Neurotoxicity of subarachnoid Gd-based contrast agent accumulation: a potential complication of intraoperative MRI?

Abstract

OBJECTIVEIntraoperative MRI with Gd-based contrast agent (GBCA) improves the extent of resection of contrast-enhancing brain tumors. Signal changes of CSF due to perioperative GBCA leakage in the subarachnoid space have been reported. However, although GBCA potentially exhibits neurotoxic effects, so far no associated complications have been described. In this case series, the authors report a single-center cohort of patients with subarachnoid GBCA extravasation after intraoperative MRI and discuss potential neurotoxic complications and potential ways of avoiding them.METHODSAll patients with CSF signal increase on unenhanced T1-weighted and FLAIR images on postoperative MRI, who had previously undergone tumor resection with use of intraoperative MRI, were retrospectively included and compared with a control cohort. The control group was matched in age, tumor characteristics, and extent of resection; comparisons were made regarding postoperative seizures and ICU stay. A subgroup with initially diagnosed malignant glioma was additionally analyzed for potential delay of initiation of adjuvant treatment and overall survival.RESULTSSeven patients with postoperative GBCA accumulation in the subarachnoid space were identified; 5 presented with focal seizures and altered mental status postoperatively. Poor patient condition led to extended ICU stay and prolonged delay of the initiation of adjuvant treatment in patients with newly diagnosed malignant glioma. Overall survival was reduced compared to the matched control group.CONCLUSIONSThe results suggest that there might be a risk of neurotoxic complications if GBCA that is intravenously applied during neurosurgery leaks into the subarachnoid space. Patients with highly vascularized tumors with intraoperative bleeding seem to be especially at risk for GBCA accumulation and neurotoxic complications. Therefore, awareness of the potential risk of complicating GBCA leakage is mandatory in the application of intraoperative GBCA.

Biocompatible and bioactivable terpolymer-lipid-MnO2 Nanoparticle-based MRI contrast agent for improving tumor detection and delineation

“…Conventional GBCAs have been reported for their Gd-related accumulations and toxicities that have raised concerns and restricted their uses in compromised patients [ 16 , 19 , 20 , 23 , 75 , 76 ]. To understand the clearance profile of TPL-MDNPs, pharmacokinetic (PK) analysis of TPL-MDNPs was performed by measuring Mn concentration in blood plasma using inductively coupled plasma-optical emission spectrometry (ICP-OES) up to 24 h after a single injection of TPL-MDNPs (35.0 μmol Mn/kg) in healthy Sprague Dawley rats.…”

“…The Gd 3+ ion has unique paramagnetic properties which allow GBCAs to exhibit strong T1-weighted signal enhancement [ [16] , [17] , [18] ]. However, in recent years studies have revealed the release of free unchelated Gd 3+ ions from GBCAs, increasing Gd-toxicity and leading to undesirable depositions in sites such as the brain and bone [ 19 , 20 ]. Moreover, lanthanides such as Gd are primarily excreted from the body through glomerular filtration, which at times may lead to precipitation in tissues and major organs [ [20] , [21] , [22] , [23] ].…”

Experience of using intraoperative magnetic resonance imaging in the surgical treatment of brain gliomas

“…У небольшого числа пациентов, у которых на иМРТ выявлено субарахноидальное скопление контраста или скопление контраста в резекционной полости, наблюдалась повышенная частота фокальных судорог и эпилептического статуса. У всех больных из этой группы хирурги отмечали повышенное кровоснабжение опухоли и проблемы в достижении гемостаза [24].…”

Ultrasmall iron oxide nanoparticles with MRgFUS for enhanced magnetic resonance imaging of orthotopic glioblastoma

“…16,17 Gd-based agents are the most prevalent commercial T 1 contrast agents in clinical studies. 18 However, more recently, the US Food and Drug Administration (FDA) has associated their application with several side effects, including nephrogenic systemic fibrosis (NSF), 19 free Gd 3+ accumulation in the human brain (gadolinium encephalopathy), 20 and limited blood circulation time. 21 On the other hand, Mn-based contrast agents have intrinsic disadvantages, such as neurodegenerative diseases caused by the toxicity of free Mn 2+ ions.…”