Longitudinal neuropsychological assessment after aneurysmal subarachnoid hemorrhage and its relationship with delayed cerebral ischemia: a prospective Swiss multicenter study

Martin N. StienenDepartment of Neurosurgery, University Hospital Zurich;
Clinical Neuroscience Center, University of Zurich;
Neuropsychology Unit, Department of Neurology, University Hospital Berne;

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Menno R. GermansDepartment of Neurosurgery, University Hospital Zurich;
Clinical Neuroscience Center, University of Zurich;

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Olivia Zindel-GeisselerNeuropsychology Unit, Department of Neurology, University Hospital Zurich;

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Noemi DanneckerNeuropsychology Unit, Department of Neurology, University Hospital Zurich;

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Yannick RothacherNeuropsychology Unit, Department of Neurology, University Hospital Zurich;

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Ladina SchlosserNeuropsychology Unit, Department of Neurology, University Hospital Zurich;

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Julia VelzDepartment of Neurosurgery, University Hospital Zurich;
Clinical Neuroscience Center, University of Zurich;

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Martina SebökDepartment of Neurosurgery, University Hospital Zurich;
Clinical Neuroscience Center, University of Zurich;

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Noemi EggenbergerNeuropsychology Unit, Department of Neurology, University Hospital Zurich;

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Adrien MayDepartment of Neurosurgery, University Hospital Geneva;

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Julien HaemmerliDepartment of Neurosurgery, University Hospital Geneva;

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Philippe BijlengaDepartment of Neurosurgery, University Hospital Geneva;

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Karl SchallerDepartment of Neurosurgery, University Hospital Geneva;

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Ursula Guerra-LopezNeuropsychology Unit, Department of Neurology, University Hospital Geneva;

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Rodolfo MaduriAvaton Surgical Group, Clinique de Genolier, Swiss Medical Network, Genolier;

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Valérie BeaudNeuropsychology Unit, Department of Neurology, University Hospital Lausanne;

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Khalid Al-TahaDepartment of Clinical Neurosciences, Service of Neurosurgery, Lausanne University Hospital (CHUV), Lausanne;

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Roy Thomas DanielDepartment of Clinical Neurosciences, Service of Neurosurgery, Lausanne University Hospital (CHUV), Lausanne;

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Alessio ChiappiniDepartment of Neurosurgery, Cantonal Hospital Lugano;

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Stefania RossiNeuropsychology Unit, Department of Neurology, Cantonal Hospital Lugano;

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Thomas RobertDepartment of Neurosurgery, Cantonal Hospital Lugano;

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Sara BonasiaDepartment of Neurosurgery, Cantonal Hospital Lugano;

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Johannes GoldbergDepartment of Neurosurgery, University Hospital Berne, Switzerland;

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Christian FungDepartment of Neurosurgery, University Hospital Berne, Switzerland;
Department of Neurosurgery, University Hospital Freiburg, Germany;

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David BerviniDepartment of Neurosurgery, University Hospital Berne, Switzerland;

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Marie Elise Maradan-GachetNeuropsychology Unit, Department of Neurology, University Hospital Berne;

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Klemens GutbrodNeuropsychology Unit, Department of Neurology, University Hospital Berne;

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Nicolai MaldanerDepartment of Neurosurgery, Cantonal Hospital St. Gallen;

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Marian C. NeidertDepartment of Neurosurgery, Cantonal Hospital St. Gallen;

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Severin FrühNeuropsychology Unit, Department of Neurology, Cantonal Hospital St. Gallen;

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Marc SchwindNeuropsychology Unit, Department of Neurology, Cantonal Hospital St. Gallen;

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Oliver BozinovDepartment of Neurosurgery, University Hospital Zurich;
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Peter BruggerNeuropsychology Unit, Department of Neurology, University Hospital Zurich;
Neuropsychology Unit, Rehabilitation Clinic Valens; and

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Emanuela KellerDepartment of Neurosurgery, University Hospital Zurich;
Clinical Neuroscience Center, University of Zurich;

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Angelina MarrGlobal Clinical Development, Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland

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Sébastien RouxGlobal Clinical Development, Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland

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Luca RegliDepartment of Neurosurgery, University Hospital Zurich;
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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)

ABBREVIATIONS

aOR = adjusted OR; aSAH = aneurysmal SAH; BNI = Barrow Neurological Institute; DCI = delayed cerebral ischemia; GCS = Glasgow Coma Scale; MoCA = Montreal Cognitive Assessment; mRS = modified Rankin Scale; SAH = subarachnoid hemorrhage; WFNS = World Federation of Neurosurgical Societies.

Supplementary Materials

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Figure from Kim et al. (pp 1601–1609).

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