Timothy N. Booth

Randomized Study of Two Chemotherapy Regimens for Treatment of Low-Grade Glioma in Young Children: A Report From the Children's Oncology Group

PURPOSE Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. PATIENTS AND METHODS Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007). On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm(2). Tumor location in the thalamus was also associated with poor OS. CONCLUSION The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.

Advantages of magnetic resonance imaging over computed tomography in preoperative evaluation of pediatric cochlear implant candidates.

Objectives: To compare magnetic resonance imaging (MRI) to high-resolution computed tomography (HRCT) in the preoperative evaluation of pediatric cochlear implant candidates. Methods: The charts of pediatric cochlear implant candidates evaluated between July 1, 2000 and November 30, 2003 with an MRI scan of the inner ear were included in the study. Fifty-six patients were included. Associated HRCT scans were examined. Abnormalities of the cochlea, cochlear nerve, endolymphatic sac, endolymphatic duct, vestibule, and modiolus were noted. A pediatric neuroradiologist gave an opinion as to whether patients with anomalies seen with MRI but without associated HRCT would have been identified by HRCT. Results: Of the 112 temporal bones imaged with MRI, the following abnormalities were encountered: 32% (36/112) had abnormalities of the cochlear turns, 30% (34/112) had abnormal signal in the modiolus, 23% (26/112) had abnormal vestibulae, 16% (18/112) had abnormal endolymphatic ducts, 15% (17/112) had abnormal endolymphatic sacs, 12% (13/112) had abnormalities of the cochlear nerves, 29% (17/56) had abnormalities of the brain. HRCT cannot directly evaluate the cochlear nerve. Available HRCT findings were combined with radiologic opinion and compared with MRI findings. The percentages of abnormalities identifiable by HRCT when compared with those seen with MRI are cochlea 42% (15/36), modiolus 35% (12/34), vestibulae 88% (23/26), endolymphatic duct 100% (18/18), and endolymphatic sac 6% (1/17). Conclusion: MRI is more sensitive and specific in diagnosing soft tissue abnormalities in the inner ear than HRCT in cochlear implant candidates (Fig. 4). Moreover, the abnormalities detected with MRI are more likely to influence the implantation process (e.g., asymmetric nerve aplasia, cochlear obstruction). FIG. 4. MRI versus HRCT. Percentages of abnormalities identified by MRI or HRCT.

Evaluation of Pediatric Sensorineural Hearing Loss With Magnetic Resonance Imaging

OBJECTIVE To evaluate the incidence and type of intracranial and inner ear abnormalities in children with sensorineural hearing loss (SNHL) identified with magnetic resonance imaging (MRI) and stratified by the degree and type of SNHL. DESIGN Retrospective review of medical records and MRIs. SETTING Tertiary care childrens hospital. PATIENTS A total of 227 children aged 1 month to 17 years (mean age, 5.3 years; male to female ratio, 1:1) with a diagnosis of SNHL underwent MRI from June 1,1996, to June 1, 2002. Of these children, 170 had clinical information available and technically adequate MRIs and were included in the study. INTERVENTION Magnetic resonance imaging. MAIN OUTCOME MEASURE Identification of an abnormality of the intracranial contents, inner ear, and cochlear nerve. RESULTS Of the 170 children, 101 (59%) had bilateral SNHL and 69 (41%) had unilateral SNHL, comprising 271 ears with SNHL. Abnormalities of the inner ear were found in 108 ears (40%) with 87 (32%) having abnormalities of the cochlea, which were considered mild in 63 (23%) and moderate to severe in 24 (9%). Forty-nine of 271 ears (18%) with SNHL demonstrated an either absent (26/49 [53%]) or deficient (23/49 [47%]) cochlear nerve. Ears with severe and profound SNHL had more abnormalities than ears with mild and moderate SNHL (66/138 [48%] vs 23/80 [29%]; P = .006), and children having ears with unilateral moderate, severe, or profound SNHL had more inner ear abnormalities than children with bilateral moderate, severe, or profound SNHL (28/45 [62%] vs 54/144 [38%]; P = .004). CONCLUSIONS The overall incidence of inner ear abnormalities in ears of children with SNHL evaluated by MRI is 40%. The most common abnormalities seen were an abnormal cochlea and abnormal cochlear nerve. Children with severe and profound SNHL have a greater percentage of inner ear anomalies than children with mild or moderate SNHL. Children with unilateral hearing loss have a greater percentage of inner ear anomalies than children with bilateral SNHL.

Clinical Presentation of Allergic Fungal Sinusitis in Children

Objective To compare the differences in the clinical and radiographic presentation of allergic fungal sinusitis in children and adults.

MR Venography in Children with Complex Craniosynostosis

Purpose: Chronic venous hypertension due to jugular foramen stenosis has been proposed as an etiology for the hydrocephalus and tonsillar herniation seen in some patients with complex craniosynostosis. We report the use of MR venography (MRV) to evaluate venous outflow obstruction in this clinical setting. Materials and Methods: We studied 17 patients, (ages 4 months to 34 years; mean 7.3 years) with complex craniosynostosis; 8 patients with Crouzon’s syndrome, 2 with Apert’s, 1 with Pfeiffer’s and 6 patients without an eponymous classification. MR imaging included routine imaging sequences and axial 2D TOF MRV. Patterns of venous drainage and the presence of hydrocephalus and tonsillar herniation were noted. Results: Jugular vein obstruction was seen in 12/17 patients; in 5/8 patients with Crouzon’s, 1/2 with Apert’s, the single patient with Pfeiffer’s and 5/6 patients with nonsyndromic craniosynostosis. The predominant collateral drainage was via the posterior condylar veins. Nine of 12 (75%) of the patients with abnormal MRV had hydrocephalus; 3/8 patients with Crouzon’s, 1/2 patients with Apert’s, and 5/6 nonsyndromic patients. Two patients had hydrocephalus with normal MRV. Ten patients had tonsillar herniation, which was associated with shunted hydrocephalus in 7/10 patients, and hydrocephalus seen prior to shunt placement in 3/9. Nine of 10 patients with tonsillar herniation had an abnormal MRV, while 1 patient had a normal MRV. Venous pressures measured in 1 patient showed an 8-mm-Hg differential across the skull base. Conclusions: The posterior condylar veins appear pivotal in maintaining venous drainage when the jugular bulbs are occluded. Although the association between venous outflow obstruction, hydrocephalus and tonsillar herniation is intriguing, evidence of venous outflow obstruction by MRV may not be indicative of significant intracranial venous hypertension.

Cochlear Implantation in Children With Cochlear Nerve Absence or Deficiency

Objective: To evaluate speech perception after cochlear implantation in children with cochlear nerve absence or deficiency. Methods: A retrospective case review was performed to identify children who underwent cochlear implantation with cochlear nerve absence or deficiency. The cochlear nerve was evaluated by high-resolution three-dimensional T2-weighted fast spin echo MR in the oblique sagittal and axial planes. A deficient cochlear nerve was defined as a cochlear nerve that is smaller in diameter when compared with the adjacent facial nerve in the midportion of the internal auditory canal. The cochlear nerve was considered absent if there was no imaging evidence of a cochlear nerve. Speech awareness threshold and the speech perception category score were used to measure speech perception after cochlear implantation. Results: Seven children who underwent cochlear implantation in an ear without imaging evidence of a cochlear nerve were identified. One child developed early closed-set speech recognition. The other 6 children developed only speech detection or pattern perception. Two children underwent cochlear implantation with a deficient cochlear nerve. One developed consistent closed-set word recognition and the other developed early closed-set word recognition. The mean follow-up time for all patients was 3.8 years (range, 1.1-7.1 yr). Conclusion: Cochlear nerve deficiency is not an uncommon cause for profound sensorineural hearing loss and presents a challenge in the decision-making process regarding whether to proceed with a cochlear implant. Children with a deficient but visible cochlear nerve on magnetic resonance image can expect to show some speech understanding after cochlear implantation; however, these children do not develop speech understanding to the level of implanted children with normal cochlear nerves. Children with an absent cochlear nerve determined by magnetic resonance imaging can be expected to have limited postimplantation sound and speech awareness.

Labyrinthitis ossificans: How accurate is MRI in predicting cochlear obstruction?

Objective: To determine the accuracy of preoperative MRI in predicting cochlear obstruction in pediatric patients with a history of bacterial meningitis. Methods: A case series with chart review was performed at a tertiary care multidisciplinary cochlear implant program. Forty-five children with hearing loss that resulted from bacterial meningitis were implanted from 1991 to 2006. Twenty-five children had preoperative MRI with high-resolution axial T2-weighted images to assess for cochlear patency. Results: Seventeen of 25 patients (68%) had surgical evidence of cochlear obstruction. Six patients (37.5%) required circummodiolar drill-outs, and one patient (6.25%) underwent placement of a double array cochlear implant. The nine remaining patients (56%) with cochlear obstruction required removal of fibrous tissue or drilling of the inferior basal turn, but did not require manipulation of the ascending basal turn to achieve full electrode insertion. The sensitivity, specificity, and positive and negative predictive value of MRI predicting intraoperative cochlear obstruction with 95 percent confidence intervals was 94.1 percent (71–99), 87.5 percent (47–99), 94.1 percent (71–99) and 87.5 percent (47–99), respectively. Conclusion: Preoperative high-resolution T2 MRI may be useful in predicting cochlear obstruction in patients with a prior history of bacterial meningitis.

Cervical Spine Evaluation in Pediatric Trauma

OBJECTIVE This article will review the current literature as it relates to imaging of the child suspected to have cervical spine injury (CSI) and the imaging findings of pediatric CSI, focusing on strategies to minimize radiation dose while maximizing diagnostic yield. CONCLUSION Although CSI is uncommon in children, the clinical implications of failure to correctly diagnose CSI are significant. Clinical decision rules proven effective in predicting CSI in adults cannot be uniformly applied to children.

The use of gated cine phase contrast and MR venography in achondroplasia

Abstract Objects: Foramen magnum and jugular foramen stenosis, well-known problems in achondroplasia, may result in brain stem compression and venous outflow obstruction, respectively. We studied a series of children with achondroplasia using gated cine phase contrast (PC) CSF flow studies to evaluate CSF dynamics across the foramen magnum and MR venography (MRV) to depict obstructed venous drainage. Methods: Ten patients (9 months to 11 years, mean 2.85 years) were referred for possible brain stem compression. MRI included routine sequences, cine PC with velocity encoding (VENC) = 5 cm/s, and MRV. Six patients, including the asymptomatic patient, had brain stem compression without tonsillar herniation; two had tonsillar herniation; and two had neither brain stem compression nor tonsillar herniation. Abnormal tonsillar movement was seen only with tonsillar herniation. MRV showed steno-occlusive disease of the internal jugular vein (IJV) in nine patients, sigmoid sinus in four, and absent or hypoplastic transverse sinus in seven. Veno-occlusive disease was not progressive. No patient had massive hydrocephalus, although larger ventricles were associated with more profuse venous collateral formation and more severe degrees of IJV stenosis. Three patients have undergone CSF diversion. Conclusions: MR imaging may be useful in defining the pathophysiology of brain stem compression and hydrocephalus in achondroplasia.

Predictive Value of Neonatal MRI Showing No or Minor Degrees of Brain Injury After Hypothermia

BACKGROUND Magnetic resonance imaging is a surrogate biomarker for major neurodevelopmental disabilities in survivors of perinatal hypoxic-ischemic encephalopathy because injury to the basal ganglia/thalami is highly predictive of major neuromotor and cognitive problems. Major disabilities and the appearance of neonatal magnetic resonance imaging are improved with therapeutic hypothermia. We evaluated neurodevelopmental outcomes when conventional magnetic resonance imaging showed minimal or no brain injury. METHODS Institutional review board-approved series of 62 infants (≥36 weeks; ≥1800 g; 34 boys/28 girls) cooled for hypoxic-ischemic encephalopathy between 2005 and 2011 who underwent neonatal magnetic resonance imaging and Bayley Scales of Infant and Toddler Development-III at 22 ± 7 months of age. Magnetic resonance imaging at 5-14 (mean 8) days was scored as normal (score = 0), showing focal gray or white matter injury only (score = 1), or basal ganglia/thalamic and/or watershed lesions with or without more extensive hemispheric injury (score = 2). Sensitivity, specificity, and positive and negative predictive values for magnetic resonance scores 0 and 1 and statistical interaction between magnetic resonance imaging score and age at magnetic resonance imaging were determined. RESULTS Magnetic resonance score = 0 was seen in 35/62 patients; 26/35 (74%) were typically developing, seven (20%) had moderate and two (6%) had severe delay. Magnetic resonance score = 1 was seen in 17/62 (27%) patients; 5/17 (29%) were normal, 11/17 (65%) had moderate delay, and 1/17 (6%) had severe neurodevelopmental delay. Of the 52 patients with magnetic resonance scores of 0 and 1, 40% were abnormal. The negative predictive value of a normal magnetic resonance imaging was 74%. For score 1, sensitivity was 95% (confidence interval 63%-83%), specificity 84% (confidence interval 70%-90%), positive predictive value 84% (confidence interval 71%-93%), and negative predictive value 74% (confidence interval 62%-82%). CONCLUSIONS Caution is warranted when prognosticating about neurodevelopmental status in early childhood after hypoxic ischemic encephalopathy with cooling, and longer follow-up studies are needed to determine the prognostic significance of a neonatal magnetic resonance imaging showing no or minor degrees of brain injury.