MRI features suggestive of gadolinium retention do not correlate with Expanded Disability Status Scale worsening in Multiple Sclerosis

Cocozza, Sirio; Pontillo, Giuseppe; Lanzillo, Roberta; Russo, Camilla; Petracca, Maria; Stasi, Martina Di; Paolella, Chiara; Vola, Elena Augusta; Criscuolo, Chiara; Moccia, Marcello; Lamberti, A.; Monti, Serena; Morra, Vincenzo Brescia; Elefante, Andrea; Palma, Giuseppe; Tedeschi, Enrico; Brunetti, Arturo

doi:10.1007/s00234-018-02150-4

Cited by 41 publications

(38 citation statements)

References 42 publications

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“…No clinical signs, symptoms, or adverse clinical outcomes have yet been associated with retained Gd in the brain following the repeated administration of any GBCA [36,37]. Nevertheless, because macrocyclic GBCAs as a class have been associated with lower levels of Gd retention in animal studies [9][10][11]13], and with only minor/negligible increases in T1-signal in the dentate nucleus or globus pallidus on unenhanced T1weighted brain images [38][39][40] when compared with certain linear GBCAs, the perception is that macrocyclic GBCAs are in some way "safer."…”

Section: Discussionmentioning

confidence: 99%

Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats

et al. 2020

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Objectives: The purpose of this study was to compare Gd levels in rat tissues after cumulative exposure to four commercially available macrocyclic gadolinium-based contrast agents (GBCAs). Methods: Sixty-five male Sprague-Dawley rats were randomized to four exposure groups (n = 15 per group) and one control group (n = 5). Animals in each exposure group received 20 GBCA administrations (four per week of ProHance®, Dotarem®, Clariscan™, or Gadovist® for 5 consecutive weeks) at a dose of 0.6 mmol/kg bodyweight. After 28-days' recovery, animals were sacrificed and tissues harvested for Gd determination by inductively coupled plasma-mass spectroscopy (ICP-MS). Histologic assessment of the kidney tissue was performed for all animals.

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Section: Discussionmentioning

confidence: 99%

Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats

et al. 2020

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“…Concerns over NSF and, more recently, Gd retention have led to a widespread migration from linear GBCAs to macrocyclic GBCAs for routine clinical use. Although studies to date suggest that GBCA exposure has no long‐term detrimental effects on human health either in terms of direct impact on tissue integrity, or global clinical disability, the possibility of long‐term effects is nevertheless a major area of current concern . Although assessment of potential long‐term safety issues was beyond the scope of this observational study, it is worth noting that all studies thus far performed in animals to evaluate Gd retention in brain and body tissues following GBCA exposure have shown that gadoteridol is retained to a lesser extent and cleared more rapidly than other GBCAs, including other macrocyclic GBCAs .…”

Section: Discussionmentioning

confidence: 99%

Prospective Multicenter Study of the Safety of Gadoteridol in 6163 Patients

Cho

Lee

Chang

et al. 2019

Magnetic Resonance Imaging

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Background: The safety of gadolinium-based contrast agents is of fundamental importance. Purpose: To determine the frequency and severity of immediate-type adverse reactions to approved doses of gadoteridol in patients referred for routine gadoteridol-enhanced MRI in actual clinical practice settings. Study Type: Prospective, observational. Population: In all, 6163 subjects were enrolled (mean age: 56.7 AE 15.4 years; range: 6-93 years). Field Strength/Sequence: 1.5T and 3.0T. Assessment: Assessment was of immediate adverse reactions by the investigating radiologist using the MedDRA System Organ Class and preferred term. Statistical Tests: Summary statistics for continuous variables, descriptive statistics for demographic characteristics. Results: Overall, 19 adverse events occurred in 13 (0.21%) patients, of which 15 in 10 (0.16%) patients were considered related to gadoteridol administration. These events were evenly distributed between male and female subjects and all occurred in adults. Twelve of the 15 related events in eight (0.13%) patients were considered mild in intensity (rapidly selfresolving), while the remaining three events in two patients (0.03%) were considered moderate in intensity. None were of severe intensity and no serious adverse events occurred. Data Conclusion: The rate of immediate-type adverse events following exposure to approved doses of gadoteridol is extremely low, and mostly limited to transient and self-resolving symptoms. Level of Evidence: 2 Technical Efficacy Stage: 5This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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“…Although some studies [48, 49] have looked to correlate T1-hyperintensity of the DN in patients with MS with loss of verbal fluency and cognition, it is difficult to separate a hypothetic effect of Gd retention from the normal effects of MS progression, especially given the difficulties in finding a matched MS group not exposed to any GBCA. Recent studies by Cocozza et al [9] and Ackermans et al [10] suggest that MRI features suggestive of Gd retention do not correlate with EDSS worsening in patients with MS. These findings are supported by studies that have shown no effects of DN T1-hyperintensity on DN tissue integrity [11, 50, 51].…”

Section: Discussionmentioning

confidence: 99%

Visible T1-hyperintensity of the dentate nucleus after multiple administrations of macrocyclic gadolinium-based contrast agents: yes or no?

et al. 2019

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Objectives To investigate the appearance of visible dentate nucleus (DN) T1-hyperintensity and quantify changes in DN/pons (DN/P) signal intensity (SI) ratio in MS patients after the exclusive administration of macrocyclic GBCAs. Materials and methods One hundred forty-nine patients with confirmed MS were evaluated. Patients received at least two administrations of gadobutrol ( n = 63), gadoterate ( n = 57), or both ( n = 29). Two experienced neuroradiologists in consensus evaluated unenhanced T1-weighted MR images from all examinations in each patient for evidence of visible DN hyperintensity. Thereafter, SI measurements were made in the left and right DN and pons on unenhanced T1-weighted images from the first and last scans. A two-sample t test compared the DN/P SI ratios for patients with and without visible T1-hyperintensity. Results Visible T1-hyperintensity was observed in 42/149 (28.2%) patients (19 after gadobutrol only, 15 after gadoterate only, 8 after both), typically at the 4th or 5th follow-up exam at 3–4 years after the initial examination. Significant increases in DN/P SI ratio from first to last examination were determined for patients with visible T1-hyperintensity (0.998 ± 0.002 to 1.153 ± 0.016, p < 0.0001 for gadobutrol; 1.003 ± 0.004 to 1.110 ± 0.014, p < 0.0001 for gadoterate; 1.004 ± 0.011 to 1.163 ± 0.032, p = 0.0004 for both) but not for patients without visible T1-hyperintensity ( p > 0.05; all groups). Conclusion Multiple injections of gadobutrol and/or gadoterate can lead to visible and quantifiable increases in DN/P SI ratio in some patients with MS.

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MRI features suggestive of gadolinium retention do not correlate with Expanded Disability Status Scale worsening in Multiple Sclerosis

Cited by 41 publications

References 42 publications

Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats

Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats

Prospective Multicenter Study of the Safety of Gadoteridol in 6163 Patients

Visible T1-hyperintensity of the dentate nucleus after multiple administrations of macrocyclic gadolinium-based contrast agents: yes or no?

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