{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:44:18Z","timestamp":1791924258948,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T00:00:00Z","timestamp":1492646400000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Lithium overdose may result in encephalopathy and electroencephalographic abnormalities. Three poisoning patterns have been identified based on the ingested dose, previous treatment duration and renal function. Whether the severity of lithium\u2010induced encephalopathy depends on the poisoning pattern has not been established. We designed a rat study to investigate lithium\u2010induced encephalopathy and correlate its severity to plasma, erythrocyte, cerebrospinal fluid and brain lithium concentrations previously determined in rat models mimicking human poisoning patterns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lithium\u2010induced encephalopathy was assessed and scored using continuous electroencephalography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated that lithium overdose was consistently responsible for encephalopathy, the severity of which depended on the poisoning pattern. Acutely poisoned rats developed rapid\u2010onset encephalopathy which reached a maximal grade of 2\/5 at 6\u00a0h and disappeared at 24\u00a0h post\u2010injection. Acute\u2010on\u2010chronically poisoned rats developed persistent and slightly fluctuating encephalopathy which reached a maximal grade of 3\/5. Chronically poisoned rats developed rapid\u2010onset but gradually increasing life\u2010threatening encephalopathy which reached a maximal grade of 4\/5. None of the acutely, 20% of the acute\u2010on\u2010chronically and 57% of the chronically lithium\u2010poisoned rats developed seizures. The relationships between encephalopathy severity and lithium concentrations fitted a sigmoidal<jats:italic>E<\/jats:italic><jats:sub>max<\/jats:sub>model based on cerebrospinal fluid concentrations in acute poisoning and brain concentrations in acute\u2010on\u2010chronic poisoning. In chronic poisoning, worsening of encephalopathy paralleled the increase in plasma lithium concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The severity of lithium\u2010induced encephalopathy is dependent on the poisoning pattern, which was previously shown to determine lithium accumulation in the brain. Our data support the proposition that electroencephalography is a sensitive tool for scoring lithium\u2010related neurotoxicity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12482","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T11:59:07Z","timestamp":1492689547000},"page":"135-145","source":"Crossref","is-referenced-by-count":14,"title":["Electroencephalographic patterns of lithium poisoning: a study of the effect\/concentration relationships in the rat"],"prefix":"10.1111","volume":"19","author":[{"given":"Anne\u2010Sophie","family":"Hanak","sequence":"first","affiliation":[{"name":"Inserm UMR\u2010S1144 Paris France"},{"name":"Universit\u00e9 Paris\u2010Descartes Paris France"},{"name":"Universit\u00e9 Paris\u2010Diderot Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Malissin","sequence":"additional","affiliation":[{"name":"Assistance Publique \u2013 H\u00f4pitaux de Paris H\u00f4pital 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