Lithium neurotoxicity – a case report and review of the literature

Introduction Lithium, a mood stabilizer, is a commonly prescribed and effective treatment for bipolar affective disorder. It´s excreted almost exclusively by the kidneys with a half-life primarily determined by renal function. Chronic intoxication results from an insidious accumulation of lithium in a chronically medicated patient (due to a reduction in renal function secondary to volume depletion, a new medication, et cetera). Patients often present with neurologic findings, including tremor, ataxia, dysarthria, confusion and neuromuscular excitability. Objectives The objective of this report is to describe a clinical case of lithium neurotoxicity (myoclonus and encephalopathy), along with a review of the literature on the topic. Methods We describe a case of lithium neurotoxicity, along with a brief non-systematic review of the literature on lithium toxicity. We conducted a PubMed bibliographic search using keywords such as “lithium intoxication”, “lithium neurotoxicity”, “lithium encephalopathy” and “lithium intoxication treatment”. Results A women aged 81 was brought to the emergency department by her daughter following 1 week of asthenia, diarrhoea, periods of confused speech and involuntary movements. In the previous week, the patient had been diagnosed with COVID-19. Her past medical history is significant for bipolar affective disorder, hypertension, diabetes mellitus, dyslipidemia and asthma. The patient has been treated with following drugs: lithium carbonate (no recent change of dose and previous serum levels around 1mmol/L), quetiapine, lisinopril, metformin, simvastatin, formoterol and budesonide. On the first examination, she had an exuberant multifocal myoclonus. Posteriorly, she became somnolent, with language impairment (verbal perseveration, echolalia) and dysarthria. Investigations revealed renal impairment (creatinine 1,5 mg/dL, blood urea nitrogen 42 mg/dL) and supratherapeutic lithium levels (lithium serum level 1,7 mmol/L). Computed tomography scan of the brain was negative for acute injuries. The electroencephalogram showed triphasic waves (1-1,5 Hz). Encephalopathy secondary to lithium intoxication was diagnosed (probably in the context of acute kidney injury precipitated by hypovolaemia – diarrhoea). Lithium was stopped and intravenous isotonic fluids were given. After 1 week, her myoclonus resolved and over the following week the other signs resolved as well. The patient was later discharged to her daughter’s home, with follow-up neurology and psychiatry visits. Conclusions Both reversible and irreversible neurotoxicity related to lithium have been reported, specially occurring alongside chronic intoxication. If not addressed, impaired consciousness can lead to coma and death. A high clinical suspicion is needed for prompt diagnosis and treatment (intravenous fluids and sometimes haemodialysis are warranted). Disclosure of Interest None Declared

Introduction: Lithium, a mood stabilizer, is a commonly prescribed and effective treatment for bipolar affective disorder.It´s excreted almost exclusively by the kidneys with a half-life primarily determined by renal function.Chronic intoxication results from an insidious accumulation of lithium in a chronically medicated patient (due to a reduction in renal function secondary to volume depletion, a new medication, et cetera).Patients often present with neurologic findings, including tremor, ataxia, dysarthria, confusion and neuromuscular excitability.Objectives: The objective of this report is to describe a clinical case of lithium neurotoxicity (myoclonus and encephalopathy), along with a review of the literature on the topic.Methods: We describe a case of lithium neurotoxicity, along with a brief non-systematic review of the literature on lithium toxicity.We conducted a PubMed bibliographic search using keywords such as "lithium intoxication", "lithium neurotoxicity", "lithium encephalopathy" and "lithium intoxication treatment".Results: A women aged 81 was brought to the emergency department by her daughter following 1 week of asthenia, diarrhoea, periods of confused speech and involuntary movements.In the previous week, the patient had been diagnosed with COVID-19.Her past medical history is significant for bipolar affective disorder, hypertension, diabetes mellitus, dyslipidemia and asthma.The patient has been treated with following drugs: lithium carbonate (no recent change of dose and previous serum levels around 1mmol/L), quetiapine, lisinopril, metformin, simvastatin, formoterol and budesonide.On the first examination, she had an exuberant multifocal myoclonus.Posteriorly, she became somnolent, with language impairment (verbal perseveration, echolalia) and dysarthria.Investigations revealed renal impairment (creatinine 1,5 mg/dL, blood urea nitrogen 42 mg/dL) and supratherapeutic lithium levels Objectives: To show the heptotoxicity potential of Clozapine and adress the importance of monitoring the liver function tests in clozapine titration to prevent sever conditions Methods: A case report of a fifty-year old Tunisian male patient diagnosed with resistant schizophrenia who developed a hepatototoxicity under a low dose of clozapine within five days of treatment .
Results: Mr F is a 50 year old patient diagnosed with schizophrenia in 2018 .He had received various antypical and typical antipsychotic treatments including ( Haloperidol , Risperidone , Amisulpride , Olanzapine ) at effective doses and minimal periods of six weeks .He had no history of systemic diseases or substance use disorder .He smokes 10 cigarettes a day .He had a history of hepatotoxicity on olanzapine.These medications have failed to resolve the persecutory delusion and auditory hallucinations , and the trial of clozapine was institued .Baseline examination and laboratory tests were normal .The previous antipsychotic medication was not continued and a dose of 25 mg clozapine was administred .A marking drowsiness was present in the fisrt days , so we decided to keep the same dose .Five days later , he had high levels of Liver function test (LFT) : Elevated aspartate ( 5 times above normal) and alanine aminotransferase levels (4 times above normal ) , white blood cell count and bilirubine levels were normal .
He had no fever or jaundice .The abdominal examination showed a mild sensiblity in the right upper quadrant .Clozapine was immediatly discontinuated .24 hours later LFT continued to escalate to 5 times greater then normal .Then it decreased continueosly Conclusions: Clozapine has a potential of hepatotoxicity even at lower dose .Screening liver function tests must be integrated in survey recommendations of clozapine treatment .Further researches must be conducted to understand the mechanism of this side effect in order to avoid sever conditions .
Disclosure of Interest: None Declared

EPV0835
Neutropenia induced by several second-generation antipsychotics :A case report H. Zarouf*, M. Chtibi, S. Belbachir and A. Ouanass Introduction: Antipsychotic medications remain the mainstay of the treatment of various psychiatric disorders, particularly schizophrenia.However, this therapeutic class can induce a range of side effects.Although the treatment with second generation antipsychotics includes a lower risk for extrapyramidal symptoms as compared to first generation antipsychotics, there are numerous adverse events that can result from atypical antipsychotics.Since the introduction of clozapine, there has been increased awareness regarding antipsychotic-induced hematological side effects.
Objectives: The objective of this case report is to highlight the importance of the management of antipsychotic-induced neutropenia.
Methods: We report a patient with history of schizophrenia who developed neutropenia induced by Haloperidol, Chlorpromazine, Olanzapine, Amisulpride and Aripiprazole.
Results: We present a case of a 43-year-old male patient with a history of schizophrenia, admitted in our department for the management of a state of agitation in the context of a relapse of his condition.On admission, the patient experienced psychotic symptoms, including delusions and auditory hallucinations, in addition to negative symptoms, such as affective flattening, alogia, avolition and asociality.He was then started on 12 mg of Haloperidol and 200 mg of Chlorpromazine with a white blood cells count (WBC) of 5.98 x 10 9 /L and absolute neutrophil count (ANC) of 2.52 x 10 9 /L (WBC reference range: 4.0-10.0x 10 9 /L; ANC reference range: 1.5-7.0x 10 9 /L).The patient did not report adverse events on this medication.15 days into hospitalization, a mild neutropenia was detected (WBC=3.92 x 10 9 /L and ANC=1.01 x 10 9 /L), leading to a discontinuation of the antipsychotic treatment.No signs of infection were found.After one month, the patient had a normal WBC and ANC.Aripiprazole was discussed as a first alternative and was begun at 5 mg/day and then at 10 mg/day.After one week of treatment with Aripiprazole, the patient's WBC was normal, but the ANC decreased again leading to a moderate neutropenia (ANC=0.91x 10 9 /L).The antipsychotic treatment was once again discontinued and the hematological evaluation found no other lithium serum level 1,7 mmol/L).Computed tomography scan of the brain was negative for acute injuries.The electroencephalogram showed triphasic waves (1-1,5 Hz).Encephalopathy secondary to lithium intoxication was diagnosed (probably in the context of acute kidney injury precipitated by hypovolaemiadiarrhoea).Lithium was stopped and intravenous isotonic fluids were given.After 1 week, her myoclonus resolved and over the following week the other signs resolved as well.The patient was later discharged to her daughter's home, with follow-up neurology and psychiatry visits.Conclusions: Both reversible and irreversible neurotoxicity related to lithium have been reported, specially occurring alongside chronic intoxication.If not addressed, impaired consciousness can lead to coma and death.A high clinical suspicion is needed for prompt diagnosis and treatment (intravenous fluids and sometimes haemodialysis are warranted).