PMC9666681_01
Initial clinical presentation timeline. Timeline depicted from first GTC seizure. Hospitalizations designated by gray rectangles. Period of burst suppression designated by red box. Treatment with high-dose intravenous corticosteroids (X) and plasmapheresis (inverted triangle) are indicated. GTC, generalized tonic-clonic; NORSE, new onset refractory status epilepticus.
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F1
He had a prolonged hospitalization at the tertiary care center (Figure 1), totaling 26 days undergoing extensive evaluation and management for new-onset refractory status epilepticus (NORSE). Outpatient medication management, including reducing levetiracetam and adjusting psychoactive medications, failed to control symptoms and the patient was readmitted to the tertiary care hospital (Figure 1). Repeat diagnostics and presurgical epilepsy evaluation were performed at our center including Epilepsy Monitoring Unit admission, where cvEEG demonstrated independent bilateral anterior temporal sharp waves and bilateral independent temporal seizures (Supplementary Figure 1).
Treatment timeline with RNS placement and temporal lobe seizure capture. (A) Timeline from initial referral for evaluation in Epilepsy clinic, pre-surgical evaluation, and RNS surgery. Timeline depicted from first GTC seizure. Evaluations and RNS programming designated by gray rectangles. (B) Sagittal head computed tomography scan showing RNS generator (black box) implanted in right frontal skull. Two 4-contact subtemporal lobe strips are implanted bilaterally (black oval). (C) Top, representative electrocorticography (ECoG) demonstrating left temporal lobe onset seizures. Time scale represents seconds from RNS seizure detection. Traces show seizure detection in LT1-2 and LT3-4 subtemporal contact. Bottom, representative ECoG demonstrating in right temporal lobe onset seizures. RNS, responsive neurostimulator; EMU, epilepsy monitoring unit; GTC, generalized tonic-clonic; RT, right temporal; LT, left temporal; Tr, treatment.
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F2
After 27 months of drug-resistant epilepsy, he presented to our institution for evaluation (Figure 2A). MRI brain demonstrated left mesial temporal sclerosis and FDG-PET brain was unremarkable (Supplementary Figure 2). Approximately 34 months after seizure onset, the patient underwent placement of RNS system with two bilateral subtemporal four-contact strips (Figure 2B). Detection settings were honed and accurate in detecting electrographic seizures within 1-2 s of seizure onset (Figure 2C). Utilizing the diagnostic capabilities of the RNS device, his seizures have been lateralized, 75% with left temporal onset, 25% with right temporal onset (Figure 2C).
Timeline of immunotherapy and quantitative seizure analysis. (A) Timeline from initial referral to evaluation in Epilepsy clinic, pre-surgical evaluation, RNS surgery, and evaluation in Neuroimmunology clinic. Timeline depicted from first GTC seizure. Treatment with high-dose intravenous corticosteroids (X) and intravenous immunoglobulin (inverted triangle) are indicated. RNS programming and treatment continuously employed (gray rectangles). (B) Quantification of seizure frequency since RNS placement. Events were extracted from the Patient Data Management System (PDMS) and annotated to yield histogram of seizure frequency in 1-week bins. Missing data are represented as zero events. Data represent detections per week. RNS programming sessions depicted for corresponding week as detection-only change (red), treatment-only change (blue), or detection and treatment changes (violet). Non-programming weeks depicted in gray. Rolling average trendline represents 0th order polynomial of 20 neighbors for each data point to aide in data visualization and reduce visual impact of data fluctuations. Corresponding time of immunotherapy shown (gray shaded area). Note the lack of significant change in seizure frequency during, and following, immunotherapy. RNS, responsive neurostimulator; EMU, epilepsy monitoring unit; GTC, generalized tonic-clonic.
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F3
The patient was evaluated in our Neuroimmunology clinic for consideration of immunotherapy (Figure 3A). This trial consisted of high-dose IV corticosteroids (1 g methylprednisolone daily for 3 days) and IVIG (2 g/kg in three divided doses) induction, followed by monthly IVIG (0.6 g/kg) for maintenance immunotherapy (Figure 3). Analysis of objective ECoG data on the Patient Data Management System (PDMS) and patient-reported seizure frequency failed to show a positive effect of immunotherapy on seizure frequency (Figure 3B).