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ObjectivesConfocal laser endomicroscopy (CLE) is an intraoperative real-time cellular resolution imaging technology that images brain tumor histoarchitecture. Previously, we demonstrated that CLE images may be interpreted by neuropathologists to determine the presence of tumor infiltration at glioma margins. In this study, we assessed neurosurgeons’ ability to interpret CLE images from glioma margins and compared their assessments to those of neuropathologists.MethodsIn vivo CLE images acquired at the glioma margins that were previously reviewed by CLE-experienced neuropathologists were interpreted by four CLE-experienced neurosurgeons. A numerical scoring system from 0 to 5 and a dichotomous scoring system based on pathological features were used. Scores from assessments of hematoxylin and eosin (H&E)-stained sections and CLE images by neuropathologists from a previous study were used for comparison. Neurosurgeons’ scores were compared to the H&E findings. The inter-rater agreement and diagnostic performance based on neurosurgeons’ scores were calculated. The concordance between dichotomous and numerical scores was determined.ResultsIn all, 4275 images from 56 glioma margin regions of interest (ROIs) were included in the analysis. With the numerical scoring system, the inter-rater agreement for neurosurgeons interpreting CLE images was moderate for all ROIs (mean agreement, 61%), which was significantly better than the inter-rater agreement for the neuropathologists (mean agreement, 48%) (p < 0.01). The inter-rater agreement for neurosurgeons using the dichotomous scoring system was 83%. The concordance between the numerical and dichotomous scoring systems was 93%. The overall sensitivity, specificity, positive predictive value, and negative predictive value were 78%, 32%, 62%, and 50%, respectively, using the numerical scoring system and 80%, 27%, 61%, and 48%, respectively, using the dichotomous scoring system. No statistically significant differences in diagnostic performance were found between the neurosurgeons and neuropathologists.ConclusionNeurosurgeons’ performance in interpreting CLE images was comparable to that of neuropathologists. These results suggest that CLE could be used as an intraoperative guidance tool with neurosurgeons interpreting the images with or without assistance of the neuropathologists. The dichotomous scoring system is robust yet simple and may streamline rapid, simultaneous interpretation of CLE images during imaging.

We present the first quantitative analysis of atypical teratoid rhabdoid tumors (ATRT) in adults, including two patients from our own institutions. These are of interest as one occurred during pregnancy and one is a long-term survivor. Our review of pathological findings of 50 reported cases of adult ATRT leads us to propose a solely ectodermal origin for the tumor and that epithelial–mesenchymal transition (EMT) is a defining feature. Thus, the term ATRT may be misleading. Our review of clinical findings shows that ATRT tends to originate in mid-line structures adjacent to the CSF, leading to a high rate of leptomeningeal dissemination. Thus, we hypothesize that residual undifferentiated ectoderm in the circumventricular organs, particularly the pituitary and pineal glands, is the most common origin for these tumors. We note that if growth is not arrested soon after diagnosis, or after the first relapse/progression, death is almost universal. While typically rapidly fatal (as in our first case), long-term remission is possible (as in our second). Significant predictors of prognosis were the extent of resection and the use of chemotherapy. Glial differentiation (GFAP staining) was strongly associated with leptomeningeal metastases (chi-squared p = 0.02) and both predicted markedly worse outcomes. Clinical trials including adults are rare. ATRT is primarily a disease of infancy and radiotherapy is generally avoided in those aged less than 3 years old. Treatment options in adults differ from infants in that cranio-spinal irradiation is a viable adjunct to systemic chemotherapy in the adult population. Given the grave prognosis, this combined approach appears reasonable. As effective chemotherapy is likely to cause myelosuppression, we recommend that stem-cell rescue be available locally.

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions.This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n=270), anterior cingulate cortex (n=256), and ventromedial prefrontal cortex (n=174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions.Significant gender differences were found in the left amygdala, where 23% (n=15/66) of neurons in men were significantly affected by facial emotion, versus 8% (n=6/76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p