Biomedical subjects

I F Pollack

Publications and source records attributed to I F Pollack.

At least 37 records · Page 2Linked to original sources

PubMed1999

Potent topoisomerase I inhibition by novel silatecans eliminates glioma proliferation in vitro and in vivo.

Although topoisomerase inhibitors, such as camptothecin and topotecan, have been widely used in the treatment of nonglial tumors, their application for gliomas has been limited by poor efficacy relative to toxicity that may in part reflect limited bioavailability and blood stability of these agents. However, the potential promise of this class of agents has fostered efforts to develop new, more potent, and less toxic inhibitors that may be clinically relevant. Using a cascade radical annulation route to the camptothecin family, we developed a series of novel camptothecin analogues, 7-silylcamptothecins ("silatecans"), that exhibited potent inhibition of topoisomerase I, dramatically improved blood stability, and sufficient lipophilicity to favor blood-brain barrier transit. We explored the efficacy of a series of these agents against a panel of five high-grade glioma cell lines to identify a promising compound for further preclinical testing. One of the most active agents in our systems (DB67) inhibited tumor growth in vitro with an ED50 ranging between 2 and 40 ng/ml, at least 10-fold more potent than the effects observed with topotecan, and at least comparable with those of SN-38, the active metabolite of CPT-11. Because DB67 also exhibited the highest human blood stability of any of the agents examined, this agent was then selected for in vivo studies. A dose-escalation study of this agent in a nude mouse U87 glioma model system demonstrated a concentration-dependent effect, with tumor growth inhibition at day 28 postimplantation (the day control animals began to require sacrifice because of large tumor size) of 61 +/- 7% and 73 +/- 3% after administration of DB67 doses of 3 and 10 mg/kg/day, respectively, for 5 days beginning on postimplantation day 7. Animals that continued treatment with 10 mg/kg/day in three additional 21-day cycles all remained progression free after >90 days of follow-up but later developed enlarging tumors after treatment was stopped. However, a slightly higher dose (30 mg/kg/day) induced complete tumor regression after only two cycles in all study animals and was effective even if treatment was delayed until large, bulky tumors had developed. Application of the 30 mg/kg/day dose to treat established intracranial glioma xenografts led to long-term (>90 day) survival in six of six animals, whereas all controls died of progressive disease (P < 0.00001). No apparent toxicity was encountered in any of the treated animals. In summary, the present studies indicate that silatecans may hold significant promise for the treatment of high-grade gliomas and provide a rationale for proceeding with further preclinical evaluation of their efficacy and safety versus commercially available camptothecin derivatives.

Animals↗

PubMed1999

Pediatric brain tumors.

Pediatric brain tumors differ from adult brain tumors in several major ways. First, the types of tumors encountered in children are uncommon in adults, and vice versa. Second, tumors of the posterior fossa comprise a far greater percentage of tumors in children as compared to adults. Third, the value of extensive tumor resection, which is controversial for malignant brain tumors in adults, has been confirmed for a variety of childhood brain tumors. Fourth, chemotherapy has been shown to be effective in improving overall outcome in several childhood brain tumors, but has yet to be demonstrated to have a major benefit for adult tumors. In addition, to avoid the morbidity of irradiation on the developing nervous system, chemotherapy is increasingly used to delay or avoid using radiotherapy in children younger than 3 years of age with high-grade and incompletely resected low-grade tumors. Fifth, the prognosis for histologically similar tumors is often more favorable in children than adults. A review of general principles in the clinical presentation, diagnostic evaluation, and treatment of childhood brain tumors is followed by discussion of surgical management, adjuvant therapy, and outcome of the more common types of tumors.

Adolescent↗

PubMed1999

Chemotherapy for high-grade gliomas of childhood.

Astrocytomas are the most common group of childhood brain tumors. Approximately 20% of these lesions are histologically malignant tumors that often prove fatal within 2 years of diagnosis, despite the use of surgery and conventional radiotherapy. During the last 15 years, considerable attention has been focused on evaluating the potential role of chemotherapy as a means of improving survival. Although several agents have been observed to have modest therapeutic activity against these tumors, the optimal strategies for improving disease control have yet to be defined. This article will review the results that have been achieved in previous studies using a variety of single and multi-agent chemotherapeutic regimens, and also the rationale for ongoing trials of the major cooperative groups, and will discuss the challenges that are inherent in designing and interpreting therapeutic studies for these tumors. Ways in which currently available approaches may be incorporated into future therapeutic strategies will also be discussed and a brief review of the extensive array of promising new treatment approaches will be presented.

Antineoplastic Agents↗

PubMed1999

The p21-Ras signal transduction pathway and growth regulation in human high-grade gliomas.

Deregulated p21-Ras function, as a result of mutation, overexpression or growth factor-induced overactivation, contributes to at least 30% of human cancer. This article reviews the potential role of the p21-Ras family of GTPases in the regulation of growth of high-grade gliomas and describes how targeting this oncoprotein clinically may provide a novel strategy to counteract glioma proliferation. The application of strategies directed at selectively opposing the deregulated signal transduction pathway of high-grade gliomas may be of potential therapeutic benefit and may offer a whole new arsenal of antineoplastic agents to be included in the multimodal treatment of these challenging neoplasms.

Animals↗

PubMed1999

Protein kinase C inhibition by UCN-01 induces apoptosis in human glioma cells in a time-dependent fashion.

Recent studies in our laboratory have shown that UCN-01 (7-hydroxystaurosporine), which is a derivative of the non-selective protein kinase inhibitor staurosporine that exhibits relative selectivity for protein kinase C (PKC), is a potent inhibitor of glioma growth in in vitro and in vivo models. This agent exhibits both cytotoxic and cytostatic effects, depending on the time period of drug exposure. In the present study, we examined whether UCN-01-induced cytotoxicity correlated with the induction of apoptosis, and characterized further the time course of this process as a prelude to application of UCN-01 in clinical trials. We first demonstrated that the cytotoxic effects of UCN-01 were associated with the induction of morphological features of apoptosis. Secondly, we identified electrophoretic features of apoptosis semiquantitatively at a series of time points using field inversion gel electrophoresis. These studies showed a peak in the induction of high-molecular-weight DNA fragmentation after 3-6 days of drug treatment. Thirdly, we measured the percentage of cells undergoing apoptosis at various time points using a terminal transferase-catalyzed in situ end-labeling technique, which confirmed a time- and concentration-dependent increase in apoptotic cell numbers. This correlated with a progressive decrease in the percentage of cells that were viable as assessed by trypan blue exclusion. Cell killing peaked within 2-4 days after beginning UCN-01 treatment, but continued at a lower level in the ensuing days. Taken together, these studies demonstrated that extended periods of exposure to UCN-01 are needed for optimal manifestation of cytotoxic effects against glioma cells, a factor that must be taken into consideration in the design of future clinical trials with this agent for malignant gliomas.

Alkaloids↗

PubMed1999

The role of surgery in pediatric gliomas.

Pediatric glial tumors differ from adult gliomas in several ways that are of major therapeutic importance. First, the value of extensive tumor resection, which is controversial for malignant intrinsic brain tumors in adults, has been confirmed for a variety of childhood brain tumors, such as supratentorial high-grade and low-grade gliomas and infratentorial low-grade gliomas, ependymomas, and some medulloblastomas. Second, chemotherapy has been found to be effective in improving overall outcome in several childhood brain tumors, such as medulloblastoma and supratentorial high-grade glioma, but has yet to be proven to have a major benefit for adult tumors. In addition, chemotherapy is increasingly used to delay or avoid radiotherapy in young children with high-grade and incompletely resected low-grade tumors to avoid the morbidity of irradiation on the developing nervous system. Third, the prognosis for histologically similar tumors is often more favorable in children than adults. The present chapter will highlight the unique features of childhood glial tumors, discuss general principles in the clinical presentation, diagnostic evaluation, and treatment of these tumors, and then focus on the surgical management and outcome of the more common types of tumors.

Brain Neoplasms↗

PubMed1999

Outcome data and analysis in pediatric neurosurgery.

OBJECTIVE: The purpose of this study was to analyze the outcomes of five commonly performed pediatric neurosurgical operations: 1) initial shunt insertion; 2) first shunt revision; 3) craniotomy for brain tumor; 4) correction of sagittal synostosis; and 5) release of tethered cords. A second purpose was to analyze the neurological outcome data after tethered cord releases. METHODS: Morbidity and mortality records, patient charts, and operative records were reviewed to determine length of hospitalization and, for each disorder, the pertinent outcomes such as duration of shunt function and incidence of infection or neurological morbidity. RESULTS: Many outcome data were expected, such as a high long-term shunt function rate after primary shunt insertion (65% at 5 yr), a low mortality rate (1%) and permanent morbidity rate (10%) after craniotomy for brain tumor, and a low frequency of transfusion (20%) for sagittal synostosis operations. The outcomes among the three neurosurgeons varied more than expected, e.g., the duration of hospitalization after sagittal reconstructions ranged from 3.1 to 5.8 days; the frequency of infections of primary shunt revisions ranged from 0 to 15%; and the neurological morbidity after tethered cord releases ranged from 0 to 12%, with all neurological morbidity occurring in patients undergoing their second or third tether release. CONCLUSION: The data may serve as a basis for outcome comparisons for these procedures. Outcome data allow us to analyze factors to improve patient care, but outcome analysis is complex.

Adolescent↗

PubMed1999

Inhibition of Ras and related guanosine triphosphate-dependent proteins as a therapeutic strategy for blocking malignant glioma growth: II--preclinical studies in a nude mouse model.

OBJECTIVE: Preliminary studies have demonstrated that the Ras family and related guanosine triphosphate-dependent proteins are overactivated in malignant gliomas and that inhibition of the activation of such proteins, by blockade of their post-translational processing, reduces tumor cell growth in vitro. The current study evaluates the utility of this therapeutic strategy in vivo, using preclinical glioma model systems. METHODS: We examined the efficacy against U-87 human malignant glioma cells, in both subcutaneous and intracranial nude mouse models, of selective peptidomimetic inhibitors of farnesyltransferase (FTI-276) and geranylgeranyltransferase (GGTI-297), which are involved in critical steps in the post-translational processing of Ras and related guanosine triphosphate-dependent proteins. For the subcutaneous model, 2 x 10(5) U-87 cells were implanted; after measurable tumors were detected on Day 7, animals were treated with either FTI-276, GGTI-297, or vehicle, administered by continuous infusion for 7 days. Differences in tumor volumes among the treatment groups were examined for significance using a Student's t test. For the intracranial model, 2 x 10(5) U-87 cells were implanted in the right frontal lobe and treatment was initiated on Day 7. In initial studies, animals received a 7-day course of either FTI-276, GGTI-297, or vehicle. In subsequent studies, a 28-day treatment period was used. Comparisons of survival times among treatment groups were performed using a rank-sum test. RESULTS: Although the two agents exhibited comparable antiproliferative activities in previous in vitro studies, an obvious difference in efficacy was apparent in this study. Whereas the geranylgeranyltransferase inhibitor failed to improve survival rates, compared with those observed for control animals, in either the subcutaneous or intracranial model, the farnesyltransferase inhibitor produced objective regression of tumor growth in the subcutaneous model and significant prolongation of survival times in the intracranial model, without apparent toxicity. In the subcutaneous model, tumor volumes for the control, GGTI-297-treated, and FTI-276-treated animals on Day 28 after implantation were 621+/-420, 107+/-104, and 18.5+/-12.7 mm3, respectively (P < 0.05). In the 7-day-treated intracranial model, survival times for the control, GGTI-297-treated, and FTI-276-treated groups were 27.7+/-2.9, 29.8+/-2.1, and 43.6+/-2.7 days, respectively (P < 0.001). In the 28-day-treated intracranial model, survival times for the control, GGTI-297-treated, and FTI-276-treated groups were 29.2+/-3.7, 28.3+/-3.9, and 58.7+/-6.2 days, respectively, with five of six animals in the latter group surviving more than 55 days after tumor implantation (P < 0.001). CONCLUSION: These studies demonstrate that farnesyltransferase inhibition is effective in diminishing the growth of human glioma cells in vivo. Evaluation of this treatment approach in clinical trials is warranted.

Alkyl and Aryl Transferases↗

PubMed1999

A randomized, controlled study of a programmable shunt valve versus a conventional valve for patients with hydrocephalus. Hakim-Medos Investigator Group.

OBJECTIVE: A multicenter prospective randomized controlled study was performed to assess the safety and efficacy of a Codman Hakim programmable shunt valve (Codman/Johnson & Johnson, Raynham, MA) versus a conventional valve system of the surgeon's choice for the treatment of patients with hydrocephalus. METHODS: Enrollment was stratified on the basis of whether the patient was undergoing initial shunt insertion or revision of an existing valve system at study entry. Study end points were: 1) valve explantation, and 2) shunt failure (surgical intervention for any component of the shunt). A total of 377 patients were enrolled onto the study, with 235 undergoing first shunt insertion (119 experimental, 116 control) and 142 undergoing revisions (75 experimental, 67 control). RESULTS: During a follow-up interval of 104 weeks after the first implantation on-study, explantation of the valve was required in 62 (32%) of 194 experimental valves, compared with 71 (39%) of 183 control valves. Two-year survival rates of the original shunt without revision of any component were 52% (62 of 119) and 50% (58 of 116) in experimental and control patients, respectively, who underwent initial shunt insertion, and 43% (32 of 75) and 43% (29 of 67) in experimental and control patients, respectively, who underwent replacement of an existing valve. No statistically significant difference was observed between experimental and control patients in the survival of either the valve or the overall shunt system. Control of hydrocephalus as assessed symptomatically and by imaging was comparable in the two treatment groups. Although problems related to inability to achieve the desired pressure setting were reported in 22 experimental valves, in all but four instances no additional programming was attempted because the patients were functioning well clinically. The most common reasons cited for valve explantation and shunt revision were infection (9.8% frequency in the overall cohort) and proximal shunt malfunction, which occurred with comparable frequency in the experimental and control groups. CONCLUSION: Safety and efficacy of the Codman Hakim programmable shunt valve is comparable to conventional valves in the overall population of patients with hydrocephalus. However, the current study was not designed to assess the efficacy of programmable versus conventional valves in the management of individual hydrocephalus problems, and it had insufficient statistical power to support such comparisons. This study provides a rationale for examining whether the theoretical advantages of a programmable valve for managing challenging hydrocephalus problems can translate into meaningful improvements in shunt and valve survival.

Adolescent↗

PubMed1999

Medical management of eosinophilic granuloma of the cervical spine.

We report a case of eosinophilic granuloma involving the vertebral bodies of the cervical spine in a 33-month-old girl. This lesion was diagnosed by needle biopsy and treated with prednisone and vinblastine therapy along with immobilization in a Minerva brace. The child has done well over a 9-month follow-up and has shown MRI evidence of resolution of the lesion, reestablishment of structural integrity within the cervical spine and potential reconstitution of the involved vertebral bodies.

Anti-Inflammatory Agents↗

PubMed1999

Spontaneous spinal subdural hematoma in a young adult with hemophilia.

Spontaneous spinal subdural hemorrhage is a rare clinical problem that usually manifests with a sudden onset of pain and paralysis. This article reports on an 18-year-old male with hemophilia A and cerebral palsy, who experienced a several month history of transient back, hip, and leg pain accompanied by gait difficulties that ultimately culminated in a more striking episode of lower extremity weakness, irritability, and diffuse pain involving the neck, back, and legs. In the absence of any clinical or radiographic evidence of hemarthrosis, osteomyelitis, or intracranial hemorrhage, imaging of the spine disclosed a large, apparently multicompartmentalized intraspinal lesion, consistent with old hemorrhage. This extended from the thoracic to the sacral region, with the largest extent at the lumbosacral junction. Following correction of factor VIII levels, surgical exploration was undertaken and demonstrated liquefied blood within the subdural space without violation of the underlying arachnoid. Because the chronic subdural blood flowed quite easily through the dural opening by simply angling the operating table, a limited exposure was required to achieve a substantial evacuation of the clot. This case calls attention to the often protean manifestations of this process, the potential for a chronic course to the clinical symptoms, and the possibility of achieving substantial clot evacuation and clinical recovery with a limited operative approach.

Adolescent↗

PubMed1999

Epidermal growth factor receptor expression and gene amplification in high-grade non-brainstem gliomas of childhood.

Epidermal growth factor receptor (EGFR) is commonly overexpressed in adult high-grade gliomas. Forty to 50% of such tumors demonstrate amplification of the EGFR gene, often with rearrangement and constitutive activation of the gene product, suggesting that EGFR might play a role in the malignant progression of a subset of these neoplasms. In this regard, several groups have shown that overexpression of EGFR is associated with an adverse outcome in adult gliomas. In contrast to the extensive studies of EGFR status that have been performed in adult high-grade gliomas, little information has been reported about EGFR expression and amplification, as well as their prognostic relevance in high-grade gliomas of childhood, which carry a somewhat more favorable prognosis than their adult counterparts. To address this issue, we examined the expression of EGFR using immunohistochemistry and screened for amplification of the EGFR gene using a competitive PCR in a series of 27 archival pediatric high-grade nonbrainstem gliomas treated consecutively at our institution between 1975 and 1992. Tumors were categorized based on protein expression patterns, and the association between expression status and outcome was examined. Although elevated immunoreactivity for EGFR was observed in 80% of tumors, only two of the cases had gene amplification. No difference in outcome was observed between tumors that exhibited extensive EGFR immunoreactivity and those that did not (P > 0.3). Although EGFR expression did not seem to be of prognostic relevance for the outcome of pediatric patients harboring high-grade nonbrainstem gliomas, the consistently high levels of expression of EGFR in these neoplasms suggest that this receptor plays a role in the malignant phenotype of these tumors. Accordingly, treatment approaches targeting EGFR might be of potential therapeutic benefit for high-grade gliomas of childhood.

Adolescent↗

PubMed1998

Current management of pediatric atlantoaxial rotatory subluxation.

STUDY DESIGN: A retrospective clinical review of 20 children seen during a 7-year period who had atlantoaxial rotatory subluxation. OBJECTIVE: To define the effectiveness of imaging and treatment measures and to identify risk factors for recurrence, the series was reviewed to analyze cause, management, and outcome. SUMMARY OF BACKGROUND DATA: Rotatory subluxation of the atlantoaxial complex remains a poorly understood entity. Despite many reports in the literature, there is no consensus about which imaging studies should be used for diagnosis and which patients benefit from collar immobilization, traction, or surgical fusion. METHODS: Between August 1990 and April 1997, 20 children with atlantoaxial rotatory subluxation were treated. Fourteen patients (70%) were girls and six (30%) were boys (mean age, 6.4 years). All patients had torticollis and neck pain with decreased cervical motion for a mean of 11.2 days before diagnosis. Seven patients (35%) had a history of pharyngitis or otitis media, four (20%) had recently undergone head or neck surgery, and four (20%) had sustained a traumatic injury; in five patients (25%), no clear cause was determined. All patients were neurologically intact and underwent plain cervical radiographs and dynamic cervical computed tomography to document atlantoaxial rotatory subluxation. Patients were then treated with a rigid cervical collar and anti-inflammatory agents (n = 5) or with cervical traction followed by immobilization (n = 15). RESULTS: In four of the five patients in collars, reduction occurred spontaneously, whereas the fifth required cervical traction and eventual fusion for recurrence. In the 16 patients treated with traction (median, 1.8 kg), the normal atlantoaxial alignment was restored in 15 patients (94%) within a mean of 4 days. Of the 20 patients treated overall, conservative management failed in 6 (30%), and they required posterior fusion because of recurrence of the atlantoaxial rotatory subluxation or unsuccessful reduction. The major factor predicting the failure of conservative management was the duration of subluxation before initial reduction. Patients with long-standing subluxation were more likely to experience recurrence and require surgery. There were no complications noted. At follow-up, all patients who were treated conservatively remained neurologically intact with a normal atlantoaxial relation. All patients who underwent surgery remained neurologically intact and had radiographic documentation of fusion. CONCLUSION: Optimal management of atlantoaxial rotatory subluxation entails early diagnosis with plain cervical radiographs and dynamic computed tomography. Closed reduction with cervical traction followed by rigid immobilization accomplished reduction in 15 of 16 patients (94%) and was curative in 10 of 16 patients (63%). Although reduction was achieved more rapidly and effectively with traction than with a collar, there may be a role for simple immobilization without reduction in patients with a short duration of symptoms. There does not appear to be a correlation between cause of atlantoaxial rotatory subluxation, age, or sex and the likelihood of recurrence.

Atlanto-Axial Joint↗

PubMed1998

Primary parafalcine chondrosarcoma in a child.

Intracranial cartilaginous tumors are rare lesions, usually arising from the skull base in older individuals. We report the case of a 12-year-old girl with a low-grade type chondrosarcoma arising from the falx cerebri. To our knowledge this is the first such case reported in a child. She was treated with gross total surgical resection followed by external beam radiation because there was evidence of dural infiltration by tumor in and around the superior sagittal sinus. The patient remains progression free 9 months after surgery.

Brain Neoplasms↗

PubMed1998

Intraoperative hypothermia and ventricular shunt infections.

Several recent studies have demonstrated a relationship between intraoperative hypothermia and postoperative infection. A study was therefore conducted to evaluate the relationship between intraoperative hypothermia and ventricular shunt infections. Sixty-eight children who underwent ventricular shunt placement, including revisions, over a six year period subsequently developed a shunt infection (overall shunt infection rate of 5%). Mean age was 8 years (range, neonate to 20 years). The last 74 children who underwent ventricular shunt placement without subsequent infection served as a comparison group. The anesthetic records of all cases were reviewed to determine the lowest core temperature recorded during the surgical procedure. The lowest core temperature varied from 33.9 degrees C to 37.7 degrees C (mean 36.0 degrees C). Hypothermia was defined as a temperature less than 35.1 degrees C. No relationship was found between hypothermia and the subsequent occurrence of a shunt infection (P = 0.45). When those children less than 2 years old were excluded from analysis, there was a trend towards statistical significance (P = 0.07). In summary, this study failed to show any significant relationship between the occurrence of intraoperative hypothermia and subsequent ventriculoperitoneal shunt infection in a group of pediatric patients.

Adolescent↗

PubMed1998

Inhibition of Ras and related G-proteins as a therapeutic strategy for blocking malignant glioma growth.

OBJECTIVE: Preliminary studies have demonstrated that the Ras family and related guanosine 5'-triphosphate-dependent proteins (G-proteins) are overactivated in malignant gliomas and may function as indirect mediators of glial transformation initiated by deregulated upstream signaling elements. We postulated that inhibiting the activation of such proteins might represent a promising strategy for blocking the aberrant proliferation of these tumors. METHODS AND RESULTS: Accordingly, we examined the therapeutic efficacy against malignant glioma cells in vitro of a series of selective peptidomimetic inhibitors of farnesylation (FTI-277) and geranylgeranylation (GGTI-286 and GGTI-298), which are critical steps in the post-translational processing (prenylation) of these proteins. We first defined concentration-response relationships for each of these agents, using MTS-based cell proliferation assays in the established malignant glioma cell lines U-87 and LN-Z308 and the low-passage malignant glioma cell line SG-388. FTI-277, GGTI-286, and GGTI-298 each produced a striking concentration-dependent antiproliferative effect on the glioma cell lines, with the median effective dose ranging from 2.5 to 15.5 micromol/L. We then assessed the effect of prenylation inhibition on cell viability using clonogenic growth assays. This demonstrated a steady drop in the number of colonies with increasing drug concentrations for all three inhibitors. Third, we examined whether the cytotoxic effects of one of these inhibitors (GGTI-298) were associated with the induction of apoptosis using a terminal transferase-catalyzed in situ end-labeling technique. This approach showed a time-dependent increase in apoptotic cell numbers, which correlated with a progressive decrease in the percentage of cells that were viable as assessed by trypan blue exclusion. CONCLUSION: Our studies demonstrated that FTI-277, GGTI-286, and GGTI-298 each yielded significant antiproliferative effects in human malignant glioma cells in vitro at low micromolar concentrations, which have been achievable in vivo without major systemic toxicity. Extended periods of drug treatment produced cytotoxicity in the tumor cells, which correlated with the induction of apoptosis. We conclude that inhibition of Ras and related G-proteins offers a promising approach for blocking glioma proliferation that justifies further investigation in vivo.

Benzamides↗

PubMed1998

Surgical management of spinal cord compression from plexiform neurofibromas in patients with neurofibromatosis 1.

OBJECTIVE: Plexiform neurofibromas with sizable intraspinal extensions and resultant spinal cord compromise pose challenging management problems, because these lesions may involve multiple nerves and engulf adjacent vascular and visceral structures. In this report, we review our experience with the surgical treatment of these lesions. METHODS: Patients were identified by a detailed review of hospital medical records and the database of our multidisciplinary neurofibromatosis clinic. Ten patients had large plexiform neurofibromas that extended intraspinally, producing a combination of myelopathy and radiculopathy. Two patients exhibited single-level intraspinal growth, and eight showed multilevel involvement. Four patients showed bilateral plexiform neurofibromatous growth intraspinally, with "hourglass" compression of the spinal cord. Operative approaches and outcomes were reviewed in detail. RESULTS: Gross total resection of the symptomatic intraspinal tumor component was achieved for nine patients. The management of the extraspinal component was individualized, depending on the pattern and extent of involvement of the surrounding structures. Nine patients experienced complete recovery of neurological function postoperatively; the remaining patient demonstrated significant functional improvement. With a median follow-up period of 4 years, only one patient has developed recurrent intraspinal compression, in this case from tumor involvement by the same plexiform lesion at a lower spinal level. Two patients treated early in the series using standard laminectomy approaches developed significant kyphotic deformities, necessitating subsequent fusion. Based on these initial results, osteoplastic laminotomy techniques were used in the last five cases, allowing anatomic reconstruction of the involved levels; none of these latter patients has developed significant kyphosis, with a median follow-up period of 3 years. CONCLUSION: Radical resection of intraspinal tumor components in patients with neurofibromatosis 1 and large plexiform neurofibromas can help to preserve excellent neurological function. Technical factors in the management of these lesions are presented.

Adolescent↗

PubMed1998

Recurrent tethering: a common long-term problem after lipomyelomeningocele repair.

The authors reviewed the records of 94 patients who underwent initial repair of a lipomyelomeningocele between 1982 and July 1996 at the Children's Hospital of Pittsburgh to determine the incidence and time course of symptomatic retethering. In each of these patients, the initial operative goals were to microsurgically debulk as much of the lipoma as possible to allow the conus to move freely within the spinal canal, to divide any tethering arachnoidal adhesions, to close the pia if possible and to reconstitute a capacious thecal sac, using a dural graft if necessary. With a median follow-up of 58 months, 19 of these patients (20.2%) required 28 subsequent operations for symptomatic retethering. Median time between the initial procedure and reoperation for retethering was 52 months. The primary complaint of 12 patients was intractable low-back or leg pain. Other common symptoms were progressive bowel and/or bladder dysfunction, deterioration of motor function and foot deformities. The decision to reoperate was based predominantly on the clinical situation of the patient; magnetic resonance imaging was used to confirm the location and extent of tethering. Patients with transitional lipomas had a significantly higher frequency of symptomatic retethering than those with caudal or dorsal lesions (p < 0.05). No other clinical or technical feature correlated with an increased frequency of retethering. In particular, none of a variety of types of dural graft materials appeared to entirely prevent symptomatic retethering. Following reoperation, pain complaints resolved and many of the other symptoms improved partially or resolved completely. Although the long-term results were also favorable in the majority of patients, a small subgroup (n = 6) exhibited repetitive symptomatic tethering that proved increasingly difficult to treat. We concluded that symptomatic retethering is a common problem in children with lipomyelomeningoceles, even after an adequate initial operation. To date, no type of graft material has been shown to entirely prevent this problem. Close long-term surveillance of such patients is required to allow detection and treatment of symptomatic retethering.

Adolescent↗