A simple method of estimating cerebrospinal fluid pressure during lumbar puncture.

It is often difficult to measure cerebrospinal fluid (CSF) pressure in children. CSF flow through a spinal needle is described by the equation: Flow = pressure/(needle constant x relative viscosity). Thus, CSF flow rate during lumbar puncture can be used to estimate CSF pressure. Because the viscosity of CSF is approximately the same as that of normal saline, 0.9% NaCl was used to model CSF flow in vitro. Flow of saline through various spinal needles was measured as pressure and temperature were varied to determine needle constants and variation in viscosity with temperature. Counting periods for which the number of drops counted equals the pressure (in centimeters of H2O) then were determined for each needle size. At patient temperatures less than 40 degrees C, counting periods were calculated at 21, 39, and 12 seconds, for 22-gauge 1.5-inch, 22-gauge 3.5-inch, and 20-gauge 3.5-inch spinal needles, respectively. Viscosity decreased slightly above 40 degrees C, and counting periods became 20, 37, and 11 seconds. Finally, the method was tested prospectively in 12 patients by comparing drop count (over the calculated counting period) to manometric pressure measurement. Drop counts were within 15% of manometric pressure in all patients. This method allows simple and rapid estimation of CSF pressure during lumbar puncture.

Cisplatin, ara-C and etoposide (PAE) in the treatment of recurrent childhood brain tumors.

Sixteen patients with recurrent childhood brain tumors were treated with intravenous cisplatin, cytosine arabinoside and etoposide (PAE), daily for three days every three to four weeks. Objective responses were observed in 6 of 15 evaluable patients and an additional six patients had stable disease for greater than 6 months. The tumor-specific response rate for astrocytoma/glioma was 3 of 7 and for medulloblastoma was 2 of 4. The mean progression-free interval was 11.0 months and the hazard rate for progression was 0.085 per patient-month of observation. The most common toxicities were neutropenia and thrombocytopenia. Clinically significant ototoxicity was identified in 7 patients. The activity of PAE chemotherapy for recurrent childhood brain tumors warrants further investigation.

Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors.

Neuraxis radiation therapy (RT) for primary intracranial tumors is associated with major late effects if administered to very young children. To control residual tumor and to delay RT, we treated eight young children (median age 6.5 months) with primary central nervous system (CNS) tumors using combination chemotherapy: cisplatin, 20 mg/M2/day plus VP-16, 75 mg/M2/day i.v. for 5 days, given q. 3-6 weeks for 8 cycles. The tumors were medulloblastoma (one), malignant ependymoma (two), primitive neuroectodermal tumor PNET (two), malignant glioma (two), astrocytoma (one). Six had measurable disease; three had positive cerebrospinal fluid (CSF) cytopathology. All patients with measurable tumor had initial objective responses (three) complete response [CR], one partial response [PR], two minor response [MR], including cytopathology (three CR of three) and metastatic deposits (two CR of two). One patient relapsed during chemotherapy. Median time to disease progression was 17.5 months; median survival was 34 months. Three patients, none of whom received RT, have prolonged progression-free intervals of 47-67 months to date. Neurodevelopmental progress continued during and after chemotherapy. Chemotherapy toxicity was mild. Median neutrophil nadir was 312/mm3, platelets 72,000. Fever during neutropenia occurred in six of 61 courses. Moderate high-frequency auditory losses were detected in three patients, and mild renal injury (GFR less than 70 ml/min) was detected in two of seven evaluable children. This pilot study demonstrates the apparent efficacy and mild toxicity of 5 day courses of cisplatin plus VP-16, with delayed RT, in young children with CNS neoplasms. A POG treatment protocol that incorporates cisplatin plus VP-16 is evaluating primary chemotherapy with delayed radiotherapy in larger numbers of pediatric brain tumor patients.