Minimal tethered cord syndrome associated with thickening of the terminal filum.

OBJECT: The authors investigated the occurrence of anatomical abnormalities of the terminal filum in children undergoing surgical filum lysis for minimal tethered cord syndrome (TCS). METHODS: Five consecutive children (age range 6-12 years) with medically refractory voiding dysfunction but no magnetic resonance (MR) imaging-documented lumbosacral abnormality on 1.5-tesla sequences underwent preoperative urodynamic studies consisting of calibrated uroflowmetry, cystometrography, and voiding cystourethrography. Urodynamic bladder function was abnormal in each case. A sixth child (5 years of age) who had progressive lower-extremity weakness, gait abnormality, and voiding dysfunction, but in whom there was no MR imaging-documented lumbosacral abnormality, was also included. These six children experienced improved bladder function after terminal filum lysis. Histologically, the terminal filum in these patients was fattier, thicker, and more densely fibrous than that in three reference patients undergoing incidental terminal filum lysis during selective dorsal rhizotomy or resection of a lumbar dermal sinus tract. All four patients with voiding dysfunction who underwent postoperative urodynamic testing experienced corresponding improvement in bladder function. CONCLUSIONS: Significant improvement of voiding dysfunction after surgical lysis of the terminal filum in children with MR imaging-documented normal lumbosacral spines was observed. In such children, in whom neurogenic dysfunction is identified by urodynamic testing, structural abnormalities of the terminal filum may exist. A prospective randomized controlled study of children undergoing surgical terminal filum lysis in cases of minimal TCS should be undertaken.

Tumour-induced polarization of tumour vaccine-draining lymph node T cells to a type 1 cytokine profile predicts inherent strong immunogenicity of the tumour and correlates with therapeutic efficacy in adoptive transfer studies.

Previously we have shown that vaccination with the poorly immunogenic B16BL6-D5 melanoma (D5) elicits a dominant type 2 (T2) cytokine response that fails to protect the host from a subsequent tumour challenge. Here we investigated whether the inherent immunogenicity of a tumour can be correlated with its ability to bias the anti-tumour cytokine response towards either a type 1 (T1) or a T2 profile. The immune response to six tumours of different inherent immunogenicity was assayed. By isolating l-selectinlow T cells from tumour vaccine draining lymph nodes (TVDLN), it was possible to detect tumour-specific cytokine responses from both immunogenic, poorly immunogenic and non-immunogenic tumours. Immunogenic tumours (MCA-304, MCA-309, MPR-4) induced a predominant tumour-specific T1 cytokine response. In contrast, weakly (MCA-310, MPR-3) and poorly/non-immunogenic tumours (MPR-5, D5) sensitized T cells with a predominant tumour-specific T2 cytokine response. A significant correlation (P < 0.025) between immunogenicity and the ratio of tumour-specific interferon-gamma : interleukin-4 (IL-4) secretion by TVDLN T cells was identified. We then documented that non-therapeutic T cells primed by the poorly immunogenic D5, recognized "tumour-rejection" antigens and that reprogramming their cytokine response, by in vitro culture with IL-12 and anti-IL-4, to a T1 profile uncovered therapeutic efficacy. In contrast, TVDLN T cells primed by a therapeutic vaccine lose therapeutic efficacy when cultured with IL-4. These results provide insights into the development of a protective anti-tumour immune response and strengthen the hypothesis that a T1 cytokine response is critical for T-cell-mediated tumour regression.