Faculty Bibliography

OBJECT/OBJECTIVE:Despite decades of surgical experience, the long-term consequences of occipitocervical (OC) and atlantoaxial (C1-2) fusions in children are unknown. The purpose of this study was to determine the long-term effects of these fusions on growth and alignment of the maturing cervical spine. METHODS:A retrospective chart review was conducted for patients 6 years of age or younger (mean 4.7 years, range 1.7-6.8 years) who underwent OC or C1-2 fusion at the Primary Children's Medical Center at the University of Utah within the last 10 years. Immediate postoperative plain radiographs and computed tomography (CT) scans were compared with the most recent plain and dynamic radiographs to assess changes in spinal growth and alignment. Seventeen children met entry criteria for the study. All patients had fusion documented on follow-up radiography or CT scans. At a mean follow up of 28 months, there were no cases of sagittal malalignment (kyphotic or swan-neck deformity), subaxial instability (osteophyte formation or subluxation), or unintended fusion of adjacent levels. The lordotic curvature of the cervical spine increased from a mean of 15 degrees postoperatively to 27 degrees at follow up (p = 0.06). A mean of 34% of the vertical growth of the cervical spine occurred within the fusion segment. When data were analyzed pertaining to a subgroup of five patients who underwent follow-up periods for longer than 48 months (mean 50.2 months, range 48-54 months), similar results were seen. CONCLUSIONS:Preliminary follow-up results indicate that, compared with older children, children 6 years of age or younger undergoing OC or C1-2 fusion are not at an increased risk of spinal deformity or subaxial instability. Longer follow-up periods, during which measurements of the spinal canal are taken, will be necessary to determine precisely how children's spines grow and remodel after an upper cervical spine fusion.

OBJECT/OBJECTIVE:Currently, no diagnostic or procedural standards exist for clearing the cervical spine in children after trauma. The establishment of protocols has been shown to reduce the time required to accomplish clearance and reduce the number of missed injuries. The purpose of this study was to determine if reeducation and initiation of a new protocol based on the National Emergency X-Radiography Utilization Study criteria could safely increase the number of pediatric cervical spines cleared by nonneurosurgical personnel. METHODS:The authors collected and reviewed data regarding cervical spine clearance in children (age range 0-18 years) who presented to the emergency department at Primary Children's Medical Center in Salt Lake City, Utah, between 2001 and 2006 after sustaining significant trauma. Radiographic and clinical methods of clearing the cervical spine, as well as the type and management of injuries, were determined for two periods: Period I (January 2001-December 2003) and Period II (January 2004-February 2006). Between 2001 and 2003, 95% of 936 cervical spines were cleared by the neurosurgical service. Twenty-one ligamentous injuries (2.2%) and 12 fracture/dislocations (1.3%) were detected, and five patients (0.5%) required operative stabilization. Since January 2004, 585 (62.4%) of 937 cervical spines have been cleared by nonneurosurgical personnel. Twelve ligamentous injuries (1.3%) and 14 fracture/dislocations (1.5%) were identified, and four patients (0.4%) required operative stabilization. No late injuries were detected in either time period. CONCLUSIONS:The protocol outlined in the paper has been effective in detecting cervical spine injuries in children after trauma and has increased the number of cervical spines cleared by nonneurosurgical personnel by nearly 60%. Reeducation with the establishment of protocols can safely facilitate clearance of the cervical spine after trauma by nonneurosurgical personnel.

OBJECTIVES: Adjuvant-linked vaccines have been shown to induce anti-tumor immunity in patients with a variety of solid tumors. In this study we describe an in vitro model of active immunotherapy using autologous fibroblasts as immunogen. Correlative results from glioma patients immunized with autologous fibroblasts are also described. METHODS: Peripheral blood lymphocytes (PBLs) from normal subjects were immunized in vitro against autologous skin fibroblasts coupled to the adjuvant muramyl dipeptide. The lymphocytes developed cell-mediated cytotoxicity that was measured with a short-term chromium release assay. Results of in vitro experiments were compared to data derived from glioma patients immunized with subcutaneous injection of an autologous adjuvant-linked fibroblast vaccine. Glioma target cells and fibroblast immunogens were derived from early passage primary tissue culture. RESULTS: A comparison of autologous vs. homologous immunogen indicated that major histocompatibility complex matching was required at the sensitization stage of immunity (17.2 +/- 3.4% specific lysis vs. 0.4 +/- 3.1%, P < 0.01). Pre-treatment of fibroblast immunogen cells with interferon gamma (IFN-gamma) was found to significantly increase immunity (42.2 +/- 10.0%, P < 0.01), as did IFN-gamma pre-treatment of tumor target cells (35.8 +/- 9.0%, P < 0.01). The positive effect of IFN-gamma was diminished by treatment of cells with IFN-alpha. These in vitro results correlated well with in vivo data derived from glioma patients immunized with an autologous adjuvant-linked fibroblast vaccine. PBLs from patients developed direct cell-mediated cytotoxicity against autologous tumor cells. Lysis of tumor targets after in vivo immunization increased over a three-week interval (from 1.2 +/- 3.0% to 21.0 +/- 3.4%, P < 0.01) while lysis of a non-MHC matched control cell line remained essentially unchanged. CONCLUSIONS: Specific lysis of glioma targets in vitro was achieved after in vivo sensitization with autologous adjuvant-linked fibroblasts. Collectively, the data indicate that biochemically modified autologous cells can stimulate anti-glioma immunity in humans. The degree of specific immunity seen in our patients compares favorably with other published series using glioma cells as an antigenic source. Accordingly, fibroblasts may represent a practical alternative to glioma cells for vaccine construction.

OBJECT: The syndrome of normal-pressure hydrocephalus (NPH) refers to the clinical triad of gait disturbance, dementia, and urinary incontinence in association with idiopathic ventriculomegaly and normal intracranial pressure. Ventriculoperitoneal (VP) shunt placement often yields significant clinical improvements, sometimes without apparent reduction of ventricular size. The authors hypothesized that careful volumetric measurements would show a decrease in ventricular volume in these patients. METHODS: Twenty consecutive patients with NPH underwent placement of VP shunts equipped with programmable valves. In 11 patients pre- and postoperative neuroimaging was performed, which allowed volumetric analysis. Volumetric measurements of the lateral ventricles were calculated in triplicate by National Institutes of Health image-processing software to assess standard computerized tomography (CT) scans (eight patients) or magnetic resonance (MR) images (three patients) obtained before and after shunt placement. Ventricular volumes were also assessed by an independent neuroradiologist. Postoperative studies were performed at a time of clinical improvement, between 1 and 9 months postsurgery (mean 5 months). Preoperative and postoperative Unified Parkinson's Disease Rating Scale evaluations were performed in four patients. Significant clinical improvement occurred in all patients after shunt placement (mean follow-up period 17.5 months). Although 10 (91%) of 11 patients demonstrated a calculable decrease in volume in the lateral ventricles (mean decrease 39%), formal interpretation of neuroimages indicated a definite decrease in lateral ventricular volume in only three (27%) of 11 patients. CONCLUSIONS: Volumetric measurements obtained to compare preoperative and postoperative CT or MR studies obtained in patients with NPH in whom clinical improvement was seen after shunt placement surgery show a demonstrable decrease in ventricular size. Volumetric measurements may be helpful in clinical assessment postoperatively and in guiding programmable valve pressure settings