Abstract | OBJECTIVES: METHODS: RESULTS: We demonstrated that lithium overdose was consistently responsible for encephalopathy, the severity of which depended on the poisoning pattern. Acutely poisoned rats developed rapid-onset encephalopathy which reached a maximal grade of 2/5 at 6 h and disappeared at 24 h post-injection. Acute-on-chronically poisoned rats developed persistent and slightly fluctuating encephalopathy which reached a maximal grade of 3/5. Chronically poisoned rats developed rapid-onset but gradually increasing life-threatening encephalopathy which reached a maximal grade of 4/5. None of the acutely, 20% of the acute-on-chronically and 57% of the chronically lithium-poisoned rats developed seizures. The relationships between encephalopathy severity and lithium concentrations fitted a sigmoidal Emax model based on cerebrospinal fluid concentrations in acute poisoning and brain concentrations in acute-on-chronic poisoning. In chronic poisoning, worsening of encephalopathy paralleled the increase in plasma lithium concentrations. CONCLUSIONS: The severity of lithium-induced 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-related neurotoxicity.
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Authors | Anne-Sophie Hanak, Isabelle Malissin, Joël Poupon, Patricia Risède, Lucie Chevillard, Bruno Mégarbane |
Journal | Bipolar disorders
(Bipolar Disord)
Vol. 19
Issue 2
Pg. 135-145
(03 2017)
ISSN: 1399-5618 [Electronic] Denmark |
PMID | 28425670
(Publication Type: Journal Article)
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Copyright | © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. |
Chemical References |
- Antimanic Agents
- Lithium Compounds
- Lithium
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Topics |
- Animals
- Antimanic Agents
(pharmacology, toxicity)
- Bipolar Disorder
(drug therapy)
- Brain
(drug effects)
- Dose-Response Relationship, Drug
- Electroencephalography
(methods)
- Lithium
(blood, pharmacokinetics)
- Lithium Compounds
(pharmacology, toxicity)
- Neurotoxicity Syndromes
(diagnosis, etiology)
- Rats
- Tissue Distribution
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