Neuroinflammation in the Cerebellum and Brainstem in Friedreich Ataxia: An [18F]-FEMPA PET Study

Mov Disord. 2022 Jan;37(1):218-224. doi: 10.1002/mds.28825. Epub 2021 Oct 13.

Abstract

Background: Neuroinflammation is proposed to accompany, or even contribute to, neuropathology in Friedreich ataxia (FRDA), with implications for disease treatment and tracking.

Objectives: To examine brain glial activation and systemic immune dysfunction in people with FRDA and quantify their relationship with symptom severity, duration, and onset age.

Methods: Fifteen individuals with FRDA and 13 healthy controls underwent brain positron emission tomography using the translocator protein (TSPO) radioligand [18 F]-FEMPA, a marker of glial activation, together with the quantification of blood plasma inflammatory cytokines.

Results: [18 F]-FEMPA binding was significantly increased in the dentate nuclei (d = 0.67), superior cerebellar peduncles (d = 0.74), and midbrain (d = 0.87), alongside increased plasma interleukin-6 (IL-6) (d = 0.73), in individuals with FRDA compared to controls. Increased [18 F]-FEMPA binding in the dentate nuclei, brainstem, and cerebellar anterior lobe correlated with earlier age of symptom onset (controlling for the genetic triplet repeat expansion length; all r part < -0.6), and in the pons and anterior lobe with shorter disease duration (r = -0.66; -0.73).

Conclusions: Neuroinflammation is evident in brain regions implicated in FRDA neuropathology. Increased neuroimmune activity may be related to earlier disease onset and attenuate over the course of the illness. © 2021 International Parkinson and Movement Disorder Society.

Keywords: TSPO; brain; inflammation; microglia; spinocerebellar.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Stem / metabolism
  • Cerebellum / pathology
  • Friedreich Ataxia* / diagnostic imaging
  • Friedreich Ataxia* / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Neuroinflammatory Diseases
  • Positron-Emission Tomography
  • Receptors, GABA / metabolism

Substances

  • Receptors, GABA
  • TSPO protein, human