CSF parameters associated with early MRI activity in patients with MS

Klein, Ana Paula; Selter, Rebecca C; Hapfelmeier, Alexander; Berthele, Achim; Müller‐Myhsok, Bertram; Pongratz, Viola; Gasperi, Christiane; Zimmer, Claus; Mühlau, Mark; Hemmer, Bernhard

doi:10.1212/nxi.0000000000000573

Cited by 22 publications

(17 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By contrast, OCB positivity failed to predict early disease activity in our study. This finding favoring the prognostic value of quantitative IgG synthesis over OCB was also indicated by several large studies before (10,(36)(37)(38)(39). A recent prospective study with 1,376 German patients found that patients with an elevated IgG index were twice more likely to develop disability worsening 4 years after onset, whereas the presence of OCB failed to show a higher risk of EDSS worsening (10).…”

Section: Discussionmentioning

confidence: 76%

“…A recent prospective study with 1,376 German patients found that patients with an elevated IgG index were twice more likely to develop disability worsening 4 years after onset, whereas the presence of OCB failed to show a higher risk of EDSS worsening ( 10 ). Klein et al also found IgG index elevation one of the strongest predictors of cMRI activity 1 year after onset in a cohort of 149 CIS patients, with OCB positivity showing a predictive value though with a smaller odds ratio ( 37 ). However, two large studies based on patients with an established diagnosis of MS revealed no association between either OCB status or quantitative measurement of IgG synthesis and disease progression in patients ( 13 , 39 ).…”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

IgG Index Revisited: Diagnostic Utility and Prognostic Value in Multiple Sclerosis

et al. 2020

View full text Add to dashboard Cite

Objective: Early and accurate diagnosis of multiple sclerosis (MS) remains a clinical challenge. The main objective is to evaluate the diagnostic and prognostic value of the routinely performed immunoglobulin G (IgG) index for MS patients in the Asian population. Methods: A retrospective study was conducted among a cohort of clinically isolated syndrome (CIS) patients in China with known oligoclonal band (OCB) status and IgG index at baseline. We first evaluated the predictive value of IgG index for OCB status. Secondly, the diagnostic utility and prognostic value of IgG index alone were tested. Lastly, we incorporated IgG index into the 2017 McDonald criteria by replacing OCB with either "IgG index or OCB" (modified criteria 1), "IgG index and OCB" (modified criteria 2), or "IgG index" (modified criteria 3). The diagnostic utility of different criteria was calculated and compared. Results: In a CIS cohort in China (n = 105), IgG index > 0.7 forecasted OCB positivity (X 2 = 22.90, P < 0.001). An elevated IgG index was highly prognostic of more clinical relapses [1-year adjusted odds ratio [OR] = 1.32, P = 0.015; 2-years adjusted OR = 1.69, P = 0.013] and Expanded Disability Status Scale worsening (1-year adjusted OR = 1.76, P = 0.040; 2-years adjusted OR = 1.85, P = 0.032). Under the 2017 McDonald criteria (Positive Likelihood Ratio = 1.54, Negative Likelihood Ratio = 0.56), an IgG index > 0.7 in CIS patients increased the likelihood of developing MS within 2 years, either when OCB status was unknown (Positive Likelihood Ratio = 2.11) or with OCB positivity (Positive Likelihood Ratio = 2.11) at baseline; An IgG index ≤ 0.7, along with a negative OCB, helped rule out the MS diagnosis (Negative Likelihood Ratio = 0.53). Conclusions: IgG index > 0.7 predicts OCB positivity at the initial attack of MS and is prognostic of early disease activity. IgG index serves as an easily-obtainable and accurate OCB surrogate for MS diagnosis in the Asian population.

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 93%

IgG Index Revisited: Diagnostic Utility and Prognostic Value in Multiple Sclerosis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Finally, a recent retrospective study involving 149 patients with CIS and MS investigated a possible association between CSF parameters and MRI activity. IgG index was highly correlated with the detection of new cerebral lesions on MRI scan and proved to be an independent predictor of future MRI activity [45] .…”

Section: Igg Indexmentioning

confidence: 86%

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Toscano¹,

Patti²

2020

View full text Add to dashboard Cite

For many years, quantifiable biomarkers in neurological diseases have represented a hot topic. In multiple sclerosis (MS), cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983, with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001. Nowadays, that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event, according to the 2017 revised McDonald criteria. Possibly kappa free light chains, N-CAM, chitinase 3-like protein 1 and IgM oligoclonal bands, not yet implemented in clinical practice, could similarly gain importance in the near future. Furthermore, the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity, better defining the MS phenotype and patients with highly active disease. Accordingly, myelin proteins, intermediate filaments, metalloproteinases and other molecules involved in the inflammatory cascade, are currently under investigation. Finally, it has long been known that axonal loss occurs from the early phases, leading to a progressive neurological deterioration. Since established criteria to assess treatment failure and transition to progressive forms are still lacking, both treatment response and prognostic biomarkers would be useful to predict MS course, and neurofilaments seem to have this potential. The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.

show abstract

“…Further, we provide evidence for a relationship between incident OCB status and subsequent disability, suggesting that it could play a role in the prognostication of MS in children. Whether active lesions are a component of this relationship in pediatric patients, as observed among adults 27 , remains to be seen. Future studies should aim to incorporate MRI data to better understand these dynamics.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid markers in incident pediatric-onset multiple sclerosis: a nationwide study

McKay

Wickström

Hillert

et al. 2021

Sci Rep

View full text Add to dashboard Cite

To investigate whether cerebrospinal fluid (CSF) markers differ between pediatric-onset multiple sclerosis (PoMS, onset < 18 years) and adult-onset (AoMS), and whether these markers are associated with clinical outcomes among PoMS. Prospective nationwide registry study of incident MS, including persons with a CSF sample < 3 years post-MS onset. We compared CSF oligoclonal band (OCB) status, immunoglobulin G (IgG) index levels, and mononuclear cell count between PoMS and AoMS. Within the PoMS cohort we analyzed the association between CSF markers, relapse rate and Expanded Disability Status Scale (EDSS) score, using negative binomial regression and generalized estimating equations, respectively. The cohort consisted of 130 PoMS and 3228 AoMS cases. The PoMS group had higher odds of OCB-positivity (odds ratio: 2.70; 95% CI 1.21–7.67). None of the CSF markers were associated with relapse rate in the PoMS cohort; however, OCB-positivity was associated with higher EDSS scores. This study suggested that PoMS more commonly display CSF evidence for intrathecal IgG production than AoMS. Further, we found evidence of a relationship between OCB-positivity and subsequent disability, suggesting that they could play a role in the prognostication of MS in children.

show abstract

CSF parameters associated with early MRI activity in patients with MS

Cited by 22 publications

References 35 publications

IgG Index Revisited: Diagnostic Utility and Prognostic Value in Multiple Sclerosis

IgG Index Revisited: Diagnostic Utility and Prognostic Value in Multiple Sclerosis

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Cerebrospinal fluid markers in incident pediatric-onset multiple sclerosis: a nationwide study

Contact Info

Product

Resources

About