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

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.

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 (V_T) were estimated using a metabolite corrected Arterial input function and an unconstrained two-tissue compartment model. V_T (mL • cm ^-3 ) values were compared between the pre and post-treatment scans across brain Regions of Interest (ROIs).  

In Subject 1, V_T 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, V_T 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.

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.