Faculty Bibliography

Soft-tissue glomus tumors (or glomangiomas) are unrelated to neuroendocrine paragangliomas (glomus tympanicum, jugulare, and vagale). The authors present the first reported case of an orbital soft-tissue glomus tumor in a child. An 8-year-old girl developed rapidly progressive right-eye blindness, proptosis, and a sixth cranial nerve palsy. Magnetic resonance imaging demonstrated a homogeneously enhancing lesion extending from the right orbit through the superior orbital fissure to the cavernous sinus and middle cranial fossa. A biopsy specimen demonstrated the lesion to be a soft-tissue glomus tumor. Following angiography and embolization, a gross-total resection of the tumor was achieved. The patient was treated with adjuvant proton-beam radiotherapy. At 24 months follow-up her proptosis and sixth cranial nerve palsy had resolved and there was no evidence of tumor recurrence

The authors describe the case of a patient with an enhancing, intramedullary cervical spinal cord lesion and associated syrinx. Biopsy sampling of the cervical lesion was performed, and the histological findings were consistent with a demyelinating process supporting the diagnosis of multiple sclerosis (MS). Syrinx formation associated with demyelinating disease has only been described in isolated cases, almost exclusively in Japanese patients with MS. A 22-year-old woman of Caribbean descent presented with a subacute, progressive myelopathy including symptoms of pain and weakness in all extremities, bladder incontinence, and the inability to ambulate. Magnetic resonance imaging of the brain and spinal cord demonstrated an enlarged cervical cord with enhancement and central cavitation consistent with a syrinx. The patient underwent a C3-7 laminoplasty and placement of a dural graft for cord decompression as well as fenestration of the central syrinx. Biopsy sampling of the lesion was performed, and the histopathological analysis, in conjunction with subsequent laboratory and diagnostic testing, supported the diagnosis of demyelinating disease. After treatment with a course of high-dose dexamethasone and inpatient rehabilitation therapy, the patient demonstrated significant clinical improvement. Spinal cord involvement is not uncommon in patients with demyelinating disease; however, enhancing lesions associated with extensive tissue loss and syrinx formation have rarely been reported. For the consulting neurological surgeon, demyelinating disease should be included in the differential diagnosis of such lesions given the level of complexity and risk to the patient associated with open biopsy of the spinal cord.

OBJECT/OBJECTIVE:Atlantoaxial and occipitocervical instability in children have traditionally been treated with posterior bone and wire fusion and external halo orthoses. Recently, successful outcomes have been achieved using rigid internal fixation, particularly C1-2 transarticular screws. The authors describe flow diagrams created to help clinicians determine which method of internal fixation to use in complex anatomical circumstances when bilateral transarticular screw placement is not possible. METHODS:The records of children who underwent either atlantoaxial or occipitocervical fixation with rigid internal fixation over an 11-year period were retrospectively reviewed to define flow diagrams used to determine treatment protocols. RESULTS:Among the 95 patients identified who underwent atlantoaxial or occipitocervical fixation, the craniocervical anatomy in 25 patients (six atlantoaxial and 19 occipitocervical fixations [26%]) required alternative methods of internal fixation. Types of screw fixation included loop or rod constructs anchored by combinations of C1-2 transarticular screws (15 constructs), C-1 lateral mass screws (11), C-2 pars screws (24), C-2 translaminar screws (one), and subaxial lateral mass screws (six). The mean age of the patients (15 boys and 10 girls) was 9.8 years (range 1.3-17 years). All 22 patients with greater than 3-month follow-up duration achieved solid bone fusion and maintained stable constructs on radiographic studies. Clinical improvement was seen in all patients who had preoperative symptoms. CONCLUSIONS:Novel flow diagrams are suggested to help guide selection of rigid internal fixation constructs when performing pediatric C1-2 and occipitocervical stabilizations. Use of these flow diagrams has led to successful fusion in 25 pediatric patients with difficult anatomy requiring less common constructs.

This article addresses the key features, presentation, and current management of pediatric patients who have Chiari I and Chiari II malformations. It further discusses syringohydromyelia and scoliosis as they relate to pediatric Chiari malformations.

The authors describe the internal cranial expansion (ICE) procedure, a surgical technique that was used to treat two chronically shunt-treated children who presented with medically and surgically refractory intracranial hypertension despite the presence of functioning cerebrospinal fluid shunt systems. The ICE procedure was used as a means to increase intracranial volume without sacrificing calvarial rigidity. Intracranial volume was increased by 5% in one case and 10% in the other. Both patients have returned to their neurological and functional baselines, and they are free of symptoms related to intracranial hypertension.

OBJECTIVE: Lack of human leukocyte antigens and costimulatory molecules have been suggested as mechanisms by which human malignant gliomas avoid immune recognition and elimination. METHODS: Using quantitative multiparameter flow cytometric analysis, tumor cells from patients with glioblastoma multiforme (n = 18) were examined ex vivo for the expression of human leukocyte antigen Class I and II molecules and the costimulatory molecules B7-1 and B7-2. They were compared with reactive astrocytes from peritumoral brain metastases (n = 7), and astrocytes removed during nontumor surgery (n = 5). RESULTS: In contrast to the vast majority of solid peripheral human tumors, these results demonstrate that glioblastoma multiforme frequently express both human leukocyte antigen Class I and II molecules. Like most solid peripheral tumors, glioblastoma multiforme tumor cells express few or no B7 costimulatory molecules. Functional assays using heterogeneous ex vivo tumor preparations or pure populations of ex vivo tumor cells and microglia obtained using fluorescence-activated cell sorting indicate that CD4+ T-cells are activated by tumor cells only in the presence of exogenous B7 costimulation (provided by addition of soluble agonist anti-CD28 monoclonal antibody). CONCLUSION: Thus, in contrast to many solid peripheral tumors, failure to present tumor antigens is not a likely impediment to immunotherapeutic strategies against malignant gliomas. Rather, immunotherapeutic strategies need to overcome low levels of B7 costimulation

We have shown that a COOH-terminal peptide of p53 (amino acids 361-382, p53p), linked to the truncated homeobox domain of Antennapedia (Ant) as a carrier for transduction, induced rapid apoptosis in human premalignant and malignant cell lines. Here, we report that human and rat glioma lines containing endogenous mutant p53 or wild-type (WT) p53 were induced into apoptosis by exposure to this peptide called p53p-Ant. The peptide was comparatively nontoxic to proliferating nonmalignant human and rat glial cell lines containing WT p53 and proliferating normal human peripheral marrow blood stem cells. Degree of sensitivity to the peptide correlated directly with the level of endogenous p53 expression and mutant p53 conformation. Apoptosis induction by p53p-Ant was quantitated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and Annexin V staining in human glioma cells in vitro and in a syngeneic orthotopic 9L glioma rat model using convection-enhanced delivery in vivo. The mechanism of cell death by this peptide was solely through the Fas extrinsic apoptotic pathway. p53p-Ant induced a 3-fold increase in extracellular membrane Fas expression in glioma cells but no significant increase in nonmalignant glial cells. These data suggest that p53 function for inducing Fas-mediated apoptosis in gliomas, which express sufficient quantities of endogenous mutant or WT p53, may be restored or activated, respectively, by a cell-permeable peptide derived from the p53 COOH-terminal regulatory domain (p53p-Ant). p53p-Ant may serve as a prototypic model for the development of new anticancer agents with unique selectivity for glioma cancer cells and it can be successfully delivered in vivo into a brain tumor by a convection-enhanced delivery system, which circumvents the blood-brain barrier.

The management of childhood spasticity requires a multidisciplinary effort. With input from pediatricians, physical and occupational therapists, neurologists, orthotists, orthopedic surgeons, neurological surgeons, and other healthcare personnel, effective treatment for spasticity can be initiated and maintained that can lead to meaningful improvements in quality of life for vast numbers of children. Neurosurgical treatment of spasticity will continue to evolve and be refined as procedures and techniques are appropriately evaluated with reliable and validated outcome measures.

Abnormal head morphology is common among infants and often leads parents to ask their pediatricians for guidance. While the vast majority of such children development and prevent adverse neurobehavioral sequelae secondary to increased intracranial pressure or impaired cerebral growth. The coordination of a multidisciplinary team in the setting of a center experienced in the management of craniosynostosis will assure the best possible results for each patient.