Overexpression of sphingosine-1-phosphate receptors on reactive astrocytes drives neuropathology of multiple sclerosis rebound after fingolimod discontinuation

Mult Scler. 2018 Jul;24(8):1133-1137. doi: 10.1177/1352458518763095. Epub 2018 Apr 30.

Abstract

We present the neuropathological description of an autoptic case of fatal rebound of disease activity after fingolimod discontinuation in a multiple sclerosis patient. MRI prior to the fatal outcome showed several large tumefactive demyelinating lesions. These lesions were characterized by prominent astrocytic gliosis, with a remarkable preponderance of large hypertrophic reactive astrocytes showing intense expression of sphingosine-1-phosphate receptor 1. Prominent astrocytic gliosis was also diffusely observed in the normal-appearing white matter. Dysregulated sphingosine-1-phosphate signaling on astrocytes following fingolimod withdrawal might represent a possible contributing mechanism to disease rebound and might account for the unusual radiological and neuropathological features observed in the present case.

Keywords: Fingolimod; demyelination; glia; histopathology; multiple sclerosis; post mortem.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Autopsy
  • Brain / metabolism
  • Brain / pathology
  • Fatal Outcome
  • Fingolimod Hydrochloride / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / metabolism
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Receptors, Lysosphingolipid / biosynthesis*
  • Recurrence

Substances

  • Immunosuppressive Agents
  • Receptors, Lysosphingolipid
  • Fingolimod Hydrochloride