Elevated levels of serum neurofilament-light chain (NfL), a marker of axonal damage, are an indicator of increased microglial activation in the brain, according to a positron emission tomography (PET) study in Finland (Saraste et al. J Neurol Neurosurg Psychiatry 2023;94:698-706).

A total of 44 MS patients and 24 healthy controls underwent TSPO-PET imaging. TSPO (translocator protein) is present on the mitochondrial membrane of activated innate immune cells. It is detectable with a radioligand that binds to TSPO. Mean age of patients was 46.5 years; mean EDSS score was 2.5; and mean time from last relapse was six years.

Overall, 43% of MS patients demonstrated increased microglial activation. The high-activation group had higher EDSS scores and annualized relapse rates. Microglial activation was also associated with a larger T1 lesion volume and a higher number and volume of rim-active lesions.

Higher sNfL levels were correlated with more pronounced microglial activation in normal-appearing white matter, at the lesion rim, and in T1 hypointensive lesions (‘black holes’). Also noteworthy was that sNfL level was significantly correlated with the number and volume of lesions containing activated microglia. sNfL was not correlated with the number/volume of inactive lesions.

Rim-active lesions are a particularly destructive aspect of the compartmentalized inflammation seen in progressive MS. Indeed, the authors noted that rim-active lesion volume accounted for >50% of the change in sNfL level. Thus, it appears that microglial activation both within the lesion and in the surrounding tissue is a major contributor to neuroaxonal damage.

While sNfL is most strongly associated with focal inflammatory activity, the authors noted that the present results suggest that sNfL may also be a marker of smouldering disease since patients had no recent Gd+ lesions and had been relapse-free for >5 years.