David I. Sandberg

Ommaya Reservoirs for the Treatment of Leptomeningeal Metastases

OBJECTIVE Ommaya reservoirs are frequently used to deliver intraventricular chemotherapy in cancer patients with leptomeningeal metastases. We review techniques of catheter placement and complication avoidance. METHODS Between January 1995 and June 1998, Ommaya reservoirs were placed in 107 patients for the treatment or prophylaxis of leptomeningeal metastases at the Memorial Sloan-Kettering Cancer Center. Patients with slit ventricles (total, 25) underwent preoperative pneumoencephalography for ventricular dilation. Intraoperative fluoroscopic guidance was used in 77 patients to confirm the catheter tip position at the foramen of Monro. Other intraoperative aids included endoscopy in 21 patients, ultrasound in 7, and stereotaxy in 6. No aids were used in 3 patients, more than one aid was used in 9, and the technique could not be determined retrospectively in 3. RESULTS The median survival of patients treated for leptomeningeal metastases was 9 months (Kaplan-Meier method). Eight patients developed hydrocephalus requiring conversion of the Ommaya reservoir to a ventriculoperitoneal shunt and precluding delivery of chemotherapeutic agents. An additional 11 patients referred for Ommaya reservoir placement demonstrated elevated intracranial pressure requiring an initial ventriculoperitoneal shunt. Complications of Ommaya reservoir placement occurred in 10 patients (9.3%) and included two infections, five catheter malpositions, and three intracranial hemorrhages. Two deaths occurred secondary to intracranial hemorrhage: one after postoperative anticoagulation for a mechanical heart valve, and one attributed to treatment-related thrombocytopenia. Nine patients (8.4%) had treatment-related imaging abnormalities; seven were asymptomatic and two developed symptomatic leukoencephalopathy. CONCLUSION Complications associated with Ommaya reservoirs can be minimized by intraoperative confirmation of the catheter position with fluoroscopic guidance and/or endoscopy. We recommend postoperative computed tomographic scans before initiation of intraventricular chemotherapy. Patients with elevated intracranial pressure may require shunting procedures in lieu of Ommaya reservoir placement.

Prolonged convection-enhanced delivery into the rat brainstem.

OBJECTIVEProlonged convection-enhanced delivery was used in an attempt to achieve large volumes of distribution (Vd) in the rat brainstem. Clinical assessment and histological analysis were performed to establish the safety of this approach. METHODSFor evaluation of Vd,, 10 rats underwent stereotactic cannula placement into the brainstem. Five rats underwent a 24-hour infusion (volume of infusion [Vi], 200 &mgr;l), and 5 rats underwent a 7-day infusion (Vi, 2 ml) of fluorescein isothiocyanate-dextran. Serial brainstem sections were imaged with ultraviolet illumination, and Vd was assessed. For assessment of clinical tolerance, 30 additional rats underwent chronic infusions of an isotonic saline solution into the brainstem. Serial neurological examinations were performed, followed by histological analysis after the animals’ death. RESULTSNo animal demonstrated clinically recognized neurological deficits. Foci of organizing necrosis were limited to the site of infusion and cannula tract. Vd increased linearly with increasing Vi (range, 24.8–130.6 mm3). Maximal cross sectional area of fluorescence and craniocaudal extent of fluorescence increased with increasing Vi. Fluorescence was detected throughout the entire brainstem beyond the compact area of highly concentrated tracer. CONCLUSIONProlonged convection-enhanced delivery can be applied safely in the rat brainstem with no recognized limitations of Vd and minimal histological changes beyond the site of infusion. Chronic brainstem infusions may enhance the potential application of convection-enhanced delivery for therapeutic purposes in treating diffuse pontine gliomas.

Symptomatic spinal epidural lipomatosis after local epidural corticosteroid injections: Case report

OBJECTIVE AND IMPORTANCE Spinal epidural lipomatosis, which causes symptomatic compression of neural elements, is a well known but uncommon complication of Cushings syndrome. Spinal epidural lipomatosis has been reported frequently in association with chronic systemic corticosteroid therapy, but thus far only one case has been attributed to local epidural corticosteroid injections. CLINICAL PRESENTATION We report another case of symptomatic spinal epidural lipomatosis after epidural corticosteroid injections. This is the first such case documented by magnetic resonance imaging and confirmed with surgical exploration. INTERVENTION The patients symptoms of neurogenic claudication resolved after lumbar laminectomy in the region of previous corticosteroid injections and the removal of epidural fat, which was compressing the thecal sac. CONCLUSION This case should alert clinicians that epidural lipomatosis, which causes symptomatic thecal sac compression, is a possible complication, not only of systemic glucocorticoid therapy, but also of local epidural corticosteroid injections.

Spontaneous intraparenchymal hemorrhage in full-term neonates.

OBJECTIVE Spontaneous intraparenchymal hemorrhage is extremely rare in full-term newborns. Reports to date have been limited to descriptions of individual cases, small groups within larger studies of intracranial hemorrhage, and one series of four patients. Structural lesions are rarely identified, and the majority of patients described have been managed without surgical intervention. METHODS Analysis of a computerized database of pediatric neurosurgical patients from January 1960 to February 2000 identified full-term newborns younger than 3 months of age with nontraumatic intraparenchymal hemorrhages. Prenatal histories, labor and delivery histories, clinical presentations, imaging studies, management, and outcomes were reviewed. RESULTS Eleven full-term newborns with spontaneous intraparenchymal hemorrhages were identified. The majority had normal prenatal courses. Most presented within the first 2 days of life (6 of 11 patients), and the most common presenting sign was seizure (7 of 11 patients). No cause was identified in 6 of 11 patients; the remainder were attributed to coagulopathy (n = 3), ruptured intracranial aneurysm (n = 1), or hemorrhagic infarction (n = 1). Eight patients underwent surgical hematoma evacuation on the basis of radiographic evidence of significant mass effect, evidence of signs of elevated intracranial pressure, or both. Three patients did not receive surgical intervention. There were no subsequent hemorrhages or deaths during a mean follow-up period of 4.5 years (range, 1–16 yr). Four patients had normal neurological outcomes, four had motor deficits (one of whom additionally demonstrated cognitive delay), and three had delayed speech. CONCLUSION No cause is identified in most newborns with spontaneous intraparenchymal hemorrhage. Radiographic evidence of mass effect or signs of elevated intracranial pressure may necessitate surgical hematoma evacuation. Outcome varies widely and may be normal, even in patients with sizeable intraparenchymal hemorrhages.

MIB-1 staining index of pediatric meningiomas

OBJECTIVEFor adult meningiomas, the staining index (SI) for the anti-Ki-67 monoclonal antibody MIB-1 is well correlated with histological atypia and tumor recurrence. MIB-1 SIs for meningiomas in the pediatric population have not been previously reported. Meningiomas tend to be more histologically aggressive and to recur more frequently in children, compared with adults. The objectives of this study were to determine whether MIB-1 SIs are correlated with pathological atypia and recurrence among pediatric meningiomas and to compare the MIB-1 SIs of pediatric meningiomas with those of adult meningiomas. METHODSMIB-1 SIs were assessed on paraffin-embedded sections of 14 pediatric meningiomas (patient age, 2–17 yr), 5 of which contained atypical or malignant features. For comparison with benign pediatric meningiomas, MIB-1 SIs were also assessed on paraffin-embedded sections of 14 adult meningiomas (patient age, 38–90 yr), none of which displayed atypical or malignant features or recurred within a 5-month median follow-up period. RESULTSMIB-1 SIs of pediatric meningiomas ranged from 1.2 to 31.6% (median, 9.1%). Significant differences were observed between the MIB-1 SIs for tumors with atypical or malignant features (median, 12.3%; range, 7.0–31.6%) and those for tumors without atypia (median, 7.0%; range, 1.2–12.6%;P = 0.045). There were six recurrences after gross total resection, during a 36.5-month median follow-up period. All five of the tumors with pathological atypia recurred; one tumor without atypia recurred. Significant differences were observed between MIB-1 SIs for nonrecurrent tumors (median, 6.6%; range, 1.2–12.2%) and those for recurrent tumors (median, 12.5%; range, 7.0–31.6%;P = 0.012). The median MIB-1 SI for adult control specimens was 8.8% (range, 1.2–19.3%), which did not differ significantly from that for pediatric meningiomas without atypia (P = 0.68). CONCLUSIONFor this cohort of pediatric meningiomas, pathological atypia and the tendency to recur were correlated with elevated MIB-1 SIs. The median MIB-1 SI for pediatric meningiomas without histological atypia did not differ significantly from that for adult meningiomas without atypia, suggesting that the more aggressive clinical features of meningiomas in children may be attributable to factors other than the rate of cellular proliferation.

Endoscopic Biopsy for Tumors of the Third Ventricle

Twelve patients underwent endoscopic biopsy of a tumor involving the third ventricle. Nine patients had no significant medical history while 3 had a history of cancer. Unique characteristics of each case dictated the optimal surgical technique. Endoscopic tumor biopsy was combined with additional procedures in 9 cases; shunt insertion (3), shunt insertion with endoscopic septostomy (5), and transcallosal craniotomy (1). Diagnosis was established in 11 patients (92%); 6 primary brain tumors, 3 metastatic central nervous system tumors, 1 metastatic systemic cancer, and 1 region of post-treatment gliosis. One case was aborted due to poor visualization. Therapy was directly influenced by endoscopic biopsy in 11/12 cases (92%) and craniotomy for tumor resection was avoided in 10/12 patients (83%). Of the 5 patients who underwent endoscopic septostomy, 4 required no subsequent procedures for hydrocephalus. There were no complications, and hospital stay averaged 1.78 days for patients who underwent successful endoscopic biopsy. Tumors of the third ventricle are amenable to endoscopic biopsy with excellent diagnostic yield and low morbidity. The procedure must be tailored depending upon the tumor location within the third ventricle, the degree of ventriculomegaly, and the need to perform a septostomy. Singularly or combined with other endoscopic procedures, patients can be spared multiple and more invasive surgical procedures.

Outcomes in pediatric patients with Chiari malformation Type I followed up without surgery: Clinical article

OBJECT The natural history of untreated Chiari malformation Type I (CM-I) is poorly defined. The object of this study was to investigate outcomes in pediatric patients with CM-I who were followed up without surgical intervention. METHODS The authors retrospectively reviewed 124 cases involving patients with CM-I who presented between July 1999 and July 2008 and were followed up without surgery. The patients ranged in age from 0.9 to 19.8 years (mean 7 years). The duration of follow-up ranged from 1.0 to 8.6 years (mean 2.83 years). Imaging findings, symptoms, and findings on neurological examinations were noted at presentation and for the duration of follow-up. RESULTS The mean extent of tonsillar herniation at presentation was 8.35 mm (range 5-22 mm). Seven patients had a syrinx at presentation. The syrinx size did not change in these patients on follow-up imaging studies. No new syrinxes developed in the remaining patients who underwent subsequent imaging. The total number of patients with presenting symptoms was 81. Of those 81 patients, 67 demonstrated symptoms that were not typical of CM-I. Of the 14 patients with symptoms attributed to CM-I, 9 had symptoms that were not severe or frequent enough to warrant surgery, and surgery was recommended in the remaining 5 patients. Chiari malformation Type I was also diagnosed in 43 asymptomatic patients who had imaging studies performed for various reasons. No new neurological deficits were noted in any patient for the duration of follow-up. CONCLUSIONS The majority of patients with CM-I who are followed up without surgery do not progress clinically or radiologically. Longer follow-up of this cohort will be required to determine if symptoms or new neurological findings develop over the course of many years.

Sclerosing Epithelioid Fibrosarcomas Involving the Neuraxis: Report of Three Cases

OBJECTIVE AND IMPORTANCESclerosing epithelioid fibrosarcoma (SEF) is a rare mesenchymal neoplasm composed of rounded, vimentin-immunoreactive tumor cells disposed in nests and cords within a hyalinized collagenous matrix. Most examples arise in the deep skeletal muscles of adults. The cases recorded to date have been characterized by protracted clinical evolutions with a tendency for stubborn local recurrence, followed by late metastasis. Accordingly, SEF has been regarded as a low-grade sarcoma. A single instance of brain and vertebral metastasis has been described. We report three examples of SEF distinguished by primary involvement of the neuraxis at initial presentation. CLINICAL PRESENTATIONTwo tumors had intracranial, calvarial and extracalvarial, soft-tissue components, whereas the third tumor manifested as a paraspinal mass with extension into the T12–L1 neural foramen and invasion of the T12 nerve root. INTERVENTIONAll three affected patients experienced local recurrence and distant metastasis after resection of the primary site. These complications appeared early in the disease course in two cases. In no case was there a response to adjuvant chemotherapy or radiotherapy. CONCLUSIONOur experience indicates that SEFs arising along the neuraxis may demonstrate unexpectedly aggressive clinical behavior, compared with those arising in the more typical location of deep skeletal muscles.

Treatment of Spinal Involvement in Neuroblastoma Patients

Introduction: Considerable controversy exists regarding the appropriate management of spinal involvement in neuroblastoma (NB) patients. We review a large group of such patients and offer treatment recommendations. Methods: Forty-six patients with epidural and/or neural foraminal involvement treated between 1987 and 1998 were staged according to the International NB Staging System (INSS) and classified as high-risk (INSS stage 4; n = 31) or low-risk (INSS stage <4; n = 15). Of 13 high- risk patients with normal neurologic examinations and no radiographic high-grade spinal cord compression (HGSCC), 12 were treated initially with chemotherapy, and only 1 demonstrated neurologic deterioration. HGSCC was present in 18 patients with high-risk NB; 7 of 10 (70%) treated initially with chemotherapy and 6 of 6 (100%) managed initially with operation improved or remained stable. All 9 low-risk patients with normal neurologic examinations and no HGSCC remained neurologically intact following operations (n = 7) or chemotherapy (n = 2). All 4 low-risk patients with HGSCC treated with operations improved or remained stable, and 0 of 2 (0%) low-risk patients treated initially with chemotherapy remained stable. Spinal deformities occurred in 2 of 16 patients (12.5%) treated nonoperatively and in 9 of 30 (30.0%) who underwent operations. Conclusions: High-risk NB patients with spinal involvement but normal neurologic examinations should be offered chemotherapy. High-risk patients with HGSCC may respond to chemotherapy, but a small percentage will require operations for progressive neurologic deficits. Chemotherapy may be avoided in low-risk patients who are offered potentially curative operations. Patients treated with operations for epidural disease are at high risk of subsequently developing spinal deformity.

Neurogenic stunned myocardium after acute hydrocephalus

Neurogenic stunned myocardium (NSM) is a syndrome of cardiac stunning after a neurological insult. It is commonly observed after aneurysmal subarachnoid hemorrhage but is increasingly being reported after other neurological events. The underlying mechanism of NSM is believed to be a hypothalamic-mediated sympathetic surge causing weakened cardiac contractility and even direct cardiac myocyte damage. The authors report 2 cases of NSM in pediatric patients after acute hydrocephalus. Both patients experienced severe cardiac dysfunction in the acute phase but ultimately had a good neurological outcome and a full cardiac recovery. The identification, treatment, and outcome in 2 rare pediatric cases of NSM are discussed, and the history of the brain-cardiac connection is reviewed.