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.
A B S T R A C T PurposeWe evaluated the feasibility of administering carboplatin as a radiosensitizer during craniospinal radiation therapy (CSRT) to patients with high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors, and we report the outcome in the subset with metastatic (Mϩ) MB. Patients and MethodsAfter surgery, patients received 36 Gy CSRT with boosts to sites of disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45 mg/m 2 /dose), along with vincristine (VCR) once per week for 6 weeks. Patients on regimen A received 6 months of maintenance chemotherapy (MC) with cyclophosphamide and VCR. Once the recommended phase II dose (RP2D) of carboplatin was determined, cisplatin was added to the MC (regimen B). ResultsIn all, 161 eligible patients (median age, 8.7 years; range, 3.1 to 21.6 years) were enrolled. Myelosuppression was dose limiting and 35 mg/m 2 /dose ϫ 30 was determined to be the RP2D of carboplatin. Twenty-nine (36%) of 81 patients with Mϩ MB had diffuse anaplasia. Four patients were taken off study within 11 months of completing radiotherapy for presumed metastatic progression and are long-term survivors following palliative chemotherapy. Excluding these four patients, 5-year overall survival Ϯ SE and progression-free survival Ϯ SE for Mϩ patients treated at the RP2D on regimen A was 82% Ϯ 9% and 71% Ϯ 11% versus 68% Ϯ 10% and 59% Ϯ 10% on regimen B (P ϭ .36). There was no difference in survival by M stage. Anaplasia was a negative predictor of outcome. ConclusionThe use of carboplatin as a radiosensitizer is a promising strategy for patients with Mϩ MB. Early progression should be confirmed by biopsy.
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