Evidence of cellular immune activation in children with opsoclonus-myoclonus: cerebrospinal fluid neopterin.
To evaluate cellular immune activation in opsoclonus-myoclonus syndrome, we measured the inflammatory marker neopterin in the cerebrospinal fluid of 16 children with opsoclonus-myoclonus and neuroblastoma, 24 children with opsoclonus-myoclonus but no tumor, and 19 age-matched controls. The mean concentration in opsoclonus-myoclonus was 2.3-fold higher than in controls (P = .008). Neopterin was greatly elevated in four of the most neurologically severe cases, up to 8.3-fold above the highest control level. Thirteen of the 40 children with opsoclonus-myoclonus but no controls had a neopterin concentration >2 SD above the control mean (P = .005). In this high neopterin subgroup, neurologic severity was significantly greater and the duration of neurologic symptoms was less. In 16 children re-examined on immunotherapy, including adrenocorticotropic hormone (ACTH) combination therapy, treatment was associated with a significant reduction in both neopterin and neurologic severity. Neopterin did not differ significantly between the tumor and non-tumor opsoclonus-myoclonus etiologies. No abnormalities of tetrahydrobiopterin were found. Although cerebrospinal fluid neopterin lacked the sensitivity to be a biomarker of disease activity in opsoclonus-myoclonus, elevated concentrations do support a role for T-cell activation and cell-mediated immunity in its pathophysiology.
Pranzatelli
Michael R
MR
National Pediatric Myoclonus Center, Southern Illinois University School of Medicine, P.O. Box 19643, Springfield, IL 62702, USA.
Hyland
Keith
K
Tate
Elizabeth D
ED
Arnold
Lauren A
LA
Allison
Tyler J
TJ
Soori
Gamini S
GS
D000293:Adolescent; D001708:Biopterins / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D019798:Neopterin / Q000134:cerebrospinal fluid*; D009447:Neuroblastoma / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000628:therapy; D020361:Paraneoplastic Syndromes, Nervous System / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000628:therapy
D001708:Biopterins; D019798:Neopterin; C003402:sapropterin