ABR change over time in neurofibromatosis 2

Objectives: To determine whether clinically obtained auditory brainstem response (ABR) shows significant changes over time associated with the growth of vestibular schwannomas related to neurofibromatosis 2 (NF2) and to evaluate the clinical use of derived band ABR in NF2 patients.Methods: Subjects meeting the NIH NF2 diagnostic criteria were enrolled (n = 103) across 9 domestic and international investigational sites. ABR and MRI exams were conducted annually. Each site was instructed to follow a comprehensive protocol for acquiring the MRI. The sites were instructed to assess the ABR either with the usual clinical parameters or using derived band methodology.Results: Wave 5 latency data were available for 35 subjects at both baseline and year 1. Average latency values were found to be clinically normal at both evaluations (average = 6.4 ms). Subjects experienced an average change in Wave 5 from baseline to year 1 of 0.06 ms. A strong association was found between Wave 5 latency at baseline and the greatest diameter measurement of the tumor (Pearson’s correlation = 0.62, P < 0.05), where larger tumors have longer latencies. The subjects with derived band ABR were further evaluated for change over time.Conclusions: ABR wave 5 latency shows a strong association with size, the longer the latency, the larger the vestibular schwannoma, regardless of how the ABR was obtained. Across evaluations, there was a nonsignificant change in wave latencies. Clinically obtained ABR provides information regarding size but provides less information about the change in vestibular schwannomas over time. Derived band ABR offers greater measurement specificity for observing NF2 patients over time.     

A distinct phenotypic change in gliomas at the time of magnetic resonance imaging detection

OBJECT: Although gliomas remain refractory to treatment, it is not clear whether this characteristic is fixed at the time of its origin or develops later. The authors have been using a model of neurocarcinogenesis to determine whether a time exists during a glioma's evolution during which it is detectable but still curable, thus providing a justification for exploring the clinical merits of an early detection and treatment strategy. The authors recently reported the presence of 2 distinct cellular subsets, 1 expressing nestin and the other both glial fibrillary acidic protein (GFAP) and osteopontin (OPN), within all examined gliomas that developed after in utero exposure to ethylnitrosourea. METHODS: In this study, the authors used magnetic resonance (MR) imaging to assess when these 2 subpopulations appeared during glioma evolution. RESULTS: Using T2-weighted and diffusion-weighted MR imaging, the authors observed that gliomas grew exponentially once detected at rates that were location-dependent. Despite large differences in growth rates, however, they determined by correlating histochemistry with imaging in a second series of animals, that all lesions initially detected on T2-weighted images contained both subsets of cells. In contrast, lesions containing only nestin-positive cells, which appeared on average 40 days before detection on MR images, were not detected. CONCLUSIONS: The sequential appearance of first the nestin-positive cells followed several weeks later by those expressing GFAP/OPN suggests that all gliomas arise through common early steps in this model. Furthermore, the authors hypothesize that the expression of OPN, a molecule associated with cancer aggressiveness, at the time of T2-weighted detection signals a time during glioma development when the lesion becomes refractory to treatment.