Faculty Bibliography

OBJECTIVE: To determine the value of delayed surgical resection in patients with central nervous system germ cell tumors who exhibit less than complete radiographic response despite declining serum and cerebrospinal fluid (CSF) tumor markers after initial chemotherapy. METHODS: We retrospectively analyzed 126 patients enrolled on two international multicenter clinical trials (the First and Second International Central Nervous System Germ Cell Tumor Studies) for patients with newly diagnosed central nervous system germ cell tumors. After at least three cycles of chemotherapy, 10 of these patients underwent delayed surgical resection owing to evidence of residual radiographic abnormalities despite declining or completely normalized serum and CSF levels of alpha-fetoprotein and human chorionic gonadotropin. RESULTS: Eight of these patients demonstrated nongerminomatous germ cell tumor elements at the time of initial diagnosis. In these patients, either serum or CSF tumor markers were elevated initially. Two patients demonstrated pure germinomas with normal levels of serum and CSF tumor markers. After chemotherapy, radiographic evaluation revealed a partial response in seven patients, a minor response in one patient, and stable disease in two patients. All 10 patients had either normal or decreasing levels of serum and CSF tumor markers before second-look surgery. At delayed surgical resection, 7 of the 10 patients underwent gross total resection, and 3 patients underwent subtotal resection of residual lesions. Pathological findings at second-look surgery demonstrated three patients to have mature teratomas, two with immature teratomas, and five with necrotic or scar tissue alone. To date, 7 of the 10 patients have had no recurrence during an average follow-up time of 36.9 months (range, 3-96 mo). Three of four patients with nongerminomatous germ cell tumors who had tumor markers that were decreased, but not normalized, before second-look surgery eventually developed tumor dissemination/progression, and they required subsequent radiation therapy despite having teratoma or necrosis/scar tissue at delayed surgery. In contrast, three of four patients with nongerminomatous germ cell tumors and completely normalized markers did not progress and did not require radiation therapy. CONCLUSION: Delayed surgical resection should be considered in patients with central nervous system germ cell tumors who have residual radiographic abnormalities and normalized tumor markers, because these lesions are likely to be teratoma or necrosis/scar tissue. However, second-look surgery should be avoided in patients whose tumor markers have not normalized completely

Intraoperative autotransfusion salvages blood shed during surgery for use in immediate resuscitation of the patient. The purpose of this study was to determine whether such autotransfusion decreases the volume of homologous blood transfused in patients undergoing primary cranial vault remodeling for craniosynostosis. The Cobe-Bret 2 autologous blood recovery system (Hemo Concepts, Union, N.J.) was used in 11 cases, and an equal number of consecutive cases did not receive intraoperative autotransfusion. There were no significant differences between the groups with respect to age, sex, and weight. Mean estimated blood loss was 43.2 ml/kg (range, 20.3 to 65.0 ml/kg) in the intraoperative autotransfusion group and 40.2 ml/kg (range, 6.8 to 72.3 ml/kg) in the control group (not statistically significant; p < 0.05). There was no significant difference in volume of homologous blood transfusion between the two groups. The autotransfusion group received 34.1 ml/kg of homologous blood (range, 0 to 60.7 ml/kg), and the control group received a mean of 32.7 ml/kg (range, 14.5 to 60.2 ml/kg). The autotransfusion group received a mean of 10.4 ml/kg of recovered autologous blood (range, 0 to 21.4 ml/kg). In four of the 11 autotransfusion patients, insufficient autologous blood was recovered intraoperatively to warrant transfusion. Results of this study suggest little benefit for the use of intraoperative autotransfusion in primary cranial vault remodeling for craniosynostosis in the young patient. It was hypothesized that this finding was a result of the following: (1) intraoperative autotransfusion blood was usually available only toward the end of the procedure, after homologous blood had already been administered, and (2) the volume of recovered intraoperative autotransfusion blood is minimal, compared with the homologous transfusion volume requirements during an extensive cranial vault remodeling and fronto-orbital advancement procedure. In the context of unproven cost benefit and increasing similar evidence from other comparative studies, emphasis should be directed to other medical and surgical strategies to minimize the need for perioperative blood transfusion

OBJECTIVE: Frameless stereotactic systems have become an integral part of neurosurgical practice. At our center, we recently introduced for clinical use a small, portable, frameless stereotactic system, namely the Cygnus PFS system (Compass International, Rochester, MN). The purpose of this study was to compare the accuracy of the Cygnus PFS system with that of two larger systems that are also currently in use at our institution, i.e., the SMN system (Zeiss, Oberkochen, Germany) and the ISG viewing wand (ISG Technologies, Toronto, Canada). These systems represent three kinds of frameless stereotactic technologies that are commercially available. Each system uses a different method of spatial localization, i.e., mechanical linkage (ISG system), magnetic field digitization (Cygnus system), or optical technology (SMN system). METHODS: Using a stereotactic 'phantom,' we measured the accuracies of all three systems with identical data sets. The errors in localization in three-dimensional space for nine targets were calculated by using 10 magnetic resonance imaging data sets. The precision of each system was also calculated. RESULTS: With this experimental protocol, the Cygnus system attained a mean accuracy of 1.90 +/- 0.7 mm, the ISG viewing wand system a mean accuracy of 1.67 +/-0.43 mm, and the SMN microscope a mean accuracy of 2.61 +/- 0.99 mm. The precision values were not significantly different among the systems. CONCLUSION: We observed only small differences in accuracy and precision among these three systems. We briefly review the advantages and disadvantages of each system and note that other factors, such as portability, ease of use, and microscope integration, should influence the selection of a frameless stereotactic system

The mechanisms that regulate the growth of the brain remain unclear. We show that Sonic hedgehog (Shh) is expressed in a layer-specific manner in the perinatal mouse neocortex and tectum, whereas the Gli genes, which are targets and mediators of SHH signaling, are expressed in proliferative zones. In vitro and in vivo assays show that SHH is a mitogen for neocortical and tectal precursors and that it modulates cell proliferation in the dorsal brain. Together with its role in the cerebellum, our findings indicate that SHH signaling unexpectedly controls the development of the three major dorsal brain structures. We also show that a variety of primary human brain tumors and tumor lines consistently express the GLI genes and that cyclopamine, a SHH signaling inhibitor, inhibits the proliferation of tumor cells. Using the in vivo tadpole assay system, we further show that misexpression of GLI1 induces CNS hyperproliferation that depends on the activation of endogenous Gli1 function. SHH-GLI signaling thus modulates normal dorsal brain growth by controlling precursor proliferation, an evolutionarily important and plastic process that is deregulated in brain tumors

Hyponatremia after cranial vault remodeling has been noted in a pediatric patient population. If left untreated, the patients may develop a clinical hypoosmotic condition that can lead to cerebral edema, increased intracranial pressure, and eventually, to central nervous system and circulatory compromise. The hyponatremia has traditionally been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH); however, in our patients the treatment has been resuscitation with normal saline as opposed to fluid restriction (the accepted treatment of SIADH), thus placing the diagnosis of SIADH in question. Patients who developed hyponatremia after intracranial injury or surgery were, until recently, grouped together as having SIADH. However, there are diagnosis and treatment differences between SIADH and another distinct but poorly understood disorder that is designated cerebral salt wasting syndrome (CSW). CSW is associated with increased urine output and increased urine sodium concentration and volume contraction, and it is frequently seen after a central nervous system trauma. We therefore developed a prospective study to evaluate the cause of the sodium imbalance.Ten consecutive pediatric patients who underwent intracranial surgery for various craniosynostotic disorders were postoperatively monitored in the pediatric intensive care unit for hemodynamic, respiratory, and fluid management. The first four patients were evaluated for electrolyte changes and overall fluid balance to determine the consistency with which these changes occurred. The remaining six patients had daily (including preoperative) measurement of serum electrolytes, urine electrolytes, urine osmolarity, serum antidiuretic hormone (ADH), aldosterone, and atrial natriuretic hormone (ANH). All patients received normal saline intravenous replacement fluid in the postoperative period.All of the patients developed a transient hyponatremia postoperatively, despite normal saline resuscitation. Serum sodium levels as low as 128 to 133 mEq per liter (normal, 137 to 145 mEq per liter) were documented in the patients. All patients had increased urine outputs through the fourth postoperative day (>1 cc/kg/h). The six patients who were measured had an increased ANH level, with a peak value as high as 277 pg/ml (normal, 25 to 77 pg/ml). ADH levels were low or normal in all but one patient, who had a marked increase in ADH and ANH. Aldosterone levels were variable. On the basis of these results, all but one patient showed evidence of CSW characterized by increased urine output, normal or increased urine sodium, low serum sodium, and increased ANH levels. The other patient had similar clinical findings consistent with CSW but also had an increase in ADH, thus giving a mixed laboratory picture of SIADH and CSW.The association of CSW to cranial vault remodeling has previously been ignored. This study should prompt reevaluation of the broad grouping of SIADH as the cause of all hyponatremic episodes in our postoperative patient population. An etiologic role has been given to ANH and to other, as yet undiscovered, central nervous system natriuretic factors. All of the patients studied required normal saline resuscitation, a treatment approach that is contrary to the usual management of SIADH. These findings should dictate a change in the postoperative care for these patients. After cranial vault remodeling, patients should prophylactically receive normal saline, rather than a more hypotonic solution, to avoid sodium balance problems

OBJECT: The goal of this study was to evaluate the safety, efficacy, and indications for repeat endoscopic third ventriculostomies (ETV). METHODS AND RESULTS: We reviewed the records of 20 patients who had undergone repeat ETV from 1987 to 1999. Their ages ranged from 8 months to 53 years (mean 17 years). The primary etiologies of hydrocephalus were: primary aqueductal stenosis (9 cases), tumor (5), Chiari malformation (2), prior infection (2), prior intraventricular hemorrhage (1), and blocked foramen of Monro (1 patient). The interval between the first and second ETVs ranged from 8 days to almost 6 years (mean 12.8 months). The intraoperative findings at repeat surgery were: occlusion of the primary orifice by scar (10 cases), virginal floor of the third ventricle (5 cases), pinhole ventriculostomy (3 cases), incompletely penetrated membrane (1 case), and blood clot occluding the orifice (1 case). The follow-up period ranged from 3 to 47 months (median 20 months). Repeat ETV was successful in 13 patients (65%). These patients did not require further shunting or other procedures during follow-up. Seven patients (35%) required placement of a shunt after repeat ETV. Several complications were observed in 1 patient (5%), including seizures, elevated ICP, bilateral pulmonary edema, and cardiac arrhythmia. This patient ultimately recovered fully; the ETV was successful, and the patient did not require a shunt. CONCLUSIONS: Based on the experience of this group of patients, repeat ETV is as effective and as safe as a primary ETV procedure, and should be attempted in selected patients

OBJECTIVE AND IMPORTANCE: Surgical intervention can reduce the burden of seizures in selected patients with tuberous sclerosis and medically refractory epilepsy. CLINICAL PRESENTATION: A child presented with tuberous sclerosis and severe epilepsy beginning in the first month of life and delayed development before 1 year of age. Video-electroencephalographic monitoring at the age of 1 year revealed a left temporal seizure focus. Repeat videoelectroencephalography at 2 years of age revealed a right posterior quadrant seizure focus. Bilateral subdural electrodes were placed, confirming independent seizure onsets from the right parietal area (overlying a tuber) and prominent interictal activity over the left superior temporal region. INTERVENTION: The right parietal focus was resected, and electrodes were maintained over the left temporal focus. After right parietal resection, ictal discharges were recorded over the left temporal region; a corticectomy was performed 2 days later. No tonicoclonic or complex partial seizures have occurred during a follow-up period of more than 24 months. Simple partial motor seizures involving the right foot have been reduced by more than 80%, and other simple partial seizures have been eliminated. Postoperatively, there has been marked improvement in the patient's cognitive and motor developmental status. CONCLUSION: In selected patients with bilateral seizure foci involving separate lobes, aggressive bilateral surgery can be safe and effective

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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

This study evaluated the quality of life and neuropsychologic functioning among patients enrolled between 1989 and 1993 in the First International CNS Germ-Cell Tumor Study. Quality-of-life questionnaires (Short Form-36 or Child Health Questionnaire) were completed on 43 patients at median follow-up of 6.1 years after diagnosis (range, 4.5-8.8 years), and intellectual and academic testing was performed on 22 patients. Psychosocial and physical functioning of patients aged 19 years and older at follow-up was within the average range, whereas the same functioning for patients aged 18 years and younger, as reported by their parents at follow-up, was low average and borderline, respectively. Overall psychosocial and physical health summary scores were positively correlated with age at diagnosis for both groups combined. Those who received CNS radiation therapy (n = 29) reported significantly worse physical health, but similar psychosocial health, compared with those treated without radiation. Neuropsychologic testing indicated full-scale and verbal IQ, reading, spelling, and math skills in the average range, and performance IQ in the low average range. Intelligence and math skills were positively correlated with age at diagnosis. Those with germinomas significantly outperformed those with nongerminomatous/ mixed tumors on all neuropsychological measures administered. Younger patients diagnosed with CNS germ-cell tumors are at increased risk for psychosocial and physical problems as well as neuropsychologic deficits. Exposure to irradiation adversely affects overall physical functioning, whereas tumor pathology appears to be a salient neurocognitive risk factor. Collaborative and randomized studies are required to further elucidate the late effects arising from factors such as age at diagnosis, tumor histology, level of irradiation therapy, and chemotherapy toxicity among these young and potentially curable patients