Background In basilar artery occlusion (BAO) stroke, the impact of the collateral circulation on infarct progression in the context of endovascular treatment (EVT) is yet poorly studied. Aim This study investigates the impact of the posterior circulation collateral score (PCCS) on functional outcome according to the extent of early ischemic changes and treatment. We hypothesized that the presence of collaterals, quantified by the PCCS, mediates the effect of EVT on functional outcome in patients with acute BAO. Methods In this multicenter observational study, patients with BAO and admission-CT were analyzed. At baseline, pcASPECTS was assessed and PCCS was quantified using an established 10-point grading system. Logistic regression analyses were performed to identify factors associated with good functional outcome (modified Rankin Scale (mRS) scores 0-2 at day-90). Results 151 patients were included, of which 112 patients (74%) underwent EVT. In patients with a better PCCS (>5), the rate of good outcome was significantly higher (55% versus 11%; p=0.001). After adjusting for PCCS, vessel recanalization was significantly associated with improved functional outcome (aOR: 4.53, 95%CI:1.25-16.4, p=0.02), while there was no association between recanalization status and outcome in univariable analysis. Patients with low pcASPECTS generally showed very poor outcomes (mean mRS 5.3, 95%CI:4.9-5.8). Conclusion PCCS modified the effect of recanalization on functional outcome, particularly in patients with less pronounced ischemic changes in admission-CT. These results should be validated to improve patient selection for EVT in BAO, particularly in uncertain indications, or to triage patients at risk for very poor outcomes.

Most individuals with rare diseases initially consult their primary care physician. For a subset of rare diseases, efficient diagnostic pathways are available. However, ultra-rare diseases often require both expert clinical knowledge and comprehensive genetic diagnostics, which poses structural challenges for public healthcare systems. To address these challenges within Germany, a novel structured diagnostic concept, based on multidisciplinary expertise at established university hospital centers for rare diseases (CRDs), was evaluated in the three year prospective study TRANSLATE NAMSE. A key goal of TRANSLATE NAMSE was to assess the clinical value of exome sequencing (ES) in the ultra-rare disease population. The aims of the present study were to perform a systematic investigation of the phenotypic and molecular genetic data of TRANSLATE NAMSE patients who had undergone ES in order to determine the yield of both ultra-rare diagnoses and novel gene-disease associations; and determine whether the complementary use of machine learning and artificial intelligence (AI) tools improved diagnostic effectiveness and efficiency. ES was performed for 1,577 patients (268 adult and 1,309 pediatric). Molecular genetic diagnoses were established in 499 patients (74 adult and 425 pediatric). A total of 370 distinct molecular genetic causes were established. The majority of these concerned known disorders, most of which were ultra-rare. During the diagnostic process, 34 novel and 23 candidate genotype-phenotype associations were delineated, mainly in individuals with neurodevelopmental disorders. To determine the likelihood that ES will lead to a molecular diagnosis in a given patient, based on the respective clinical features only, we developed a statistical framework called YieldPred. The genetic data of a subcohort of 224 individuals that also gave consent to the computer-assisted analysis of their facial images were processed with the AI tool Prioritization of Exome Data by Image Analysis (PEDIA) and showed superior performance in variant prioritization. The present analyses demonstrated that the novel structured diagnostic concept facilitated the identification of ultra-rare genetic disorders and novel gene-disease associations on a national level and that the machine learning and AI tools improved diagnostic effectiveness and efficiency for ultra-rare genetic disorders.

Purpose Evidence regarding the effect of mechanical thrombectomy (MT) of basilar artery occlusion (BAO) stroke is yet sparse. As successful recanalization has been suggested as major determinant of outcome, the early identification of modifiable factors associated with successful recanalization could be of importance to improve functional outcome. Hyperglycemia has been associated with enhanced thrombin generation and unfavorably altered clot features. Objective We hypothesized that serum baseline glucose is associated with likelihood of vessel recanalization mediated by collateral quality and clot burden in BAO stroke. Methods BAO stroke patients who received multimodal CT on admission were analyzed. The association of vessel recanalization defined using modified Thrombolysis in cerebral infarction scale (mTICI) scores 2b-3, and baseline imaging and clinical parameters were tested in logistic regression analyses. Collateral quality and clot burden were evaluated using the Basilar Artery on CT-Angiography (BATMAN) score. Results Out of 117 BAO patients, 91 patients (78%) underwent MT. In 70 patients (77%), successful recanalization could be achieved (mTICI 2b/3). In multivariable logistic regression analysis, only a higher BGL (aOR 0.97, 95% CI 0.96–0.99, p = 0.03) and higher BATMAN score (aOR 1.77, 95% CI 1.11–2.82, p = 0.02) were independently associated with vessel recanalization. Application of alteplase, or time from symptom onset-imaging revealed no independent association with recanalization status. Conclusion Higher BGL was significantly associated with reduced likelihood for recanalization success besides BATMAN score as a measure of collateral quality and clot burden. BGL could be tested as a modifiable parameter to increase likelihood for recanalization in BAO stroke, aiming to improve functional outcome.