New-onset refractory status epilepticus (NORSE) has high morbidity and mortality. The authors describe the successful surgical treatment of a 56-year-old man presenting with NORSE. Magnetic resonance imaging showed a left temporal lobe lesion suspicious for a low-grade tumor, while PET imaging with the alpha[11C]methyl-L-tryptophan (AMT) radiotracer showed increased cortical uptake extending beyond this lesion and partly overlapping with epileptogenic cortex mapped by chronic intracranial electroencephalographic monitoring. Resection of the epileptic focus resulted in long-term seizure freedom, and the nonresected portion of the PET-documented abnormality normalized. Histopathology showed reactive gliosis and inflammatory markers in the AMT-PET–positive cortex. Molecular imaging of neuroinflammation can be instrumental in the management of NORSE by guiding placement of intracranial electrodes or assessing the extent and severity of inflammation for antiinflammatory interventions.
Csaba Juhász, Amy Buth, Diane C. Chugani, William J. Kupsky, Harry T. Chugani, Aashit K. Shah and Sandeep Mittal
Sandeep Mittal, Neil V. Klinger, Sharon K. Michelhaugh, Geoffrey R. Barger, Susan C. Pannullo and Csaba Juhász
Treatment for glioblastoma (GBM) remains largely unsuccessful, even with aggressive combined treatment via surgery, radiotherapy, and chemotherapy. Tumor treating fields (TTFs) are low-intensity, intermediate-frequency, alternating electric fields that have antiproliferative properties in vitro and in vivo. The authors provide an up-to-date review of the mechanism of action as well as preclinical and clinical data on TTFs.
A systematic review of the literature was performed using the terms “tumor treating fields,” “alternating electric fields,” “glioblastoma,” “Optune,” “NovoTTF-100A,” and “Novocure.”
Preclinical and clinical data have demonstrated the potential efficacy of TTFs for treatment of GBM, leading to several pilot studies, clinical trials, and, in 2011, FDA approval for its use as salvage therapy for recurrent GBM and, in 2015, approval for newly diagnosed GBM.
Current evidence supports the use of TTFs as an efficacious, antimitotic treatment with minimal toxicity in patients with newly diagnosed and recurrent GBM. Additional studies are needed to further optimize patient selection, determine cost-effectiveness, and assess the full impact on quality of life.
Min-Hee Lee, Nolan B. O’Hara, Yasuo Nakai, Aimee F. Luat, Csaba Juhasz, Sandeep Sood, Eishi Asano and Jeong-Won Jeong
This study is aimed at improving the clinical utility of diffusion-weighted imaging maximum a posteriori probability (DWI-MAP) analysis, which has been reported to be useful for predicting postoperative motor, language, and visual field deficits in pediatric epilepsy surgery. The authors determined the additive value of a new clustering mapping method in which average direct-flip distance (ADFD) reclassifies the outliers of original DWI-MAP streamlines by referring to their minimum distances to the exemplar streamlines (i.e., medoids).
The authors studied 40 children with drug-resistant focal epilepsy (mean age 8.7 ± 4.8 years) who had undergone resection of the presumed epileptogenic zone and had five categories of postoperative deficits (i.e., hemiparesis involving the face, hand, and/or leg; dysphasia requiring speech therapy; and/or visual field cut). In pre- and postoperative images of the resected hemisphere, DWI-MAP identified a total of nine streamline pathways: C1 = face motor area, C2 = hand motor area, C3 = leg motor area, C4 = Broca’s area–Wernicke’s area, C5 = premotor area–Broca’s area, C6 = premotor area–Wernicke’s area, C7 = parietal area–Wernicke’s area, C8 = premotor area–parietal area, and C9 = occipital lobe–lateral geniculate nucleus. For each streamline of the identified pathway, the minimal ADFD to the nine exemplars corrected the pathway membership. Binary logistic regression analysis was employed to determine how accurately two fractional predictors, Δ1–9 (postoperative volume change of C1–9) and γ1–9 (preoperatively planned volume of C1–9 resected), predicted postoperative motor, language, and visual deficits.
The addition of ADFD to DWI-MAP analysis improved the sensitivity and specificity of regression models for predicting postoperative motor, language, and visual deficits by 28% for Δ1–3 (from 0.62 to 0.79), 13% for Δ4–8 (from 0.69 to 0.78), 13% for Δ9 (from 0.77 to 0.87), 7% for γ1–3 (from 0.81 to 0.87), 1% for γ4–8 (from 0.86 to 0.87), and 24% for γ9 (from 0.75 to 0.93). Preservation of the eloquent pathways defined by preoperative DWI-MAP analysis with ADFD (up to 97% of C1–4,9) prevented postoperative motor, language, and visual deficits with sensitivity and specificity ranging from 88% to 100%.
The present study suggests that postoperative functional outcome substantially differs according to the extent of resected white matter encompassing eloquent cortex as determined by preoperative DWI-MAP analysis. The preservation of preoperative DWI-MAP–defined pathways may be crucial to prevent postoperative deficits. The improved DWI-MAP analysis may provide a complementary noninvasive tool capable of guiding the surgical margin to minimize the risk of postoperative deficits for children.
Min-Hee Lee, Nolan B. O’Hara, Hirotaka Motoi, Aimee F. Luat, Csaba Juhász, Sandeep Sood, Eishi Asano and Jeong-Won Jeong
In this study the authors investigated the clinical reliability of diffusion weighted imaging maximum a posteriori probability (DWI-MAP) analysis with Kalman filter prediction in pediatric epilepsy surgery. This approach can yield a suggested resection margin as a dynamic variable based on preoperative DWI-MAP pathways. The authors sought to determine how well the suggested margin would have maximized occurrence of postoperative seizure freedom (benefit) and minimized occurrence of postoperative neurological deficits (risk).
The study included 77 pediatric patients with drug-resistant focal epilepsy (age 10.0 ± 4.9 years) who underwent resection of their presumed epileptogenic zone. In preoperative DWI tractography from the resected hemisphere, 9 axonal pathways, Ci=1–9, were identified using DWI-MAP as follows: C1–3 supporting face, hand, and leg motor areas; C4 connecting Broca’s and Wernicke’s areas; C5–8 connecting Broca’s, Wernicke’s, parietal, and premotor areas; and C9 connecting the occipital lobe and lateral geniculate nucleus. For each Ci, the resection margin, di, was measured by the minimal Euclidean distance between the voxels of Ci and the resection boundary determined by spatially coregistered postoperative MRI. If Ci was resected, di was assumed to be negative (calculated as –1 × average Euclidean distance between every voxel inside the resected Ci volume, ri). Kalman filter prediction was then used to estimate an optimal resection margin, d*i, to balance benefit and risk by approximating the relationship between di and ri. Finally, the authors defined the preservation zone of Ci that can balance the probability of benefit and risk by expanding the cortical area of Ci up to d*i on the 3D cortical surface.
In the whole group (n = 77), nonresection of the preoperative preservation zone (i.e., actual resection margin d*i greater than the Kalman filter–defined d*i) accurately predicted the absence of postoperative motor (d*1–3: 0.93 at seizure-free probability of 0.80), language (d*4–8: 0.91 at seizure-free probability of 0.81), and visual deficits (d*9: 0.90 at seizure-free probability of 0.75), suggesting that the preservation of preoperative Ci within d*i supports a balance between postoperative functional deficit and seizure freedom. The subsequent subgroup analyses found that preservation of preoperative Ci =1–4,9 within d*i =1–4,9 may provide accurate deficit predictions independent of age and seizure frequency, suggesting that the DWI-based surgical margin can be effective for surgical planning even in young children and across a range of epilepsy severity.
Integrating DWI-MAP analysis with Kalman filter prediction may help guide epilepsy surgery by visualizing the margins of the eloquent white matter pathways to be preserved.