The anti-epileptic effect of anterior thalamic DBS may be dependent on stimulation site especially in the anterior to posterior axis. Extensive anatomical variation confounds severely the targeting of ANT. Therefore, direct visualization of the desired target for stimulation is essential for favourable outcome in refractory epilepsy.

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Purpose: Carbonic anhydrase IX (CA IX) is a hypoxia-inducible enzyme, which is associated with neoplastic growth. Ectopic CA IX expression has been observed in several tumors, whose normal counterparts do not express this enzyme. Normal human brain tissue shows only slight or no expression of CA IX. Experimental Design: We describe CA IX expression in human diffusely infiltrating astrocytomas. The association of CA IX is evaluated with clinicopathologic and molecular factors including cell proliferation and apoptosis as well as the expression of p53 and epidermal growth factor receptor. Results: CA IX immunopositivity was observed in 284 cases of 362 (78%) tumors.The positive areas were often located in close proximity to necrotic regions (P < 0.001). The CA IX immunoreactivity showed strong association with tumor malignancy grades (P < 0.0001). CA IX showed no association with p53 expression nor did it correlate with epidermal growth factor receptorâ mplification, apoptosis, or cell proliferation. CA IX intensity had significant prognostic value in univariate (P=0.0011, log-rank test) and multivariate survival analysis (P = 0.038, Cox analysis). Conclusions: CA IX expression is common in diffusely infiltrating high-grade astrocytomas. Our results suggest that CA IX is a useful biomarker for predicting poor prognosis of astrocytic tumors. It may also be a promising target molecule for the improvement of therapeutic interventions in astrocytomas.

BackgroundDeep brain stimulation (DBS) is a minimally invasive and reversible method to treat an increasing number of neurological and psychiatric disorders, including epilepsy. Targeting poorly defined deep structures is based in large degree on stereotactic atlas information, which may be a major source of inconsistent treatment effects.Aim of the studyIn the present study, we aimed to study whether a recently approved target for epilepsy (anterior nucleus of thalamus, ANT) is visualized in clinically established 3 T MRI and whether ANT is delineated using intraoperative microelectrode recording (MER). We have especially focused on individual variation in the location of ANT in stereotactic space. We also aimed to demonstrate the role of individual variation in interpretation of MER data by projecting samples onto AC–PC (anterior and posterior commissure) and ANT-normalized coordinate systems.MethodsDetailed analysis of ANT delineations in 3 T MRI short tau inversion recovery (STIR) images from eight patients undergoing DBS for refractory epilepsy was performed. Coronal and sagittal cross-sectional models of ANT were plotted in the AC–PC coordinate system to study individual variation. A total of 186 MER samples collected from 10 DBS trajectories and 5 patients were analyzed, and the location of each sample was calculated and corrected accordingly to the location of the final DBS electrode and projected to the AC–PC or coordinate system normalized to ANT.ResultsMost of the key structures in the anatomic atlas around ANT (mammillothalamic tract and external medullary lamina) were identified in STIR images allowing visual delineation of ANT. We observed a high degree of anatomical variation in the location of ANT, and the cross-sectional areas overlapped by study patients decreased in a linear fashion with an increasing number of patients. MER information from 10 individual trajectories correlated with STIR signal characteristics by demonstrating a spike-negative zone, presumably white matter layer, at the lateral aspect of ANT in ANT-normalized coordinate system as predicted by STIR images. However, MER information projected to the AC–PC coordinate system was not able to delineate ANT.ConclusionsANT is delineated in 3 T MRI by visualization of a thin white matter lamina between ANT and other nuclear groups that lack spiking activity. Direct targeting in the anterior thalamic area is superior to indirect targeting due to extensive individual variation in the location of ANT. Without detailed imaging information, however, a single trajectory MER has little localizing value.

Vagus nerve stimulation (VNS) is used for treating refractory epilepsy and major depression. While the impact of this treatment on seizures has been established, its impact on human cognition remains equivocal. The goal of this study is to elucidate the immediate effects of vagus nerve stimulation on attention, cognition, and emotional reactivity in patients with epilepsy. Twenty patients (12 male and 8 female; 45 ± 13 years old) treated with VNS due to refractory epilepsy participated in the study. Subjects performed a computer-based test of executive functions embedded with emotional distractors while their brain activity was recorded with electroencephalography. Subjects' cognitive performance, early visual event-related potential N1, and frontal alpha asymmetry were studied when cyclic vagus nerve stimulation was on and when it was off. We found that vagus nerve stimulation improved working memory performance as seen in reduced errors on a subtask that relied on working memory, odds ratio (OR) = 0.63 (95% confidence interval, CI [0.47, 0.85]) and increased N1 amplitude, F(1, 15) = 10.17, p = .006. In addition, vagus nerve stimulation resulted in longer reaction time, F(1, 16) = 8.23, p = .019, and greater frontal alpha asymmetry, F(1, 16) = 11.79, p = .003, in response to threat-related distractors. This is the first study to show immediate improvement in working memory performance in humans with clinically relevant vagus nerve stimulation. Furthermore, vagus nerve stimulation had immediate effects on emotional reactivity evidenced in behavior and brain physiology.