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Published on: December 9, 2015
Predictors of risk of secondary progression in multiple sclerosis
Sini Laaksonen1,2,3,4, Marcus Sucksdorff5,2,3,4, Anna Vuorimaa5,2,3,4
1Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, Turku 20521, Finland.
Background:
Multiple sclerosis (MS) manifests clinically as relapsing disease (relapsing-remitting MS (RRMS)), progressive disease, or as combination of these phenotypes. The underlying pathology for relapses and focal inflammatory activity is driven by adaptive immune cells, whereas brain-compartmentalized pathology promoted by innate immune cell activation likely contributes to progression.
Objectives:
To explore the usability of various imaging and soluble biomarkers in predicting change in clinical phenotype from RRMS to secondary progressive MS (SPMS).
Design:
Prospective longitudinal study.
Methods:
Twenty-three RRMS patients aged 40-50 years had clinical evaluation, brain MR imaging, serum neurofilament light and glial fibrillary acidic protein (GFAP) measurements, and brain positron emission tomography with translocator protein (TSPO)-binding radioligand [11C](R)-PK11195 at baseline. Patients were followed for 5 years and assessed for signs of conversion to SPMS at the end of follow-up. Evolution to SPMS was determined based on an increased Expanded Disability Status Score and significant accrual of clinical symptoms.
Results:
After 5 years, 8/23 (35%) patients had converted to SPMS. At baseline, they had increased TSPO-binding in the normal appearing white matter, thalamus, and perilesional area compared to patients who did not convert to SPMS. The proportion and number of TSPO-rim-active lesions were higher among patients developing SPMS. Higher concentration of GFAP and more pronounced thalamic atrophy were also observed among the SPMS convertors.
Conclusion:
The results suggest that imaging and serum biomarkers reporting on compartmentalized central nervous system inflammation support identification of MS patients at risk of SPMS conversion. Evaluation of thalamic atrophy and measurement of soluble biomarkers can be implemented in the assessment of individual patients' progression risk in daily clinical practice. This can help in identifying patients who are at greatest need of smoldering pathology-targeting therapy. Larger studies are needed to validate these results.
Trial Registration:
NCT3134716 role of microglia in the pathogenesis of progressive multiple sclerosis, https://clinicaltrials.gov/study/NCT03134716.
Insights
Biomarkers like TSPO-binding and GFAP can identify multiple sclerosis (MS) patients at risk of progressing from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS). Early identification aids in timely treatment for neuroinflammation.
Area of Science:
- Neuroimmunology
- Neuroimaging
- Biomarker Discovery
Background:
- Multiple sclerosis (MS) presents with diverse clinical phenotypes, including relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS).
- While adaptive immunity drives relapses, innate immune activation in the brain contributes to MS progression.
- Identifying biomarkers for RRMS to SPMS conversion is crucial for effective therapeutic strategies.
Purpose of the Study:
- To assess the predictive value of imaging and serum biomarkers for the clinical transition from RRMS to SPMS.
- To explore the role of neuroinflammation markers in predicting MS disease progression.
Main Methods:
- A prospective longitudinal study followed 23 RRMS patients (aged 40-50) for 5 years.
- Evaluated were clinical status, brain MRI, serum GFAP and NfL, and [¹¹C](R)-PK11195 PET for TSPO binding.
- Conversion to SPMS was defined by increased disability (EDSS) and clinical symptom accrual.
Main Results:
- 35% of patients converted to SPMS within 5 years.
- SPMS converters showed higher baseline TSPO binding in normal-appearing white matter, thalamus, and perilesional areas.
- Increased TSPO-positive lesions, higher GFAP levels, and greater thalamic atrophy were observed in SPMS converters.
Conclusions:
- Imaging and serum biomarkers reflecting CNS inflammation can identify MS patients at risk of SPMS conversion.
- Thalamic atrophy and soluble biomarkers (GFAP) can be integrated into clinical practice to assess progression risk.
- This approach may help target therapies for smoldering MS pathology, though larger validation studies are needed.
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