Toxic Encephalopathy Research Articles

Pharmacovigilance study of famciclovir in the Food and Drug administration adverse event reporting system database

Famciclovir, mainly used to treat herpes zoster, is rapidly transforms into penciclovir when administered orally. Our study evaluated adverse events (AEs) associated with famciclovir by mining data from the publicly available Food and Drug Administration Adverse Event Reporting System (FAERS) database, providing a reference for clinical safety. Disproportionality analysis (including reported odds ratio and proportional reporting ratio) and Bayesian methods (including Bayesian Confidence Propagation Neural Network and Gamma-Poisson Shrinkage) were used to quantify the AE signals associated with famciclovir. A total of 17,652,186 case reports were obtained from the FAERS database, and 432 famiclovir-related AEs were identified. Nausea, headache, altered mental status, vomiting, and dizziness were found to be the most common Aes, corresponding to those reported in the Food and Drug Administration (FDA) drug labelling and clinical trials. Our study found some potential AEs of famciclovir that were not mentioned in the FDA drug labelling, such as toxic encephalopathy, encephalopathy, ataxia, dysarthria, dementia, cerebral infarction, tremor, purpura, skin ulcers, acute pancreatitis, rhabdomyolysis, muscle twitching, increased blood urea, lowered blood pressure, hepatitis, disease recurrence, drug interactions, and pancytopenia. Our study identified potential famciclovir AE signals, providing insights for physicians to reduce possible side effects and promote the safe implementation of the drug in clinical settings.

Abnormalities along the cortico-medullary junction on brain MRI caused by 1,2-dichloroethane-induced toxic encephalopathy

Background1,2-dichloroethane (DCE) induced toxic encephalopathy, a rare toxic disease of the central nervous system, is mainly reported in developing countries. Although clinicians have got some understanding about the clinical and neuroimaging features of 1,2-DCE-induced toxic encephalopathy, abnormality along the cortico-medullary junction on diffusion-weighted image (DWI) mimicking neuronal intranuclear inclusion disease (NIID) has not yet been described in this entity.Case presentationWe reported a patient with 1,2-DCE-induced toxic encephalopathy who was admitted to our department due to a 7-day history of nausea, vomiting, and cognitive decline. Brain magnetic resonance imaging (MRI) showed symmetrical hyperintensities in bilateral subcortical white matte on T2-weghted and Fluid-attenuated inversion recovery (FLAIR) images. In addition, abnormal signal intensity could also be found in the cortico-medullary junction on DWI, mimicking NIID. After treated with glucocorticoid, dehydrating agents, neuroprotective agents, and hyperbaric oxygen, our patient received a partial recovery.ConclusionOur case highlights a special MRI finding—abnormalities along the cortico-medullary junction—that can be seen in 1,2-DCE-induced toxic encephalopathy. When confronted with patients with lesion located in the cortico-medullary junction and neuropsychiatric symptoms, our clinicians should not neglect the detailed inquiry of history of toxic exposure.

Lead encephalopathy presenting as status epilepticus: a case report

BackgroundLead encephalopathy, while thankfully rare, is a devastating and potentially fatal consequence of lead intoxication. Owing to successful public health measures, severe lead toxicity is not often encountered by most practicing physicians in the United States, making both its recognition and management challenging.Article summaryA case study of a 4-year-old female presenting in refractory status epilepticus, found to have severe microcytic anemia and lead level > 100 mcg/dL.Case presentationWe report a case of a 4-year-old girl who presented with refractory seizures, severe microcytic anemia, and a history of developmental delay who was ultimately diagnosed with lead encephalopathy, requiring multiple courses of calcium disodium ethylenediaminetetraacetic acid (EDTA) and succimer for rebounding lead levels.ConclusionRapid recognition and appropriate management is essential to ensure neurologically intact survival. This case documents one of the first cases of successful lead chelation after multiple courses of calcium disodium EDTA and succimer dual therapy since the removal of dimercaprol from the United States market. This case also highlights the importance of using body surface area dosing for chelation therapy in order to prevent under-dosing in young children.

Differences in safety profiles of anti-herpesvirus medications: a real-world pharmacovigilance study based on the FAERS database

ABSTRACT Background Anti-herpesvirus drug safety profiles have not been systematically compared. Understanding variations in adverse events (AEs) could provide reference for rational clinical use. Methods We collected data on acyclovir, ganciclovir, valaciclovir, and foscarnet from the FDA Adverse Event Reporting System (FAERS) database from Q1 2004 to Q3 2023. Disproportionality analyses were conducted to evaluate the risk of AEs. Results All drugs exhibited significant associations with hematotoxicity, with ganciclovir and foscarnet being more myelosuppressive. The correlation with renal impairment ranked as follows: foscarnet, ganciclovir, valaciclovir, and acyclovir (ROR = 16.72, 7.06, 3.51, and 2.02, respectively). Regarding hepatotoxicity, ganciclovir was associated with acute-on-chronic liver failure (ROR = 52.83), and foscarnet was associated with fulminant hepatitis (ROR = 49.91). In the nervous system, acyclovir showed the highest intensity of neurotoxicity (ROR = 14.95). Valaciclovir ranked first in toxic encephalopathy (ROR = 64.70). Foscarnet showed the highest intensity of status epilepticus (ROR = 6.45). Besides, acyclovir showed the strongest association with severe cutaneous adverse reactions (SCARs). Conclusions Our study revealed differences in safety profiles of four anti-herpesvirus medications. Ganciclovir exhibited the highest risk of hematotoxicity but appeared relatively safe in seizures and SCARs. Foscarnet was more likely to induce nephrotoxicity, seizures, and electrolyte imbalances than others. Acyclovir and valaciclovir were strongly associated with plasmacytosis, neurotoxicity, and SCARs.

Diquat exacerbates oxidative stress and neuroinflammation by blocking the autophagic flux of microglia in the hippocampus

Diquat (DQ) is a widely utilized nonselective herbicide that is primarily used to control a wide range of weeds and crop residues. It also has significant environmental implications. DQ exposure can cause severe damage to the central nervous system (CNS), a critical symptom of acute poisoning that endangers patients. Despite its severity, the underlying mechanisms of DQ-induced toxic encephalopathy remain unclear, hindering the development of precise treatments. Our research demonstrated that acute DQ exposure in mice significantly increases oxidative stress and triggers neuroinflammation in the hippocampus. Furthermore, in vitro findings indicate that the detrimental effects of DQ are mediated by its disruption of autophagic processes, leading to exacerbated neural damage. DQ initially promotes autophagy in BV2 microglia for self-protection against oxidative stress and inflammation. However, this process is subsequently blocked, intensifying neural damage. Crucially, our results show that the activation of autophagy can reverse these adverse effects. This study not only sheds light on the intricate mechanisms of DQ neurotoxicity but also provides potential therapeutic targets for mitigating DQ-induced toxic encephalopathy.

The Approach to Altered Mental Status in the Intensive Care Unit.

Altered mental status (AMS) is a syndrome posing substantial burden to patients in the intensive care unit (ICU) in both prevalence and intensity. Unfortunately, ICU patients are often diagnosed merely with syndromic labels, particularly the duo of toxic-metabolic encephalopathy (TME) and delirium. Before applying a nonspecific diagnostic label, every patient with AMS should be evaluated for specific, treatable diseases affecting the central nervous system. This review offers a structured approach to increase the probability of identifying specific causal etiologies of AMS in the critically ill. We provide tips for bedside assessment in the challenging ICU environment and review the role and yield of common neurodiagnostic procedures, including specialized bedside modalities of diagnostic utility in unstable patients. We briefly review two common etiologies of TME (uremic and septic encephalopathies), and then review a selection of high-yield toxicologic, neurologic, and infectious causes of AMS in the ICU, with an emphasis on those that require deliberate consideration as they elude routine screening. The final section lays out an approach to the various etiologies of AMS in the critically ill.

Altered Mental Status in Cancer.

Patients with cancer experience high rates of alterations in mental status. The mechanisms for altered mental status (AMS) in this population are manifold. The cancer itself may cause AMS through direct invasion of the central nervous system or as metastatic leptomeningeal spread. However, cancer patients are also vulnerable to tumor-associated complications such as seizures, cerebral edema, strokes, or cancer treatment-related complications such as infections, direct neural injury from radiation or chemotherapy, edema, or dysregulated autoimmune response from immunotherapies. Both during treatment and as sequelae, patients may suffer neurocognitive complications from chemotherapy and radiation, medications or opportunistic infections, as well as toxic-metabolic, nutritional, and endocrine complications. In this review, we describe a clinical approach to the cancer patient presenting with AMS and discuss the differential drivers of AMS in this patient population. While common etiologies of AMS in noncancer patients (toxic-metabolic or infectious encephalopathy, delirium) are also applicable to cancer patients, we additionally provide a cancer-specific differential diagnosis that warrants special consideration in the cancer patient with AMS.

CHANTER syndrome in the context of pain medication: a case report

BackgroundCHANTER (Cerebellar Hippocampal and Basal Nuclei Transient Edema with Restricted diffusion) is a recently described syndrome occurring in the context of drug abuse. While clinical findings are rather unspecific (disorientation, unresponsiveness), MR imaging (MRI) discloses a characteristic pattern (restricted diffusion in the basal ganglia and hippocampi, cerebellar oedema and haemorrhage), allowing for timely diagnosis before complications such as cerebellar swelling and herniation do occur. Here we report a case of CHANTER primarily based on imaging findings, as there was no evidence of drug abuse on admission.Case presentationA 62-year-old Patient was admitted to our hospital after being unresponsive at home. Prehospital intubation was performed, which limited neurological assessment. Under these circumstances no obvious symptoms could be determined, i.e. pupils were isocoric and responsive, and there were no signs of seizures. While the initial CT scan was unremarkable, the subsequent MRI scan showed a distinct imaging pattern: moderately enhancing areas in the basal ganglia and hippocampi with diffusion restriction, accompanied by cerebellar haemorrhage and oedema (Figs. 1 and 2). A comprehensive clinical and laboratory work-up was performed, including drug screening, spinal tap, Holter ECG, echocardiography and EEG. The only conspicuous anamnestic finding was a chronic pain syndrome whose medication had been supplemented with opioids two months previously. The opioid medication was discontinued, which led to a rapid improvement in the patient’s clinical condition without any further measures. The patient was able to leave the intensive care unit and was discharged 10 days after admission without persistent neurological deficits.ConclusionFamiliarity with typical MRI patterns of toxic encephalopathy in patients from high-risk groups, such as drug abusers, is crucial in emergency neuroradiology. In the presence of typical MRI findings, CHANTER syndrome should be included in the differential diagnosis, even if there is no history of drug abuse, to avoid delay in diagnosis and treatment.

Tralopyril poisoning due to respiratory exposure

Introduction Tralopyril is a metabolite of the pesticide chlorfenapyr. Direct toxicity by tralopyril has not been described. We report two cases of tralopyril poisoning via inhalation. Case presentations Two workers developed heat intolerance, diaphoresis, and weight loss after occupational inhalational exposure to tralopyril. Patient 1: The exposure was due to the absence of respiratory protection. Magnetic resonance imaging showed abnormal signals in the bilateral periventricular white matter, corpus callosum, basal ganglia, brainstem, and spinal cord. The patient’s blood tralopyril concentrations on days 1, 3, 5, 8, and 11 post-admission were 1.09 mg/L, 1.04 mg/L, 1.01 mg/L, 0.71 mg/L, and 0.313 mg/L, respectively. Haemoperfusion (HA330), haemoperfusion (HA380), and haemodiafiltration were performed on days 1–3, 5–8, and 9–10, respectively. Patient 2: The patient’s symptoms followed inappropriate use of respiratory protection. His blood tralopyril concentrations on days 1, 4, 5, and 6 were 0.592 mg/L, 0.482 mg/L, 0.370 mg/L, and 0.228 mg/L, respectively. Discussion The patients presented with features typical of chlorfenapyr poisoning, which suggests that tralopyril is the main toxic metabolite of chlorfenapyr. Conclusion Tralopyril can be absorbed by inhalation, leading to delayed clinical symptoms and organ damage, including toxic encephalopathy and spinal cord damage.

Treatment of manganese and lead poisoning with sodium para-aminosalicylic acid: A contemporary update

Sodium para-aminosalicylic acid (PAS-Na) treatment for manganese (Mn) intoxication has shown efficacy in experimental and clinical studies, giving rise to additional studies on its efficacy for lead (Pb) neurotoxicity and its associated mechanisms of neuroprotection. The difference between PAS-Na and other metal complexing agents, such as edetate calcium sodium (CaNa2-EDTA), is firstly that PAS-Na can readily pass through the blood-brain barrier (BBB), and complex and facilitate the excretion of manganese and lead. Secondly, PAS-Na has anti-inflammatory effects. Recent studies have broadened the understanding on the mechanisms associated with efficacy of PAS-Na. The latter has been shown to modulate multifarious manganese- and lead- induced neurotoxicity, via its anti-apoptotic and anti-inflammatory effects, as well as its ability to inhibit pyroptosis, and regulate abnormal autophagic processes. These observations provide novel scientific bases and new concepts for the treatment of lead, mercury, copper, thallium, as well as other toxic encephalopathies, and implicate PAS-Na as a compound with greater prospects for clinical medical application.

Sex disparities in short-term outcomes among patients with diffuse large B cell lymphoma undergoing chimeric antigen receptor T-cell therapy in the United States.

e19062 Background: Chimeric Antigen Receptor (CAR) T-cell therapy, a promising immunotherapy used in various cancers, including Diffuse large B cell lymphoma (DLBCL), can involve multiple complications and the need for medical interventions. Our retrospective study strives to gain up-to-date insight into sex-based differences among DLBCL patients undergoing CAR T-cell therapy. Methods: We focussed on DLBCL patients undergoing CAR T-cell therapy via the 2017-2020 National Inpatient Sample(NIS). The events of complications between males and females were examined via multivariate regression models. Since the ICD-10 code for cytokine release syndrome (CRS) involved cases between October and December 2020, we used samples for that timeline while evaluating that particular complication. Results: Our study involved 3280 adult cases of DLBCL undergoing CAR T-cell therapy, with 1930 (58.8%) males and 1350(41.2%) females. Age differences were seen as females were older(mean age 61.93 vs. 60.40 years, p<0.01). Females also had lower odds of atrial fibrillation (6.7% vs. 14.2%, aOR 0.440, p<0.01) and acute kidney injury (AKI) (10.0% vs. 18.4%, aOR 0.458, p<0.01), while having higher odds of use of invasive mechanical ventilation (5.6% vs. 5.2%, aOR 2.179, p<0.01), events of sepsis (9.6% vs. 7.8%, aOR 1.575, p<0.01), pancytopenia (69.6% vs. 64.0%, aOR 1.454, p<0.01), and cryoprecipitate transfusion (2.2% vs. 1.8%, aOR 2.325, p=0.041) than males. We did not find any statistically significant differences for events of gastrointestinal bleeding (GIB)(aOR 0.866, p=0.636), tumor lysis syndrome(aOR 0.980, p=0.890), acute pulmonary embolism(aOR 1.133, p=0.719), toxic encephalopathy(aOR 1.009, p=0.935), platelet transfusion(aOR 0.994, p=0.976), RBC transfusion(aOR 0.828, p=0.192), or all-cause mortality(aOR 1.829, p=0.064). In addition, while 51.6% of males and 51.7% of females reported CRS, it was not statistically valid (aOR 0.923, p=0.850). Conclusions: The sex of DLBCL patients undergoing CAR T-cell therapy can influence multiple complications, as described in our study. Further research and endeavors aimed to deepen our understanding of our findings will help bring changes in protocols by physicians to improve the quality of care and outcomes of these patients.

Food poisoning due to money tree seeds: a case report of toxic encephalopathy

Abstract Background The money tree is a favored indoor potted plant in China. Its seeds resemble chestnuts in both shape and flavor when cooked, which are generally considered non-toxic and safe for consumption. Case presentation This report presents the first published case of food poisoning due to the ingestion of large amounts of money tree seeds. A 67-year-old man exhibited toxic encephalopathy symptoms and dyspnea after consuming the seeds for approximately 6 months. After empirical mechanical ventilation, therapeutic plasma exchange, and other medical interventions, the patient’s clinical status improved significantly. He was subsequently discharged from the hospital. Conclusion Consuming a substantial quantity of money tree seeds within a limited timeframe can lead to poisoning, resulting in adverse outcomes, particularly toxic encephalopathy. Moreover, plasma exchange may have some therapeutic effect.

Reversible Toxic Encephalopathy related to Treatment with Capecitabine: A Discussion about Chemotherapy-Induced Neurotoxicity and a Case Report

Reversible Toxic Encephalopathy related to Treatment with Capecitabine: A Discussion about Chemotherapy-Induced Neurotoxicity and a Case Report

Two cases of pyridaben poisoning were successfully treated by blood purification

Pyridaben is a broad-spectrum acaricide widely used in agriculture, accidental or self-administration of large doses of pyridaben can cause multiple organ failure in patients. Due to its damage to multiple organs and no specific antidote, the mortality rate is high. This paper reports two patients who took a large amount of pyridaben, developed severe metabolic acidosis, hyperlactatemia, toxic encephalopathy, and liver, kidney, heart and digestive tract damage. After timely gastric lavage, catharsis, organ support andblood purification treatment, the condition improved and discharged. It is expected to provide clinical ideas for the treatment of pyridaben poisoning.

Carbon monoxide poisoning with hippocampi lesions on MRI: cases report and literature review

BackgroundCarbon monoxide (CO) poisoning is now one of the leading causes of poisoning-related mortality worldwide. The central nervous system is the most vulnerable structure in acute CO poisoning. MRI is of great significance in the diagnosis and prognosis of CO toxic encephalopathy. The imaging features of CO poisoning are diverse. We report atypical hippocampal lesions observed on MRI in four patients after acute CO exposure.Case presentationsWe report four patients who presented to the emergency department with loss of consciousness. The diagnosis of CO poisoning was confirmed on the basis of their detailed history, physical examination and laboratory tests. Brain MRI in all of these patients revealed abnormal signal intensity in hippocampi bilaterally. They all received hyperbaric oxygen therapy. The prognosis of all four patients was poor.ConclusionHippocampi, as a relatively rare lesion on MRI of CO poisoning, is of important significance both in the early and delayed stages of acute CO poisoning. In this article, we summarize the case reports of hippocampal lesions on MRI in patients with CO poisoning in recent years, in order to provide reference for the diagnosis and prognosis of CO poisoning.

Neurological Presentation of Lead Toxicity: A Case Report

Acute encephalopathy, caused by infectious agents, metabolic or mitochondrial dysfunction, brain tumor, or prolonged exposure to toxic elements, is a significant cause of morbidity and mortality in young children. Lead encephalopathy that occurs due to prolonged lead ingestion or exposure in children is not uncommon, and many such cases have been reported in the past. This report shares the authors’ experience of the missed diagnosis of lead encephalopathy, its red flags, and its relation to pica as a root cause. A 14-month-old boy, resident of Delhi, India, was admitted with vomiting, irritability, and two episodes of abnormal limb movements, with the first symptom starting when he was 11 months old. His case was initially treated as acute disseminated encephalomyelitis, but he showed no improvement. The child was then referred to the Sir Ganga Ram Hospital, New Delhi, India. The boy presented with severe anemia, along with basophilic stippling on the peripheral smear during routine investigations. Suspecting lead poisoning, blood lead levels were checked, and were found to be grossly elevated. The child was then started on chelation therapy. Multiple doses of chelation (dimercaprol and D-penicillamine) were given, and sequential blood lead levels were monitored, which showed a marked decrement. The child was discharged, and is being monitored routinely. Lead poisoning remains a neglected public health issue, especially in children, and delay in identification can cause significant morbidity and mortality. Pediatricians and general practitioners must be aware of this risk, especially in children with iron deficiency anemia exhibiting pica.

Toxic-Induced Encephalopathy Following Chemsex in a Young HIV-Positive Male: A Complex Case of Acute Cognitive Impairment with Anterograde Amnesia and Behavioral Alterations.

A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the 'chemsex' context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization. After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3mg/dl - elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1. The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.

Toxic Encephalopathy After Dioxin Effects Preceding Clinical and Lethal Breast Cancer or Tumours of Secretory Organs as Pertinent Hazard Following Lacking Prevention?

Toxic Encephalopathy After Dioxin Effects Preceding Clinical and Lethal Breast Cancer or Tumours of Secretory Organs as Pertinent Hazard Following Lacking Prevention?

EEG and acute confusional state at the emergency department

ObjectivesAcute confusional state (ACS) is a common cause of admission to the emergency department (ED). It can be related to numerous etiologies. Electroencephalography (EEG) can show specific abnormalities in cases of non-convulsive status epilepticus (NCSE), or metabolic or toxic encephalopathy. However, up to 80% of patients with a final diagnosis of NCSE have an ACS initially attributed to another cause. The exact place of EEG in the diagnostic work-up remains unclear. MethodsData of consecutive patients admitted to the ED for an ACS in a two-year period and who were referred for an EEG were collected. The initial working diagnosis was based on medical history, clinical, biological and imaging investigations allowing classification into four diagnostic categories. Comparison to the final diagnosis was performed after EEG recordings (and sometimes additional tests) were performed, which allowed the reclassification of some patients from one category to another. ResultsSeventy-five patients (mean age: 71.1 years) were included with the following suspected diagnoses: seizures for 8 (11%), encephalopathy for 14 (19%), other cause for 34 (45%) and unknown for 19 (25%). EEG was recorded after a mean of 1.5 days after symptom onset, and resulted in the reclassification of patients as follows: seizure for 15 (20%), encephalopathy for 15 (20%), other cause for 29 (39%) and unknown cause for 16 (21%). Moreover, ongoing epileptic activity (NCSE or seizure) and interictal epileptiform activity were found in eight (11%) patients initially diagnosed in another category. DiscussionIn our cohort, EEG was a key examination in the management strategy of ACS in 11% of patients admitted to the ED. It resulted in a diagnosis of epilepsy in these patients admitted with unusual confounding presentations.

Requesting That Delirium Achieve Parity With Acute Encephalopathy in the MS-DRG System

Since 2007, the Medicare Severity Diagnosis Related Groups (MS-DRG) classification system has favored billing codes for acute encephalopathy over delirium codes in determining hospital reimbursement and several quality-of-care value metrics, despite broad overlap between these sets of diagnostic codes. Toxic and metabolic encephalopathy codes are designated as major complication or comorbidity (MCC) whereas causally specified delirium codes are designated as complication or comorbidity (CC) and thus associated with lower reimbursement and lesser impact on value metrics.