Background: Intrathecal IgM synthesis is reported to be associated with a worse prognosis in adults with multiple sclerosis (MS).
Objective: To study the predictive value of intrathecal IgM synthesis for the clinical course of pediatric MS.
Methods: Seventy children with onset of MS before the age of 16 years and followed for a median period of 10.4 years (range: 0.4–22.8 years) were studied. The two subgroups with (n = 44) or without (n = 26) intrathecal IgM synthesis were distinguished by a new, very sensitive, evaluation of quantitative analysis in cerebrospinal fluid (CSF)/serum quotient diagrams (Reibergrams). The clinical course and EDSS (Expanded Disability Status Scale) scores at five and ten years were compared with IgM frequencies between both groups with a new statistics program for CSF data.
Results: The cohort of children without intrathecal IgM production had higher numbers of attacks in the first two years and shorter time intervals between first and second attack, although this was not statistically significant (p = 0.04, p = 0.15 respectively). In addition there was also a trend for girls without intrathecal IgM synthesis to have a higher EDSS score after 10 years compared with the group with IgM synthesis.
Conclusion: Intrathecal IgM synthesis is not associated with a more rapid progression of disability in pediatric MS. Reevaluation of data from previous reports about the negative predictive value of intrathecal IgM synthesis in adult MS with a CSF statistics tool show that the apparent contradiction is due to a methodological bias in the qualitative detection of ‘oligoclonal’ IgM or linear IgM index.
ReiberHTeutMPohlDRostasyKMHanefeldF. Pediatric Multiple sclerosis: Age related differences and time course of the neuroimmunological reponse in CSF. Mult Scler2009; 15: 1466–1480.
2.
ReiberHAlbaumW. Statistical evaluation of intrathecal protein synthesis in CSF/Serum quotient diagrams. Acta Neuropsychiatrica2008; 20: 48–49.
Wildemann B, Oschmann P, Reiber H (eds) (2010). Laboratory diagnosis in Neurology. Thieme, Stuttgart, Germany.
5.
ReiberHPeterJB. Cerebrospinal fluid analysis – disease-related data patterns and evaluation programs. J Neurol Sci2001; 184: 101–122.
6.
VillarLMMasjuanJGonzalez-PorqueP. Intrathecal IgM synthesis predicts the onset of new relapses and a worse disease course in MS. Neurology2002; 59: 555–559.
7.
ShariefMKThompsonEJ. Intrathecal immunglobulin M synthesis in multiple sclerosis. Brain1991; 114: 181–195.
8.
VillarLMMasjuanJGonzalez-PorquePPlazaJ. Intrathecal IgM Synthesis in neurologic diseases: Relationship with disability in MS. Neurology2002; 58: 824–826.
9.
VillarLMSadabaMCRoldanE. Intrathecal synthesis of oligoclonal IgM against myelin basic protein predicts an aggressive disease course in MS. J Clin Invest2005; 115: 187–194.
10.
PoserCMPatyDWScheinbergLC. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol1983; 13: 227–231.
11.
McDonaldWICompstonAEdanG. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol2001; 50: 121–127.
12.
Lechner-ScottJKapposLHofmanM. Can the Expanded Disability Status Scale be assessed by telephone?. Mult Scler2003; 9: 154–159.
13.
ReiberHUngefehrSJacobiC. The intrathecal, polyspecific and oligoclonal immune response in multiple sclerosis. Mult Scler1998; 4: 111–117.
14.
PohlDRostasyKReiberHHanefeldF. CSF characteristics in early-onset multiple sclerosis: A tool for early diagnosis. Neurology2004; 63: 1966–1967.
15.
FranciottaDSalvettiMLolliFSerafiniBAloisiF. B cells and multiple sclerosis. Lancet Neurology2008; 7: 852–858.
16.
MeinlEKrumbholzMHohlfeldR. B lineage cells in the inflammatory central nervous system environment: Migration, maintenance, local antibody production and therapeutic modulation. Ann Neurol2006; 59: 880–892.
17.
SchneiderREulerBRauerS. Intrathecal IgM-synthesis does not correlate with the risk of relapse in patients with a primary demyelinating event. Euro J Neurol2007; 14: 907–911.
18.
MikaeloffYSuissaSValleeLLubetzkiCPonsotGConfavreuxC. KIDMUS Study Group. First episode of acute inflammatory demyelinisation in childhood: prognostic factors for multiple sclerosis. J Pediatr2004; 144: 246–252.
19.
MikaeloffYCaridadeGAssiSSuissaSTardieuM. Prognostic factors forearly severity in a childhood multiple sclerosis cohort. Pediatrics2006; 118: 1133–1139.
20.
SimoneILCarraraDTortorellaC. Course and prognosis in early-onset MS. Comparison with adult-onset forms. Neurology2002; 59: 1922–1928.
21.
ReiberH. Flow rate of cerebrospinal fluid (CSF) – a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci1994; 122: 189–203.
