A substantial number of Rasmussen syndrome patients have increased IgG, CD4(+) T cells, TNF alpha, and Granzyme B in CSF

Purpose: We studied the immunologic molecules in cerebrospinal fluid (CSF) and discussed their evolutional changes in pediatric patients with Rasmussen syndrome (RS). Methods: CSF samples collected from 27 patients with RS (average onset age, 7.5 +/- 5.6 years) were studied. Cell count, protein, glucose, albumin, chloride, and immunoglobulin G (IgG) levels were measured by conventional methods. Surface markers of lymphocytes in CSF were examined by a cell sorter. Granzyme B, interferon gamma (IFN gamma), interleukin 4 (IL-4), tumor necrosis factor alpha (TNF alpha), and IL-12 in CSF were quantitated by enzyme-linked immunosorbent assay (ELISA). Autoantibodies against GluR epsilon 2 (NR2B) were examined by immunoblot. Results: The data of the first CSF examination showed that IgG levels (Mann-Whitney U test, p < 0.01), CD4(+) T cells (p = 0.02), TNF alpha levels (p < 0.01), and Granzyme B levels (p < 0.01) were elevated compared with disease controls. White blood cell count, IFN gamma level, IL-12 level, and Granzyme B level were elevated, especially in the early stage of disease. CD4(+) T cells, CD8(+) cells, CD3(+) T cells, IgG levels, and TNF alpha levels were elevated at all stages of disease evolution. Protein levels and albumin levels were elevated in the progressed stage. Autoantibodies against GluR epsilon 2 (NR2B) (IgG) were found in 50% of patients in the early stage, and the positive rate was low at the progressed stage. Discussion: The present findings suggest that complex pathophysiologic mechanisms involving CD4(+) T cells and CD8(+) T cells change evolutionally during the progression of RS. A crucial cytotoxic process occurs in the early stage, and declines in the progressed stage.