Non-Ischemic Cerebral Enhancing (NICE) lesions after flow diversion for intracranial aneurysms: a systematic review with case-level synthesis

Abstract

Non-ischemic cerebral enhancing (NICE) lesions are rare delayed inflammatory brain lesions reported after flow-diverter (FD) treatment of intracranial aneurysms. We systematically reviewed their reported incidence, clinical and imaging characteristics, diagnostic findings, management, and outcomes. We performed a PROSPERO-registered systematic review. MEDLINE, Embase, Scopus, and Cochrane CENTRAL were searched for reports of delayed NICE lesions after FD treatment of intracranial aneurysms that were not better explained by infarction or alternative causes. Two reviewers independently screened studies and extracted data. Findings were synthesized narratively because heterogeneity precluded meta-analysis. Twenty-two studies met inclusion criteria; seven reported incidence data. One multicenter survey provided the only FD-specific denominator (12 NICE cases among 1201 FD-treated aneurysms; 1.0%), but the true incidence remains uncertain. Other estimates, using all aneurysm endovascular procedures as denominators, ranged from 0.05% to 1.3%. Overall, 40 unique FD-associated NICE patients were identified. Among cases with available individual data, median age was 54 years; all patients with reported sex were women, and all aneurysms with reported location involved the anterior circulation. NICE lesions appeared after a median of 73 days, most often with headache, focal deficits, or seizures, and as multifocal, predominantly ipsilateral enhancing lesions with edema on MRI. Brain biopsy was performed in six patients and identified hydrophilic polymer or other foreign material in four; in one additional case, device-coating detachment was observed directly. Both coated and uncoated FDs were represented, although the source component was usually undetermined. Systemic corticosteroids were administered in 22/24 cases with treatment data. Radiologic improvement or resolution occurred in 12/25, recurrent or fluctuating activity in 11/25, and 19/23 patients with reported functional outcomes were asymptomatic or independent at last follow-up. Reported NICE lesions after flow diversion appear uncommon, but the true incidence remains uncertain. The available evidence supports a foreign-body inflammatory mechanism potentially related to hydrophilic coatings or other materials within the endovascular construct, without establishing a single culprit device. Corticosteroid-associated improvement is common, but relapsing or fluctuating courses require prolonged clinical and imaging follow-up. PROSPERO CRD420251186127.