Journal of Neurology

, Volume 265, Issue 4, pp 966–967 | Cite as

The cortical blood–brain barrier in multiple sclerosis: a gateway to progression?

  • Jack S. Bell
  • Jonathan I. Spencer
  • Richard L. Yates
  • Gabriele C. DeLucaEmail author
Letter to the Editors

Dear Sirs,

Despite the historical focus on white matter pathology, it is now increasingly recognised that cortical tissue injury is critical to disease outcome. Cortical pathology occurs from the earliest disease stages, predominates in progressive MS, and correlates with physical and cognitive disability [1]. However, our understanding of disease processes operative in the MS cortex remains poor and, in particular, the contribution of BBB dysfunction has been relatively overlooked. A recent radiological study and pathological findings from our group make steps to address these shortcomings and provide fresh insight into the role of BBB dysfunction in cortical pathology.

Maranzano et al. undertook a retrospective analysis of serial MRI scans from an early MS cohort. Over a 2-year period, 36% of MS patients had cortical gadolinium (Gd)-enhancing lesions, of which 95% were leukocortical [2]. While MRI studies are limited in their ability to detect cortical lesions, these findings...


Compliance with ethical standards

Conflicts of interest

The authors declare that they have no competing interests.

Ethical standard statement

For this type of study formal consent is not required.


  1. 1.
    Calabrese M, Poretto V, Favaretto A et al (2012) Cortical lesion load associates with progression of disability in multiple sclerosis. Brain 135:2952–2961. CrossRefPubMedGoogle Scholar
  2. 2.
    Maranzano J, Rudko DA, Nakamura K et al (2017) MRI evidence of acute inflammation in leukocortical lesions of patients with early multiple sclerosis. Neurology. PubMedGoogle Scholar
  3. 3.
    Lucchinetti CF, Popescu BFG, Bunyan RF et al (2011) Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 365:2188–2197. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Yates RL, Esiri MM, Palace J et al (2017) Fibrin(ogen) and neurodegeneration in the progressive multiple sclerosis cortex. Ann Neurol. PubMedGoogle Scholar
  5. 5.
    Davalos D, Akassoglou K (2012) Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 34:43–62. CrossRefPubMedGoogle Scholar
  6. 6.
    Chang A, Staugaitis SM, Dutta R et al (2012) Cortical remyelination: a new target for repair therapies in multiple sclerosis. Ann Neurol 72:918–926. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Stoll G, Kleinschnitz C, Meuth SG et al (2009) Transient widespread blood—brain barrier alterations after cerebral photothrombosis as revealed by gadofluorine M-enhanced magnetic resonance imaging. J Cereb Blood Flow Metab 29:331–341. CrossRefPubMedGoogle Scholar
  8. 8.
    Tiwari YV, Lu J, Shen Q et al (2017) Magnetic resonance imaging of blood–brain barrier permeability in ischemic stroke using diffusion-weighted arterial spin labeling in rats. J Cereb Blood Flow Metab 37:2706–2715. CrossRefPubMedGoogle Scholar
  9. 9.
    Cramer SP, Larsson HB (2014) Accurate determination of blood-brain barrier permeability using dynamic contrast-enhanced T1-weighted MRI: a simulation and in vivo study on healthy subjects and multiple sclerosis patients. J Cereb Blood Flow Metab 34:1655–1665. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Wunder A, Schoknecht K, Stanimirovic DB et al (2012) Imaging blood-brain barrier dysfunction in animal disease models. Epilepsia 53:14–21. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jack S. Bell
    • 1
  • Jonathan I. Spencer
    • 1
  • Richard L. Yates
    • 1
    • 2
  • Gabriele C. DeLuca
    • 2
    Email author
  1. 1.University of Oxford Medical School, Level 2 Academic CentreJohn Radcliffe HospitalOxfordUK
  2. 2.Nuffield Department of Clinical Neurosciences, Level 1 West WingJohn Radcliffe HospitalOxfordUK

Personalised recommendations