Investigating synaptic changes in Essential Tremor with PET Imaging (P7-11.005)

Abstract

<h3>Objective:</h3> To utilize positron emission tomography (PET) imaging with the synaptic density tracer [¹¹ C] UCB-J to characterize the distribution in the cerebellum and other brain areas in essential tremor (ET) compared to healthy controls (HC). <h3>Background:</h3> Numerous lines of evidence point to a cerebellar origins of ET, with a number of studies pointing to Purkinje cell loss. Studying potential markers of cell loss <i>in vivo</i> would be of great value. [¹¹ C] UCB-J has been found to be an excellent tracer for quantitative imaging of synaptic vesicle glycoprotein 2A (SV2A), a marker of synaptic density, in the human brain. This tracer has not been used to study the ET brain. <h3>Design/Methods:</h3> Six individuals with ET with a mean age (SD) of 65 (10); three males), and sixteen demographically matched healthy comparison controls (HC; 63 (9); six males) participated in an [¹¹ C] UCB-J PET scan. Binding potential value (<i>BP</i>_ND: binding potential of available receptors) was the primary outcome measure and using the centrum semiovale as the reference region. Muller Gartner partial volume correction (PVC) was applied to control for possible volumetric differences. T-tests were calculated for between group differences, and p values were uncorrected for multiple comparisons given the exploratory nature. <h3>Results:</h3> We observed significantly lower synaptic availability in ET compared to HC in the cerebellum (−11%, p=0.04), right cerebellum (−11%, p=0.03), vermis (−12%, p=0.04), motor cortex (−21%, p=0.001), and supplementary motor cortex (−20%, p=0.006). <h3>Conclusions:</h3> This <i>in vivo</i> investigation with [¹¹ C] UCB-J PET in ET is the first sample to date (to our knowledge) and found preliminary evidence of lower synaptic availability in key brain areas. Additional data analysis is ongoing, such as applying Iterative-Yang PVC, correlating synaptic changes with clinical scores, and exploring network-based analyses. <b>Disclosure:</b> Ms. Yang has nothing to disclose. Mika Naganawa has nothing to disclose. Nora Hernandez has nothing to disclose. Mr. Nguyen has nothing to disclose. Nabeel Nabulsi, 21953 has nothing to disclose. An immediate family member of Yiyun Huang, 8202 has stock in Pfiy. An immediate family member of Yiyun Huang, 8202 has stock in Johnson and Johnson . Yiyun Huang, 8202 has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH. Richard Carson has nothing to disclose. Dr. Matuskey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Eleisver. The institution of Dr. Matuskey has received research support from Abbvie. Dr. Louis has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwer - Merritt’s Textbook of Neurology. The institution of Dr. Louis has received research support from National Institutes of Health.