Skin Autofluorescence is an Independent Predictor of Post Stroke Infection in Diabetes.

Post stroke infection occurs in 15-20% of acute stroke patients and is associated with a poor longterm outcome. In a prospective study on 113 acute ischemic stroke patients with diabetes mellitus 15.9% suffered nosocomial infection. We found chronic hyperglycemia measured by skin autofluorescence in arbitrary units to be an independent predictor of a nosocomial infection post stroke (OR = 3.24 [CI 95%: 1.13; 9.26], p = 0.029). Skin autofluorescence represents the glycemic memory beyond HbA1c. Potential mechanisms leading from increased skin autofluorescence to vulnerability for infectious complications include more severe strokes due to preexisting vasculopathy and exacerbated post stroke immunosuppression.

Left atrial area index provides the best prediction of atrial fibrillation in ischemic stroke patients: results from the LAETITIA observational study.

Background and aims: Left atrial (LA) enlargement has been repeatedly shown to be associated with the diagnosis of atrial fibrillation (AF). In clinical practice, several parameters are available to determine LA enlargement: LA diameter index (LADI), LA area index (LAAI), or LA volume index (LAVI). We investigated the predictive power of these individual LA parameters for AF in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: LAETITIA is a retrospective observational study that reflects the clinical reality of acute stroke care in Germany. Consecutive patient cases with acute ischemic cerebrovascular event (CVE) in 2019 and 2020 were identified from the Mannheim stroke database. Predictive power of each LA parameter was determined by the area under the curve (AUC) of receiver operating characteristic curves. A cutoff value was determined. A multiple logistic regression analysis was performed to confirm the strongest LA parameter as an independent predictor of AF in patients with acute ischemic CVE. Results: A total of 1,910 patient cases were included. In all, 82.0% of patients had suffered a stroke and 18.0% had a TIA. Patients presented with a distinct cardiovascular risk profile (reflected by a CHA2DS2-VASc score ≥2 prior to hospital admission in 85.3% of patients) and were moderately affected on admission [median NIHSS score 3 (1; 8)]. In total, 19.5% of patients had pre-existing AF, and 8.0% were newly diagnosed with AF. LAAI had the greatest AUC of 0.748, LADI of 0.706, and LAVI of 0.719 (each p < 0.001 vs. diagonal line; AUC-LAAI vs. AUC-LADI p = 0.030, AUC-LAAI vs. AUC-LAVI p = 0.004). LAAI, increasing NIHSS score on admission, and systolic heart failure were identified as independent predictors of AF in patients with acute ischemic CVE. To achieve a clinically relevant specificity of 70%, a cutoff value of ≥10.3 cm2/m2 was determined for LAAI (sensitivity of 69.8%). Conclusion: LAAI revealed the best prediction of AF in patients with acute ischemic CVE and was confirmed as an independent risk factor. An LAAI cutoff value of 10.3 cm2/m2 could serve as an inclusion criterion for intensified AF screening in patients with embolic stroke of undetermined source in subsequent studies.

Measuring of Advanced Glycation End Products in Acute Stroke Care: Skin Autofluorescence as a Predictor of Ischemic Stroke Outcome in Patients with Diabetes Mellitus.

Background: Patients with diabetes mellitus (DM) are known to show poor recovery after stroke. This specific burden might be due to acute and chronic hyperglycemic effects. Meanwhile, the underlying mechanisms are a cause of discussion, and the best measure to predict the outcome is unclear. Skin autofluorescence (SAF) reflects the in-patient load of so-called advanced glycation end products (AGEs) beyond HbA1c and represents a valid and quickly accessible marker of chronic hyperglycemia. We investigated the predictive potential of SAF in comparison to HbA1c and acute hyperglycemia on the functional outcome at 90 days after ischemic stroke in a cohort of patients with DM. Methods: We prospectively included 113 patients with DM type 2 hospitalized for acute ischemic stroke. SAF was measured on each patient's forearm by a mobile AGE-Reader mu© in arbitrary units. HbA1c and the area under the curve (AUC) of the blood sugar profile after admission were assessed. Functional outcome was assessed via phone interview after 90 days. A poor outcome was defined as a deterioration to a modified Rankin Scale score ≥ 3. A good outcome was defined as a modified Rankin Scale score < 3 or as no deterioration from premorbid level. Results: Patients with a poor outcome presented with higher values of SAF (mean 3.38 (SD 0.55)) than patients with a good outcome (mean 3.13 (SD 0.61), p = 0.023), but did not differ in HbA1c and acute glycemia. In logistic regression analysis, age (p = 0.021, OR 1.24 [1.12−1.37]) and SAF (p = 0.021, OR 2.74 [1.16−6.46]) significantly predicted a poor outcome, whereas HbA1c and acute glycemia did not. Patients with a poor 90-day outcome and higher SAF experienced more infections (4.2% vs. 33.3% (p < 0.01)) and other various in-hospital complications (21.0% vs. 66.7% (p < 0.01)) than patients with a good outcome and lower SAF levels. Conclusions: SAF offers an insight into glycemic memory and appears to be a significant predictor of poor stroke outcomes in patients with DM exceeding HbA1c and acute glycemia. Measuring SAF could be useful to identify specifically vulnerable patients at high risk of complications and poor outcomes.

Intrathecal activation of CD8+ memory T cells in IgG4-related disease of the brain parenchyma.

IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4-restricted plasma cells into a variety of organs. Clinical presentation is heterogeneous, and pathophysiological mechanisms of IgG4-RD remain elusive. There are very few cases of IgG4-RD with isolated central nervous system manifestation. By leveraging single-cell sequencing of the cerebrospinal fluid (CSF) of a patient with an inflammatory intracranial pseudotumor, we provide novel insights into the immunopathophysiology of IgG4-RD. Our data illustrate an IgG4-RD-associated polyclonal T-cell response in the CSF and an oligoclonal T-cell response in the parenchymal lesions, the latter being the result of a multifaceted cell-cell interaction between immune cell subsets and pathogenic B cells. We demonstrate that CD8+ T effector memory cells might drive and sustain autoimmunity via macrophage migration inhibitory factor (MIF)-CD74 signaling to immature B cells and CC-chemokine ligand 5 (CCL5)-mediated recruitment of cytotoxic CD4+ T cells. These findings highlight the central role of T cells in sustaining IgG4-RD and open novel avenues for targeted therapies.