Oakes Wj

Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study.

PURPOSE The Pediatric Oncology Group (POG) conducted a randomized phase II study to evaluate the activity of carboplatin and iproplatin in children with progressive or recurrent brain tumors. PATIENTS AND METHODS The study was designed to evaluate the activity of these agents and to compare the toxicities associated with their use. Treatment consisted of carboplatin 560 mg/m2 at 4-week intervals or iproplatin 270 mg/m2 at 3-week intervals. RESULTS The major toxicity observed was myelosuppression, particularly thrombocytopenia, for both agents. Ototoxicity (grade 1 or 2) was seen in 2.5% of patients treated with carboplatin and 1.3% of patients treated with iproplatin. The majority of patients with low-grade astrocytic neoplasms treated with carboplatin (nine of 12 patients) or iproplatin (eight of 12 patients) demonstrated tumor response or prolonged stable disease that persisted off-therapy. The duration of stable disease produced by carboplatin was particularly striking, ranging from 2 months to 68 + months (median, 40 + months). Neither drug demonstrated appreciable activity in the treatment of medulloblastoma (two of 26 responses to carboplatin, one of 14 responses to iproplatin), ependymoma (two of 17 responses to carboplatin, none of seven responses to iproplatin), high-grade glioma (two of 19 responses to carboplatin, one of 14 responses to iproplatin), or brain-stem tumors (one of 23 responses to carboplatin, none of 14 responses to iproplatin). CONCLUSION Carboplatin is active against low-grade gliomas. Further evaluation of the role of carboplatin in the preirradiation treatment of children with low-grade gliomas of the optic pathway is currently underway in a clinical trial.

Adipose Tissue in the Filum Terminale: A Computed Tomographic Finding That May Indicate Tethering of the Spinal Cord

&NA; Adipose tissue in the filum terminale is frequently associated with tethering of the spinal cord in patients with spina bifida occulta (3, 8). We recently saw a patient with low back pain and no spina bifida occulta, in whom adipose tissue was noted in the area of the filum on an unenhanced computed tomographic (CT) scan. The patient had a tethered cord. This case suggested that, when CT scanning is done as the first imaging study in the evaluation of low back pain, fatty tissue in the area of the filum may be an indicator for tethering of the spinal cord. The present study was undertaken to determine the validity of using CT scan‐detectable filal fat in the identification of possible tethered spinal cords among a group of patients experiencing low back pain. The presence of fat in the fila of 12 patients with the radiologically and histologically tethered cord syndrome was evaluated and the fila of 47 autopsied patients whose clinical history showed no back pain were examined histologically. There were accumulations of adipose tissue in the fila of 11 of the 12 (91%) patients with the tethered cord syndrome and in the fila of 9 of the 47 patients (17%) in the autopsy series. Of the 9 autopsy patients with fat in their fila, however only 3 patients (6%) exhibited collections of adipose tissue in the CT detection range (2 mm). These results demonstrate that, although CT scan‐detectable adipose tissue can be found in the filum of an occasional patient without tethered cord, CT detectable fat in the filum of a patient with low back pain should prompt an evaluation for a tethered spinal cord. CT scanning has potential as a noninvasive tool in such a work‐up.

Efficacy of vincristine and cyclophosphamide in the therapy of recurrent medulloblastoma

We conducted a Phase II study of combination therapy with vincristine and cyclophosphamide in the treatment of patients with recurrent or metastatic medulloblastoma. Fourteen patients were treated with vincristine 2 mg/m2 (2.0-mg maximal dose) by intravenous bolus on Day 1 and cyclophosphamide 1 g/m2 by intravenous infusion on Days 1 and 2, with cycles repeated every 4 weeks. All 4 patients with extraneural disease (biopsy-proven bony metastases) responded (duration of responses 2+, 6+, 8, and 16+ months) and 4 of 8 evaluable patients with neuraxis disease responded (duration of response 2, 2+, 2+, and 21+ months). Toxicity was limited to neutropenia without any episodes of infection. These therapeutic results compare favorably with other reports of therapy for recurrent medulloblastoma and support the inclusion of vincristine and cyclophosphamide in randomized adjuvant therapy trials of patients with medulloblastoma.

Phase II treatment of medulloblastoma and pineoblastoma with melphalan: clinical therapy based on experimental models of human medulloblastoma.

We conducted a phase II study of intravenous (IV) melphalan in the treatment of children with recurrent medulloblastoma and in the initial treatment of children with poor-prognosis medulloblastoma and pineoblastoma. There was one complete response (CR) and two partial responses (PRs) among the 12 children with recurrent medulloblastoma. There were three PRs in the four patients initially treated with melphalan for poor-prognosis medulloblastoma or pineoblastoma. Toxicity was limited to severe myelosuppression with marked neutropenia and thrombocytopenia. These results support our laboratory studies demonstrating melphalan activity in human medulloblastoma, suggest that similar activity may be demonstrated against pineoblastoma, and support further trials with this agent (administered prior to radiotherapy) in the treatment of patients with newly diagnosed poor-prognosis medulloblastoma.

FDG-PET in pediatric posterior fossa brain tumors

Seventeen pediatric patients with posterior fossa brain tumors were studied with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET). The FDG uptake was ranked by two observers, and the results were correlated with tumor histology. Increased FDG uptake was associated with more malignant and aggressive tumor types. Heterogeneity of FDG uptake was associated with previous therapy, including radiation therapy and chemotherapy. 2-[18F]Fluoro-2-deoxy-D-glucose PET will likely be an important adjunct in the management of pediatric posterior fossa tumors, much as in adult patients with brain tumors.

Klüver-Bucy Syndrome in a Child with Bilateral Arachnoid Cysts: Report of a Case

Klüver-Bucy syndrome is an uncommon constellation of behavioral abnormalities resulting from bilateral temporal lobe damage. The syndrome is rare in adults and even less commonly seen in children. In this paper we present a child with Klüver-Bucy syndrome and bilateral temporal arachnoid cysts.

Parietal cephaloceles: radiographic and magnetic resonance imaging evaluation.

Three patients with parietal cephaloceles underwent evaluation and treatment at Duke University Medical Center between 1984 and 1987. All presented within the first 2 years of life with painful swelling near the vertex of the head. All patients had skull films and computed tomography, and two underwent magnetic resonance imaging (MRI). All 3 children had associated hindbrain deformities; two with Dandy-Walker malformation, the third with a Chiari II malformation. Each child eventually developed hydrocephalus. MRI is the procedure of choice to evaluate these patients, providing direct sagittal imaging of the posterior fossa and craniocervical junction, and displaying communication of the cephalocele with intracranial structures as well as associated venous vascular anomalies.

clinical/scientific notes: Sagittal sinus thrombosis and leptomeningeal medulloblastoma

Rosalind W. Picard, ScD Matteo Migliorini, PhD Chiara Caborni, MSc Francesco Onorati, PhD Giulia Regalia, PhD Daniel Friedman, MD Orrin Devinsky, MD WRIST SENSOR REVEALS SYMPATHETIC HYPERACTIVITY AND HYPOVENTILATION BEFORE PROBABLE SUDEP We report a probable sudden unexpected death in epilepsy (SUDEP) in a 20-year-old man wearing a smartwatch that recorded wrist motion via 3-axis accelerometer (ACC) and electrodermal activity (EDA). EDA reflects sympathetic activity without parasympathetic antagonism. The smartwatch (Empatica [Milan, Italy] Embrace, with CE Medical clearance from the European Union for seizure detection) issued an alert, received by the caregiver at 8:50 AM, indicating a probable convulsive seizure. An adult trained in cardiopulmonary resuscitation (CPR) arrived at 9:05 AM, found the patient pulseless, prone, face in pillow with mucus in his mouth, and commenced CPR for 15 minutes without recovery. The family declined autopsy. The patient had been diagnosed at age 5 with epilepsy. He had 3–4 generalized tonic-clonic seizures (GTCS) a year, typically during mornings before awakening. More than 6 antiepileptic medications failed to control seizures. Routine and prolonged EEGs were normal. At the time of death, he was taking lamotrigine twice daily and extended-release oxcarbazepine each night. The figure shows the smartwatch data. The red vertical line marks the time of automated seizure detection. Panel A shows an unusual fast rising, up to 1.5 mS/s, and large, 66.7 mS, postictal electrodermal response (EDR). An inset utilizing exponentially weighted moving averages magnifies the preictal period, revealing EDRs typical within non-REM sleep. Panel B shows the ACC data, indicating convulsive movements lasting 94 seconds, with little or no movement following. Panel C shows the estimated respiration rate using a validated method that extracts subtle respiration-induced body movements from wrist ACC in a relatively motionless person. The thin red traces indicate tracking of 18.9 breaths/min before the convulsions, rising to 24.6 breaths/min, and reaching 28.5 breaths/min with the large EDR. After 8:52 AM, despite no detected position-changing movements, a steady respiration signal ceases to be detected. While this respiration estimator does not work with strong movements (grayed region; figure, C), it should work during low-movement postictal periods. The inability to identify any regular breathing pattern following 8:52 AM suggests either an unusually irregular breathing pattern or respiratory cessation. Panel D shows the skin surface temperature.

Continuous External Drainage in the Treatment of Subdural Hematomas of Infancy

A series of 16 patients with chronic or subacute subdural hematomas treated with continuous external drainage of the subdural space is reviewed. Of these only 44% went on to require subdural-peritoneal shunt placement. There were no complications in treatment and no clinical or laboratory evidence of infection in any case. The outcome, measured by neurological examination, was not different between the shunted and nonshunted groups. In conclusion, continuous external drainage of the subdural space in chronic and subacute hematomas of infancy frequently is an effective, definitive treatment. This approach should be considered as the initial procedure prior to subdural-peritoneal shunting.

Inflammatory lesion mimicking a metastatic ependymoma

A 2.5-year-old child who had undergone nearly total resection of an infratentorial ependymoma demonstrated a new enhancing lesion on the undersurface of the right cerebellar hemisphere 7 weeks after the initiation of adjuvant chemotherapy. The residual primary tumor demonstrated continued regression during chemotherapy, and magnetic resonance imaging of the spine and cytopathological examination of the cerebrospinal fluid showed no evidence for other sites of metastatic tumor. Because of the unusual anatomic and temporal characteristics of this lesion and despite radiographic criteria highly suspicious for a metastatic lesion, a biopsy was performed, revealing histological evidence of an inflammatory process.