Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat

Abstract

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.

Does lithium poisoning induce brain injuries?—A histopathological rat study

“…We may also have used insufficient doses or duration of exposure in our prolonged lithium treatment regimens to induce lithium‐related brain injuries. However, our findings were consistent with our previous observations of reversible hypolocomotion and electroencephalography‐based encephalopathy in the three lithium‐poisoning patterns 9,10 . Additionally, neuroprotective rather than neurotoxic effects have been reported extensively in animals receiving lithium at pharmacological doses, 16 thus supporting our findings.…”

“…Lithium dose regimens used in this study were similar to those used in our previous works, which characterized lithium kinetics in the plasma, erythrocytes, cerebrospinal fluid and brain and described the time course and extent of reversible lithium‐induced neurotoxicity (i.e., electroencephalography‐graded encephalopathy and impairment of locomotion activity and anxiety‐like behaviour) 7,9,10 . All our previous findings showed that the dose regimens used in the rat adequately mimicked the three patterns of lithium poisonings observed in humans 2 .…”

“…Whether determination of the medical history and the readily available plasma lithium concentration are useful to identify the poisoning pattern in humans, 2 we showed that brain lithium accumulation, as both level and duration of brain exposure, is the most relevant parameter to explain the resulting neurotoxicity observed in the rat. 7,9,10 However, these parameters are not routinely accessible in humans, although 7 Li-magnetic resonance imaging appears to represent a useful emerging mean to study the relationships between brain lithium distribution and its therapeutic response in chronically lithium-treated bipolar disorder patients. 11 In clinical practice, lithium is usually administered lifelong to bipolar disorder patients.…”

Assessment of Extracorporeal Treatments in Poisoning criteria for the decision of extracorporeal toxin removal in lithium poisoning

“…The exact mechanisms involved in lithium‐induced neurotoxicity remain unknown. Recent rat studies mimicking acute and acute‐on‐chronic lithium poisoning have shown that lithium‐induced neurotoxicity was associated with lithium accumulation in the brain followed by slower and delayed elimination in comparison to the blood . If pharmacokinetic studies have demonstrated the effectiveness of ECTR in removing lithium from the blood, there is no evidence that ECTR could enhance lithium elimination from the brain .…”

“…Recent rat studies mimicking acute and acute-on-chronic lithium poisoning have shown that lithium-induced neurotoxicity was associated with lithium accumulation in the brain followed by slower and delayed elimination in comparison to the blood. [14][15][16] If pharmacokinetic studies have demonstrated the effectiveness of ECTR in removing lithium from the blood, 17,18 there is no evidence that ECTR could enhance lithium elimination from the brain. 1,3 In accordance, no difference in outcome was reported between lithium-poisoned patients for whom haemodialysis was carried out and those for whom it was recommended by the poison control centre but not done, suggesting that indications for haemodialysis in lithium poisoning should be reconsidered to include only the more severe cases.…”