Longitudinal neuropsychological assessment after aneurysmal subarachnoid hemorrhage and its relationship with delayed cerebral ischemia: a prospective Swiss multicenter study
Authors: Stienen Martin N. , Germans Menno R. , Zindel-Geisseler Olivia , Dannecker Noemi , Rothacher Yannick , Schlosser Ladina , Velz Julia , Sebök Martina , Eggenberger Noemi , May Adrien , Haemmerli Julien , Bijlenga Philippe , Schaller Karl , Guerra-Lopez Ursula , Maduri Rodolfo , Beaud Valérie , Al-Taha Khalid , Daniel Roy Thomas , Chiappini Alessio , Rossi Stefania , Robert Thomas , Bonasia Sara , Goldberg Johannes , Fung Christian , Bervini David , Maradan-Gachet Marie Elise , Gutbrod Klemens , Maldaner Nicolai , Neidert Marian C. , Früh Severin , Schwind Marc , Bozinov Oliver , Brugger Peter , Keller Emanuela , Marr Angelina , Roux Sébastien , Regli Luca , _ _ , _ _ , Krayenbühl Niklaus , Esposito Giuseppe , Moiraghi Alessandro , Starnoni Daniele , Rocca Alda , Seule Martin A. , Zeitlberger Anna-Maria , Weyerbrock Astrid , Hlavica Martin , Müller Mandy 
Published: May 2022

OBJECTIVE
While prior retrospective studies have suggested that delayed cerebral ischemia (DCI) is a predictor of neuropsychological deficits after aneurysmal subarachnoid hemorrhage (aSAH), all studies to date have shown a high risk of bias. This study was designed to determine the impact of DCI on the longitudinal neuropsychological outcome after aSAH, and importantly, it includes a baseline examination after aSAH but before DCI onset to reduce the risk of bias.

METHODS
In a prospective, multicenter study (8 Swiss centers), 112 consecutive alert patients underwent serial neuropsychological assessments (Montreal Cognitive Assessment [MoCA]) before and after the DCI period (first assessment, < 72 hours after aSAH; second, 14 days after aSAH; third, 3 months after aSAH). The authors compared standardized MoCA scores and determined the likelihood for a clinically meaningful decline of ≥ 2 points from baseline in patients with DCI versus those without.

RESULTS
The authors screened 519 patients, enrolled 128, and obtained complete data in 112 (87.5%; mean [± SD] age 53.9 ± 13.9 years; 66.1% female; 73% World Federation of Neurosurgical Societies [WFNS] grade I, 17% WFNS grade II, 10% WFNS grades III–V), of whom 30 (26.8%) developed DCI. MoCA z-scores were worse in the DCI group at baseline (−2.6 vs −1.4, p = 0.013) and 14 days (−3.4 vs −0.9, p < 0.001), and 3 months (−0.8 vs 0.0, p = 0.037) after aSAH. Patients with DCI were more likely to experience a decline of ≥ 2 points in MoCA score at 14 days after aSAH (adjusted OR [aOR] 3.02, 95% CI 1.07–8.54; p = 0.037), but the likelihood was similar to that in patients without DCI at 3 months after aSAH (aOR 1.58, 95% CI 0.28–8.89; p = 0.606).

CONCLUSIONS
Aneurysmal SAH patients experiencing DCI have worse neuropsychological function before and until 3 months after the DCI period. DCI itself is responsible for a temporary and clinically meaningful decline in neuropsychological function, but its effect on the MoCA score could not be measured at the time of the 3-month follow-up in patients with low-grade aSAH with little or no impairment of consciousness. Whether these findings can be extrapolated to patients with high-grade aSAH remains unclear.
Clinical trial registration no.: NCT03032471 (ClinicalTrials.gov)