Contributions
Abstract: EP1309
Type: ePoster
Abstract Category: Clinical aspects of MS - 3 Paediatric MS
Background: Inflammatory patterns in cerebrospinal fluid (CSF) are fully evolved already at the first clinical manifestation of multiple sclerosis (MS), therefore CSF analysis may help considerably in establishing correct diagnosis in childhood or adolescence. CSF specific oligoclonal bands (OB) demonstrate comparable diagnostic sensitivity in early and adult-onset MS, however result is only qualitative and rater-dependent. Measurement of kappa free light chains (KFLC) could provide a faster and easier to standardize tool but was not yet performed in paediatric MS.
Objective: In our study we aimed to evaluate the diagnostic significance of CSF KFLC in paediatric MS.
Methods: CSF and serum samples of paediatric patients with MS (n = 18, 15 girls) and other non-inflammatory neurological disorders (n = 9, 5 girls) were analysed. Median age at the time of spinal tap was 16 years (range 13-17) in the MS group and 13 years (range 7-17) in controls who presented mainly with headache syndromes. KFLC concentrations were measured by nephelometry, using monoclonal antibody immunoassay. The presence of OB was determined with agarose isoelectric focusing followed by alkaline phosphatase immunoblotting.
Results: Eighty-nine percent of our MS patients had CSF specific oligoclonal bands. CSF KFLC concentrations were higher in MS patients with a median 2.7 mg/l (range 0.1 - 19.4 mg/l) compared to the controls median 0.1 mg/l (range 0 - 1.1 mg/l); p < .0001. Diagnostic sensitivity of CSF KFLC concentration was 83% if the cut-off 0.3 mg/l derived from our previous adult-onset MS data was used. Diagnostic specificity of OB was 100% and 89% for the CSF KFLC concentration. CSF KFLC to total protein ratio, which roughly accounts for brain CSF barrier integrity, demonstrated the same diagnostic accuracy as KFCL concentration with a median 1.0% (range 0.02% - 5.5%) in young MS compared to 0.03% (range 0.02% - 0.26%) in the control group (p < .0001).
Conclusion: Our results show the relevance of KFLC as a diagnostic biomarker in the early MS. Study in a larger paediatric cohort is needed to investigate the age-related differences in CSF concentrations and to elucidate characteristics in other demyelinating disorders. Quantitative differences in CSF KFLC levels among the young and adult onset MS patients may require adjustment of the optimal cut-off value.
Disclosure:
Andreja Emersic: nothing to disclose.
Neli Bizjak: nothing to disclose.
Uros Rot received grants/research support from Biogen Idec and consultation fees/travel grants from Bayer, Biogen Idec, Genzyme, Merck-Serono, Novartis and Teva.
Support by the University Medical Centre Ljubljana research programme is acknowledged.
Abstract: EP1309
Type: ePoster
Abstract Category: Clinical aspects of MS - 3 Paediatric MS
Background: Inflammatory patterns in cerebrospinal fluid (CSF) are fully evolved already at the first clinical manifestation of multiple sclerosis (MS), therefore CSF analysis may help considerably in establishing correct diagnosis in childhood or adolescence. CSF specific oligoclonal bands (OB) demonstrate comparable diagnostic sensitivity in early and adult-onset MS, however result is only qualitative and rater-dependent. Measurement of kappa free light chains (KFLC) could provide a faster and easier to standardize tool but was not yet performed in paediatric MS.
Objective: In our study we aimed to evaluate the diagnostic significance of CSF KFLC in paediatric MS.
Methods: CSF and serum samples of paediatric patients with MS (n = 18, 15 girls) and other non-inflammatory neurological disorders (n = 9, 5 girls) were analysed. Median age at the time of spinal tap was 16 years (range 13-17) in the MS group and 13 years (range 7-17) in controls who presented mainly with headache syndromes. KFLC concentrations were measured by nephelometry, using monoclonal antibody immunoassay. The presence of OB was determined with agarose isoelectric focusing followed by alkaline phosphatase immunoblotting.
Results: Eighty-nine percent of our MS patients had CSF specific oligoclonal bands. CSF KFLC concentrations were higher in MS patients with a median 2.7 mg/l (range 0.1 - 19.4 mg/l) compared to the controls median 0.1 mg/l (range 0 - 1.1 mg/l); p < .0001. Diagnostic sensitivity of CSF KFLC concentration was 83% if the cut-off 0.3 mg/l derived from our previous adult-onset MS data was used. Diagnostic specificity of OB was 100% and 89% for the CSF KFLC concentration. CSF KFLC to total protein ratio, which roughly accounts for brain CSF barrier integrity, demonstrated the same diagnostic accuracy as KFCL concentration with a median 1.0% (range 0.02% - 5.5%) in young MS compared to 0.03% (range 0.02% - 0.26%) in the control group (p < .0001).
Conclusion: Our results show the relevance of KFLC as a diagnostic biomarker in the early MS. Study in a larger paediatric cohort is needed to investigate the age-related differences in CSF concentrations and to elucidate characteristics in other demyelinating disorders. Quantitative differences in CSF KFLC levels among the young and adult onset MS patients may require adjustment of the optimal cut-off value.
Disclosure:
Andreja Emersic: nothing to disclose.
Neli Bizjak: nothing to disclose.
Uros Rot received grants/research support from Biogen Idec and consultation fees/travel grants from Bayer, Biogen Idec, Genzyme, Merck-Serono, Novartis and Teva.
Support by the University Medical Centre Ljubljana research programme is acknowledged.