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Smouldering neuroinflammation starts at disease onset and increasingly drives disability accumulation1,2 

The relative contribution of both acute and smouldering neuroinflammation shifts as patients progress across the disease process.1,3
 

Biological changes in the prodromal phase of MS and microglial activation in clinically isolated syndrome (CIS)/radiologically isolated syndrome (RIS) demonstrate that smouldering 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 smouldering neuroinflammation persists in the absence of relapses and acute lesions1
  • Disability accumulation driven by smouldering neuroinflammation can happen throughout the disease spectrum9

     

Illustration depicting shifting contribution to disability of acute and smouldering neuroinflammation.RRMS=relapsing-remitting MS; SPMS=secondary progressive MS.
Adapted from Giovannoni G, et al. Ther Adv Neurol Disord. 2022;15:1-18. doi:10.1177/17562864211066751

Hear from the experts

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

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Smouldering Stories

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

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References:

  1. Giovannoni G, Popescu V, Wuerfel J, et al. Smouldering multiple sclerosis: the ‘real MS’. Ther Adv Neurol Disord. 2022;15:1-18.

  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.

  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.

  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.

  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.

MAT-XU-2500915 v1.0 May 2025