PSEN1/SLC20A2 double mutation causes early-onset Alzheimer's disease and primary familial brain calcification co-morbidity.

Primary familial brain calcification (PFBC; formerly Fahr's disease) and early-onset Alzheimer's disease (EOAD) may share partially overlapping pathogenic principles. Although the heterozygous loss-of-function mutation c.1523 + 1G > T in the PFBC-linked gene SLC20A2 was detected in a patient with asymmetric tremor, early-onset dementia, and brain calcifications, CSF ß-amyloid parameters and FBB-PET suggested cortical ß-amyloid pathology. Genetic re-analysis of exome sequences revealed the probably pathogenic missense mutation c.235G > A/p.A79T in PSEN1. The SLC20A2 mutation segregated with mild calcifications in two children younger than 30 years. We thus describe the stochastically extremely unlikely co-morbidity of genetic PFBC and genetic EOAD. The clinical syndromes pointed to additive rather than synergistic effects of the two mutations. MRI data revealed the formation of PFBC calcifications decades before the probable onset of the disease. Our report furthermore exemplifies the value of neuropsychology and amyloid PET for differential diagnosis.

[Acute ischemic stroke and troponin elevation: update of the Mannheim clinical algorithm]. / Akuter ischämischer Schlaganfall und erhöhter Troponinwert ­ Update des Mannheimer Algorithmus.

Elevated high-sensitivity cardiac troponin (hs-cTn) levels should be expected in about half of all patients with acute ischemic stroke (AIS). Since those patients are at risk of increased morbidity and mortality, often attributable to cardiac causes, an adequate work-up of the underlying etiology is required. This can only be achieved by a team of cardiologists and neurologists. Since underlying causes of hs-cTn elevation in AIS patients are diverse, often atypical or silent in their clinical presentation and some, such as an accompanying myocardial infarction, can be acutely life-threatening, the work-up should follow a standardized clinical algorithm. The vast majority of hs-cTn elevations are caused by non-ischemic myocardial injury associated with AIS. This work presents a practice-oriented approach to differential diagnosis with the update of the Mannheim clinical algorithm for acute ischemic stroke and troponin elevation.

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.

Functional dissociation of multiple-object tracking mechanisms based on hemispheric asymmetries.

BACKGROUND: A number of theoretical accounts have been put forward to explain the ability to simultaneously track multiple visually indistinguishable objects over a period of time. Serial processing models of visual tracking focus on the maintenance of the spatial locations of every single item over time. A more recent mechanism describes multiple object tracking as the ability to maintain a higher order representation of an abstract spatial configuration built by the illusory connection of the tracked items through their transition. OBJECTIVE: The current study investigates the correspondence between these serial and parallel tracking accounts and the right hemispheric specialization for the space-based vs. left hemispheric for object-based attentional processing. METHODS: Electrophysiological brain responses were recorded in two groups of patients with right- and left hemispheric lesions while performing in a multiple object tracking task. RESULTS: The results suggest a failure to distinguish single item information for the right hemispheric patients accompanied by the absence of a known electrophysiological marker associated with single item tracking. Importantly, left hemispheric patients showed a graded behavioral and electrophysiological response to probe stimuli as a function of the congruence of the probe with the relevant target stimuli. CONCLUSIONS: The current data suggest that the differential contribution of serial and parallel tracking mechanisms during object tracking can partly be explained by the different functional contributions of the right and left brain hemispheres.