Biological changes in the prodromal phase of MS and microglial activation in clinically isolated syndrome (CIS)/radiologically isolated syndrome (RIS) demonstrate that smoldering neuroinflammation begins even before the first clinically apparent relapse or acute lesion.1,2,4-8

  • Over the course of MS, acute neuroinflammation may decline, but smoldering neuroinflammation persists in the absence of relapses and acute lesions1
  • Disability accumulation driven by smoldering neuroinflammation can happen throughout the disease spectrum9
Illustration depicting shifting contribution to disability of acute and smoldering neuroinflammation.

naSPMS=non-active secondary progressive MS; RRMS=relapsing-remitting MS.

With the increasing contribution of smoldering neuroinflammation to disability accumulation over the course of MS, specific therapeutic approaches that address this process across the disease spectrum from RRMS to naSPMS are required.9

Hear from the experts

Bhupendra O. Khatri, MD, FAAN, discusses the onset of smoldering neuroinflammation at the 2023 AAN Annual Meeting

Headshot of Bhupendra O. Khatri, MD, FAAN.

Smoldering Stories

Smoldering neuroinflammation may drive Albert's disability accumulation—hear his story.

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Learn About the Impact

Identify the early physical and cognitive changes of disability accumulation

   References:

  1. Giovannoni G, Popescu V, Wuerfel J, et al. Smouldering multiple sclerosis: the ‘real MS’. Ther Adv Neurol Disord. 2022;15:17562864211066751. doi:10.1177/17562864211066751
  2. Giovannoni G. The neurodegenerative prodrome in multiple sclerosis. Lancet Neurol. 2017;16(6):413-414.
  3. Filippi M, Amato MP, Centonze D, et al. Early use of high-efficacy disease-modifying therapies makes the difference in people with multiple sclerosis: an expert opinion. J Neurol. 2022;269(10):5382-5394.
  4. Absinta M, Lassmann H, Trapp BD. Mechanisms underlying progression in multiple sclerosis. Curr Opin Neurol. 2020;33(3):277-285.
  5. Giannetti P, Politis M, Su P, et al. Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome. Brain. 2015;138(1):110-119.
  6. Suthiphosuwan S, Sati P, Absinta M, et al. Paramagnetic rim sign in radiologically isolated syndrome. JAMA Neurol. 2020;77(5):653-655. doi:10.1001/jamaneurol.2020.0124
  7. Bjornevik K, Munger KL, Cortese M, et al. Serum neurofilament light chain levels in patients with presymptomatic multiple sclerosis. JAMA Neurol. 2020;77(1):58-64. doi:10.1001/jamaneurol.2019.3238
  8. Cortese M, Riise T, Bjørnevik K, et al. Preclinical disease activity in multiple sclerosis: a prospective study of cognitive performance prior to first symptom. Ann Neurol. 2016;80(4):616-624. doi:10.1002/ana.24769
  9. Cree BAC, Hollenbach JA, Bove R, et al; University of California, San Francisco MS-Epic Team. Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol. 2019;85(5):653-666.