MR Imaging Correlates for Molecular and Mutational Analyses in Children with Diffuse Intrinsic Pontine Glioma.

BACKGROUND AND PURPOSE: Recent advances in molecular techniques have characterized distinct subtypes of diffuse intrinsic pontine gliomas. Our aim was the identification of MR imaging correlates of these subtypes. MATERIALS AND METHODS: Initial MRIs from subjects with diffuse intrinsic pontine gliomas recruited for a prospective clinical trial before treatment were analyzed. Retrospective imaging analyses included FLAIR/T2 tumor volume, tumor volume enhancing, the presence of cyst and/or necrosis, median, mean, mode, skewness, kurtosis of ADC tumor volume based on FLAIR, and enhancement at baseline. Molecular subgroups based on EGFR and MGMT mutations were established. Histone mutations were also determined (H3F3A, HIST1H3B, HIST1H3C). Univariate Cox proportional hazards regression was used to test the association of imaging predictors with overall and progression-free survival. Wilcoxon rank sum, Kruskal-Wallis, and Fisher exact tests were used to compare imaging measures among groups. RESULTS: Fifty patients had biopsy and MR imaging. The median age at trial registration was 6 years (range, 3.3-17.5 years); 52% were female. On the basis of immunohistochemical results, 48 patients were assigned to 1 of 4 subgroups: 28 in MGMT-/epidermal growth factor receptor (EGFR)-, 14 in MGMT-/EGFR+, 3 in MGMT+/EGFR-, and 3 in MGMT+/EGFR+. Twenty-three patients had histone mutations in H3F3A, 8 in HIST1H3B, and 3 in HIST1H3C. Enhancing tumor volume was near-significantly different across molecular subgroups (P = .04), after accounting for the false discovery rate. Tumor volume enhancing, median, mode, skewness, and kurtosis ADC T2-FLAIR/T2 were significantly different (P ≤ .048) between patients with H3F3A and HIST1H3B/C mutations. CONCLUSIONS: MR imaging features including enhancement and ADC histogram parameters are correlated with molecular subgroups and mutations in children with diffuse intrinsic pontine gliomas.

Moyamoya following cranial irradiation for primary brain tumors in children.

OBJECTIVE: To study the risk factors for the development of moyamoya syndrome after cranial irradiation for primary brain tumors in children. METHODS: We reviewed neuroimaging studies and dosimetry data for 456 children who were treated with radiation for a primary brain tumor and who were prospectively evaluated with serial neuroimaging studies and neurologic evaluations. A total of 345 patients had both adequate neuroimaging and radiation dosimetry data for further analysis. We used survival analysis techniques to examine the relationship of clinically important variables as risk factors for the development of moyamoya over time. RESULTS: Overall, 12 patients (3.5%) developed evidence of moyamoya. The onset of moyamoya was more rapid for patients with neurofibromatosis type 1 (NF1) (median of 38 vs 55 months) and for patients who received >5,000 cGy of radiation (median of 42 vs 67 months). In a multiple Cox proportional hazards regression analysis controlling for age at start of radiation, each 100-cGy increase in radiation dose increased the rate of moyamoya by 7% (hazard ratio [HR] = 1.07, 95% CI: 1.02 to 1.13, p = 0.01) and the presence of NF1 increased the rate of moyamoya threefold (HR = 3.07, 95% CI: 0.90 to 10.46, p = 0.07). CONCLUSIONS: Moyamoya syndrome is a potentially serious complication of cranial irradiation in children, particularly for those patients with tumors in close proximity to the circle of Willis, such as optic pathway glioma. Patients who received higher doses of radiation to the circle of Willis and with neurofibromatosis type 1 have increased risk of the development of moyamoya syndrome.

Multiparametric MR assessment of pediatric brain tumors.

MR assessment of pediatric brain tumors has expanded to include physiologic information related to cellular metabolites, hemodynamic and diffusion parameters. The purpose of this study was to investigate the relationship between MR and proton MR spectroscopic imaging in children with primary brain tumors. Twenty-one patients (mean age 9 years) with histologically verified brain tumors underwent conventional MR imaging, hemodynamic MR imaging (HMRI) and proton MR spectroscopic imaging (MRSI). Fourteen patients also had diffusion-weighted MR imaging (DWMRI). Metabolic indices including choline-containing compounds (Cho), total creatine (tCr) and lipids/lactate (L) were derived by proton MRSI, relative cerebral blood volume (rCBV) by HMRI, and apparent tissue water diffusion coefficients (ADC) by DWMRI. Variables were examined by linear regression and correlation as well as by ANOVA. Cho (suggestive of tumor cellularity and proliferative activity) correlated positively with rCBV, while the relationship between Cho and ADC (suggestive of cellular density) was inverse ( P<0.001). The relationship between rCBV and ADC was also inverse ( P=0.004). Cho and lipids (suggestive of necrosis and/or apoptosis) were not significantly correlated ( P=0.51). A positive relationship was found between lipids and ADC ( P=0.002). The relationships between Cho, rCBV, ADC and lipids signify that tumor physiology is influenced by the tumor's physical and chemical environment. Normalized Cho and lipids distinguished high-grade from low-grade tumors ( P<0.05). Multiparametric MR imaging using MRSI, HMRI and DWMRI enhances assessment of brain tumors in children and improves our understanding of tumor physiology while promising to distinguish higher- from lower-malignancy tumors, a distinction that is particularly clinically important among inoperable tumors.

Stereotactic radiotherapy for pediatric intracranial germ cell tumors.

PURPOSE: Intracranial germ cell tumors are rare, radiosensitive tumors seen most commonly in the second and third decades of life. Radiotherapy alone has been the primary treatment modality for germinomas, and is used with chemotherapy for nongerminomatous tumors. Stereotactic radiotherapy techniques minimize the volume of surrounding normal tissue irradiated and, hence, the late radiation morbidity. This study reports our experience with stereotactic radiotherapy in this group of tumors. METHODS AND MATERIALS: Between December 1992 and December 1998, 18 patients with intracranial germ cell tumors were treated with stereotactic radiotherapy. A total of 23 histologically proven tumors were treated. Thirteen patients had a histologic diagnosis of germinoma, and 5 patients had germinoma with nongerminomatous elements. Of those patients with a histologic diagnosis of germinoma, 5 had multiple midline tumors. The median age of the patients was 12.9 years (range, 5.6-17.5 years). RESULTS: A boost using stereotactic radiotherapy was delivered to 19 tumors following whole-brain radiation in 8 cases and craniospinal radiation in 11 cases. Three tumors were treated with stereotactic radiotherapy to the tumor volume alone following chemotherapy, and 1 tumor received a boost using stereotactic radiosurgery following craniospinal radiation. A median dose of 2520 cGy (range, 1500-3600) cGy was given to the whole brain, and a median dose of 2160 (range, 2100-2600) cGy was given to the spinal field. The median boost dose to the tumor was 2600 (range, 2160-3600) cGy, given by stereotactic radiotherapy delivered to the 95% isodose line. At a median follow-up time of 40 (range, 12-73) months, no local or marginal recurrences were reported in patients with germinoma. Two patients with nongerminomatous tumors have relapsed. One had elevation of tumor markers only at 37 months following treatment, and the other had persistent disease following chemotherapy and radiation therapy. Eight patients documented pituitary-hypothalamic dysfunction; in 7 (87.5%) of these patients, the dysfunction was present before commencing radiotherapy. Four patients (22%) developed newly diagnosed diabetes insipidus following surgery. Three patients (17%) received antidepressant medication at follow-up. CONCLUSION: Our series shows that stereotactic radiotherapy is achievable and well tolerated in this group of patients. Longer follow-up is required to fully assess the impact on long-term toxicity. Psychologic assessment of mood and affect should be performed as part of routine follow-up in this group of adolescent children.

Measurements of intraventricular pressure in a patient shunted from the ventricle to the internal jugular vein against the direction of blood flow (the El-Shafei shunt).

OBJECT: After demonstrating the anti-siphoning properties of a distensible tube in vitro, El-Shafei constructed a shunting system that directs CSF flow into the internal jugular vein against the flow of blood. Though clinically effective, the in vivo pressure dynamics of this type of shunt system have not been investigated. METHODS: After failure at multiple other extracranial absorptive sites, an 18-year-old woman was shunted from the lateral ventricle to the internal jugular vein against the direction of blood flow. The shunt system contained an in-line noninvasive telemonitor allowing examination of postural intracranial pressure dynamics in the awake state. This shunt system demonstrated postural pressure dynamics that were consistent with a stringent nonsiphoning shunting system. CONCLUSIONS: These observations validate the use of the El-Shafei shunt placement as a biologically nonsiphoning CSF absorptive system. In addition, the stringency of the anti-siphoning properties of the internal jugular vein open the possibility of preferentially using this shunting system in patients who clearly exhibit symptoms of shunt overdrainage.

Radiosurgery in the management of pediatric brain tumors.

OBJECTIVE: To describe the outcome of pediatric brain tumor patients following stereotactic radiosurgery (SRS), and factors associated with progression-free survival. METHODS: We reviewed the outcome of 90 children treated with SRS for recurrent (n = 62) or residual (n = 28) brain tumors over a 10-year period. Median follow-up from SRS was 24 months for all patients and 55.5 months for the 34 patients currently alive. RESULTS: The median progression-free survival (PFS) for all patients was 13 months. Median PFS according to tumor histology was medulloblastoma = 11 months, ependymoma = 8.5 months, glioblastoma and anaplastic astrocytoma = 12 months. Median PFS in patients treated to a single lesion was 15.4 months. No patient undergoing SRS to more than 1 lesion survived disease free beyond 2 years. After adjusting for histology and other clinical factors, SRS for tumor recurrence (RR = 2.49) and the presence of > 1 lesion (RR = 2.3) were associated with a significantly increased rate of progression (p < 0.05). Three-year actuarial local control (LC) was as follows: medulloblastoma = 57%, ependymoma = 29%, anaplastic astrocytoma/glioblastoma = 60%, other histologies = 56%. Nineteen patients with radionecrosis and progressive neurologic symptoms underwent reoperation after an interval of 0.6-62 months following SRS. Pathology revealed necrosis with no evidence of tumor in 9 of these cases. CONCLUSION: SRS can be given safely to selected children with brain tumors. SRS appears to reduce the proportion of first failures occurring locally and is associated with better outcome when given as a part of initial management. Some patients with unresectable relapsed disease can be salvaged with SRS. SRS to multiple lesions does not appear to be curative. Serious neurologic symptoms requiring reoperation is infrequently caused by radionecrosis alone.

Proton magnetic spectroscopic imaging of the child's brain: the response of tumors to treatment.

Our aim was to determine and/or predict response to treatment of brain tumors in children using proton magnetic resonance spectro-scopic imaging (MRSI). We studied 24 patients aged 10 months to 24 years, using MRI and point-resolved spectroscopy (PRESS; TR 2000 TE 65 ms) with volume preselection and phase-encoding in two dimensions on a 1.5 T imager. Multiple logistic regression was used to establish independent predictors of active tumor growth. Biologically vital cell metabolites, such as N-acetyl aspartate and choline-containing compounds (Cho), were significantly different between tumor and control tissues (P < 0.001). The eight brain tumors which responded to radiation or chemotherapy, exhibited lower Cho (P = 0.05), higher total creatine (tCr) (P = 0.02) and lower lactate and lipid (L) (P = 0.04) than 16 tumors which were not treated (except by surgery) or did not respond to treatment. The only significant independent predictor of active tumor growth was tCr (P < 0.01). We suggest that tCr is useful in assessing response of brain tumors to treatment.

Memory deficits among children with craniopharyngiomas.

OBJECTIVE: To describe neuropsychological functioning (with a specific focus on cognition and memory) after surgical treatment of craniopharyngiomas. METHODS: Sixteen patients who were between 6 and 15 years of age at the time of surgery comprised the sample. Each child had been treated for a craniopharyngioma with surgery only, on Dana-Farber Cancer Institute Protocol 92-077. RESULTS: The overall level of cognitive functioning was well within the average range, with both language and visuospatial functioning being generally intact; however, specific memory problems, in both the language and visuospatial domains, were evident. CONCLUSION: Although general cognitive functioning was intact after the surgical treatment of craniopharyngiomas, difficulties in the retrieval of learned information were observed. Neuropsychological assessments, with a focus on memory recall, should be a component of the medical management plan for each child.

Neurological dysfunction associated with postoperative cerebellar mutism.

BACKGROUND AND OBJECTIVES: The postoperative cerebellar mutism syndrome (CMS) is an unique acute postoperative complication characterized by transient decrease in speech output (often mutism), apathy, irritability as well as global cerebellar dysfunction. As much as 25% of patients undergoing a resection of a cerebellar or IV ventricular tumor may develop such a syndrome. In this retrospective study we characterize the clinical features of the CMS and explore potential etiologic mechanisms. METHODS: We conducted a retrospective analysis of medical records and imaging tests of 8 consecutive patients with the CMS identified through the database of the Children's Hospital and Dana-Farber Cancer Institute, Boston, and compared with a control group of 8 unaffected children undergoing a comparable tumor resection. RESULTS: In contrast to the control group, children in the affected group had marked decrease in speech output and comprehension, apathy and lack of initiative, inattention, persistent eye closure, flaccid hemiparesis and a severe global cerebellar dysfunction. Swallowing difficulties and bowel and bladder dysfunction were also observed. The median duration of the syndrome as judged by the persistence of the communication abnormalities was 4 weeks. The recovery was near complete with exception for a persistent global cerebellar dysfunction. A comparison of CT and MRI scans of children in both groups failed to identify distinguishing features. CONCLUSION: A surgical lesion of the midline cerebellum can cause a complex neurological dysfunction such as the CMS. Thus, we postulate that the cerebellum and its connections function as a 'modulatory system' in control of both motor and non-motor functions, including attention and language.

In vivo intracranial pressure dynamics in patients with hydrocephalus treated by shunt placement.

OBJECT: With the commercial availability of a variety of shunt systems, there is considerable controversy over the choice of the most appropriate shunt valve for each individual with hydrocephalus. Although the performance characteristics of all shunt systems are well documented in the laboratory setting, there is little description of the in vivo dynamics of intracranial pressure (ICP) after implantation of commonly used shunt systems in humans. The authors coupled telemonitoring devices to several different shunt systems to measure the performance characteristics of these valve systems with respect to intraventricular pressure (IVP) at increments of head elevation. METHODS: Twenty-five patients with different shunt systems and three control patients without shunts were studied for IVP at 0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees, and 90 degrees of head elevation, and the resultant curves were analyzed for the best-fit regression coefficient. For purposes of analysis the authors grouped shunt valve systems by design characteristics into three groups: differential-pressure valves (r = -0.321 +/- 0.061; 11 patients), nonsiphoning systems (r = -0.158 +/- 0.027; 10 patients), and flow-regulated valves (r = -0.16 +/- 0.056; four patients); there were three control patients without shunts (r = -0.112 +/- 0.037). CONCLUSIONS: The authors found that differential-pressure valves always caused ICP to drop to 0 by 30 degrees of head elevation, whereas all other valve systems caused a more gradual drop in ICP, more consistent with pressures observed in the control patients without shunts. Not surprisingly, the differential-pressure valve group was found to have a significant difference in mean regression coefficient when compared with those in whom nonsiphoning shunts (p < 0.023) or no shunts were placed (p < 0.049). These data provide a basis for evaluating shunt valve performance and for predicting valve appropriateness in patients in whom characteristics such as pressure and flow dynamics are weighed in the choice of a specific valve for implantation.

Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas.

Elevated expression of the neurotrophin-3 (NT-3) receptor TrkC by childhood medulloblastomas is associated with favorable clinical outcome. Here, we provide evidence that TrkC is more than simply a passive marker of prognosis. We demonstrate that: (a) medulloblastomas undergo apoptosis in vitro when grown in the presence of NT-3; (b) overexpression of TrkC inhibits the growth of intracerebral xenografts of a medulloblastoma cell line in nude mice; and (c) trkC expression by individual tumor cells is highly correlated with apoptosis within primary medulloblastoma biopsy specimens. TrkC-mediated NT-3 signaling promotes apoptosis by activating multiple parallel signaling pathways and by inducing immediate-early gene expression of both c-jun and c-fos. Considered collectively, these results support the conclusion that the biological actions of TrkC activation affect medulloblastoma outcome by inhibiting tumor growth through the promotion of apoptosis.

Endoscopic approach to noncommunicating fluid spaces in the shunted patient.

INTRODUCTION: It is well known that shunted hydrocephalic patients can, over time, develop entrapped ventricles or cystic spaces not in communication with the remaining ventricles. This situation has traditionally been treated with placement of an additional catheter or shunt system in the noncommunicating fluid space. With the advent of minimally invasive endoscopic techniques, it has become possible to fenestrate trapped fluid spaces into the shunted ventricular system, thus preventing the need for additional catheters. METHODS: Fifteen shunted patients presented with noncommunicating fluid spaces over a 4-year period at our two institutions. We attempted fenestration procedures in 14 of those patients. The various procedures included: septum pellucidum fenestration, cyst fenestration, third ventriculocisternostomy and a combination of the above. RESULTS: Thirteen of 16 (81%) endoscopic fenestrations successfully prevented the need for a complicated shunting system. There were 3 technical failures (3/16, 19%) in which an additional catheter was added to the existing shunt system at the time of the endoscopic procedure. There were no adverse neurologic effects from the endoscopic procedures; however, in 4 of the 14 patients (29%) a shunt revision was performed between 2 and 30 days following the fenestration. CONCLUSIONS: These results show that the endoscopic approach to establishing communication between noncommunicating CSF spaces in the shunted patient is safe and efficacious in preventing the need for additional CSF catheters. Though we encountered failures, the majority of cases are technically feasible. In these patients early shunt malfunction may occur, most likely due to intraoperative bleeding and will require shunt revision.

Tectal tumors of childhood: clinical and imaging follow-up.

PURPOSE: This study was done to determine which clinical and imaging findings best correlate with outcome in children with tectal tumors. METHODS: A retrospective review was done of the medical records and imaging studies of 32 children (16 boys and 16 girls; mean age, 8 years) with tectal tumors. Eight children had CT, 11 had MR imaging, and 13 had both CT and MR studies. Findings from surgical and pathologic reports as well as from follow-up examinations (mean follow-up period, 5 years; range, 3.6 months to 17 years) were included in the review. RESULTS: All patients had hydrocephalus and all but one required CSF diversion. The tectum was the center of the tumor in all cases and the majority of the tumors appeared isodense on CT scans, isointense on T1-weighted MR images, and hyperintense on T2-weighted images. Twenty patients required no further treatment. In this group, the mean maximum tumor diameter was 1.8 cm and enhancement occurred in two cases. At follow-up, 18 patients had stable tumor size, one had an increase in tumor size with cyst formation but no worsening of symptoms, and one had a decrease in tumor size. Twelve patients required further treatment (excision and/or radiotherapy) because of progression as indicated by either increased tumor size or worsening of symptoms. In this group, the mean maximum tumor diameter was 2.5 cm and contrast enhancement occurred in nine cases. Further follow-up in this group showed decreased tumor size in eight and stable residual tumor in three. CONCLUSION: Tectal tumors in childhood have variable behavior. MR imaging assists in the clinical determination of which children need treatment beyond CSF diversion. Larger tumor size and enhancement are radiologic predictors of the need for further treatment.

The use of clinical practice guidelines (CPGs) to evaluate practice and control costs in ventriculoperitoneal shunt management.

BACKGROUND: As a step toward maximizing the quality and cost-effectiveness of neurosurgical care, we designed clinical practice guidelines (CPGs) for the management of VP shunt malfunctions and infections at a tertiary care pediatric teaching institution. The detailed CPGs determine the use of radiographic studies, laboratory tests, and invasive procedures in the management of this problem. One purpose of the CPGs is to provide clear clinical guidelines for the medical trainee, thereby reducing variability in care and unnecessary utilization of resources. METHODS: The CPGs were developed in stages over a 2-year period. The practice patterns in our institution for the management of shunt malfunctions and infections were articulated. They were compared with those published in the neurosurgical literature, and areas of clinical decision-making variability were identified. Preliminary guidelines were formulated, and data regarding patient care were prospectively collected. Based on this data, final CPGs were formulated and implemented. Total and itemized hospital charges for patients managed according to the CPGs were compared with those for patients in the 3 years before CPG implementation. RESULTS: CPG-managed patients had generally lower total and itemized charges as compared with control patients. Decreased charges per hospital day and charges for shunt films in the CPG group were statistically significant. CONCLUSIONS: The process by which the CPGs were developed and implemented, as well as the CPGs themselves, are described. We also present the clinical, demographic, and financial data that were prospectively collected for all patients managed within the CPGs over an initial 1-year period and compare it with data obtained for control groups of shunt malfunction patients admitted during the 3 years before implementation of the CPGs. We find a trend toward reduction of charges after implementation of the CPG.

Intraventricular urokinase for the treatment of posthemorrhagic hydrocephalus.

This case series pilot study assessed the safety of intraventricular urokinase administration, alternating with cerebrospinal fluid (CSF) drainage. A secondary objective was to comment on whether this therapy achieves fibrinolysis, and whether this fibrinolysis is sufficient to prevent progression of hydrocephalus to requirement for ventriculoperitoneal shunt. Six preterm infants with progressive posthemorrhagic hydrocephalus requiring treatment with a ventricular drain received an infusion of intraventricular urokinase alternating with CSF drainage for 3 days. Of the 6 treated patients, the median gestation at birth was 26.5 weeks and the median age at treatment was 30 days. One patient had an elevation in CSF erythrocyte count most likely due to successful clot lysis. One patient had an elevated CSF leukocyte count consistent with transient meningeal irritation. No other side effects were noted. Fibrinolysis was achieved in the CSF, as documented by markedly elevated D-dimer levels. Clot size diminished ultrasonographically. However, all 6 patients eventually required a ventriculoperitoneal shunt. We conclude that intermittent infusion of intraventricular urokinase alternating with periods of CSF drainage is probably a safe way to achieve a fibrinolytic state. However, when administered at the relatively late point in the neonatal course when a ventricular drain is required, this fibrinolytic state is not sufficient to decrease the requirement for ventriculoperitoneal shunt.

Telemetric intraventricular pressure measurements after third ventriculocisternostomy in a patient with noncommunicating hydrocephalus.

OBJECTIVE: To examine and document intraventricular pressure (IVP) dynamics in an adult after endoscopic third ventriculocisternostomy performed as treatment for hydrocephalus associated with aqueductal stenosis. METHODS: A 30-year-old man who had undergone ventriculoperitoneal shunting at age 21 years for aqueductal stenosis caused by a tectal mass presented with symptoms and imaging studies consistent with shunt malfunction. He underwent urgent ventriculoscopic third ventricular ventriculocisternostomy, which resolved his symptomatology. The existing shunt was not revised. At the time of surgery, a catheter connected to an intracranial pressure TeleSensor device (Radionics, Burlington, MA) was inserted into the ventricular system. Postoperatively, the patient's recovery was assessed by IVP recordings. This system allowed us to record IVP in an awake patient with a functioning third ventriculocisternostomy. RESULTS: We observed an initial postoperative IVP of 17 cm H2O in the supine position, which decreased to 0 cm H2O at 90 degrees of head elevation. The IVP decreased during the first 48 hours postoperatively to 0 to 2 cm H2O when supine. By 1 week postoperatively, the patient's IVP had returned to a baseline of 15 to 17 cm H2O when supine, with a gradual decrease to 0 cm H2O at 30 degrees of head elevation. Three months postoperatively, the patient's IVP in the supine position was 8 cm H2O, with IVP decreasing to 0 cm H2O at 45 degrees of head elevation. Magnetic resonance (MR) imaging performed at that time revealed evidence of flow through the third ventriculocisternostomy. CONCLUSION: We conclude that after an initial period of adjustment, the IVP in this patient returned to an unremarkable baseline despite the novel fluid pathway into the prepontine cistern. This may represent maturation of the breach through the third ventricular floor or brain recovery from a period of high pressure. Also, the shape of the postural IVP curve closely resembled that observed in patients who are not hydrocephalic. These data represent the first documentation of the intraventricular pressure response to ventriculocisternostomy and suggest possible intracerebral responses to this alteration in cerebrospinal fluid flow.

Diencephalic syndrome: clinical features and imaging findings.

PURPOSE: To emphasize the importance of imaging in children with diencephalic syndrome due to hypothalamic/chiasmatic astrocytomas. METHODS: Findings in nine patients (mean age, 26 months) with diencephalic syndrome and hypothalamic/chiasmatic astrocytomas were analyzed retrospectively, including reviewing clinical records, imaging examinations, and follow-up studies. RESULTS: Symptoms and signs included failure to thrive (n = 9), nystagmus (n = 3), visual field defects (n = 1), optic pallor (n = 1), emesis (n = 2), and headache (n = 1). All patients had hypothalamic/chiasmatic masses. Five patients underwent biopsy, and, in all cases, specimens showed low-grade astrocytoma. Imaging studies were available in eight patients. All tumors were large (median maximum diameter, 3.5 cm), involved the chiasm and hypothalamus, and showed homogeneous enhancement. Three patients had hydrocephalus and two had metastases. At follow-up, five patients had recurrent disease and two had died. CONCLUSION: Diencephalic syndrome is a rare cause of failure to thrive in childhood, and diagnosis of a hypothalamic/ chiasmatic astrocytoma might therefore be delayed. The astrocytomas associated with this syndrome are larger, occur at a younger age, and are often more aggressive than other astrocytomas arising in this region.

Presentation and management of Chiari I malformation in children.

To determine the efficacy of operative treatment for children with Chiari I malformation, the medical records and magnetic resonance imaging (MRI) studies of 68 consecutive patients cared for at The Children's Hospital, Boston, Mass., USA, from December, 1988 to November, 1996 were retrospectively reviewed. All patients underwent suboccipital craniectomy, C1 laminectomy, and dural grafting. Bipolar coagulation to shrink and reduce the volume of the cerebellar tonsils was carried out in 40 patients. In 32 of 40 patients with associated syringomyelia, the procedure included placement of a IVth ventricle to cervical subarachnoid space shunt. Twenty-three patients with syringomyelia also had plugging of the obex. There was no operative mortality. Morbidity included a 22% incidence of nausea/vomiting and a 10% incidence of headache, both limited to the immediate postoperative period. Within the first postoperative month, all patients or their parents reported clear improvement in their presenting symptoms and 93% were found to have clear improvement in their presenting signs. In follow-up periods of 6-70 months, all patients had continued unequivocal symptom improvement and all patients were found on examination to have clear improvement in neurological signs. In patients with syringomyelia, MRI studies carried out at least 6 months postoperatively revealed near total or total syrinx resolution in 80% of the cases. This study demonstrates that a standard bony and dural decompression of the foramen magnum region with modifications designed to maximize the restoration of CSF circulation across the foramen magnum is a safe, effective operative treatment for Chiari I malformation in children.

Neurotrophins in cerebellar granule cell development and medulloblastoma.

Medulloblastomas may be derived from granule cells of the developing cerebellum. Children with tumors expressing high levels of the neurotrophin-3 receptor, TrkC, have a more favorable outcome. During development, TrkC is expressed in the most mature granule cells. Favorable medulloblastomas may be derived from more highly differentiated granule cells.