Intrathecal IgM synthesis in pediatric MS is not a negative prognostic marker of disease progression: quantitative versus qualitative IgM analysis.
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.


CONCLUSIONS
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.
Department of Pediatrics and Pediatric Neurology, Georg-August University Göttingen, Germany.
C
C
Stauch
H
H
Reiber
M
M
Rauchenzauner
A
A
Strasak
D
D
Pohl
F
F
Hanefeld
J
J
Gärtner
K M
KM
Rostásy
D000293:Adolescent; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D007155:Immunologic Factors / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D009391:Nephelometry and Turbidimetry; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D013116:Spinal Cord / Q000276:immunology*; D013129:Spinal Puncture; D013997:Time Factors
D015415:Biomarkers; D007075:Immunoglobulin M; D007155:Immunologic Factors