A. Leland Albright

Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children's Cancer Group.

Childrens Cancer Group Protocol CCG-9882 was designed to determine the effectiveness of hyperfractionated radiation for the treatment of children and young adults with brain stem gliomas. The study opened for the accrual of patients on September 21, 1988, and was closed on June 30, 1991. The first 54 children in the study were treated with irradiation doses of 100 cGy given twice daily to a total dosage of 7200 cGy. The next 66 children were treated with a similar daily regimens to a total of 7800 cGy. Tumors were diagnosed by clinical and radiographic criteria. Decisions about the need for surgery were left to the discretion of the treating neurosurgeon; tissue diagnosis did not alter the therapy in patients with diffuse infiltrating tumors. We reviewed the neuroradiology and neurosurgery reports as well as the pathological specimens of children entered on the study. By magnetic resonance (MR) imaging criteria, tumors involved the majority of the brain stem in 76% of cases; only three patients had tumors localized to the midbrain or medulla. Operations were performed on 56 of 120 patients (47%). Cerebrospinal fluid shunts were inserted in 27 (23%) of the children; insertion of a shunt was the only operation in 11, and a shunt was inserted in conjunction with a tumor operation in 16. Tumor operations were performed in 45 (38%) of the patients; 24 had stereotactic biopsies, and 21 had craniotomies. Of the 21 patients who had craniotomies, only biopsies were performed in 11; partial tumor resections were performed in 5 patients and subtotal resection in 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracranial Ependymomas of ChildhoodLong-term Outcome and Prognostic Factors

A detailed outcome analysis was performed on 40 children with intracranial ependymomas treated at our institution between 1975 and 1993 to identify those factors that were predictive of overall and progression-free survival. Three patients (7.5%) who were treated in the first 5 years of the study died within 3 months of surgery and were excluded from further outcome assessments. Eight (22%) of the 37 patients who survived the perioperative period had evidence of leptomeningeal dissemination at presentation, on the basis of either imaging (three children) and/or cytological (six children) results. The 5- and 10-year progression-free survival rates among these 37 patients were 45.1 and 36.1%, respectively; overall survival rates were 57.1 and 45.0%, respectively. The site of progression was local in 17 of 19 patients with progressive disease. Three factors were found to have a significant association (P < or = 0.05) with the outcome on both univariate and multivariate analyses: 1) the extent of the resection, 2) the age of the patient at diagnosis, and 3) the duration of the symptoms before diagnosis. The 5-year progression-free and overall survivals were 8.9 and 22%, respectively, among patients who had evidence of residual disease on postoperative imaging studies, compared with 68 and 80% rates among patients with no apparent residual disease (P = 0.0001 and P < 0.0001, respectively). Patients younger than 3 years fared significantly worse than older children (5-year progression-free and overall survival rates of 12 and 22%, respectively, in the younger children versus 60 and 75% in older children (P = 0.003 and P = 0.01, respectively). In addition, patients with a duration of symptoms before diagnosis of < 1 month had a worse outcome than those with a more protracted course (5-year progression-free and overall survival rates of 33 and 33%, respectively, versus rates of 53 and 64%, respectively (P = 0.02 for both). Neither the finding of evidence for dissemination at presentation nor the detection of anaplastic histological features (e.g., dense cellularity or high numbers of mitoses) were associated with a significantly worse outcome in this series. The combination of variables that had the strongest association with both favorable and unfavorable outcomes was the combination of the age of the patient and the resection extent. Only 2 of 17 patients older than 3 years with gross total resections have died, whereas 13 of 20 children who were either younger than 3 years or had radiologically incomplete resections have died (P < 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

A randomized, controlled study of a programmable shunt valve versus a conventional valve for patients with hydrocephalus

OBJECTIVE: A multicenter prospective randomized controlled study was performed to assess the safety and efficacy of a Codman Hakim programmable shunt valve (Codman/Johnson & Johnson, Raynham, MA) versus a conventional valve system of the surgeons choice for the treatment of patients with hydrocephalus. METHODS: Enrollment was stratified on the basis of whether the patient was undergoing initial shunt insertion or revision of an existing valve system at study entry. Study end points were: 1) valve explantation, and 2) shunt failure (surgical intervention for any component of the shunt). A total of 377 patients were enrolled onto the study, with 235 undergoing first shunt insertion (119 experimental, 116 control) and 142 undergoing revisions (75 experimental, 67 control). RESULTS: During a follow-up interval of 104 weeks after the first implantation on-study, explantation of the valve was required in 62 (32%) of 194 experimental valves, compared with 71 (39%) of 183 control valves. Two-year survival rates of the original shunt without revision of any component were 52% (62 of 119) and 50% (58 of 116) in experimental and control patients, respectively, who underwent initial shunt insertion, and 43% (32 of 75) and 43% (29 of 67) in experimental and control patients, respectively, who underwent replacement of an existing valve. No statistically significant difference was observed between experimental and control patients in the survival of either the valve or the overall shunt system. Control of hydrocephalus as assessed symptomatically and by imaging was comparable in the two treatment groups. Although problems related to inability to achieve the desired pressure setting were reported in 22 experimental valves, in all but four instances no additional programming was attempted because the patients were functioning well clinically. The most common reasons cited for valve explantation and shunt revision were infection (9.8% frequency in the overall cohort) and proximal shunt malfunction, which occurred with comparable frequency in the experimental and control groups. CONCLUSION: Safety and efficacy of the Codman Hakim programmable shunt valve is comparable to conventional valves in the overall population of patients with hydrocephalus. However, the current study was not designed to assess the efficacy of programmable versus conventional valves in the management of individual hydrocephalus problems, and it had insufficient statistical power to support such comparisons. This study provides a rationale for examining whether the theoretical advantages of a programmable valve for managing challenging hydrocephalus problems can translate into meaningful improvements in shunt and valve survival.

Intrathecal baclofen for generalized dystonia

The aim of this study was to evaluate the effects of intrathecal bacolfen (ITB) on patients with severe generalized dystonia. Eighty-six participants ranging in age from 3 to 42 years (median age 13 years) with generalized dystonia refractory to oral medications were offered treatment with ITB. Dystonia was associated with cerebral palsy in 71% of participants. Response to ITB was tested by continuous infusions in 72%, and by bolus injections in 17% of participants who had both dystonia and spasticity. Ninety-one percent of participants responded to the screening infusion and 93% to the bolus injections. Pumps were implanted in 77 participants. Dystonia scores at 3, 6, 12, and 24 months were significantly decreased (p<0.005) compared with baseline scores. Dystonia scores were significantly lower in those with intrathecal catheters positioned at T4, or higher than in those with catheters at T6 or lower (p=0.005). Ninety-two percent of participants implanted with a pump retained their responses to ITB during a median follow-up of 29 months. Patient questionnaires indicated that quality of life and ease of care improved in 86% and speech improved in 33%. Side effects of ITB occurred in 26% of participants. Surgical complications occurred in 38% and included CSF leaks, infections, and catheter problems. ITB is probably the treatment of choice for generalized dystonia if oral medications are ineffective.

Topical Review: Baclofen in the Treatment of Cerebral Palsy

Baclofen, a γ-aminobutyric acid agonist, acts at the spinal cord level to impede the release of excitatory neurotransmitters that cause spasticity. Oral baclofen improves cerebral spasticity mildly, but its activity is limited because of its poor lipid solubility. Cerebrospinal fluid baclofen levels after intrathecal administration are many times higher than those achieved after oral administration. Continuous intrathecal baclofen infusion has been used to treat cerebral spasticity in two patient groups: in older ambulatory children with inadequate underlying leg strength, and in patients with severe spasticity in both the upper and lower extremities. Responsiveness to intrathecal baclofen is confirmed by test injections before insertion of a programmable subcutaneous pump. Continuous intrathecal baclofen infusion dosages vary from 27 to 800 μg/day. Continuous intrathecal baclofen infusion reduces spasticity in the upper and lower extremities, and improves upper extremity function and activities of daily living but has no effect on athetosis in the dosages used to treat spasticity. Complications related to the intrathecal catheter occur in approximately 20% of patients, and infection requiring pump removal occurs in approximately 5%. Preliminary studies indicate that continuous intrathecal baclofen infusion alleviates some forms of generalized dystonia associated with cerebral palsy. (J Child Neurol 1996;11:77-83).

Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A childrens cancer group phase 1/11 trial

Background. Brain stem gliomas remain the childhood brain tumors most resistant to treatment. Treatments with hyperfractionated radiotherapy at doses as high as 7560 cGy have been fairly well tolerated. This study was undertaken to determine the toxicity and possible efficacy of hyperfractionated radiotherapy in children with brain stem gliomas using 100 cGy of radiation twice daily, to a total dose of 7800 cGy.

Brainstem Gliomas in Children

Brainstem gliomas (BSG) with intrinsic and extensive brainstem involvement continue to have a poor outlook despite current treatment approaches. Neuroimaging studies have aided in the differentiation

Hyperfractionated radiation therapy (72 Gy) for children with brain stem gliomas A childrens cancer group phase I/II trial

Background. Most children with brain stem gliomas (BSG) die within 18 months of diagnosis. Early experience suggested that hyperfractionated radiation therapy (RT) at a dose of 72 Gy, administered in 1‐Gy fractions twice daily, possibly improved disease‐free survival for children with BSG.

Intrathecal Baclofen in Cerebral Palsy Movement Disorders

Intrathecal baclofen reduces spasticity in individuals with cerebral palsy. Intrathecal doses are far lower than oral doses and the effects are considerably greater, and the side effects are fewer. Response to intrathecal baclofen must be confirmed by a screening trial before implantation of a pump for chronic infusion. Intrathecal baclofen reduces spasticity in the upper and lower extremities and is often associated with improved gait and upper extremity function. Quality of life improves for patients and caregivers. The Medtronic pump has been exceedingly reliable and typically functions for 4 or 5 years. The currently available intrathecal catheter is associated with far fewer complications than the initial catheter. Baclofen overdoses are unusual and are usually caused by pump programming errors rather than pump malfunction. Preliminary studies suggest that continuous intrathecal baclofen infusion reduces generalized dystonia in cerebral palsy. Screening to determine response of dystonia to intrathecal baclofen is by continuous infusion. The doses required to reduce dystonia are higher than those for cerebral spasticity. Additional investigations are underway to quantify the effects of continuous intrathecal baclofen infusion on communication, disability, and dystonia. (J Child Neurol 1996;11(Suppl 1): S29-S35).

Prognostic Factors in Children with Supratentorial (Nonpineal) Primitive Neuroectodermal Tumors

Supratentorial primitive neuroectodermal tumors (S-PNETs), which have also been called cerebral neuroblastomas, have been considered to be the hemispheric equivalent of posterior fossa medulloblastomas. Twenty-seven children with S-PNETs (excluding pineoblastomas) which were confirmed by central pathology review were treated on the CCG-921 protocol from 1986 to 1992. After operation, all patients were staged with CSF cytology and spinal myelography or magnetic resonance scans and were treated with craniospinal irradiation and chemotherapy. Data from these 27 patients have been reviewed to evaluate neurosurgical treatment, survival, and prognostic variables that correlate with survival. Overall survival at 5 years was 34% (SE 20%) and progression-free survival (PFS) was 31% (SE 18%), which is lower than the survival of patients with posterior fossa PNETs (medulloblastomas). PFS was significantly worse in children 1.5-3 years of age at diagnosis and in those with evidence of tumor dissemination at the time of diagnosis. Large preoperative tumors were more likely to be associated with greater than 1.5 cm2 residual tumor postoperatively. Neurosurgeons estimated that less than 1.5 cm2 of residual tumor was present in 52% of the cases; postoperative scans confirmed that in 58%. For children with less than 1.5 cm2 residual tumor, postoperative survival at 4.0 years was 40% (SE 22%); for those with greater than 1.5 cm2 residual tumor, survival was 13% (SE 8%). The difference did not reach statistical significance, due to small numbers in this series, though a trend did exist (p = 0.19). Large series will be required to clarify the effects of extent of resection on survival.