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Abstract
Objectives To evaluate intrathecal immunoglobulin M (IgM) production, as compared to previously established risk factors, as risk factor for conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and to explore the association of intrathecal IgM production with onset age and radiologic and CSF findings in CIS/early MS.
Methods Comprehensive CSF data, including oligoclonal immunoglobulin G (IgG) bands (OCB) and calculated intrathecal IgM and IgG production, were collected in a prospective study of 150 patients with CIS/early MS with regular clinical and MRI assessments.
Results Intrathecal IgM production >0% occurred in 23.2% (33/142) of patients, who were on average 5 years younger at disease onset (p = 0.013) and more frequently had infratentorial lesions (18/32, 56.3%) than patients without intrathecal IgM production (33/104, 31.7%, p = 0.021). In multivariable Cox regression analyses, intrathecal IgM production in patients with a CIS (n = 93, median clinical and MRI follow-up 24 and 21 months) was strongly associated with conversion to MS according to the McDonald 2010 criteria (hazard ratio [95% confidence interval] 3.05 [1.45–6.44], p = 0.003) after adjustment for age (0.96 [0.93–1.00], p = 0.059), OCB (0.92 [0.33–2.61], p = 0.879), intrathecal IgG production (0.98 [0.48–1.99], p = 0.947), and radiologic evidence of dissemination in space (2.63 [1.11–6.22], p = 0.028).
Conclusion Intrathecal IgM production is a strong independent risk factor for early conversion to MS and may thus represent a clinically meaningful marker for predicting future disease activity in patients with a CIS.
Glossary
- CEL=
- contrast-enhancing lesions;
- CI=
- confidence interval;
- CIS=
- clinically isolated syndrome;
- DIS=
- dissemination in space;
- DIT=
- dissemination in time;
- EDSS=
- Expanded Disability Status Scale;
- HR=
- hazard ratio;
- IEF=
- isoelectric focusing;
- IgA=
- immunoglobulin A;
- IgG=
- immunoglobulin G;
- IgM=
- immunoglobulin M;
- IQR=
- interquartile range;
- MPRAGE=
- magnetization prepared rapid gradient echo;
- MS=
- multiple sclerosis;
- OCB=
- oligoclonal bands;
- OR=
- odds ratio;
- RRMS=
- relapsing-remitting multiple sclerosis;
- T2W=
- T2-weighted;
- TE=
- echo time;
- TI=
- inversion time;
- TR=
- repetition time
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
CME Course: NPub.org/cmelist
- Received July 14, 2018.
- Accepted in final form May 10, 2019.
- © 2019 American Academy of Neurology
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