Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT): A Preventable Cerebellar Disorder.

We report a case study of a 60-year-old man with bipolar disorder on stable lithium treatment who developed severe toxicity while admitted to ICU with sepsis and multiorgan failure. Despite unchanged lithium administration, his serum levels escalated due to renal dysfunction, resulting in lithium toxicity. After regaining consciousness, he exhibited a cerebellar syndrome marked by ataxia, tremor, and scanning speech. MRI revealed cerebellar atrophy. Following discontinuation of lithium and hemodialysis, the patient's symptoms remained static. The patient was diagnosed with syndrome of irreversible lithium-effectuated neurotoxicity (SILENT), a chronic cerebellar disorder characterized by persistent ataxia, nystagmus, and gait abnormalities extending beyond two months post-lithium exposure. The disorder has a predilection for cerebellar and basal ganglia dysfunction. MRI findings include cerebellar gliosis and atrophy and leptomeningeal enhancement. This case report highlights that SILENT is both preventable and permanent, urging heightened awareness among clinicians to facilitate early detection and intervention. Patients on lithium with compromised renal function or fever necessitate vigilant lithium level monitoring, dose adjustment, or cessation, to forestall enduring morbidity. This case emphasizes the significance of recognizing and managing SILENT, particularly in critical care settings, to mitigate long-term cerebellar impairment and optimize patient outcomes.

Challenges in the Clinical Diagnosis of Lithium Toxicity: A Case Report.

Lithium, a medication commonly used to treat bipolar disorders, has a narrow therapeutic index, putting patients at risk of lithium toxicity. Such toxicity could entail neurological-related complications and could be precipitated by several factors. In this paper, the authors discuss a case of a middle-aged woman taking lithium for bipolar disorder who presented to the emergency department with altered mental status, tremors, generalized weakness, and dysarthria. Multiple differential diagnoses were considered during her hospitalization, which included an admission to the intensive care unit. This case highlights the variability of lithium toxicity presentations and its management challenges. Further research is needed to understand such manifestations, potential precipitating factors, differential diagnoses, and effective detection and management.

Manic Episodes in a Patient With Neurosyphilis Following Brief Discontinuation of Bipolar Medication.

Bipolar disorder is a mood disorder resulting in episodes of either mania or hypomania. The episodes can manifest themselves as a period of abnormally and persistently elevated mood, abnormally and persistently increased activity or energy, distractibility, insomnia, grandiosity, flight of ideas, increased activity, pressured speech, and racing thoughts. Neurosyphilis is a progression of syphilis infection involving the brain, meninges, or spinal cord. The interaction between bipolar disorder and neurosyphilis has not been extensively studied, but it has been theorized that neurosyphilis can exacerbate mood disorders. This case study details a patient with concurrent late-onset bipolar disorder and neurosyphilis and how the discontinuation of bipolar medication resulted in an acute manic episode. In addition, this case underscores the importance of differentiating the presenting symptoms between bipolar disorder and neurosyphilis.

Lithium Toxicity - A Chameleon to Gastrointestinal Vasculitis as an Initial Presenter of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. Gastrointestinal manifesting as nausea, vomiting, and pain abdomen are not so uncommon in SLE flare. However, gastrointestinal intestinal vasculitis as an initial presenter of SLE is very rare. This case report narrated gastrointestinal vasculitis as an initial presentation of systemic lupus erythematous, which mimicked lithium toxicity in a patient of preexisting bipolar disorder who was on long-term lithium therapy. A 26-year-old female presented with abdominal pain and persistent vomiting for 2 months. On further workup, she was antinuclear, anti-Smith, and anti-ds-DNA antibody positive. The serum lithium level was found to be normal computed tomography angiogram of the abdomen suggestive of vasculitis. A final diagnosis of SLE with gastrointestinal vasculitis as an initial presenter was made. She was treated with high-dose corticosteroid, cyclophosphamide, and other supportive care. She improved dramatically and was discharged with an oral corticosteroid, hydroxychloroquine, and ramipril.

A Unique Case of the Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) Presenting With Multiple Neurological Sequelae.

Lithium can have toxic effects on the central nervous system (CNS) that can be both acute and chronic. The syndrome of irreversible lithium-effectuated neurotoxicity (SILENT) was suggested in the 1980s to describe lithium intoxication-induced persistent neurological sequelae. In this article, we report a 61-year-old patient with bipolar disorder who had developed expressive aphasia, ataxia, cogwheel rigidity, and fine tremors after acute on chronic lithium toxicity. These neurological symptoms remained for four months after discontinuation of lithium, confirming the persistence of CNS signs and symptoms, which makes this case meets the SILENT syndrome criteria. Although rare, our report - which shows a severe and disabling form of SILENT syndrome - highlights the need for additional caution when treating patients with lithium and the need to perform strict control of the putative risk factors argued to be associated with the development of this syndrome.

Acute-on-Chronic Lithium Toxicity: A Simulation Case for Emergency Medicine Residents.

Introduction: Simulation-based education has become standard within emergency medicine training. Toxicological clinical presentations are challenging to identify and treat in the emergency department. Recognizing that active teaching methods are superior to standard lecture for learner retention, we created an experiential simulation case for education on lithium toxicity. The case was written after an extensive literature review followed by consultation with a medical toxicologist and an expert in simulation-based education. Methods: Fifty-three residents participated in a simulation scenario involving a lithium-poisoned patient over the course of eight simulation sessions. The scenario ran approximately 10 minutes and was followed by postevent debriefing. Debriefing was facilitated by an emergency medicine attending with specialized training in simulation-based education. Following the completion of the scenario, residents received an anonymous educational quality improvement survey assessing residents' perception of their ability to recognize and manage lithium toxicity as well as their comfort level with the lithium-poisoned patient. Results: After the simulation, residents reported an increased comfort level with managing lithium-poisoned patients. Residents also self-reported an increased ability to recognize the signs and symptoms of lithium toxicity. Additionally, residents cited the case's educational importance and a desire to include this specific scenario in future simulation sessions. Discussion: Compared to other disease processes, toxicological overdoses are infrequently seen in the emergency department. Health care simulation can effectively portray lithium toxicity for emergency medicine resident education in a safe, controlled environment to increase repetitive practice in caring for this challenging population.

Insights into Chronic Lithium Toxicity - A Case Report.

BACKGROUND: Bipolar disorder is a chronic psychological disorder, and lithium remains the mainstay of therapy. Lithium toxicity can be acute or chronic and the effects may be disabling or life-threatening. The presence of risk factors can increase the chances of lithium toxicity in a patient on long-term lithium therapy. We hereby report a case of chronic lithium toxicity in a patient with a known case of bipolar disorder. CASE PRESENTATION: A 44-year-old female patient with a known case of bipolar disorder presented with altered sensorium, seizures, and renal insufficiency. On admission, the patient was severely dehydrated and the serum lithium level was 3.43 mEq/L. Hemodialysis was performed and she improved gradually. CONCLUSION: Lithium has constantly proven to be beneficial in lowering suicide rates in bipolar disorder patients over the years since its approval. However, its use is limited due to the risk of toxicity. The chances of developing toxicity are higher in patients on long-term lithium therapy. Patients with high risk factors for toxicity should be monitored frequently as the effects of lithium toxicity can be fatal.

"SILENT": A case report of a rare syndromal presentation of chronic lithium toxicity.

This text discusses a case report of an affected person with bipolar ailment who developed the syndrome of irreversible lithium effectuated neurotoxicity (SILENT). In this case of a 62-year-old man with bipolar affective disorder, we found how continual lithium therapy can position a patient requiring chronic mood stabilizer treatment vulnerable to developing the silent syndrome. The case presentation covered a set of symptoms inclusive of encephalopathy, cerebellar dysfunction, stress, and limb tremors at the time of admission. A serial neurological examination and mental status examination for ascertaining the diagnosis of the silent syndrome were carried out, and the affected person was advised to discontinue lithium and was handled symptomatically for other symptoms. We ought to identify and manage the hazard elements contributing to the development of this syndrome.

A Case Report: Lithium-Induced Neurotoxicity, a Differential to Always Consider.

Lithium, a mood stabilizer commonly prescribed for bipolar disorder, has a narrow therapeutic index that increases the risk of toxicity for patients who are prescribed this medication. Patients presenting with lithium toxicity could have a wide array of symptoms triggered by several factors that mimic other neurological conditions. In this paper, we discuss the case of an 81-year-old male who presented to the emergency department with worsening tremors and visual hallucinations, ataxia, and cognitive decline. He was initially thought to have Parkinson's disease with dementia in the outpatient setting and was later found to have lithium toxicity. Swift identification and management, involving fluid diuresis, led to the complete resolution of the patient's neurological symptoms by the fourth day of hospitalization. This case calls attention to the challenges of diagnosing lithium toxicity due to the variability in presentation as well as precipitating factors that clinicians must be cognizant of when working up patients who are prescribed lithium.

Lithium Toxicity With Lasting Mental Status Impairment.

A 49-year-old female taking lithium for bipolar affective disorder for over 20 years presented with lithium toxicity resulting in declining mentation. Lithium poisoning has been well documented to cause acute gastrointestinal, cardiac, and neurological side effects, along with long-term neurologic sequelae. There has, however, been scant discussion on the potential long-term effects on mentation. The following case report illustrates a possible example.

Lithium toxicity following Roux-en-Y gastric bypass: Mini review and illustrative case.

Lithium is among the mainstays of treatment for bipolar disorder. Bariatric surgery can considerably change the oral bioavailability of drugs, particularly lithium. In this review, a 36-year-old male patient is described, who presented with lithium toxicity, including neurologic and gastric symptoms after undergoing Roux-en-Y gastric bypass. The mechanism of lithium toxicity is discussed; recommendations for clinicians regarding lithium use in postsurgical patients are provided; and previous case reports of lithium toxicity post-gastric bypass surgery are analyzed. Awareness and education of lithium absorption changes postbariatric surgery is essential for optimal patient care. Close clinical and drug concentration level monitoring is warranted.

Sodium zirconium cyclosilicate to increase lithium elimination.

Lithium is considered a mood stabilizer for bipolar affective disorders, but it has a narrow therapeutic index of 0.6-1.2 mEq/L. This can easily result in toxic levels after minimal changes in renal function or individual patient's pharmacokinetics. Lithium toxicity can arise with levels as low as 1.5 mEq, and there are limited therapeutic options to treat these patients presenting to the emergency department (ED). At therapeutic levels 95% of lithium is eliminated unchanged by the kidneys. However, previous literature has examined sodium polystyrene sulfonate (SPS) as an option to reduce lithium levels by binding the lithium cation and enhancing its excretion via the gastrointestinal tract. This suggests there may be an increased degree of non-renal clearance and altered toxicokinetics at supratherapeutic levels. However, SPS has been associated with intestinal necrosis and may cause treatment limiting hypokalemia, and is therefore not commonly recommended in treatment algorithms for lithium toxicity. A newer cation exchange resin, sodium zirconium cyclosilicate (SZC), may provide a safer alternative to SPS while also aiding in the clearance of lithium. We present a patient case where a patient with symptomatic acute-on-chronic lithium toxicity had increased clearance of lithium after a dose of SZC.

Toxicological impacts of excessive lithium on largemouth bass (Micropterus salmoides): Body weight, hepatic lipid accumulation, antioxidant defense and inflammation response.

The unreasonably anthropogenic activities make lithium a widespread pollutant in aquatic environment, and this metallic element can enter the food chain to influence humans. Therefore, the study was designed to explore the influence of dietary lithium supplementation on body weight, lipid deposition, antioxidant capacity and inflammation response of largemouth bass. Multivariate statistical analysis confirmed the toxicological impacts of excessive lithium on largemouth bass. Specifically, excessive dietary lithium (≥87.08 mg/kg) significantly elevated weight gain and feed intake of largemouth bass. Meanwhile, overload lithium inclusion aggravated the accumulation of hepatic lipid and serum lithium. Gene expression results showed that lithium inclusion, especially overload lithium, promoted the transcription of lipogenesis related genes, PPARγ, ACC and FAS, inhibited the expression of fatty acid oxidation related genes, PPARα and ACO, and lipolysis related genes, HSL and MGL. Meanwhile, high lithium inclusion caused the oxidative stress, which was partly through the inhibition of Nrf2/Keap1 pathway. Moreover, dietary lithium inclusion significantly depressed the activity of hepatic lysozyme, and promoted the transcription of proinflammation factors, TNF-α, 5-LOX, IL-1ß and IL-8, which was suggested to be regulated by the p38 MAPK pathway. Our findings suggested that overload lithium resulted in increased body weight, hepatic lipid deposition, oxidative stress and inflammation response. The results obtained here provided novel insights on the toxicological impacts of excessive lithium on aquatic animals.

Symptom Overlap of Acute Mountain Sickness and Lithium Toxicity: A Case Report.

Uber, Amy, and Claire Twark. Symptom overlap of acute mountain sickness and lithium toxicity: a case report. High Alt Med Biol. 23:291-293, 2022.-Mild lithium toxicity and acute mountain sickness share multiple overlapping features. We report a case of a patient with bipolar disorder on lithium who hiked to altitude and experienced symptoms that are shared by both conditions. We review the literature on lithium fluctuations under similar conditions showing that acute altitude exposure may elevate serum lithium levels and excess sweating may lower lithium levels, despite the prevailing thought that fluid loss concentrates serum lithium levels. We advise individualized testing of athletes' lithium levels in response to exercise and altitude, and we recommend physicians counsel their patients on ways to maintain therapeutic lithium levels during their athletic pursuits, including the importance of hydration and avoidance of nonsteroidal anti-inflammatory drugs. Further research is needed on lithium pharmacokinetics in conditions of exercise and altitude exposure.

Validation of a nomogram used to predict lithium concentration in overdose.

INTRODUCTION: Extracorporeal Treatment (ECTR) is an essential component in management of severe lithium toxicity. The Extracorporeal Treatments in Poisoning (EXTRIP) group's suggested indications for ECTR include "if the expected time to obtain a [Li+] < 1.0mEq/L with optimal management is >36h". Buckley et al. developed a lithium nomogram which could help predict the fall in lithium concentrations for chronic poisoning. Our aim is to externally validate the lithium nomogram in a cohort of cases with chronic accumulation and acute on chronic lithium poisoning. METHODS: A retrospective analysis of suspected cases of chronic accumulation and acute on chronic lithium poisoning referred to our Toxicology Unit from May 2013 to 2020 was performed. RESULTS: Out of 51 cases, 29 cases of chronic accumulation and eight cases of acute on chronic poisoning were analysed after excluding 14 cases who required haemodialysis. In chronic accumulation cases, the nomogram correctly identified 10 out of 14 patients whose [Li+] failed to drop below 1.0 mmol/L by 36 h (sensitivity 71.4% [95% CI 42 - 92%]), and 8 out of 15 patients whose [Li+] dropped below 1.0 mmol/L by 36 h (specificity 53.3% [95% CI 27 - 78%]), resulting in the positive predictive value (PPV) of 58.8%, negative predictive value (NPV) of 66.7% and accuracy of 62.1%. CONCLUSIONS: Our study shows that the lithium nomogram is moderately sensitive at identifying patients with chronic lithium accumulation who will have a serum lithium concentration >1 mmol/L at 36 h without ECTR.

A rare case of fatal poisoning during long-term therapy with lithium carbonate - chronic poisoning, suicide or psychiatric malpractice? / Rzadki przypadek smiertelnego zatrucia w trakcie dlugotrwalej terapii weglanem litu ­ samobójstwo, przewlekle zatrucie czy blad medyczny psychiatry?

The study aims to present a case of atypical poisoning with lithium carbonate in a 57-year-old woman treated for bipolar affective disorder with lithium carbonate for about 30 years. The patient was admitted to the hospital with significant agitation. An important finding obtained from the family interview was the patient's significant weight loss over the past year. In the hospital, the patient received haloperidol and clonazepam. Laboratory tests showed a very high blood lithium concentration of 3.79 mmol/l [N: 0.6─1.2 mmol/l] and elevated serum concentrations of creatinine (3.6 mg/dl) and urea (110 mg/dl). The patient was transferred to the toxicology department, where hemodialysis was performed and intensive treatment initiated. Despite the rapid decrease in lithium levels, her condition gradually deteriorated. The patient died on the fifth day of hospitalization. The autopsy revealed polycystic kidney disease (PKD). During the preparation of the medico-legal report on the correctness of the medical treatment, it was assumed that the cause of death was lithium carbonate poisoning in the course of advanced chronic kidney disease due to PKD, probably a consequence of long-term lithium therapy. The analysis of medical records revealed that despite her psychiatrist's recommendation, the patient had been refusing the monitoring of lithium levels for the past 18 years. This case demonstrates that both psychiatrists and toxicologists should be aware of possible lithium poisoning upon the deterioration of renal function. Therefore, assessment of renal function should be an integral part of monitoring lithium therapy.

Lithium Intoxication in an Elderly Woman.

Acute confusional state or delirium in the elderly frequently requires a lengthy differential diagnosis in the emergency room (ER) to determine the factors of its multiple causes. Iatrogeny can be one of the causes, especially in elderly people with polypharmacy. We present a case of a 77-year-old female, independent in activities of daily living, with no cognitive impairment and a history of hypertension, dyslipidemia, and manic-depressive disorder. She arrived at the ER with diarrhea, vomiting, and myalgias. A blood test revealed an acute kidney injury. The patient was discharged with the diagnosis of acute gastroenteritis and prerenal acute kidney injury. The patient returned to the ER two days later due to worsening symptoms, including spatial and temporary disorientation and a marked prostration. The attending physician recommended a lithium blood level test due to the patient's history and the outpatient's psychiatric medication. The tests revealed a value of 2.18 mmol/L (toxic levels: >2.0 mmol/L). Support measures were initiated with diuresis control and vigorous hydration, with subsequent clinical and biochemical improvement (lithium blood levels reduced to 0.97 mmol/L). Lithium toxicity causes acute nausea, vomiting, diarrhea, and neurological symptoms that have a slower onset and correlate with chronic toxicity. A declining renal function and reduced volume of distribution (due to increased body fat mass and decreased total body water) contribute to more significant pharmacological toxicity in the elderly. In this case, dehydration triggered by diarrhea and vomiting may have been a cause or a consequence. Reviewing chronic medication and a detailed investigation of all etiological causes was essential for the patient's rehabilitation, avoiding possible irreversible neurological damage.

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157.

Due to endothelial impairment, high-dose lithium may produce an occlusive-like syndrome, comparable to permanent occlusion of major vessel-induced syndromes in rats; intracranial, portal, and caval hypertension, and aortal hypotension; multi-organ dysfunction syndrome; brain, heart, lung, liver, kidney, and gastrointestinal lesions; arterial and venous thrombosis; and tissue oxidative stress. Stable gastric pentadecapeptide BPC 157 may be a means of therapy via activating loops (bypassing vessel occlusion) and counteracting major occlusion syndromes. Recently, BPC 157 counteracted the lithium sulfate regimen in rats (500 mg/kg/day, ip, for 3 days, with assessment at 210 min after each administration of lithium) and its severe syndrome (muscular weakness and prostration, reduced muscle fibers, myocardial infarction, and edema of various brain areas). Subsequently, BPC 157 also counteracted the lithium-induced occlusive-like syndrome; rapidly counteracted brain swelling and intracranial (superior sagittal sinus) hypertension, portal hypertension, and aortal hypotension, which otherwise would persist; counteracted vessel failure; abrogated congestion of the inferior caval and superior mesenteric veins; reversed azygos vein failure; and mitigated thrombosis (superior mesenteric vein and artery), congestion of the stomach, and major hemorrhagic lesions. Both regimens of BPC 157 administration also counteracted the previously described muscular weakness and prostration (as shown in microscopic and ECG recordings), myocardial congestion and infarction, in addition to edema and lesions in various brain areas; marked dilatation and central venous congestion in the liver; large areas of congestion and hemorrhage in the lung; and degeneration of proximal and distal tubules with cytoplasmic vacuolization in the kidney, attenuating oxidative stress. Thus, BPC 157 therapy overwhelmed high-dose lithium intoxication in rats.

Lithium-Induced Sinoatrial Node Dysfunction.

Lithium is a common mood-stabilizing drug for manic patients. We describe a case of sinoatrial node dysfunction in a patient with serum lithium levels within the therapeutic range. Given the symptomology and severity of the patient's illness, after placing a permanent pacemaker, the patient was discharged on the preadmission dose of lithium.

Lithium orotate: A superior option for lithium therapy?

Bipolar disorder (BD) poses a significant public health concern, with roughly one-quarter of sufferers attempting suicide. BD is characterized by manic and depressive mood cycles, the recurrence of which can be effectively curtailed through lithium therapy. Unfortunately, the most frequently employed lithium salt, lithium carbonate (Li2 CO3 ), is associated with a host of adverse health outcomes following chronic use: these unwanted effects range from relatively minor inconveniences (e.g., polydipsia and polyuria) to potentially major complications (e.g., hypothyroidism and/or renal impairment). As these undesirable effects can limit patient compliance, an alternative lithium compound with a lesser toxicity profile would dramatically improve treatment efficacy and outcomes. Lithium orotate (LiC5 H3 N2 O4 ; henceforth referred to as LiOr), a compound largely abandoned since the late 1970s, may represent such an alternative. LiOr is proposed to cross the blood-brain barrier and enter cells more readily than Li2 CO3 , which will theoretically allow for reduced dosage requirements and ameliorated toxicity concerns. This review addresses the controversial history of LiOr, complete with discussions of experimental and clinical efficacy, putative mechanisms of action, adverse effects, and its potential future in therapy.