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This randomized clinical trial evaluates the safety and efficacy of the monoclonal anti-tau antibody semorinemab in individuals with prodromal to mild Alzheimer disease.

Background: Seizures related to ischemic strokes are harmful. Their pathogenesis is not very well understood. The present study investigates whether diffusion-weighted imaging (DWI) can detect if those seizures are due to recurrent infarction or responsible for secondary ischemic changes. Patients and Methods: DWI was obtained within 8 days in 60 patients with seizures (7 early and 53 late onset) related to an ischemic stroke. Results: In 30 patients, positive DWI with decreased apparent diffusion coefficient was found. In 11 patients with late-onset seizures, the DWI showed a positive rim, surrounding the old infarct, while in 12 patients a large positive zone corresponding to a new infarct was observed. All 7 patients with early-onset seizures had positive DWI corresponding to the establishing infarct. A large positive zone on DWI was mainly observed in cardioembolic stroke. Conclusions: The positive rim around the old infarct can be considered as cytotoxic edema. Recurrent acute infarction, mainly of cardioembolic origin, seems to be a significant cause of so-called late-onset seizures, making the subdivision into early- and late-onset seizures arbitrary.

Background and purpose Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (FLAIR-rSI) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial, intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of DWI-FLAIR mismatch, i.e., in those with no marked FLAIR hyperintensity in the region of the acute DWI lesion. In this post-hoc analysis, we investigated if quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analysed by binary logistic regression using different endpoints, i.e., favourable outcome defined as mRS 0-1, independent outcome defined as mRS 0-2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for NIHSS at symptom onset and stroke lesion volume. Results FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS 0-1 (p=0.169) and shift analysis (p=0.086), but 2 reached significance for mRS 0-2 (p=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical endpoints with increasing FLAIR-rSI. Conclusion In patients in whom no marked parenchymal FLAIR hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of DWI lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.

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