Regional brain injury on conventional and diffusion weighted MRI is associated with outcome after pediatric cardiac arrest.

BACKGROUND: To assess regional brain injury on magnetic resonance imaging (MRI) after pediatric cardiac arrest (CA) and to associate regional injury with patient outcome and effects of hypothermia therapy for neuroprotection. METHODS: We performed a retrospective chart review with prospective imaging analysis. Children between 1 week and 17 years of age who had a brain MRI in the first 2 weeks after CA without other acute brain injury between 2002 and 2008 were included. Brain MRI (1.5 T General Electric, Milwaukee, WI, USA) images were analyzed by 2 blinded neuroradiologists with adjudication; images were visually graded. Brain lobes, basal ganglia, thalamus, brain stem, and cerebellum were analyzed using T1, T2, and diffusion-weighted images (DWI). RESULTS: We examined 28 subjects with median age 1.9 years (IQR 0.4-13.0) and 19 (68 %) males. Increased intensity on T2 in the basal ganglia and restricted diffusion in the brain lobes were associated with unfavorable outcome (all P < 0.05). Therapeutic hypothermia had no effect on regional brain injury. Repeat brain MRI was infrequently performed but demonstrated evolution of lesions. CONCLUSION: Children with lesions in the basal ganglia on conventional MRI and brain lobes on DWI within the first 2 weeks after CA represent a group with increased risk of poor outcome. These findings may be important for developing neuroprotective strategies based on regional brain injury and for evaluating response to therapy in interventional clinical trials.

Redefining the Guillain-Barré spectrum in children: neuroimaging findings of cranial nerve involvement.

GBS and its MFS variant are acute polyneuropathies that are considered to represent a continuum rather than distinct entities, due to the overlap in their clinical features. Enhancement of the CE roots represents the neuroradiologic hallmark of GBS, while findings of neuroimaging studies in MFS are usually unremarkable. Our purpose was to evaluate the MR imaging findings of polyneuropathy in 17 children affected by GBS and its MFS variant. Fourteen of our 17 patients demonstrated CE enhancement, with predominant involvement of the anterior roots. Of 6 patients who underwent MR imaging of the brain, 5 had cranial nerve involvement. In children affected by GBS-MFS, involvement of the CE roots may be considered part of a more extensive autoimmune neuropathy, as demonstrated by enhancement of cranial nerves. Brain MR imaging should be considered in the routine evaluation in pediatric patients with GBS-MFS for the evaluation of the cranial nerves.

Non-endoscopic removal of radiologically placed percutaneous primary gastrostomy tubes: a new technique.

PURPOSE: To present a new technique for non-endoscopic removal of radiologically inserted primary percutaneous gastrostomy tubes (PGT) and to assess the utility and safety of this technique in the pediatric population. MATERIALS AND METHODS: Over a 9-year period 172 children (80 F, 92 M) mean age 10 years (range 0.29-24 years) underwent removal of radiologically placed PGTs in the Radiology Department. All procedures were performed with conscious sedation. The procedure time ranged from 20 to 45 min (mean 30 min). The procedures were performed electively at > or = 3 14 months for either gastrostomy button placement (70), balloon gastrostomy and jejunostomy placement (55), or G tube removal at termination of enteral feeding (15). RESULTS: PGT disc retrievals were successful performed in 169 of 173 (98%). No technical failures occurred, but five procedures failed due to PGT disc lodgement in gastric wall (four), and gastrocolic fistula (one). One child had a repeat procedure due to premature removal of the primary PGT necessitating replacement. No deaths occurred. PGT discs retrieval was performed at a mean time interval of 14 months from initial PGT insertion (range 3-40 months). CONCLUSION: Non-endoscopic GT disc removal is a quick and safe procedure. It facilitates easy conversion to a gastrostomy button in the radiology setting and avoids the risk of a retained percutaneous gastrostomy tube remnant and intra/transmural migration of discs.

"Push-pull" gastrostomy: a new technique for percutaneous gastrostomy tube insertion in the neonate and young infant.

OBJECTIVE: To evaluate a newly developed method combining antegrade and retrograde techniques for percutaneous gastrostomy tube (PGT) insertion in the neonate and young infant. MATERIALS AND METHODS: From January 1994 to December 2000, 85 children (47 male, 38 female), mean age 4.5 months (range 0.44-9.13 months) underwent PGT insertion using the "push-pull" technique. With the addition, 57 children had a jejunostomy tube placed as well at or within 24 h of the PGT procedure. The mean weight was 3.74 kg, range 1.5-7.0 kg. The indications for the procedure included failure to thrive in 40 patients (25%), static encephalopathy in 21 (25%), neurological/congenital abnormalities in 12 (14%), aspiration in 7 (8%), and cardiac problems in 5 (6%). RESULTS: Eighty-five PGTs were successfully inserted in 85 children. One procedure was initially unsuccessful due to failed conscious sedation and was completed under general anesthesia. Four of 85 patients initially had attempted antegrade placement that failed, and the procedure was successfully completed using the "push-pull" method. One major complication occurred: a gastrocolic fistula at day 5 post-procedure, which was surgically repaired without sequelae. Tube-related problems included; tube dislodgement (n = 1) and procedure-related stomal infection (n = 3). CONCLUSION: The "push-pull" gastrostomy technique is a safe, effective method of percutaneous gastrostomy tube placement in neonates. It facilitates successful placement of the PGT in patients in whom the classic antegrade method is not possible. It has become the procedure of choice in this group.

Congenital reactive myofibroblastic tumor of the petrous bone: case report.

OBJECTIVE AND IMPORTANCE: Myofibroblastic tumors are members of a diverse spectrum of neoplastic and quasineoplastic lesions that occur most commonly during childhood and typically involve soft tissues. We present a case of a congenital reactive myofibroblastic tumor of the petrous bone (i.e., cranial fasciitis) that was successfully treated with surgical excision. CLINICAL PRESENTATION: A newborn girl with congenital right facial palsy and deafness was noted during imaging evaluation to have a large enhancing mass that was destroying the right petrous bone and extending into the posterior and middle cranial fossae. INTERVENTION: After embolization, an open biopsy was performed, which revealed a moderately cellular, spindle cell neoplasm without mitosis or necrosis, with scattered lymphocytes, eosinophils, and multinucleated giant cells. The spindle cells demonstrated strong immunoreactivity for vimentin, muscle-specific actin, and alpha-smooth muscle actin, with prominent reticulin staining between individual cells. Staining for CD68, a histiocyte marker, was positive within the multinucleated giant cells and many of the spindle cells; CD34, S-100, and desmin staining was absent. On the basis of these findings, the lesion was classified as a reactive myofibroblastic tumor, consistent with a cranial variant of nodular fasciitis. Because of the large size and significant mass effect of the tumor, a resection was performed several days later, using a combined supra- and infratentorial approach. Dense adherence of the mass to the walls of the sigmoid sinus and the carotid artery precluded complete resection without sacrifice of these vessels, which was not performed because of the known potential of these tumors to remain stable or regress after extensive subtotal resection. The presumed residual tumor subsequently regressed, and the patient has exhibited no detectable residual disease in 2 years of follow-up monitoring. CONCLUSION: Reactive myofibroblastic tumors of the calvarium are uncommon lesions that superficially resemble sarcomas. Recognition of this diagnostic entity is important, to avoid unnecessary treatment with intensive adjuvant therapy. Although the management of these tumors relies predominantly on surgical resection, surgical decision-making should take into account the fact that small areas of residual disease can regress spontaneously.

An intrasylvian "fibroma" in a child with cystic fibrosis: case report.

OBJECTIVE AND IMPORTANCE: Intracranial fibrous tumors are uncommon during childhood. An unusual case of benign intrasylvian "fibroma" that has remained clinically and radiographically stable more than 3 years after a subtotal resection is described. CLINICAL PRESENTATION: A 9-year-old girl with cystic fibrosis presented with new-onset focal seizures referable to a large calcified left sylvian fissure mass. INTERVENTION: An open biopsy with subtotal resection of the lesion revealed a benign process characterized by exuberant fibrocollagenous tissue intermeshed with chronic inflammatory cells and foreign body giant cells, encompassing islands of gliotic brain tissue. Immunohistochemical analysis showed staining for epithelial membrane antigen and reticulin within some of the spindle cells, although the majority were nonreactive. The majority of tumor cells exhibited staining for laminin; CD34 staining was absent. Ultrastructural studies were also suggestive of a fibroblastic rather than a meningothelial origin of the lesion, with elongated cells separated by abundant extracellular collagen. Although dense adherence of the mass to the pial surface and the middle cerebral artery vessels precluded a complete resection, the patient remains seizure-free without anticonvulsant therapy more than 3 years postoperatively with no evidence of growth of the lesion. CONCLUSION: The lesion in this patient bears morphological similarity to a rare group of tumors referred to as "intracerebral fibromas," although a variety of other rare mesenchymal neoplasms were also considered within the differential diagnosis. However, the absence of any definite neoplastic features, the finding of chronic inflammatory changes, and the lack of growth of the residual tumor during an extended follow-up interval indicate that the mass may represent either an extremely indolent neoplasm or a nonneoplastic process. The differential diagnosis of intracranial fibrous tumors is contrasted with that of the reported case.

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.

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.

Percutaneous gastrostomy tube placement in patients with ventriculoperitoneal shunts.

OBJECTIVE: The purpose of this study is to determine the risk of CNS and/or peritoneal infection in children with ventriculoperitoneal shunts in whom a percutaneous gastrostomy tube is placed. MATERIALS AND METHODS: We placed 205 gastrostomy or gastrojejunostomy tubes from January of 1991 to December 1996. Twenty-three patients (10 boys, 13 girls) had ventriculoperitoneal shunts at the time of placement. All shunts were placed at least 1 month prior to placement of the gastrostomy tube. The patients ranged in age from 8 months to 16 years with a mean age of 6 years, 9 months. Patient weight ranged from 2 kg to 60 kg. All 23 children required long-term nutritional support due to severe neurologic impairment. No prophylactic antibiotics were given prior to the procedure. Of the patients, 21/23 had a 14-F Sacks-Vine gastrostomy tube with a fixed terminal retention device inserted, using percutaneous fluoroscopic antegrade technique. Two of the 23 patients had a Ross 14-F Flexi-flo gastrostomy tube which required a retrograde technique due to a small caliber esophagus in these children. RESULTS: All 23 children had technically successful placements of percutaneous gastrostomy (7) or gastrojejunostomy (16) tubes. Of the children, 21/23 (91%) had no complications from the procedure. Two of 23 (9%) patients demonstrated signs of peritonitis after placement of their gastrostomy tubes and subsequently had shunt infections. In both, children CSF culture grew gram-positive cocci. The antegrade technique was used in both children who developed peritonitis. CONCLUSION: Our study indicates children with ventriculoperitoneal shunts who undergo percutaneous gastrostomy are at greater risk for infection and subsequent shunt malfunction. Therefore, we recommend prophylactic antibiotic therapy to cover for skin and oral flora.

Orbital hydrocephalus: a proven cause for optic atrophy.

A 4-year-old boy with bilateral optic sheath enlargement and progressive optic atrophy and blindness is presented. Computed tomography demonstrated hydrocephalus and enlargement of the optic nerve sheath complex. The child died during an attempted repair of hypoplastic atrioventricular valves. Autopsy demonstrated a patulous perioptic subarachnoid space and optic atrophy. This condition has been described in the literature but has not had radiologic-pathologic correlation. With the availability of magnetic resonance imaging, this diagnosis may be made prospectively, thus, it is important for the radiologist to be aware of this entity because optic atrophy and blindness may be prevented by early diagnosis and surgery.

Recognition of central nervous system metastases in children with metastatic primary extracranial neuroblastoma.

In children with primary extracranial neuroblastoma (NB), intrinsic central nervous system (CNS) metastases (brain parenchyma or leptomeninges) are thought to occur rarely. This study was done to evaluate our anecdotal experience, which suggested that CNS involvement is becoming more frequent. Reports of computed tomographic (CT) and magnetic resonance (MR) imaging scans, biopsies, cerebrospinal fluid (CSF) cytologies, and autopsies were reviewed for children with stage IV NB diagnosed in 1978-1993 and followed at the Children's Hospital of Pittsburgh. Of 43 children over the age of 1 year, CNS metastases were documented in 7 (16.2%). Six patients developed signs or symptoms best explained by the presence of CNS tumor and had radiographic and/or histologic evidence of parenchymal disease (cortical masses on CT and MR, n = 3; suprasellar mass on CT, n = 1; diffuse leptomeningeal carcinomatosis by MR and/or autopsy, n = 2). CSF cytologies were positive in the one patient so tested. An additional asymptomatic patient had extensive CNS involvement at autopsy. In two of these children, the CNS was the first or only site of recurrent disease. It is concluded that intrinsic CNS disease is not uncommon in children with NB over the age of 1 year and there has been a trend toward its increasing recognition in recent years. Whether this is a function of wider use of diagnostic tools or a true change in natural history over time with increased intensity of chemotherapy is not clear. A study that prospectively monitors children with advanced neuroblastoma, radiographically and with CSF cytologies (prior to treatment and at 6-monthly intervals), is under way and should help to better define the natural history in the context of current therapies.

Drug retention, efflux, and resistance in tumor cells.

Multiple drug resistance (MDR) in tumor cells has been related to the expression of transport proteins which alter cellular drug transport and distribution. Three different genes (mdr, MRP, and LRP) and their products have been implicated in MDR. Several fluorescent dyes have been used to monitor the effect of these transport proteins on drug retention, as well as for screening of drugs which block drug efflux and thus enhance cellular drug retention and cytotoxicity. The present review summarizes current knowledge about MDR phenotypic markers and techniques available for study of MDR by flow cytometry.

Craniocervical junction subarachnoid hemorrhage associated with atlanto-occipital dislocation.

STUDY DESIGN: The sensitivity of plain radiographs for diagnosing traumatic atlanto-occipital dislocation and its association with craniocervical junction subarachnoid hemorrhage was examined in a retrospective review of seven patients. OBJECTIVE: The purpose of this study was to demonstrate the frequency of nondiagnostic plain radiographs and the common association of craniocervical junction subarachnoid hemorrhage in the context of reported cases of atlanto-occipital dislocation to facilitate better recognition of this injury. The use of sagittal reconstructions of computed tomography or sagittal magnetic resonance imaging for diagnosis was evaluated. SUMMARY OF BACKGROUND DATA: Although traumatic atlanto-occipital dislocation is a common cause of motor vehicle fatalities, survival has been more common in the last 16 years. However, the diagnosis was missed on lateral cervical radiographs in 38% of children and 59% of adults; fewer than half were diagnosed subsequently with plain radiography. Moreover, the diagnosis of traumatic atlanto-occipital dislocation often was not considered, because more than half of the survivors had no neurologic abnormality or unilateral deficit. Consequently, more than one third of initially undiagnosed patients experienced neurologic deterioration due to inadequate cervical immobilization. Additional radiographic studies allowing diagnosis were prompted by the neurologic worsening. METHODS: The authors reviewed seven patients treated with traumatic atlanto-occipital dislocation during a 14-year period. Emergency department records were compared with reexamination of initial cervical radiographs to determine the success in diagnosis by means of published methods. The frequency of cranio-cervical junction subarachnoid hemorrhage on computed tomography was determined, and the use of sagittal imaging for subsequent diagnosis was evaluated. RESULTS: In the emergency department, only one patient's condition was diagnosed as atlanto-occipital dislocation. Review of the initial radiographs identified an additional four patients for whom atlanto-occipital dislocation could be diagnosed. Sagittal computed tomography reconstruction or sagittal magnetic resonance imaging identified the remaining two. All but one patient had craniocervical junction subarachnoid hemorrhage. A review of reported cases revealed a common association of craniocervical junction subarachnoid hemorrhage with traumatic atlanto-occipital dislocation but not with traumatic head injury. CONCLUSIONS: The diagnosis of traumatic atlanto-occipital dislocation is often missed in the emergency department, and current methods for evaluating the integrity of the atlanto-occipital joint on cervical radiographs fail to identify all patients with this injury. Although infratentorial subarachnoid hemorrhage is uncommon in traumatic head injury, craniocervical junction subarachnoid hemorrhage is often associated with atlanto-occipital dislocation and should raise the suspicion of severe craniocervical ligamentous injury. Sagittal computed tomography reconstructions or sagittal magnetic resonance imaging can allow for the diagnosis when plain radiography is inconclusive.

Treatment of children with newly diagnosed brain stem gliomas with intravenous recombinant beta-interferon and hyperfractionated radiation therapy: a childrens cancer group phase I/II study.

BACKGROUND: Prognosis for the majority of children with brain stem gliomas is dismal. In previous studies, recombinant beta-interferon (r beta IF) has been shown to be effective for children with recurrent brain stem gliomas and may also act synergistically with radiotherapy (RT). METHODS: Thirty-two children with diffuse intrinsic brain stem gliomas were treated with (r beta IF) and 7200 centigray (cGy) of hyperfractionated RT (100 cGy twice-daily fractions) to determine the toxicity of treatment and the tolerance of the brain stem to this regimen, as well as to assess survival. Patients were treated with r beta IF 3 times per week during RT and then for 8 weeks following RT. Initially, a dose escalation trial was performed. RESULTS: Interferon was initially begun at 12.5 x 10(6) IU/m2 and escalated up to 400 x 10(6) IU/m2. The safe starting dose was determined to be 100 x 10 (6) IU/m2. Due to unacceptable toxicity, the maintenance dose was reduced to 200 x 10 (6) IU/m2. Therapy was relatively well tolerated, although 13 of the patients required dose modifications due to hepatic or hematologic toxicity. Four of the patients had to discontinue treatment due to this toxicity. One patient died while receiving maintenance IF of encephalopathy, seizures, and brain stem dysfunction; believed possibly due to the r beta IF. Thirty of the 32 patients have developed progressive disease. The median time to progression from study entry was five months and the median time to death was 9 months. CONCLUSIONS: We conclude that r beta IF plus hyperfractionated therapy can be tolerated by children with newly diagnosed brain stem gliomas, although there is occasional dose-limiting hepatic, blood, and central nervous system toxicity. This therapy did not result in a higher rate of disease control.

Intracranial abnormalities in infants treated with extracorporeal membrane oxygenation: update on sonographic and CT findings.

PURPOSE: To determine the frequency of intracranial lesions in infants treated with extracorporeal membrane oxygenation (ECMO), to evaluate trends in frequency during an 8-year period, and to determine which infants are at highest risk for intracranial injury. METHODS: Daily sonograms were obtained in 386 infants during treatment with ECMO. Cranial CT scans were acquired after decannulation in 286 of 322 survivors. Abnormalities were classified as major or minor and hemorrhagic or nonhemorrhagic. Results were correlated with infant demographic data. RESULTS: Intracranial abnormalities were detected in 203 (52%) of the 386 infants; 73 (19%) hemorrhagic, 86 (22%) nonhemorrhagic, and 44 (11%) combined lesions. Eighty-two lesions (21%) were classified as major. Forty-six (94%) of 49 major hemorrhages were identified at sonography. CT contributed additional information in 73% of neonates with intracranial abnormalities, of which 17 were major lesions not identified at sonography. The frequency of intracranial hemorrhage was increased in infants who were septic or premature or weighed less than 2.5 kg. An increase in time spent on ECMO bypass increased the risk for nonhemorrhagic injury. During an 8-year period, the frequency of hemorrhagic and major nonhemorrhagic lesions remained constant, whereas minor nonhemorrhagic abnormalities increased significantly. CONCLUSION: Infants treated with ECMO continue to be at high risk for cerebrovascular injury. Although daily sonograms are useful in identifying major hemorrhages, follow-up CT scans are crucial for accurate evaluation of intracranial abnormalities.

Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology.

MUTISM AND A variety of other neurobehavioral symptoms have been reported anecdotally after the removal of posterior fossa mass lesions. To determine the incidence and clinical spectrum of this syndrome, a detailed review was performed of patients undergoing resection of infratentorial tumors at our institution during the last 9 years; 12 of 142 patients (8.5%) manifested this syndrome, the largest series of such patients reported to date. Each child had a lesion that involved the vermis; seven had medulloblastomas, three had astrocytomas, and two had ependymomas. The incidence among children with vermian neoplasms was 13%. Ten children underwent division of the inferior vermis during tumor resection, and three had a superior vermian incision; one child underwent both superior and inferior vermian incisions. In 10 children, mutism developed in a delayed fashion postoperatively. The speech disturbance was associated with poor oral intake in 9 children, urinary retention in 5, long-tract signs in 6, and bizarre personality changes, emotional lability, and/or decreased initiation of voluntary movements in all 12. Neuropsychiatric testing, performed in seven children, confirmed impairments not only in speech but also in initiation of other motor activities. Ten children regained normal speech, bladder control, and neurological functioning, other than ataxia and mild dysarthria, within 1 to 16 weeks; two children had significant residual deficits. Characteristically, affect and oral intake returned to their preoperative baseline before the speech difficulties began to resolve. A detailed radiological review of these cases in parallel with 24 cases of vermian tumors without mutism identified only one factor that was significantly associated with the mutism syndrome, bilateral edema within the brachium pontis (P < 0.01). Neither the size of the tumor nor the length of vermian incision was associated with the development of mutism. The clinical features of this syndrome in the context of these imaging findings suggest that the mutism syndrome results from transient impairment of the afferent and/or efferent pathways of the dendate nuclei that are involved in initiating complex volitional movements. The clinical courses of our patients are presented and compared with those of similar cases in the literature in an attempt to evaluate the validity of this hypothesis.

The role of frameless stereotactic techniques in the treatment of pediatric CNS lesions.

The surgical management of children with deep-seated lesions within the brain and skull base or with superficial lesions within functionally important regions of the brain is often challenging. In order to optimize the functional outcome of an affected child, it is essential not only to adequately treat the offending lesion, but also to minimize injury to the surrounding brain. In this study, we examined the applicability of a video-interactive frameless stereotactic system for intraoperative localization and treatment of a variety of pediatric central nervous system problems, including craniotomy for tumor (n = 14), vascular malformation (n = 3), or cortical resection for intractable epilepsy (n = 4); ventricular puncture for shunt insertion in a patient with slit ventricles (n = 2); transoral odontoid resection (n = 1); cannulation of a brainstem syrinx (n = 1); removal of a foreign body (n = 1); and posterior craniocervical decompression (n = 1). The efficacy of the system was judged on several criteria: (1) the accuracy of the targeting achieved; (2) whether the system facilitated treatment of the lesions of interest; and (3) whether neurologic function was preserved. In general, the accuracy of the system for target localization was within 2-4 mm when rigid head fixation was employed intraoperatively. In such cases, frameless stereotactic guidance was extremely helpful in providing rapid and reliable assistance with operative planning, which facilitated the treatment of a variety of lesions in critical areas of brain with minimal neurologic morbidity. Limitations of this technology and potential solutions to these shortcomings are discussed. We conclude that the application of frameless stereotaxis for intraoperative localization represents a major advance in the treatment of a variety of intracranial processes in children by providing a means for accurately directing the approach to and removal of a targeted lesion while minimizing injury to the surrounding brain.

Holoprosencephaly and septo-optic dysplasia.

Holoprosencephaly is a rare brain anomaly, which may be seen in liveborn neonates, although it is more common in stillbirths and abortions. It may occur alone or as part of a large number of genetic syndromes and associations. It is thought to arise early in embryogenesis (6 weeks), as the prosencephalon is separating into the two hemispheres. It is a complex anomaly with markedly varying degrees of severity. The most severe alobar form affects the entire prosencephalon. The brain shows no evidence of division into two hemispheres. The central thalami and basal ganglia remain undivided and confluent, and there is a large, dorsally located cyst connected to the large single ventricle. These infants usually die shortly after birth. The semilobar form has variable amounts of hemispheric formation with normalization occurring from dorsal to ventral. Some posterior falx, occipital, and temporal horn formation and evidence of a third ventricle are present. It is compatible with life. The lobar form has the most nearly normal appearance. It often exhibits a well-formed ventricular system, absence of the septum pellucidum, a shallow falx, abnormal connection of gray and white matter across the midline, and partially formed frontal lobes. Facial anomalies, especially hypotelorism and midline clefts, generally parallel the brain malformation in severity. Visual and olfactory symptoms plus pituitary abnormalities are often present. Septo-optic dysplasia is a related entity. It has a constellation of symptoms of hypotelorism, severe visual problems, and short stature or other pituitary symptoms. Primary imaging findings include optic nerve hypoplasia and absent septum pellucidum. Septo-optic dysplasia somewhat resembles lobar holoprosencephaly. Septo-optic dysplasia is more common than holoprosencephaly. Isolated absence of the septum pellucidum is also thought to be a mild brain anomaly.

Staging and surveillance of children with central nervous system neoplasms: recommendations of the Neurology and Tumor Imaging Committees of the Children's Cancer Group.

Standardization of the baseline and surveillance evaluation of children with central nervous system (CNS) tumors could contribute to understanding tumor behavior, establishing prognoses, directing treatment, and interpreting multi-institutional cooperative study data. A tumor categorization schedule, based on recognized patterns of CNS tumor behavior involving 'aggressiveness' as assessed by the likelihood for neuraxis dissemination, relative time to progression and pattern of disease recurrence is presented. Included are the most common histologic subtypes of pediatric CNS neoplasms. No attempt has been made to include all histologic subtypes of pediatric CNS neoplasms. Using this categorization as a framework, recommendations are suggested for baseline evaluation at diagnosis and in surveillance.

Subchronic toxicity of cupric sulfate administered in drinking water and feed to rats and mice.

The effects of acute poisoning by cupric sulfate in a number of species are well known; however, the effects of chronic low-level ingestion of cupric sulfate are less well characterized. Because exposure of humans to cupric sulfate may occur through drinking water, food, soil, or ambient air, subchronic toxicity studies were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week exposure) and dosed feed (2- and 13-week exposure) routes. Animals were evaluated for histopathology, clinical pathology, reproductive toxicity, and tissue metal accumulation, and target organs were examined by a variety of special stains and by electron microscopy to characterize the observed lesions. In drinking water, cupric sulfate concentrations of 300 to 100 ppm produced no ill effects, whereas concentrations of 3000 to 30,000 ppm were lethal to rats and mice within 2 weeks. In feed, cupric sulfate concentrations of 4000 to 16,000 ppm caused significant reductions in body weight gain in both species in the 2- and 13-week studies. Hyperplasia and hyperkeratosis of the limiting ridge of the forestomach were present in both species in the 2- and 13-week studies. Rats in the dosed feed studies had a dose-related increase in inflammation in the liver and changes in clinical chemistry parameters which were indicative of hepatocellular damage and cholestasis. Histologic changes in the kidneys of rats consisted of a dose-related increase in the number and size of eosinophilic protein droplets in the epithelial cytoplasm and the lumina of the proximal convoluted tubules. Droplets were larger and more numerous in males than in females. Urinalysis results were suggestive of renal tubular epithelial damage. Iron staining of spleens from treated animals indicated a marked depletion of iron stores in both male and female rats, but not in mice, while hematologic and clinical chemistry alterations in rats in the 13-week study, along with histologic changes in bone in the 2-week dosed feed study, were indicative of a microcytic anemia. Cupric sulfate produced no adverse effects on any of the reproductive parameters measured in rats or mice of either sex. These results indicate that cupric sulfate at high exposure levels is a hepatic and renal toxicant, as well as an inducer of anemia in rodents, with rats more sensitive than mice following subchronic exposure.