Abstract Background and aims In the ZODIAC trial, 0° head positioning before thrombectomy in LVO stroke reduced early neurological deterioration (END) and 90-day mortality. We evaluated whether END, 24-h neurological improvement, or successful reperfusion mediated the effects of head-of-bed (HoB) on disability and mortality. Methods Multiple-mediator models were constructed using HoB assignment (0° vs 30°) as the exposure. Mediators included END, 24-hour NIHSS improvement, and TICI 2b–3 reperfusion. Outcomes were discharge mRS, 90-day mRS, in-hospital death, and 90-day mortality. Models were adjusted for age and sex. Mediation effects were expressed as odds ratios (OR) with 95% confidence intervals (CI). Results Early neurological improvement at 24 hours showed evidence of mediation for discharge mRS (OR 1.26, 95% CI 0.96–2.11) and 90-day mRS (OR 1.34, 95% CI 0.99–2.41), although the confidence intervals crossed unity. No evidence of an indirect pathway through reperfusion success was observed. END significantly mediated in-hospital death (OR 2.31, 95% CI 1.03–7.06), consistent with the observation that reduced END in the 0° group was associated with lower early mortality. None of the mediators explained the 90-day mortality difference observed in the ZODIAC trial. Conclusions Early neurological improvement appeared to mediate the effect of HoB on functional outcomes after thrombectomy. END mediated a small portion of early mortality but not disability, suggesting that 0° positioning may protect patients by preventing early neurological worsening, while its long-term mortality benefit likely reflects a direct physiological effect not captured by the measured mediators. Conflict of interest All authors: nothing to disclose
Torrealba-Acosta et al. (2026) studied this question.