Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat
Objectives 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‐induced encephalopathy depends on the poisonin...
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| Veröffentlicht in: | Bipolar disorders 2017-03, Vol.19 (2), p.135-145 |
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| creator | Hanak, Anne‐Sophie Malissin, Isabelle Poupon, Joël Risède, Patricia Chevillard, Lucie Mégarbane, Bruno |
| description | Objectives
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‐induced encephalopathy depends on the poisoning pattern has not been established. We designed a rat study to investigate lithium‐induced encephalopathy and correlate its severity to plasma, erythrocyte, cerebrospinal fluid and brain lithium concentrations previously determined in rat models mimicking human poisoning patterns.
Methods
Lithium‐induced encephalopathy was assessed and scored using continuous electroencephalography.
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. |
| doi_str_mv | 10.1111/bdi.12482 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_03822921v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1920448808</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3872-d033103b2b572423c9de94d162edecb3d72b208e5e4ca7ec6890687069e3caf73</originalsourceid><addsrcrecordid>eNp1kclOwzAQhi0EglI48ALIEicOpV6yONxKKYtUiQucLceZEKM0DrYD6tvjtiwnfPHI8-nTjH-Ezii5ovFMy8pcUZYItodGlBfFJM2o2N_WItZJfoSOvX8jhGaMpIfoiImEpVlORsgvWtDBWeg09I1q7atTfWM07lUI4DqPbY1bExozrHBvjbed6V6vscI-DNV60w0NYKjrqJlqGzVdcCoY22EH7bbwjek9Nt2WjL0TdFCr1sPp9z1GL3eL5_nDZPl0_zifLSeai5xNKsI5JbxkZZqzhHFdVFAkVdwBKtAlr3JWMiIghUSrHHQmCpKJnGQFcK3qnI_R5c4b95K9Myvl1tIqIx9mS7l5I1wwVjD6QSN7sWN7Z98H8EG-2cF1cTxJC0aSRAgi_ozaWe8d1L9aSuQmChmjkNsoInv-bRzKFVS_5M_fR2C6Az5NC-v_TfLm9nGn_ALve5NU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1920448808</pqid></control><display><type>article</type><title>Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Hanak, Anne‐Sophie ; Malissin, Isabelle ; Poupon, Joël ; Risède, Patricia ; Chevillard, Lucie ; Mégarbane, Bruno</creator><creatorcontrib>Hanak, Anne‐Sophie ; Malissin, Isabelle ; Poupon, Joël ; Risède, Patricia ; Chevillard, Lucie ; Mégarbane, Bruno</creatorcontrib><description>Objectives
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‐induced encephalopathy depends on the poisoning pattern has not been established. We designed a rat study to investigate lithium‐induced encephalopathy and correlate its severity to plasma, erythrocyte, cerebrospinal fluid and brain lithium concentrations previously determined in rat models mimicking human poisoning patterns.
Methods
Lithium‐induced encephalopathy was assessed and scored using continuous electroencephalography.
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.</description><identifier>ISSN: 1398-5647</identifier><identifier>EISSN: 1399-5618</identifier><identifier>DOI: 10.1111/bdi.12482</identifier><identifier>PMID: 28425670</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Animal models ; Animals ; Antimanic Agents - pharmacology ; Antimanic Agents - toxicity ; Bipolar Disorder - drug therapy ; Brain - drug effects ; Cerebrospinal fluid ; Dose-Response Relationship, Drug ; EEG ; effect/concentration relationship ; electroencephalogram ; Electroencephalography ; Electroencephalography - methods ; Encephalopathy ; Life Sciences ; Lithium ; Lithium - blood ; Lithium - pharmacokinetics ; Lithium Compounds - pharmacology ; Lithium Compounds - toxicity ; Mimicry ; Neurotoxicity ; Neurotoxicity Syndromes - diagnosis ; Neurotoxicity Syndromes - etiology ; Overdose ; Poisoning ; rat ; Rats ; Renal function ; Rodents ; Seizures ; Tissue Distribution ; Toxicology</subject><ispartof>Bipolar disorders, 2017-03, Vol.19 (2), p.135-145</ispartof><rights>2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2017 John Wiley & Sons A/S</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3872-d033103b2b572423c9de94d162edecb3d72b208e5e4ca7ec6890687069e3caf73</citedby><cites>FETCH-LOGICAL-c3872-d033103b2b572423c9de94d162edecb3d72b208e5e4ca7ec6890687069e3caf73</cites><orcidid>0000-0002-2522-2764 ; 0000-0003-2910-9117</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbdi.12482$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbdi.12482$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28425670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03822921$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Hanak, Anne‐Sophie</creatorcontrib><creatorcontrib>Malissin, Isabelle</creatorcontrib><creatorcontrib>Poupon, Joël</creatorcontrib><creatorcontrib>Risède, Patricia</creatorcontrib><creatorcontrib>Chevillard, Lucie</creatorcontrib><creatorcontrib>Mégarbane, Bruno</creatorcontrib><title>Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat</title><title>Bipolar disorders</title><addtitle>Bipolar Disord</addtitle><description>Objectives
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‐induced encephalopathy depends on the poisoning pattern has not been established. We designed a rat study to investigate lithium‐induced encephalopathy and correlate its severity to plasma, erythrocyte, cerebrospinal fluid and brain lithium concentrations previously determined in rat models mimicking human poisoning patterns.
Methods
Lithium‐induced encephalopathy was assessed and scored using continuous electroencephalography.
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.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antimanic Agents - pharmacology</subject><subject>Antimanic Agents - toxicity</subject><subject>Bipolar Disorder - drug therapy</subject><subject>Brain - drug effects</subject><subject>Cerebrospinal fluid</subject><subject>Dose-Response Relationship, Drug</subject><subject>EEG</subject><subject>effect/concentration relationship</subject><subject>electroencephalogram</subject><subject>Electroencephalography</subject><subject>Electroencephalography - methods</subject><subject>Encephalopathy</subject><subject>Life Sciences</subject><subject>Lithium</subject><subject>Lithium - blood</subject><subject>Lithium - pharmacokinetics</subject><subject>Lithium Compounds - pharmacology</subject><subject>Lithium Compounds - toxicity</subject><subject>Mimicry</subject><subject>Neurotoxicity</subject><subject>Neurotoxicity Syndromes - diagnosis</subject><subject>Neurotoxicity Syndromes - etiology</subject><subject>Overdose</subject><subject>Poisoning</subject><subject>rat</subject><subject>Rats</subject><subject>Renal function</subject><subject>Rodents</subject><subject>Seizures</subject><subject>Tissue Distribution</subject><subject>Toxicology</subject><issn>1398-5647</issn><issn>1399-5618</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kclOwzAQhi0EglI48ALIEicOpV6yONxKKYtUiQucLceZEKM0DrYD6tvjtiwnfPHI8-nTjH-Ezii5ovFMy8pcUZYItodGlBfFJM2o2N_WItZJfoSOvX8jhGaMpIfoiImEpVlORsgvWtDBWeg09I1q7atTfWM07lUI4DqPbY1bExozrHBvjbed6V6vscI-DNV60w0NYKjrqJlqGzVdcCoY22EH7bbwjek9Nt2WjL0TdFCr1sPp9z1GL3eL5_nDZPl0_zifLSeai5xNKsI5JbxkZZqzhHFdVFAkVdwBKtAlr3JWMiIghUSrHHQmCpKJnGQFcK3qnI_R5c4b95K9Myvl1tIqIx9mS7l5I1wwVjD6QSN7sWN7Z98H8EG-2cF1cTxJC0aSRAgi_ozaWe8d1L9aSuQmChmjkNsoInv-bRzKFVS_5M_fR2C6Az5NC-v_TfLm9nGn_ALve5NU</recordid><startdate>201703</startdate><enddate>201703</enddate><creator>Hanak, Anne‐Sophie</creator><creator>Malissin, Isabelle</creator><creator>Poupon, Joël</creator><creator>Risède, Patricia</creator><creator>Chevillard, Lucie</creator><creator>Mégarbane, Bruno</creator><general>Wiley Subscription Services, Inc</general><general>Wiley</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-2522-2764</orcidid><orcidid>https://orcid.org/0000-0003-2910-9117</orcidid></search><sort><creationdate>201703</creationdate><title>Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat</title><author>Hanak, Anne‐Sophie ; Malissin, Isabelle ; Poupon, Joël ; Risède, Patricia ; Chevillard, Lucie ; Mégarbane, Bruno</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3872-d033103b2b572423c9de94d162edecb3d72b208e5e4ca7ec6890687069e3caf73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antimanic Agents - pharmacology</topic><topic>Antimanic Agents - toxicity</topic><topic>Bipolar Disorder - drug therapy</topic><topic>Brain - drug effects</topic><topic>Cerebrospinal fluid</topic><topic>Dose-Response Relationship, Drug</topic><topic>EEG</topic><topic>effect/concentration relationship</topic><topic>electroencephalogram</topic><topic>Electroencephalography</topic><topic>Electroencephalography - methods</topic><topic>Encephalopathy</topic><topic>Life Sciences</topic><topic>Lithium</topic><topic>Lithium - blood</topic><topic>Lithium - pharmacokinetics</topic><topic>Lithium Compounds - pharmacology</topic><topic>Lithium Compounds - toxicity</topic><topic>Mimicry</topic><topic>Neurotoxicity</topic><topic>Neurotoxicity Syndromes - diagnosis</topic><topic>Neurotoxicity Syndromes - etiology</topic><topic>Overdose</topic><topic>Poisoning</topic><topic>rat</topic><topic>Rats</topic><topic>Renal function</topic><topic>Rodents</topic><topic>Seizures</topic><topic>Tissue Distribution</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hanak, Anne‐Sophie</creatorcontrib><creatorcontrib>Malissin, Isabelle</creatorcontrib><creatorcontrib>Poupon, Joël</creatorcontrib><creatorcontrib>Risède, Patricia</creatorcontrib><creatorcontrib>Chevillard, Lucie</creatorcontrib><creatorcontrib>Mégarbane, Bruno</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Bipolar disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hanak, Anne‐Sophie</au><au>Malissin, Isabelle</au><au>Poupon, Joël</au><au>Risède, Patricia</au><au>Chevillard, Lucie</au><au>Mégarbane, Bruno</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat</atitle><jtitle>Bipolar disorders</jtitle><addtitle>Bipolar Disord</addtitle><date>2017-03</date><risdate>2017</risdate><volume>19</volume><issue>2</issue><spage>135</spage><epage>145</epage><pages>135-145</pages><issn>1398-5647</issn><eissn>1399-5618</eissn><abstract>Objectives
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‐induced encephalopathy depends on the poisoning pattern has not been established. We designed a rat study to investigate lithium‐induced encephalopathy and correlate its severity to plasma, erythrocyte, cerebrospinal fluid and brain lithium concentrations previously determined in rat models mimicking human poisoning patterns.
Methods
Lithium‐induced encephalopathy was assessed and scored using continuous electroencephalography.
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.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28425670</pmid><doi>10.1111/bdi.12482</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2522-2764</orcidid><orcidid>https://orcid.org/0000-0003-2910-9117</orcidid></addata></record> |
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| ispartof | Bipolar disorders, 2017-03, Vol.19 (2), p.135-145 |
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| source | MEDLINE; Access via Wiley Online Library |
| subjects | Animal models Animals Antimanic Agents - pharmacology Antimanic Agents - toxicity Bipolar Disorder - drug therapy Brain - drug effects Cerebrospinal fluid Dose-Response Relationship, Drug EEG effect/concentration relationship electroencephalogram Electroencephalography Electroencephalography - methods Encephalopathy Life Sciences Lithium Lithium - blood Lithium - pharmacokinetics Lithium Compounds - pharmacology Lithium Compounds - toxicity Mimicry Neurotoxicity Neurotoxicity Syndromes - diagnosis Neurotoxicity Syndromes - etiology Overdose Poisoning rat Rats Renal function Rodents Seizures Tissue Distribution Toxicology |
| title | Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat |
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