Treating a GAD65 Antibody-Associated Limbic Encephalitis with Basiliximab: A Case Study

Background: Antibodies (ABs) against the 65-kDa isoform of the intracellular enzymeglutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) andother neurological conditions. The direct significance of anti-GAD65-ABs for epilepsyis unclear. However, in histological preparations from biopsies of resective epilepsysurgeries, predominantly cytotoxic T-lymphocytes were detected making close contactsto neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeuticinterleukin-2 receptor Abs, such as basiliximab.Case presentation: We report of a 25-year-old male patient with epilepsy since theage of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebro-spinal fluid (CSF) and serum. Monthly, repetitive, intravenous cortisone pulse therapiesthat were initially administered for 6 months failed to improve his condition. Subsequentflow-cytometry analysis of CSF showed especially an increased fraction of activatedHLA-DR+CD8+T-lymphocytes (fCD8+TL) when compared to controls. Thus, a second,intravenous cortisone pulse therapy with an additional basiliximab dose of 20 mg/monthwas started. After 3 months, the fCD8+TL in the CSF normalized; after 6 months, thepsychological impulse-control deficits normalized; and after 11 months the patientwas seizure free. However, 7 weeks later, seizures and, later on, psychological deficitsrecurred and fCD8+TL was once again present in the CSF. Flumazenil PET, magneticresonance imaging-volumetry, and neuropsychological changes during therapy aredescribed.Conclusion: The correlation of the fCD8+TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to basiliximabstrongly argues in favor of the putative pathogenic role fCD8+TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation ofhuman anti-drug ABs, a well-known complication of therapy with chimeric ABs

The influence of filtered back-projection and iterative reconstruction on partial volume correction in PET

Aim: We assess the influence of the reconstruction algorithms [OS-EM for the iterative one vs. a filtered back-projection in Fourier space (DiFT)] on partial volume correction in PET employing a fully 3D 3-compartment MR based PV-correction algorithm. The gray matter voxels in the PET image - after removal of the white matter and cerebrospinal fluid contribution - are corrected voxel-by-voxel using the image resolution. Material, methods: Phantom measurements and one healthy human brain FDG study were carried out. For the OSEM reconstruction, a combination of iteration steps and subset numbers (It/Sub) was used, whereby in case of no-convergence the image resolution had to be fined. The results from the DiFT reconstruction were equivalent to those obtained from the OSEM reconstruction with 10/32 combination for objects with widespread activity concentration. For the sphere phantom, the mean recovery based on the actual values achieved 99.2% +/- 1.8 for all spheres and all reconstruction modes and It/sub combinations (except for 2/8). In case of the Hoffman 3D brain phantom the mean recovery of the cortical regions was 101% +/- 1.2 (the increase based on the uncorrected values: 35.5% +/- 1.5), while the subcortical regions reached a mean recovery of 80% with an increase of 43.9% +/- 2.5. For the human data, an increase of the metabolized values of several cortical regions ranged between 42% and 48% independent from the reconstruction mode. Conclusions: Our data show that the 3-compartment fully 3-D MR based PV-correction is sensitive to the choice of reconstruction algorithms and to the parameter choice. They indicate that despite improved spatial resolution, the use of the iterative reconstruction algorithm for PV-correction results in similar recovery factors when compared to a correction using DiFT reconstruction, insofar the image resolution values are fitted at the It/Sub combinations