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A reappraisal of the role of fever in the occurrence of neurological sequelae following lithium intoxication: a systematic review
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  • Hélène Verdoux,
  • Anne-Laure Debruyne,
  • Emmanuelle Queuille,
  • J de Leon
Hélène Verdoux
Université de Bordeaux

Corresponding Author:hverdoux@ch-perrens.fr

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Anne-Laure Debruyne
Centre Hospitalier Charles Perrens
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Emmanuelle Queuille
Centre Hospitalier Charles Perrens
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J de Leon
University of Kentucky
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Aim We aimed to review cases of Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) characterized by neurological sequelae following acute lithium toxicity and to explore whether cerebellar sequelae are more frequent in cases presenting with fever and/or infection. Methods Case reports were identified from: (i) 6 reviews published up to 2005; (ii) MEDLINE, Web of Sciences, Cochrane Library and PsycINFO search. Results We identified 123 SILENT cases published from 1965 to 2019, in which cerebellar sequelae were observed in an overwhelming proportion (79%). Nearly two out of three cases (63%) had maximal lithium plasma level <2.5 mEq/l (low/mild toxicity). Fever and/or infection were reported in nearly half of the patients (48%). The likelihood of presenting with cerebellar vs. other neurological sequelae was independently increased by elevated plasma lithium level ( 2.5 mEq/l) (OR=4.36, 95%CI 1.31-14.52, p = 0.02) and by a history of fever and/or infection (OR=6.48, 95%CI 2.0-21.0, p = 0.002). Conclusions During the SARS-CoV-2 pandemic, prescribers have to be aware of the risks of cerebral sequelae associated with infection and fever in lithium users, and should warn them of the need to consult in case of fever to adjust their lithium dosage. As the occurrence of SILENT is exceptional, there is no need to modify lithium treatment preventively because of the pandemic as the benefit/risk balance of this drug remains largely positive.
03 Jul 2021Published in Expert Opinion on Drug Safety volume 20 issue 7 on pages 827-838. 10.1080/14740338.2021.1912011