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Abstract

Background:

Leptomeningeal inflammation in patients with multiple sclerosis (MS) mainly affects meningeal B-cell follicle-like structures linked to cortical and subpial lesions and can be visualized as leptomeningeal enhancement (LME).

Objective:

To evaluate the evolution of LME under different MS immunotherapies.

Methods:

A total of 214 MS patients treated with anti-CD20 therapies or fingolimod at the university hospital Bern were screened for LME. Magnetic resonance imaging (MRI) and medical records were retrospectively evaluated, and comparative statistics were applied.

Results:

We compared MS patients treated with anti-CD20 therapies (128 patients (59.8%)) or fingolimod (86 patients (40.2%)). Of 128 anti-CD20-treated patients, 108 (84.4%) had no LME, 11 (8.6%) had persistent LME, and 9 (7.0%) showed resolution of LME. Of 86 fingolimod-treated MS patients, 81 (94.2%) had no LME and 5 (5.8%) persistent LME. Patients with LME persistence were older than those without or resolution of LME (p = 0.039). Resolution of LME was more frequent during anti-CD20 compared with fingolimod treatment (p = 0.019).

Conclusion:

We observed LME resolution under treatment with anti-CD20 therapies. As LME might play an important role in cerebral gray matter pathology in MS, further investigations including extensions to higher field strengths, correlation with clinical phenotypes, and comparison with other immunotherapies are needed.

Keywords

Multiple sclerosis immunotherapy MRI biomarker LME

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References

Bergsland

Ramasamy

Tavazzi

, et al. Leptomeningeal contrast enhancement is related to focal cortical thinning in relapsing-remitting multiple sclerosis: A cross-sectional MRI study. AJNR Am J Neuroradiol 2019; 40(4): 620–625.

Absinta

Vuolo

Rao

, et al. Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis. Neurology 2015; 85: 18–28.

Absinta

Cortese

ICM

Vuolo

, et al. Leptomeningeal gadolinium enhancement across the spectrum of chronic neuroinflammatory diseases. Neurology 2017; 88: 1439–1444.

Engisch

Titelbaum

Chilver-Stainer

, et al. Susac’s syndrome: Leptomeningeal enhancement on 3D FLAIR MRI. Mult Scler 2016; 22(7): 972–974.

Lexa

Grossman

RI.

MR of sarcoidosis in the head and spine: Spectrum of manifestations and radiographic response to steroid therapy. AJNR Am J Neuroradiol 1994; 15(5): 973–982.

Haddad

Roussel

Pelcovits

, et al. Optic neuritis, encephalitis and leptomeningeal enhancement in a patient with anti-MOG antibodies: A case study. Mult Scler Relat Disord 2019; 34: 14–16.

Titelbaum

Engisch

Schwartz

, et al. Leptomeningeal enhancement on 3D-FLAIR MRI in multiple sclerosis: Systematic observations in clinical practice. J Neuroimaging 2020; 30(6): 917–929.

Eisele

Griebe

Szabo

, et al. Investigation of leptomeningeal enhancement in MS: A postcontrast FLAIR MRI study. Neurology 2015; 84: 770–775.

Harrison

Wang

Fiol

, et al. Leptomeningeal enhancement at 7T in multiple sclerosis: Frequency, morphology, and relationship to cortical volume. J Neuroimaging 2017; 27(5): 461–468.

10.

Magliozzi

Howell

Vora

, et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 2007; 130(Pt. 4): 1089–1104.

11.

Howell

Reeves

Nicholas

, et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 2011; 134(Pt. 9): 2755–2771.

12.

Lassmann

van Horssen

Mahad

Progressive multiple sclerosis: Pathology and pathogenesis. Nat Rev Neurol 2012; 8: 647–656.

13.

Silva

Miglietta

Ferrari

CC.

Insights into the role of B cells in the cortical pathology of multiple sclerosis: Evidence from animal models and patients. Mult Scler Relat Disord 2021; 50: 102845.

14.

Weber

Bar-Or

Herman

, et al. Modulation of CSF immunoglobulins by ocrelizumab treatment. In: Proceedings of the 8th joint ACTRIMS—ECTRIMS meeting—MS virtual 2020, Online, 11–13 September 2020.

15.

Sicotte

NL.

New imaging approaches for precision diagnosis and disease staging of MS?

Mult Scler 2020; 26(5): 568–575.

16.

Bhargava

Wicken

Smith

, et al. Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement. Mult Scler Relat Disord 2019; 30: 136–140.

17.

Rechtman

Brill

Zveik

, et al. Volumetric brain loss correlates with a relapsing MOGAD disease course. Front Neurol 2022; 13: 867190.

18.

Hertel

Wenz

Al-Zghloul

, et al. Crossed cerebellar diaschisis in Alzheimer’s disease detected by arterial spin-labelling perfusion MRI. In Vivo 2021; 35(2): 1177–1183.

19.

Gardner

Magliozzi

Durrenberger

, et al. Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats. Brain 2013; 136(Pt. 12): 3596–3608.

20.

Zurawski

Lassmann

Bakshi

Use of magnetic resonance imaging to visualize leptomeningeal inflammation in patients with multiple sclerosis: A review. JAMA Neurol 2017; 74: 100–109.

21.

Zivadinov

Ramasamy

Vaneckova

, et al. Leptomeningeal contrast enhancement is associated with progression of cortical atrophy in MS: A retrospective, pilot, observational longitudinal study. Mult Scler 2017; 23(10): 1336–1345.

22.

Magliozzi

Howell

Reeves

, et al. A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 2010; 68(4): 477–493.

23.

Ineichen

Tsagkas

Absinta

, et al. Leptomeningeal enhancement in multiple sclerosis and other neurological diseases: A systematic review and meta-analysis. Neuroimage Clin 2022; 33: 102939.

24.

Syed

YY.

Ocrelizumab: A review in multiple sclerosis. CNS Drugs 2018; 32: 883–890.

25.

Ineichen

Moridi

Granberg

, et al. Rituximab treatment for multiple sclerosis. Mult Scler J 2020; 26: 137–152.

26.

Yang

Tian

Chen

, et al. The efficacy and safety of fingolimod in patients with relapsing multiple sclerosis: A meta-analysis. Br J Clin Pharmacol 2020; 86(4): 637–645.

27.

Banks

WA.

Characteristics of compounds that cross the blood-brain barrier. BMC Neurol 2009; 9: 5–9.

28.

Avasarala

It’s time for combination therapies in multiple sclerosis. Innov Clin Neurosci 2017; 14(5–6): 28–30.

29.

Pyzik

Sand

KMK

Hubbard

, et al. The neonatal Fc receptor (FcRn): A misnomer? Front Immunol 2019; 10: 1540.

30.

Sellebjerg

Blinkenberg

Sorensen

PS.

Anti-CD20 monoclonal antibodies for relapsing and progressive multiple sclerosis. CNS Drugs 2020; 34(3): 269–280.

31.

Rubenstein

Combs

Rosenberg

, et al. Rituximab therapy for CNS lymphomas: Targeting the leptomeningeal compartment. Blood 2003; 101: 466–468.

32.

Ruhstaller

Amsler

UCT

. Rituximab: Active treatment of central nervous system involvement by non-Hodgkin’s lymphoma? Ann Oncol 2000; 11: 374–375.

33.

Cross

Stark

Lauber

, et al. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 2006; 180(1–2): 63–70.

34.

Ortiz

Pacheco-Moisés

Macías-Islas

MÁ

, et al. Role of the blood-brain barrier in multiple sclerosis. Arch Med Res 2014; 45: 687–697.

35.

Vidal-Jordana

Montalban

Multiple sclerosis: Clinical aspects. Curr Opin Neurol 2018; 31: 752–759.

36.

Bhargava

Kim

Reyes

, et al. Imaging meningeal inflammation in CNS autoimmunity identifies a therapeutic role for BTK inhibition. Brain 2021; 144: 1396–1408.

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Leptomeningeal enhancement under different MS immunotherapies: A monocentric retrospective cohort study of 214 patients

Abstract

Background:

Objective:

Methods:

Results:

Conclusion:

Keywords

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References

Supplementary Material