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Published on: September 21, 2021
Subclinical central inflammation is risk for RIS and CIS conversion to MS
1Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Rome, Italy/IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy.
Background:
Subtle diffuse intrathecal inflammation is undetectable by conventional neuroimaging, and could influence multiple sclerosis (MS) disease course.
Objective:
To explore the role of subclinical persisting intrathecal inflammation in radiologically isolated syndrome (RIS) or clinically isolated syndrome (CIS) conversion to MS, and in early MS disease reactivation.
Methods:
One-hundred ninety-three subjects with RIS, CIS, relapsing-remitting (RR), or primary progressive (PP) MS were included, along with 76 matched controls. Cerebrospinal fluid (CSF) levels of interleukin-8 (IL-8), a major proinflammatory cytokine, were measured as a biomarker of intrathecal inflammation. Patients were followed up for 2 years. Clinical and imaging measures of disease progression were recorded.
Results:
High central contents of IL-8 were associated to clinical progression in subjects with RIS, and to the risk of conversion to MS in subjects with CIS. Asymptomatic intrathecal inflammation placed subjects at risk for MS conversion, even regardless lesion load. CSF IL-8 levels were higher in RR MS with high disease activity. Higher number of relapses in the first two years since diagnosis and shorter first inter-attack intervals were observed in patients with high levels of IL-8.
Conclusion:
IL-8 might provide utility in determining the presence of active intrathecal inflammation, and could be important in diagnostically undefined cases.
Insights
Subtle intrathecal inflammation, indicated by interleukin-8 (IL-8), predicts conversion to multiple sclerosis (MS) in early stages and disease activity in established MS.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
Background:
- Subtle intrathecal inflammation is often undetectable by conventional neuroimaging.
- This inflammation may significantly impact the disease course of multiple sclerosis (MS).
Purpose of the Study:
- To investigate the role of subclinical intrathecal inflammation in the conversion of radiologically isolated syndrome (RIS) and clinically isolated syndrome (CIS) to MS.
- To assess the link between intrathecal inflammation and early MS disease reactivation.
Main Methods:
- Cerebrospinal fluid (CSF) levels of interleukin-8 (IL-8) were measured in 193 subjects with RIS, CIS, relapsing-remitting MS (RRMS), or primary progressive MS (PPMS), and 76 controls.
- Subjects were followed for 2 years, monitoring clinical and imaging disease progression.
- IL-8 served as a biomarker for intrathecal inflammation.
Main Results:
- Elevated CSF IL-8 levels were associated with clinical progression in RIS and increased MS conversion risk in CIS, irrespective of lesion load.
- Higher IL-8 levels correlated with increased disease activity in RRMS.
- Patients with high IL-8 experienced more relapses and shorter inter-attack intervals.
Conclusions:
- Interleukin-8 (IL-8) can identify active intrathecal inflammation.
- IL-8 may be valuable for diagnosing and managing MS, particularly in ambiguous cases.
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