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

Comparison of Template-Based Versus CT-Based Attenuation Correction for Hybrid MR/PET Scanners

Attenuation correction (AC) of cerebral PET data acquired in hybrid MR/PET scanners is still a challenge. To overcome this problem we previously proposed a correction method by obtaining template-based attenuation maps (AM) using MR and ECAT EXACT HR+ transmission scans. In the present study we investigated (a) the basic difference between template-based and CT-based AC methods and (b) their influence on reconstructed PET images. The data of 11 subjects undergoing 18FDG imaging in the Siemens 3T MR-BrainPET scanner were used. Additionally, from all participants a CT scan of the whole head was acquired at the same day. These CT images were transformed to CT-based AMs. They were filtered by a 3D Gaussian kernel with 3 mm (BrainPET resolution) filter width, which was considered as reference. Comparisons between both AMs (CT-based and template-based) were performed by estimating the Dice coefficients D and calculating the numbers of true positive, true negative and false negative voxels. The BrainPET emission data were reconstructed with both AMs ( AMCT3mm and AMTemplate). All reconstructed PET images were scaled to standardized uptake values (SUVs) and normalized to the MNI brain for using the AAL-VOI Atlas analysis. Correlation plots with regression equation, coefficients of determination R2 and relative differences (RD) between AMCT3mm and the AMTemplate were derived. The fraction of the overall true positive voxels averaged over the 11 subjects was 80.4 ±7.5% for AMTemplate compared to AMCT3mm ( Dbone = 0.63 ±0.08; Dsoft - tissue = 0.85 ±0.08; Dair = 0.79 ±0.04). A misclassification of bone as soft tissue and vice versa was evident in the comparison. The correlation plot of all VOIs considered (1,276 values) showed a mean R2 of 0.964 and a slope of 1.02. A mean RD of 1.33 ±0.95% ( min = - 0.12%, max = 2.85%) was found. The template-based AC method proposed by our group shows considerable differences in comparison to the higher resolution CT-based AM with respect to the Dice coefficients, in particular in the classification of bone and soft tissue. However, this has no major influence on the reconstructed 18FDG PET data

Atypical bilateral ventilation/perfusion mismatches in an asymptomatic patient suffering from metastatic thyroid cancer

Background!#!Pulmonary embolism is indicated by ventilation/perfusion (V/P) mismatches in ventilation/perfusion scintigraphy. However, other pathologies may also evoke segmental or lobar mismatches. Thus, diagnosis can be difficult in asymptomatic patients with equivocal clinical presentation.!##!Case presentation!#!We present a case of multiple bilateral pulmonary ventilation/perfusion mismatches in a poorly differentiated thyroid cancer patient. Exact diagnosis was difficult, as the patient was asymptomatic and pulmonary embolism is commonly unilateral in tumour patients and not typical for thyroid cancer. External pulmonary artery compression by aortic aneurysm, multiple metastases or additional bronchopulmonary malignancies were considered as differential diagnosis. After unilateral pulmonary and hilar metastasectomy, perfusion normalised on the operated side. Pulmonary perfusion defects due to pulmonary artery compression by hilar metastases were finally diagnosed. Pulmonary embolism was deemed unlikely due to the left-sided post-operative normalisation, persistence of right-sided V/P mismatches, and the lack of clinical symptoms.!##!Conclusion!#!Pulmonary artery compression may mimic pulmonary artery embolism in lung perfusion scintigraphy and should be considered in bronchopulmonary tumour patients with hilar metastases and unilateral ventilation/perfusion mismatches affecting a complete lobe or even lung. Following the presented case, also bilateral segmental and subsegmental mismatches in patients with hilar metastases from non-bronchopulmonary cancer entities should be carefully evaluated