[show abstract][hide abstract] ABSTRACT: Indwelling intrathecal drug delivery systems are becoming increasingly important as a method of neuromodulation within the nervous system. In particular, intrathecal baclofen therapy has shown efficacy and safety in the management of spasticity and dystonia in children. The most common complications leading to explantation of the pumps are skin breakdown and infection at the pump implantation site. The pediatric population poses particular challenges with regard to these complications because appropriate candidates for intrathecal baclofen therapy are often undernourished and thus have a dearth of soft tissue mass to cover a subcutaneously implanted baclofen pump. We report a technique of subfascial implantation that provides greater soft tissue coverage of the pump, thereby reducing the potential for skin breakdown and improving the cosmetic appearance of the implantation site.
Eighteen consecutively treated children (average age, 8 yr, 7 mo) with spasticity and/or dystonia underwent subfascial implantation of a baclofen pump. These children's mean weight of 42.9 lb is less than the expected weight for a group of children in this age group, ranging from 4 years, 8 months, to 15 years, 7 months. In all patients, the pump was inserted into a pocket surgically constructed between the rectus abdominus and the external oblique muscles and the respective anterior fascial layers.
At an average follow-up of 13.7 months, no infection or skin breakdown had occurred at the pump surgical site in any of the 18 patients.
At this early follow-up, the subfascial implantation technique was associated with a reduced rate of local wound and pump infections and provided optimal cosmetic results as compared with that observed in retrospective cases.
[show abstract][hide abstract] ABSTRACT: X-linked adrenoleukodystrophy is a progressive neurodegenerative disorder involving the destruction of white matter in the brain and adrenocortical hormone deficiency. Clinical symptoms first appear between 4 and 8 years of age and include spasticity, visual loss, dysphagia, and seizures. In this report, continuous infusion of intrathecal baclofen was used to treat the severe spasticity of an 8-year-old patient with X-linked adrenoleukodystrophy. The improvement in this patient's quality of life, including the elimination of pain and the increased ease of care, suggests that intrathecal baclofen should be considered as part of the treatment strategy for spasticity associated with X-linked adrenoleukodystrophy and other neurodegenerative disorders in children and adults.
[show abstract][hide abstract] ABSTRACT: Few molecular targets are both consistently and selectively expressed in a majority of central nervous system (CNS) neoplasms. Receptor tyrosine kinases have been implicated in brain tumor oncogenesis. We previously isolated one such receptor, discoidin domain receptor-1 (DDR1), from high-grade pediatric brain tumors. Here, we analyze the cellular origin and distribution of DDR1 expression in human brain tumors and its expression in tumor cells relative to surrounding brain.
By use of a digoxigenin-labeled DDR1 riboprobe, we investigated the expression of DDR1 messenger ribonucleic acid in a prospective series of 30 resected human primary and metastatic brain neoplasms, nonneoplastic human brain, and mouse embryonic brain, as well as a mouse glioblastoma model, by in situ hybridization.
All the high-grade primary brain and metastatic brain tumors showed unequivocal, intense DDR1 expression within the majority of tumor cells, whereas expression was not observed in hyperplastic tumor blood vessels, normal brain blood vessels, inflammatory cells, or in the normal brain tissue that surrounded the tumor. Receptor expression was limited to tumor cells located within solid tumor tissue. Overall, 27 of 29 resected CNS tumors exhibited tumor cell-specific DDR1 expression, whereas one specimen composed of isolated glioblastoma cells within invaded brain parenchyma showed no detectable staining for this receptor. DDR1 was also expressed preferentially in the ventricular zone (a region of highly proliferating precursor cells) of mice at embryonic Day 15.5.
We found that DDR1 is consistently expressed in all high-grade brain neoplasms studied and is selective for tumor cells in the specimens analyzed. The expression of DDR1 by tumor cells of CNS neoplasms and by primitive cells of the embryonic ventricular zone suggests that DDR1 is a potentially useful marker of tumor cells within the CNS.
[show abstract][hide abstract] ABSTRACT: Intramedullary spinal cord tumors (IMSCTs) of the pediatric population are rare and comprise thirty-five percent of intraspinal neoplasms. Low-grade astrocytomas predominate; ependymomas increase in frequency with ascending age and become the most frequent IMSCT in adults. Gangliogliomas are very rare in adults but comprise nearly thirty percent of tumors in children under three years of age. The cervical spine is the region of the spine most affected. Pain is the most common presenting symptom with weakness, gait deterioration, torticollis also frequently reported. Hydrocephalus occurs with greater frequency than in adult patients and often requires a shunt. Motor and sensory evoked potential monitoring is routinely utilized. Osteoplastic laminotomy is performed to forestall the development of progressive spinal deformity. Gross total resection is feasible in most ependymomas and results in surgical cure. Astrocytomas are infiltrating neoplasms and gross total resection is occasionally possible only in the pediatric population. However, the role of radical resection of low-grade fibrillary astrocytomas of the spinal cord in children has not been definitively demonstrated in the literature. Outcome for low-grade astrocytomas is better in children than adults, but not as favorable as that for ependymomas. Malignant tumors have dismal outcomes and surgery in these patients serves only to provide a diagnosis.
Journal of Neuro-Oncology 06/2000; 47(3):225-30. · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Until recently, intra-axial brainstem tumors were traditionally regarded as surgically inaccessible lesions with a uniformly poor prognosis. However, increasing data indicate that distinct subgroups of brainstem tumors exist that are amenable to surgical intervention. To address this question, we reviewed our experience in the operative management of 39 consecutive patients, in the magnetic resonance imaging (MRI) era, with intra-axial cervicomedullary tumors, in order to determine those factors associated with long-term outcome. Thirty-nine patients (26 male, 13 female) underwent surgery by a single surgeon (F.J.E.) between 1985 and 1994. Mean age of diagnosis was 14 years (range 3 months - 60 years); mean duration of preoperative symptoms was 24 weeks (range 1-168). Twenty patients presented with lower cranial nerve dysfunction and 19 presented with motor and/or sensory dysfunction. All patients were graded according to the McCormick Scale, pre- and postoperatively, and at the time of follow-up. All patients were evaluated with MRI scanning. Twenty-three patients had either previous biopsy or subtotal resection, 13 previous radiation therapy, and 6 previous chemotherapy. The mean time to follow-up was 48 months (range 7-138). Twelve patients underwent gross total resection, 7 near total resection (>90%), 15 subtotal resection (50-90%), and 5 partial resection (< 50%). Histologically, there were 15 low-grade fibrillary astrocytomas, 9 ependymomas, 7 gangliogliomas, 3 anaplastic astrocytomas, 3 juvenile pilocytic astrocytomas, and 2 mixed gliomas. Although the vast majority of tumors were low grade histologically, a higher proportion of the patients with high-grade lesions experienced tumor progression when compared to low-grade tumors (75 vs. 30%). Overall, the 5-year progression-free and total survivals were 60 and 89%, respectively. There was 1 death within the first postoperative month. Preoperative duration of symptoms greater than 15 weeks was associated with a longer progression-free survival. There was a trend for preoperative neurologic grade to predict functional neurologic outcome at follow-up. In summary, intra-axial tumors of the cervicomedullary junction are a distinct subset of brainstem tumors, predominantly of low-grade histology, with favorable long-term progression-free and total survivals following surgical resection. A long duration of preoperative symptoms may indicate an indolent clinical course and a more favorable prognosis. Our data also indicate that early surgical intervention is warranted prior to neurologic deterioration.
[show abstract][hide abstract] ABSTRACT: Progressive multifocal leukoencephalopathy (PML), a demyelinating disease caused by the JC papovavirus, is an opportunistic infection afflicting patients with impaired cellular immunity. Although initially described in patients with hematological malignancies, PML has become associated with several other immunocompromised states, particularly human immunodeficiency virus (HIV) infection. There are numerous central nervous system manifestations in patients with acquired immunodeficiency syndrome. A major characteristic that distinguishes PML from other more common lesions, such as toxoplasmosis or non-Hodgkin's lymphoma, is the lack of contrast enhancement. We describe a case of PML that exhibits contrast enhancement, and we conclude that the diagnosis of PML must be considered in patients with HIV who have contrast-enhancing lesions.
A 40-year-old woman presented with progressive hemiparesis, blurred vision, and ataxia. Magnetic resonance imaging revealed a contrast-enhancing lesion involving the left middle cerebellar peduncle, causing mild compression of the fourth ventricle.
The patient underwent a stereotactic serial biopsy with the presumptive diagnosis of moderate- to high-grade glioma. Histological examination of the biopsy specimen revealed early PML. Subsequently, a test for HIV was obtained and the results were positive.
We have reported another atypical radiographic characteristic of PML associated with HIV. We conclude that PML lesions can enhance after the administration of gadolinium. Therefore, the diagnosis of PML must be entertained in patients whose test results were positive for HIV with contrast-enhancing lesions and that a stereotactic serial biopsy may be necessary to provide a definitive diagnosis.
[show abstract][hide abstract] ABSTRACT: We have used the polymerase chain reaction to clone and characterize growth factor receptor tyrosine kinases (RTKs) expressed in 3 pathologically distinct pediatric brain tumors, an anaplastic ependymoma, a glioblastoma multiforme and a primitive neuroectodermal tumor (PNET). These neoplasms are presumed to be derived from embryonic neuroepithelial precursor cells of the central nervous system. This cloning demonstrated expression of 24 distinct kinase genes: 16 receptor type kinases and 8 nonreceptor type kinases. The expression of 6 receptors, including Hek2, IRR, Ryk, FGFR3, and 2 members of the newly identified cell adhesion kinase receptor family, DDR and TKT, in such tumors has not been reported previously. Northern analysis of mRNA levels revealed DDR expression in 6 of 7 pediatric brain tumors including an ependymoma, PNET, glioblastoma and astrocytoma, and also in an adult pheochromocytoma. Thus, the DDR cell adhesion kinase may be widely expressed in pediatric brain tumors. Also, PCR cloning may be an effective procedure for characterizing RTKs in clinical tissue samples and revealing the expression of novel RTK species.
[show abstract][hide abstract] ABSTRACT: The authors report their experience using a novel surgical approach for resecting tumors located in the posterior parahippocampal gyrus. Prior attempts to resect epileptogenic foci in this location have been limited by a significant risk of injury to lateral temporal lobe cortical and vascular structures. To avoid these potential complications, the authors have used a lateral occipitosubtemporal, computer-assisted stereotactic volumetric approach to resect radiographically defined tumors in seven patients with intraaxial neoplasms of the posteromedial temporal lobe. This series included one female and six male patients, ranging in age from 15 to 67 years, who presented with seizures, visual field loss, or headache. Gross-total resection of three high-grade gliomas, two gangliogliomas, and one mixed glioma was accomplished with no permanent morbidity or operative mortality. The authors conclude that this approach is advantageous for resecting tumors in this location because, by avoiding unnecessary brain resection or retraction, it significantly reduces the risk of injury to lateral temporal lobe structures, helps maintain precise spatial and anatomical orientation for the surgeon, and, like all computer-assisted volumetric approaches, delineates the margin between the tumor and surrounding neural tissue.
Journal of Neurosurgery 09/1996; 85(2):272-7. · 3.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: FROM THE RECORDS of approximately 1500 shunt operations performed between 1987 and 1992, we identified 37 adults between ages 38 and 86 years (mean, 70 yr) with the normal-pressure hydrocephalus (NPH) syndrome who underwent surgery by a single surgeon. Since 1990, we have routinely used a flow-regulated shunt system (Orbis-Sigma valve [OSV]; Cordis Corporation, Miami, FL) in these patients. In this study, we compared the OSV system with conventional differential-pressure (DP) shunt systems uniformly used before 1990. This series (n = 37) consisted of 62% men (n = 23) and 38% women (n = 14). We excluded all patients with hydrocephalus associated with central nervous system neoplasms, intracerebral hemorrhage, or trauma as well those with radiographically documented late-onset aqueductal stenosis. All patients presented with the NPH clinical syndrome, chiefly with magnetic gait. In addition, 75% of patients experienced cognitive loss and 59% experienced urinary incontinence. The mean duration of preoperative symptoms was 35 months (range, 7-120 mo). Eight patients (22%) had undergone previous shunting procedures before referral to our service. A total of 89 shunt operations were performed in the 37 patients. Using actuarial methods and controlling for a history of prior shunt surgery, we found no significant difference in the time to initial malfunction (shunt survival) between the OSV and the DP shunts. There were three subdural hematomas and one infection in the OSV group compared with no complications in the DP valve group (P = 0.11). Thirty-six patients were available for follow-up, at a mean of 14 months after surgery. Nearly 90% of all patients experienced improvement in gait after shunting, regardless of the valve system that was used. There was one unrelated death. Realizing the limitations of a retrospective analysis and on the basis of the limited number of patients in this study, we conclude that using actuarial methods, we found no significant difference in shunt survival when comparing the OSV with the standard DP valve shunt systems with antisiphon devices in patients with NPH. Contrary to previous reports, the OSV is not free of overdrainage complications. Most patients (89%) with the NPH syndrome who primarily presented with gait disorder experienced significant improvement in gait after either OSV or DP shunting procedures when selected for surgery on the basis of the clinical syndrome and confirmatory radiographic data.
[show abstract][hide abstract] ABSTRACT: Future advances in neuro-oncology will increasingly rely on an understanding of the molecular biology of brain tumors. Recent laboratory work, including the identification of oncogenes and tumor suppressor genes, has elucidated many of the molecular events contributing to oncogenesis. In particular, the signaling pathways for the growth factors have been implicated in the genesis and the maintenance of several human tumors, including neoplasms of the central nervous system (CNS). Growth factor autocrine and paracrine stimulatory loops promote tumor proliferation and angiogenesis. A family of structurally related growth factor receptors, the receptor tyrosine kinases, are particularly relevant to tumors of the CNS. This large family includes the receptors for the epidermal growth factor, the platelet-derived growth factor, the fibroblast growth factor, the insulin-like growth factor, the neurotrophins related to the nerve growth factor, and the vascular endothelial growth factor, as well as several receptors for which no growth factor ligand has been identified. Several of these receptor molecules and their growth factor ligands are preferentially expressed in the embryonic brain and are thought to play a central role in regulating the determination of the cell fate during the development of the CNS. Moreover, the overexpression or the mutation of genes encoding these receptors can be oncogenic. Researchers think that some receptors in this family (i.e., those that have been shown to be overexpressed or mutated in human brain tumors) contribute to brain tumor oncogenesis. This article will focus on recent experimental work and will discuss the classification and the biology of the receptor tyrosine kinases, as well as their roles in the development of the CNS and in tumorigenesis.
[show abstract][hide abstract] ABSTRACT: Fourth-ventricular shunting is commonly used to treat symptomatic posterior fossa cysts of the Dandy-Walker malformation and trapped fourth ventricle. Although the benefits of this procedure have been widely reported, there is a paucity of data on the pitfalls of posterior fossa shunting in the neurosurgical literature. During the 4-year period from July 1989 to June 1993, we placed fourth-ventricular shunts in 12 patients. Remarkably, 5 patients suffered complications related to posterior fossa catheter placement (42% rate). Three of these patients developed new cranial nerve dysfunction caused by direct injury to the floor of the fourth ventricle, 1 patient suffered an intracystic hemorrhage and acute shunt malfunction, and 1 patient had the catheter tip in the brainstem on postoperative studies without new neurological deficit. We conclude that placement of fourth-ventricular shunts can be fraught with complications which we believe is related to technique. We propose that altering the trajectory of the ventricular catheter from our usual midline technique to a more lateral position will lessen the chances for injury to the floor of the fourth ventricle. In this manner we hope to decrease our incidence of complications for this procedure.
[show abstract][hide abstract] ABSTRACT: Pathological and clinical data from 56 patients operated on for craniopharyngioma since 1981 were analyzed to determine the utility of dividing patients with this tumor into distinct clinical groups based on recognized pathological type and to determine the prognostic import of brain invasion. Of the tumors in the 30 adult patients, 66% were adamantinomatous, 28% were squamous papillary, and the remainder were mixed. However, of the tumors in the 26 children, 96% were adamantinomatous and none were pure squamous papillary (P < 0.01). Forty-six percent of the children compared with 17% of the adults had brain invasion (P < 0.01). Brain invasion was present in 37% of the adamantinomatous but in only 13% of the squamous papillary tumors. Seventy-seven percent of the children underwent gross total resection (GTR) compared with 27% of the adults (P < 0.01). Sixty-three percent of the squamous papillary tumors underwent GTR compared with 54% of the adamantinomatous and mixed tumors. Follow-up ranged from 7 to 187 months (mean, 49 mo). After subtotal resection, with or without radiation therapy, 58% of the tumors recurred compared with 17% recurrence after GTR (P < 0.01), with a mean time to recurrence of 34 months. In both tumor histological types, subtotal resection was associated with a higher rate of tumor recurrence compared with gross total resection. Among the subtotally resected craniopharyngiomas, 2 of the 3 (67%) squamous papillary and 11 of the 21 (52%) adamantinomatous and mixed tumors recurred. In contrast, among the totally resected tumors, none of the 5 squamous papillary and only 5 of the 25 (20%) adamantinomatous and mixed tumors recurred. There were no significant differences in Karnofsky performance status score, mortality rate, or visual and endocrine outcomes when comparing patients based on histological tumor type. When controlling for age and extent of resection, we found that brain invasion had no significant effect on recurrence rate in totally resected tumors. Based on the limited number of patients in this series, we conclude as follows. 1) Contrary to previous reports, squamous papillary craniopharyngiomas, like adamantinomatous tumors, may recur when subtotally resected. 2) For both tumor variants, the most significant factor associated with craniopharyngioma recurrence is the extent of surgical resection rather than histopathological subtype. 3) Contrary to prior hypotheses, brain invasion in totally resected tumors does not predict higher recurrence. 4) GTR is associated with a significantly lower recurrence rate and can be achieved without sacrificing functional outcome.
[show abstract][hide abstract] ABSTRACT: Perforation of colonic diverticula is a complication of corticosteroid use that has not been described in the neurosurgical literature. Between 1987 and 1992, 719 patients who underwent surgery for primary and metastatic brain and spinal tumors of the central nervous system received 2246 to 4936 mg of methylprednisolone given over at least 7 days. Five patients in this group (all men, ages 50-69 yr) experienced a sigmoid diverticular perforation at a mean dose of 3947 mg of methylprednisolone (range, 2240-6160 mg). Of these five, two had a known history of diverticular disease. In contrast, during this same period, 3749 patients who underwent neurosurgical procedures for non-neoplastic conditions did not receive corticosteroids and experienced no colonic perforations. All five patients with colonic perforations presented with abdominal pain and had free intraperitoneal air that was revealed on radiographs of the abdomen. Perforation of a sigmoid diverticulum was confirmed in all five at exploratory laparotomy. Four patients had good outcomes, and one died. We conclude the following: 1) patients over age 50 who receive high-dose corticosteroids are at risk for sigmoid colonic perforation, and these medications should be used with caution in such patients; 2) if possible, lower total doses of perioperative corticosteroids should be used in patients with known diverticular disease; and 3) because corticosteroids mask many of the inflammatory signs of perforation, this diagnosis should be considered in any patient with abdominal discomfort, fever of unknown origin, or unexplained leukocytosis.
[show abstract][hide abstract] ABSTRACT: Two cases of cystic brainstem schwannomas protruding into the fourth ventricle are described. Both patients presented with hemifacial spasm. While there is only one previous case report of an intraventricular brainstem schwannoma, there has been no prior description in the literature of hemifacial spasm associated with such a tumor. The clinical, radiographic, surgical, and histopathological features of these tumors are elaborated. The relationship of hemifacial spasm to the various putative theories of origin proposed for intraparenchymal schwannomas is discussed.
Journal of Neuro-Oncology 02/1993; 15(1):37-43. · 3.12 Impact Factor