Microglial activation correlates with disease progression in multiple sclerosis

      Background: Activation of microglia is considered a crucial step in CNS response to injury. Measuring microglial activation in vivo is possible using PET imaging and radioligands binding to 18 kDa translocator protein (TSPO).
      Objective: The aim of this cross-sectional study was to investigate how activation of microglia relates to certain milestones related to MS progression.
      Patients and methods: MS patients with secondary progressive (SPMS,n = 10) or relapsing remitting (RRMS,n = 10) disease, and healthy controls (n = 8) were imaged using PET and the TSPO-binding radioligand 11C-PK11195. Diffusion tensor imaging was performed for assessment of structural integrity of the normal appearing white matter (NAWM) tracts. In addition, we compaired the ex vivo tissue binding characteristics of PK11195 to immunostained cryosections of post mortem autopsy samples from progressive MS patients(n = 5).
      Results: PK11195 binding was significantly increased in the perilesional white matter and in the NAWM of SPMS compared to RRMS patients (p = 0.011 and p < 0.001, respectively). A cut-off value of 1.02 in PK11195 binding in the NAWM separated the RRMS and SPMS groups from each other. The increased radioligand binding in perilesional WM and NAWM correlated to increasing clinical disability measured using EDSS (p = 0.030 and p < 0.001 respectively). In evaluation of tissue sections, there was increased rim-like perilesional PK11195 signal co-localised with increased microglial/macrophage activation around, but not within the chronic demyelinating lesions.
      Conclusion: TSPO PET imaging can be used as a biomarker of diffuse neuroinflammation related to disease progression in MS, and can potentially be utilized to help identify patients entering the progressive phase of the disease.