Longitudinal Synaptic Density PET with ¹¹ C-UCB-J 6 Months After Ischemic Stroke

The purpose of this study was to explore longitudinal changes in synaptic density after ischemic stroke in vivo with synaptic vesicle protein 2A (SV2A) positron emission tomography (PET).

We recruited patients with an ischemic stroke to undergo ¹¹ C-UCB-J PET/MR within the first month and 6 months after the stroke. We investigated longitudinal changes of partial volume corrected ¹¹ C-UCB-J standardized uptake value ratio (SUVR; relative to centrum semiovale) within the ischemic lesion, peri-ischemic area and unaffected ipsilesional and contralesional grey matter. We also explored crossed cerebellar diaschisis at 6 months. Additionally, we defined brain regions potentially influencing upper limb motor recovery after stroke and studied ¹¹ C-UCB-J SUVR evolution in comparison to baseline.

In 13 patients (age = 67 ± 15 years) we observed decreasing ¹¹ C-UCB-J SUVR in the ischemic lesion (ΔSUVR = -1.0, p = 0.001) and peri-ischemic area (ΔSUVR = -0.31, p = 0.02) at 6 months after stroke compared to baseline. Crossed cerebellar diaschisis as measured with ¹¹ C-UCB-J SUVR was present in 11 of 13 (85%) patients at 6 months. The ¹¹ C-UCB-J SUVR did not augment in ipsilesional or contralesional brain regions associated with motor recovery. On the contrary, there was an overall trend of declining ¹¹ C-UCB-J SUVR in these brain regions, reaching statistical significance only in the nonlesioned part of the ipsilesional supplementary motor area (ΔSUVR = -0.83, p = 0.046).

At 6 months after stroke, synaptic density further declined in the ischemic lesion and peri-ischemic area compared to baseline. Brain regions previously demonstrated to be associated with motor recovery after stroke did not show increases in synaptic density. ANN NEUROL 2023;93:911-921.