Question: Is early neurological deterioration of ischemic origin (END i ) predictable in minor strokes with large vessel occlusion (LVO) treated with intravenous thrombolysis (IVT)?Findings: In a multicentric retrospective cohort of minor stroke patients (NIHSS≤5) with LVO intended for IVT alone (n=729), an easily applicable score based on occlusion site and thrombus length -two independent predictors of END i -showed good discriminative power for END i risk prediction, and was successfully validated in an independent cohort (n=347).Meaning: END i can be reliably predicted in IVT-treated minor strokes with LVO, which may help to select the best candidates for direct transfer for additional thrombectomy.

Background and purposeBetter understanding the incidence, predictors and mechanisms of early neurological deterioration (END) following intravenous thrombolysis (IVT) for acute stroke with mild symptoms and isolated internal carotid artery occlusion (iICAo) may inform therapeutic decisions.MethodsFrom a multicenter retrospective database, we extracted all patients with both National Institutes of Health Stroke Scale (NIHSS) score <6 and iICAo (i.e. not involving the Willis circle) on admission imaging, intended for IVT alone. END was defined as ≥4 NIHSS points increase within 24 h. END and no‐END patients were compared for (i) pre‐treatment clinical and imaging variables and (ii) occurrence of intracranial occlusion, carotid recanalization and parenchymal hemorrhage on follow‐up imaging.ResultsSeventy‐four patients were included, amongst whom 22 (30%) patients experienced END. Amongst pre‐treatment variables, suprabulbar carotid occlusion was the only admission predictor of END following stepwise variable selection (odds ratio = 4.0, 95% confidence interval: 1.3–12.2; P = 0.015). On follow‐up imaging, there was no instance of parenchymal hemorrhage, but an intracranial occlusion was now present in 76% vs. 0% of END and no‐END patients, respectively (P < 0.001), and there was a trend toward higher carotid recanalization rate in END patients (29% vs. 9%, P = 0.07). As compared to no‐END, END was strongly associated with a poor 3‐month outcome.ConclusionsEarly neurological deterioration is a frequent and highly deleterious event after IVT for minor stroke with iICAo, and is of thromboembolic origin in three out of four patients. The strong association with iICAo site—largely a function of underlying stroke etiology—may point to a different response of the thrombus to IVT. These findings suggest END may be preventable in this setting.

Among paraneoplastic syndromes (PNS) associated with malignant hemopathies, there are few reports of PNS of the central nervous system and most of them are associated with lymphomas. Limbic encephalitis is a rare neurological syndrome classically diagnosed in the context of PNS. We report the case of a 81-year-old man who presented with a relapsed acute myeloid leukemia (AML) with minimal maturation. He was admitted for confusion with unfavorable evolution as he presented a rapidly progressive dementia resulting in death. A brain magnetic resonance imaging, performed 2 months after the onset, was considered normal. An electroencephalogram showed non-specific bilateral slow waves. We received the results of the blood screening of neuronal autoantibodies after the patient's death and detected the presence of anti-voltage-gated potassium channel (VGKC) antibodies at 102 pmol/l (normal at <30 pmol/l). Other etiologic studies, including the screening for another cause of rapidly progressive dementia, were negative. To our knowledge, this is the first case of anti-VGKC paraneoplastic limbic encephalitis related to AML.

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The modeling and simulation of a realistic nervous tissue are difficult because of the number of implied cell types (neuronal and glial), the topology of the networks, and the various heterogeneous molecular mechanisms. The MTIP (Mathematical Theory of Integrative Physiology) is used as a new modeling approach based on a representation in terms of functional interactions and a formalism (S-Propagator) related to n-level field theory. This work presents the passage from a theoretical description of the biological system to a computing implementation in the general case. The specific case of the hippocampus is presented, as well as how a drug allows learning and memory improvement in the local circuit of the CA1 area of the hippocampus. This in silico result is used to experimentally predict the drug effect in vitro to confirm the accuracy of MTIP.