Spike-Associated Networks Predict Postsurgical Outcomes in Children With Refractory Epilepsy.

PURPOSE: Up to half of the children undergoing epilepsy surgery will continue to have seizures (szs) despite a cortical resection or ablation. Functional connectivity has shown promise in better identifying the epileptogenic zone. We hypothesized that cortical areas showing high information outflow during interictal epileptiform discharges are part of the epileptogenic zone. METHODS: We identified 22 children with focal epilepsy who had undergone stereo electroencephalography, surgical resection or ablation, and had ≥1 year of postsurgical follow-up. The mean phase slope index, a directed measure of functional connectivity, was calculated for each electrode contact during interictal epileptiform discharges. The positive predictive value and negative predictive value for a sz-free outcome were calculated based on whether high information outflow brain regions were resected. RESULTS: Resection of high outflow (z-score ≥ 1) and very high outflow (z-score ≥ 2) electrode contacts was associated with higher sz freedom (high outflow: χ 2 statistic = 59.1; P < 0.001; very high outflow: χ 2 statistic = 31.3; P < 0.001). The positive predictive value and negative predictive value for sz freedom based on resection at the electrode level increased at higher z-score thresholds with a peak positive predictive value of 0.86 and a peak negative predictive value of 0.9. CONCLUSIONS: Better identification of the epileptogenic zone has the potential to improve epilepsy surgery outcomes. If the surgical plan can be modified to include these very high outflow areas, more children might achieve sz freedom. Conversely, if deficits from resecting these areas are unacceptable, ineffective surgeries could be avoided and alternative therapies offered.

Spike-associated networks and intracranial electrographic findings.

Functional connectivity is providing new insights into the network nature of epilepsy with growing clinical applications. Our objective was to validate a novel magnetoencephalography-based method to non-invasively measure the epileptic network. We retrospectively identified pediatric and adult patients with refractory focal epilepsy who underwent pre-surgical magnetoencephalography with subsequent intracranial electrographic monitoring. Magnetoencephalography tracings were visually reviewed, and interictal epileptiform discharges ("spikes") were individually marked. We then evaluated differences in whole-brain connectivity during brief epochs preceding the spikes and during the spikes using the Network-Based Statistic to test differences at the network level. In six patients with statistically-significant network differences, we observed substantial overlap between the spike-associated networks and electrographically active areas identified during intracranial monitoring (the spike-associated network was 78% and 83% sensitive for intracranial electroencephalography-defined regions in the irritative and seizure onset zones, respectively). These findings support the neurobiological validity of the spike-associated network method. Assessment of spike-associated networks has the potential to improve surgical planning in epilepsy surgery patients by identifying components of the epileptic network prior to implantation.

Dynamic evolutionary changes in blood flow measured by MDCT in a hepatic VX2 tumor implant over an extended 28-day growth period: time-density curve analysis.

RATIONALE AND OBJECTIVES: The enhancement pattern of malignant tumors has been studied in short-term animal models (7-14 days), but the reported results have been variable and inconsistent. The purpose of this study was to investigate the changing blood flow characteristics of VX2 tumors implanted in rabbit livers with contrast-enhanced multidetector computed tomography (MDCT) to establish a predictable pattern of vascular evolution over an extended 28-day growth period. MATERIALS AND METHODS: VX2 carcinoma was implanted in livers of 10 male New Zealand White rabbits. Dynamic CT (2/seconds x 60 seconds) was conducted on days 7, 14, 21, and 28 after tumor implantation. Enhancement parameters of time-density curve (TDC), time to start (T0), time to peak (TP), maximum enhancement (DeltaH), slope of enhancement (SLe), and washout (SLw) in tumor center, tumor rim, and normal liver were analyzed. Tumor samples corresponding to CT images of one tumor on days 14 and 21 and seven tumors on day 28 were stained with hematoxylin and eosin and anti-CD31 monoclonal antibody. The relationship between enhancement parameters and histology parameters (thickness of tumor border, extent of blood stasis, and luminar vessel density) was analyzed. RESULTS: Consistent growth, appearance, and vascular changes occurred in 7 of 10 animals over the 4-week observation period. Peripheral rim-like enhancement was noted in CT images. TDC analysis showed that tumor rim enhancement was pronounced and more rapid than normal liver initially but this difference diminished with tumor progression. The SLe, SLw, and DeltaH decreased from 10.03 +/- 3.25 Hu/second, 0.42 +/- 0.25 Hu/sec, and 58.00 +/- 25.27 Hu on day 7 to 5.86 +/- 2.73 Hu/second, 0.10 +/- 0.13 Hu/second, and 37.78 +/- 8.89 Hu/second on day 28, respectively. TP increased from 12.71 +/- 4.85 seconds on day 7 to 25.57 +/- 7.75 seconds on day 28. No significant changes were noted on the TDC parameters in normal liver. The maximum density difference between tumor rim and normal liver (D(rim-liver)) appeared 10.5 +/- 2.1 seconds after contrast injection. The maximum D(rim-liver) decreased from 54.33 +/- 37.86 Hu on day 7 to 11.16 +/- 13.03 Hu on day 28. On histological analysis, viable tumor cells were found in tumor rim with few luminar vessels. The tumor border showed desmoplastic reaction, vascular dilation and proliferation, inflammatory cell infiltration, and blood stasis. These findings were more obvious on day 28 than those on day 14. TP showed significant positive correlations with the extent of blood stasis in tumor border and adjacent liver and the maximum thickness of the tumor border (r = 0.945 and 0.893 respectively, P < .05). CONCLUSION: The rabbit VX2 liver tumor is a hypovascular tumor with perilesional enhancement over its lifespan as imaged by MDCT. Consistent changes in the measured vascular parameters correlated with the size/age of the tumor implants. These findings suggest that the accuracy of CT enhancement imaging for VX2 liver tumor detection might be decreased with tumor development.