PET of Brain Prion Protein Amyloid in Gerstmann–Sträussler–Scheinker Disease

In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann-Sträussler-Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d-glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism ([F-18]FDG) reduction was observed in neocortex, basal ganglia and/or thalamus, which supports the close relationship between [F-18]FDDNP binding and neuronal dysfunction. Two asymptomatic gene carriers displayed no cortical [F-18]FDDNP binding, yet progressive [F-18]FDDNP retention in caudate nucleus and thalamus was seen at 1- and 2-year follow-up in the older asymptomatic subject. In vitro FDDNP labeling experiments on brain tissue specimens from deceased GSS subjects not participating in the in vivo studies indicated that in vivo accumulation of [F-18]FDDNP in subcortical structures, neocortices and cerebellum closely related to the distribution of prion protein pathology. These results demonstrate the feasibility of detecting prion protein accumulation in living patients with [F-18]FDDNP PET, and suggest an opportunity for its application to follow disease progression and monitor therapeutic interventions

Long-Term Viability of Isolated Bovine Adrenal Medullary Chromaffin Cells following Intrastriatal Transplantation

Adrenal medullary grafts generally exhibit poor viability when grafted into the striatum. Previous work in our laboratory demonstrated that chromaffin cells can survive well for up to 2 mo following grafting into the intact rat striatum after cells are isolated from the nonchromaffin supporting cells (fibroblasts and endothelial cells) of the adrenal medulla. The aim of the present study was to assess the long-term viability of isolated bovine chromaffin cells following grafting into the intact rat striatum. The viability of grafted bovine adrenal medullary chromaffin cells was compared in rats receiving either (a) perfused adrenal medulla; (b) isolated chromaffin cells; or (c) isolated chromaffin cells that were subsequently recombined with their nonchromaffin supporting cells. One year postimplantation, all graft types which included fibroblasts and endothelial cells were infiltrated with macrophages and demonstrated an abundance of cellular debris. No viable chromaffin cells were observed. In contrast, healthy tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DβH) immunoreactive chromaffin cells survived for 1 yr posttransplantation when grafted in isolation from the nonchromaffin constituents of the adrenal medulla. Good xenograft survival was achieved in this group despite the fact that these rats were only immunosuppressed for 1 mo postimplantation. Grafted cells demonstrated morphological characteristics of chromaffin cells in situ and these implants were not accompanied by macrophage infiltration. These data demonstrate that long-term survival of chromaffin cells can be achieved following intra-striatal implantation and the viability of grafted chromaffin cells is dependent upon the removal of the nonchromaffin supporting cells

Characterization and analysis of neurologic adverse events associated with COVID-19 vaccination (S12.006)

Objective: To characterize the incidence and spectrum of neurological adverse events (AE) after COVID-19 vaccination. Background: The devastating COVID-19 pandemic has led to 230 million people diagnosed and greater than 4.8 million deaths worldwide. Widespread vaccination efforts have resulted in administration of over 6 million vaccine doses to curb the significant health and socioeconomic impacts of the disease. While there are numerous reports of adverse events following COVID-19 vaccine, there is limited characterization of the spectrum of neurological AEs post-vaccination. Design/Methods: Data was gathered from the publicly available Vaccine Adverse Event Reporting System (VAERS), a passive reporting system not implying causality. Among individuals who received the J&J, Moderna, and Pfizer vaccines from 1/1/2021–6/14/2021, 314,610 adverse events were reported and these were reviewed by Neurology trained clinicians to determine the presence of various neurological AEs (40 conditions coded). Results: 306,473,169 COVID vaccine dose were administered in the USA during the study period with 314,610 total AEs (0.10%) and 105,930 neurological AEs (0.03%) reported. J&J vaccine was associated with the most AEs (17,670, 0.15%), followed by Moderna (42656, 0.03%) and Pfizer (42267, 0.03%). On average more events were reported in women (71%) and a majority occurred after the first dose (54%). < 1 events were reported per million vaccine doses for serious neurological conditions such as Bell’s palsy (0.0007%), Guillain-Barre syndrome (0.00009%), cerebral venous thrombosis (0.00005%), transverse myelitis (0.00003%), and acute disseminated encephalomyelitis (0.00006%). Overall neurological complications following vaccine were drastically lower than complications post-COVID infection (14–80%). Conclusions: Adverse neurological events following COVID-19 vaccination are extremely rare and significantly less common than adverse neurological effects following SARS-CoV-2 infection. Current evidence suggests that along with being up to 100,000 times more likely to experience a major complication from COVID infection vs. vaccine, the risk of neurological complication is up to 5000 times more likely from infection itself