Changes in 11C-ER176 Uptake in Two Patients Treated for Autoimmune Encephalitis Associated Epilepsy with Immunomodulation
Eden Tefera1, Zanetta Kovbasyuk2, Maria Pleshkevich1, Patryk Filipiak2, Kamri Clarke2, Patrick Carberry2, Jakub Mroz2, Amit Ahituv1, Jean Logan2, Benjamin Brush1, Kara Melmed1, Binita Shah3, Eytan Raz1, Anureet Kaur1, Timothy Shepherd1, W. Gordon Frankle4, Steven Baete2, Claude Steriade1
1Neurology, 2Radiology, 3Cardiology, 4Psychiatry, NYU School of Medicine
Objective:

We measured changes in 11C-ER176 uptake in subjects treated with autoimmune encephalitis associated epilepsy (AEAE) before and after standard of care immunomodulation. 

Background:

There is a need for quantitative biomarkers of neuroinflammation in patients with AEAE. Previously, TSPO-PET imaging (e.g. with radioligand 11C-ER176) has been shown to correlate with microglial activation and may help to track neuroinflammatory response to treatment.

Design/Methods:

Here we describe two cases. Subject 1 is a 62-year old woman with GAD65 antibody associated AEAE who received steroids. Subject 2 is a 34-year old woman with antibody-negative AEAE who received intravenous immunoglobulin. Seizure frequency and cognitive ability were recorded prior to and after treatment.

Both subjects were immunotherapy-naïve at the time of baseline 11C-ER176 PET-MRI scan and underwent a repeat 11C-ER176 PET-MRI scan 12 weeks after the start of immunomodulation. 11C-ER176 PET-MRI scans were completed over 90 minutes and TSPO distribution volumes (VT) were estimated using a metabolite corrected Arterial input function and an unconstrained two-tissue compartment model. VT (mL • cm -3 ) values were compared between the pre and post-treatment scans across brain Regions of Interest (ROIs).  

Results:

In Subject 1, VT values increased following immunomodulation in the following ROIs: Whole Brain 3.93 (1.81, 5.74), Hippocampus 4.34 (2.23, 6.57), Amygdala 5.12 (2.63, 7.75) and Lateral Temporal Neocortex 3.67 (1.85, 5.52). In Subject 2, VT values also increased following immunomodulation: Whole Brain 0.56 (6.29, 6.86), Hippocampus 0.43 (6.49, 6.92), Amygdala 0.05 (8.61, 8.56) and Lateral Temporal Neocortex 0.97 (6.11, 7.08). Neither patient significantly improved in seizure frequency or cognitive status following immunomodulation.

Conclusions:

In two subjects treated for AEAE who did not significantly respond to immunomodulation, 11C-ER176 uptake increased after treatment. Incompletely treated AEAE, post-ictal neuroinflammation, or natural fluctuations may affect changes in 11C-ER176 uptake in patients with AEAE undergoing trials of immunomodulation.

10.1212/WNL.0000000000206252