WMLs per case)

• 1 had the lowest proportion
• f CVS+ WML (31%)

Figures: High %CVS = 92% PRS+ = 30%

Figures: Low %CVS = 31% No PRS

Results:

Regression Analyses Evaluating the Association of Baseline Characteristics with the Proportion of CVS+ WMLs

Univariable model Multivariable model p - value p - value Age 0.584 0.830 Sex 0.907 0.920 Total No. Brain lesion 0.970 0.049

• No. Cervical spinal cord lesion

0.096 0.027 Proportion of PRS+WML 0.015 0.015 Variable

Discussion:

• A large number of WMLs in RIS demonstrates CVS.
• The majority of RIS cases had > 40% CVS+ per case.
• Meets 40% threshold that has been proposed to distinguish MS from Non-

MS.

• A large (though smaller) proportion of WMLs in RIS also had PRS+
• RIS without PRS had low WML load and/or low proportion of

CVS+WML

• %CVS+WML had significant correlation with %PRS+WML
• Number of total brain lesions and cervical spinal cord lesions are also

associated with %CVS+.

Conclusions

• Most RIS cases had a large proportion of CVS+ WMLs and also had

PRS+WMLs

• RIS subjects harbor both perivenular inflammation and subclinical

chronic active demyelination similar to MS

• RIS with high %CVS+ and PRS+ may be at risk of eventually

developing progressive clinical symptoms

• Both CVS and PRS could potentially be useful to differentiate true RIS

(i.e. subclinical inflammatory demyelination) from mimickers.

• Prospective follow-up of this cohort is planned
• Better understanding of the differential diagnostic and predictive

value of the CVS in RIS.

References

• Okuda DT, Mowry EM, Beheshtian A, et al. Incidental MRI anomalies suggestive of

multiple sclerosis: the radiologically isolated syndrome. Neurology 2009;72:800-805

• Maggi P, Absinta M, Grammatico M, et al. Central vein sign differentiates Multiple

Sclerosis from central nervous system inflammatory vasculopathies. Ann Neurol. 2018;83(2):283-294.

• Absinta M et al., Persistent 7-tesla phase rim predicts poor outcome in new multiple

sclerosis patient lesions. JCI 2016;126(7):2597-609

• Absinta M, Sati P, Fechner A, et al. Identification of Chronic Active Multiple Sclerosis

Lesions on 3T MRI. Am J Neuroradiol. 2018; Advance online publication.

• Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the

diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12(12):714-722.

• Tallantyre EC, Dixon JE, Donaldson I, et al. Ultra-high-field imaging distinguishes MS

lesions from asymptomatic white matter lesions. Neurology 2011;76:534-539

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