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An immunotherapy effect analysis in Rasmussen encephalitis.

Zuzana Liba1, Martina Vaskova2, Josef Zamecnik3

  • 1Department of Pediatric Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 15006, Prague, Czech Republic. zuzana.liba@fnmotol.cz.

BMC Neurology
|September 25, 2020
PubMed
Summary

T cell-targeted immunotherapies reduced neuroinflammation in Rasmussen encephalitis (RE) patients. However, intractable epilepsy persisted, indicating a need for new therapeutic targets beyond T cells, such as CXCL10, CXCL13, and BAFF.

Keywords:
AlemtuzumabChemokinesCytokinesImmunotherapy effectIntrathecal methotrexateLymphocyte subpopulationsRasmussen encephalitis

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Area of Science:

  • Neuroscience
  • Immunology
  • Pediatric Neurology

Background:

  • Rasmussen encephalitis (RE) is characterized by immune-mediated mechanisms contributing to its pathology.
  • Immunotherapy is often ineffective in RE patients with established intractable epilepsy, with limited laboratory data available.
  • This study investigated the effects of various immunotherapies on neuroinflammation in pediatric RE patients.

Purpose of the Study:

  • To evaluate the efficacy of different T cell-targeted immunotherapies in reducing neuroinflammation in Rasmussen encephalitis.
  • To analyze changes in lymphocyte subpopulations, chemokines, and cytokines in brain tissue, cerebrospinal fluid (CSF), and blood.
  • To identify potential new therapeutic targets for RE, especially in the context of persistent epilepsy.

Main Methods:

  • Analysis of brain tissue, CSF, and blood samples from seven children with RE undergoing immunotherapy and hemispherotomy.
  • Utilized immunohistochemistry, flow cytometry, Luminex multiplex bead assay, and ELISA techniques.
  • Assessed inflammatory changes, lymphocyte subpopulations (including CD8+ T cells), and levels of 12 chemokines/cytokines (including CXCL10, CXCL13, BAFF).

Main Results:

  • T cell-targeted therapies (cyclophosphamide, natalizumab, alemtuzumab, intrathecal methotrexate) reduced brain tissue inflammation, unlike azathioprine.
  • Elevated levels of CD8+ T cells, CXCL10, CXCL13, and BAFF persisted in CSF despite therapy.
  • A combination of alemtuzumab and intrathecal methotrexate showed the most significant reduction in inflammation and T cell markers in both brain tissue and CSF.

Conclusions:

  • Various T cell-targeted immunotherapies can reduce brain inflammation in Rasmussen encephalitis.
  • Intractable epilepsy in RE patients appears relatively independent of T cell presence later in the disease, necessitating new therapeutic targets.
  • Elevated CXCL10, CXCL13, and BAFF in CSF warrant further investigation for their role in RE pathology.