RESUMO
BACKGROUND: We aimed to investigate the clinical, imaging and fluid biomarker characteristics in patients with antidiacylglycerol lipase alpha (DAGLA)-autoantibody-associated cerebellitis. METHODS: Serum and cerebrospinal fliud (CSF) samples from four index patients were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IIFA). Immunoprecipitation, mass spectrometry and recombinant protein assays were used to identify the autoantigen. Sera from 101 patients with various neurological symptoms and a similar tissue staining pattern as the index patient samples, and 102 healthy donors were analysed in recombinant cell-based IIFA (RC-IIFA) with the identified protein. Epitope characterisation of all positive samples was performed via ELISA, immunoblot, immunoprecipitation and RC-IIFA using different DAGLA fragments. RESULTS: All index patients were relatively young (age: 18-34) and suffered from pronounced gait ataxia, dysarthria and visual impairments. Paraclinical hallmarks in early-stage disease were inflammatory CSF changes and cerebellar cortex hyperintensity in MRI. Severe cerebellar atrophy developed in three of four patients within 6 months. All patient samples showed the same unclassified IgG reactivity with the cerebellar molecular layer. DAGLA was identified as the target antigen and confirmed by competitive inhibition experiments and DAGLA-specific RC-IIFA. In RC-IIFA, serum reactivity against DAGLA was also found in 17/101 disease controls, including patients with different clinical phenotypes than the one of the index patients, and in 1/102 healthy donors. Epitope characterisation revealed that 17/18 anti-DAGLA-positive control sera reacted with a C-terminal intracellular DAGLA 583-1042 fragment, while the CSF samples of the index patients targeted a conformational epitope between amino acid 1 and 157. CONCLUSIONS: We propose that anti-DAGLA autoantibodies detected in CSF, with a characteristic tissue IIFA pattern, represent novel biomarkers for rapidly progressive cerebellitis.
RESUMO
In 2016, the new bedside tool quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) was presented to identify patients at high risk of developing sepsis or adverse outcome. The aim of this study was to investigate the diagnostic performance of the qSOFA scoring system as a screening in patients presenting at an emergency department (ED) of any cause. Therefore, we compared qSOFA with the systemic inflammatory response syndrome (SIRS) criteria and two modifications of qSOFA score. This is a prospective single-center study including patients presenting to the ED of any non-traumatic cause. Primary outcome was development of sepsis within 48 h, secondary outcomes were 30-day mortality and ICU stay for > 3 days. Data were collected within one hour after arrival to indicate an impression of initial medical contact. Among 1,668 patients, 105 sepsis cases were identified. 8.4% presented with qSOFA ≥ 2, 27.2% with SIRS ≥ 2 within one hour. Sensitivity of qSOFA in predicting sepsis was lower compared to the SIRS criteria. qSOFA showed better prognostic accuracy for 30-day mortality compared to SIRS (p < 0.05), but not for prolonged ICU stay (p = 0.56). Modification of qSOFA in replacing GCS by other scoring systems recording altered mental status did not improve its sensitivity. The qSOFA score has poor sensitivity to identify patients at risk of developing sepsis and can therefore not be considered as an adequate screening for sepsis in patients presenting to the ED. Furthermore, a positive qSOFA at arrival at the ED showed no sufficient reliability in detecting patients with adverse clinical course.
