Successful surgical treatment of an inflammatory lesion associated with new-onset refractory status epilepticus

Abstract

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[(11)C]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.

Fig. 1

Pre- and postoperative MRI and AMT-PET scans. Upper: Preoperative FLAIR and T1-weighted postcontrast images showing a nonenhancing hyperintense left midtemporal lesion. On PET images, increased AMT uptake is noted in the left mid- and posterior temporal cortex with partial overlap with the MRI-defined lesion. The regions with the highest AMT uptake in the mid- and posterior temporal areas are indicated with arrows (high AMT uptake in visual cortex is symmetrical, physiological). Lower: Follow-up MR images 3 months after prolonged intracranial EEG-guided resection of left lateral temporal lobe show the resection cavity with no residual lesion and preservation of mesial temporal lobe structures. Follow-up AMT-PET scan shows absence of AMT uptake in the resection cavity and normalization of AMT uptake in the residual posterior temporal region behind the resection cavity.

Fig. 2

Immunostaining findings of resected epileptogenic tissue. A: Curvilinear 3D reconstruction of the brain (5 mm under the cortical surface to emphasize gyri and sulci) using the preoperative volumetric MRI with overlay of intracranial subdural electrodes. The arrow indicates the MRI-defined lesion in the subcortical area, whereas the outlined region in red corresponds to the highest AMT uptake in the superior temporal gyrus. Electrodes in yellow represent seizure onset, and those in blue showed rapid seizure propagation. Electrodes No. 30 (superior temporal gyrus) and No. 4 (middle temporal gyrus) are labeled because the cortex under these electrodes was sampled for immunohistochemistry (see below). B: GFAP immunohistochemistry showing extensive reactive astrocytes in the image-guided biopsy obtained from the nonenhancing, T2-weighted/FLAIR hyperintense lesion prior to implantation of intracranial electrodes. C: Strong IDO (red) and IL-1β (green) coexpression in tissue obtained from electrode No. 30 corresponding to an AMT-positive region involved in seizure onset in the superior temporal gyrus. D: In contrast, there is sparse IDO and IL-1β coexpression in the tissue obtained from electrode No. 4 corresponding to an AMT-negative region involved in seizure onset in the anterolateral temporal cortex. Nuclei are stained in blue by DAPI counterstaining. E and F: Immunostaining for IL-1R1 in the same regions again demonstrating higher expression in the AMT-positive tissue (electrode No. 30; E) compared with AMT-negative tissue (electrode No. 4; F). Original magnification ×20 (B–F).