Search

Long-term exposure to high-level ambient PM 2.5 was associated with increased risks of brain disorders, while the associations remain uncertain when the exposure is lower than current air quality standards in numerous countries. This study aimed to assess the effects of PM 2.5 exposure on the brain system in the population with annual mean concentrations ≤15 μg/m 3 . We analyzed data from 260,922 participants without preexisting brain diseases at baseline in the UK Biobank. The geographical distribution of PM 2.5 in 2010 was estimated by a land use regression model and linked with individual residential address. We investigated associations of ambient PM 2.5 with incident neurological (dementia, Parkinson's diseases [PD], epilepsy, and migraine) and psychiatric (major depressive disorder [MDD] and anxiety disorder) diseases through Cox proportional hazard models. We further estimated the links with brain imaging phenotypes by neuroimaging analysis. Results showed that in the population with PM 2.5 concentrations ≤15 μg/m 3 , each interquartile range (IQR, 1.28 μg/m 3 ) increment in PM 2.5 was related to incidence risks of dementia, epilepsy, migraine, MDD, and anxiety disorder with hazard ratios of 1.08 (95% confidence interval [CI]: 1.03, 1.13), 1.12 (1.05, 1.20), 1.07 (1.00, 1.13), 1.06 (1.03, 1.09), and 1.05 (1.02, 1.08), respectively. We did not observe a significant association with PD. The association with dementia was stronger among the population with poor cardiovascular health (measured by Life's Essential 8) than the counterpart (P for interaction = 0.037). Likewise, per IQR increase was associated with specific brain imaging phenotypes, including volumes of total brain (β = -0.036; 95% CI: -0.050, -0.022), white matter (-0.030; -0.046, -0.014), grey matter (-0.030; -0.042, -0.017), respectively. The findings suggest long-term exposure to ambient PM 2.5 at low-level still has an adverse impact on the neuro-psychiatric systems. The brain-relevant epidemiological assessment suggests that each country should update the standard for ambient PM 2.5 following the World Health Organization Air Quality Guidelines 2021., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Contrast-induced encephalopathy (CIE) is a rare complication of angiography. According to our knowledge, the majority of CIE reports is imaging observations and rarely includes results of cerebrospinal fluid (CSF) tests. Furthermore, among the cases reporting the data for CSF testing, most of the results were normal. Here, we report a case of CIE presenting with significantly elevated levels of CSF protein. We found that the course of improvement in brain imaging findings was not consistent with the severity of clinical manifestations. The diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) sequences were normal. Considering the lack of convenient direct indicators to observe blood-brain barrier (BBB) function, changes in the levels of CSF protein may be related to BBB permeability and recovery and may serve as a potential prognostic marker.

New human life begins in the uterus in a period of both extreme plasticity and sensitivity to environmental disturbances. The fetal stage is also a vital period for central nervous system development, with experiences at this point profoundly and permanently shaping brain structure and function. As such, some brain disorders may originate in utero. Glucocorticoids, a class of essential stress hormones, play indispensable roles in fetal development, but overexposure may have lasting impacts on the brain. In this review, we summarize data from recent clinical and non-clinical studies regarding alterations in fetal brains due to prenatal glucocorticoid overexposure that are associated with nervous system disorders. We discuss relevant changes to brain structure and cellular functions and explore the underlying molecular mechanisms. In addition, we summarize factors that may cause differential outcomes between varying brain regions, and outline clinically feasible intervention strategies that are expected to minimize negative consequences arising from fetal glucocorticoid overexposure. Finally, we highlight the need for experimental evidence aided by new technologies to clearly determine the effects of excessive prenatal glucocorticoid exposure. This review consolidates diverse findings to help researchers better understand the relationship between the prenatal glucocorticoid overexposure and the effects it has on various fetal brain regions, promoting further development of critical intervention strategies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: The authors have no conflict of interest to declare.

Encephalopathy is the most severe complication of various common infections, including influenza and herpes, and it often results in death or severe neurological disability. The risk factors for viral encephalopathy include non-steroidal anti-inflammatory drug (NSAID) use; however, studies on NSAID-related encephalopathy are limited. In this study, we aimed to investigate the characteristics of NSAID-related encephalopathy. We investigated the incidence of NSAID-related encephalopathy using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases containing reports on spontaneous adverse effects (AEs) published by the Pharmaceuticals and Medical Devices Agency. We used these databases to detect AEs based on reported odds ratios. By separating suspicious drugs, concomitant drugs, and drug interactions involving NSAIDs, we investigated the relationship between encephalopathy pathology and AEs of NSAIDs. Significant encephalopathy signals were detected for loxoprofen and etodolac in the FAERS database and loxoprofen in the JADER database. In the JADER database, significant encephalopathy signals in loxoprofen-treated patients were detected in 70-79-year-old, ≥80-year-old, influenza viral infection, and herpes virus infection groups. Significant encephalopathy signals in patients with herpes virus infection were detected in the ≥80-year-old and loxoprofen-treated groups. Regarding the involvement of loxoprofen in the development of encephalopathy, the JADER database listed loxoprofen as a suspect drug, without indicating any concomitant drug interactions. In conclusion, our findings suggest that loxoprofen and etodolac may be associated with viral encephalopathy. Accordingly, prudence is recommended when using loxoprofen in older individuals with viral infections.

Ornithine transcarbamylase deficiency (OTCD) is a rare, X linked disorder that can manifest in late adulthood in heterozygous females as severe hyperammonaemia following environmental stressors. We present a case of hyperammonaemic encephalopathy that was triggered by glucocorticoid administration in an adult woman with heterozygous OTCD with clinical response to haemodialysis, ammonia scavengers and a high-calorie, low-protein diet., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Metronidazole central nervous system toxicity is a rare finding in patients receiving the medication. We report a peculiar case of metronidazole central nervous system toxicity in which both the underlying condition (Crohn disease) and the drugs used to treat it are potential causes of encephalopathy., Methods: A 26-year-old female with 6-year history of Crohn's disease for 6 years presented acute-onset encephalopathy. We provide bibliographic evidence to support metronidazole toxicity and potential Crohn disease-associated neurologic involvement., Results: The patient presented dystonia, cerebellar ataxia, and altered mental status. Magnetic resonance imaging of the brain revealed typical findings of metronidazole toxicity and white matter involvement of the centrum semiovale. Immunoelectrophoresis and immunofixation of serum and cerebrospinal fluid proteins were consistent with a systemic inflammatory process. We concluded on an association between drug toxicity and probable Crohn-associated neurologic involvement. Metronidazole was stopped and the patient was placed on vitamin therapy and diazepam to control dystonia. She deteriorated and was transferred to the intensive care unit where she expired., Conclusions: Acute behavioral changes in a young patient constitute an emergency and differential diagnoses should include infective, inflammatory, metabolic, and toxic causes. Metronidazole is a potential toxic etiology., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Contrast-induced encephalopathy is a neurological complication related to contrast used in endovascular procedures or computed tomography (CT). The main risk factors are arterial hypertension, diabetes mellitus, chronic kidney disease (CKD), hyperosmolar contrasts, the amount of infused contrast and its direct infusion in the posterior cerebral territory, or pathologies with blood-brain barrier damage. Symptomatology is non-specific and may present as altered level of consciousness, neurological focality or seizures. Diagnosis is done by exclusion after ischemic or hemorrhagic stroke has been ruled out; CT or MRI are useful for differentiation. Generally, it appears shortly after exposure and the symptoms lasts 48-72h with complete recovery, although cases with persistence of symptoms or longer duration have been described. Treatment consists of monitoring, supportive measures and kidney replacement therapy (KRT) with hemodialysis (HD) in patients in chronic KRT program. It is important for the nephrologist to be aware of this entity given the susceptibility of the patient on HD as well as its potential therapeutic role in these patients., (Copyright © 2023 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Little is known about the risk factors and frequency of metronidazole-associated neurological adverse events., Objective: To investigate the risk factors and frequency of metronidazole-associated neurological adverse events., Design: This retrospective study contained two parts. First, we investigated metronidazole treatment-associated neurologic adverse events by performing a population-based cohort study using the Korea Adverse Event Reporting System (KAERS) database from January 2011 to December 2020. Second, we conducted a matched case-control study based on a retrospective cohort of patients treated with metronidazole between January 2006 and July 2021 at a tertiary hospital in South Korea. The data analysis was performed from August 2021 to April 2022., Participants: In the case-control study, case patients were defined as those diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy during the study period with causal assessment based on the clinical diagnoses and findings from associated tests. In a ratio of 1:3, case patients were compared to a control group of patients prescribed metronidazole without neurologic adverse events matched for age and cumulative dose of metronidazole., Main Measures: Frequency and risk factors for metronidazole-associated neurological adverse events., Key Results: Overall, 2,309 cases of neurologic adverse events were reported to the KAERS from 2011 to 2020, and the number of reported neurological adverse events showed an increasing trend. Further, 92,838 patients were prescribed metronidazole during the study period at the Severance Hospital; 54 patients were diagnosed with metronidazole-associated encephalopathy or peripheral neuropathy, 40 with central and 28 with peripheral nervous system adverse events. Liver cirrhosis, chronic kidney disease, intravenous administration, and lower body weight were identified as risk factors for these adverse events., Conclusions: The number of reported metronidazole-associated neurological adverse events are increasing. Prolonged metronidazole treatment in patients with the aforementioned factors requires careful examination for neurological adverse events., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

The world population is rapidly aging. Societal aging poses many challenges for individuals, families, nations, and the global healthcare system. Therefore, geriatric care is a crucial issue that demands our attention. In this case report, we describe a woman in her early 70s with multiple comorbidities, polypharmacy, and renal insufficiency who developed cefepime-induced encephalopathy with moderate to severe cerebral dysfunction during treatment of a urinary tract infection. The patient's consciousness level gradually improved, and no further seizures were observed following the discontinuation of cefepime for several days. This case report underscores the fact that polypharmacy and medication safety are significant concerns that are often overlooked when caring for older patients. The report also highlights the increased susceptibility of older individuals to antibiotic-associated adverse reactions during the management of infectious diseases. Therefore, optimization of antibiotic therapy for older patients is a critical issue that requires thorough investigation and consideration in geriatric care., Competing Interests: Declaration of conflicting interestsThe authors declare no conflict of interest.

This study aimed to evaluate the incidence and likelihood of antibiotic-associated encephalopathy (AAE), comparing rates among the classes of antibiotics in monotherapy or in combination therapy. We also investigated the associations between the incidence of AAE and the glomerular filtration rate (GFR) and electroencephalogram features. Consecutive admissions that used any kind of antibiotics to treat infectious diseases were identified from six hospitals. We classified antibiotics according to three distinct pathophysiologic mechanisms and clinical subtypes. We searched for the incidence of AAE as the primary outcome. A total of 97,433 admission cases among 56,038 patients was identified. Cases that received type 1 antibiotics had significantly more frequent AAE compared to those that received type 2 antibiotics (adjusted odds ratio [OR], 2.62; 95% confidence interval [CI] 1.15-5.95; P = 0.021). Combined use of type 1 + 2 antibiotics was associated with a significantly higher incidence of AAE compared to the use of type 2 antibiotics alone (adjusted OR, 3.44; 95% CI 1.49-7.93; P = 0.004). Groups with GFR < 60 mL/min/1.73 m 2 had significantly higher incidence rates of AAE compared to those with GFRs ≥ 90 mL/min/1.73 m 2 among cases that received type 1 + 2 antibiotics. Detection of spike-and-wave or sharp-and-wave patterns on electroencephalogram was significantly more common in the combination therapy group. Combination use of antibiotics was associated with a higher incidence of AAE compared to monotherapy. The incidence of AAE significantly increased as renal function decreased, and epileptiform discharges were more likely to be detected in cases receiving combined antibiotics., (© 2024. The Author(s).)

Purpose: Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events., Methods: We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use., Findings: Out of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59-1.64, P = 0.95) with no statistically significant association across different subgroups and time windows., Implications: Our findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use., Competing Interests: Declaration of competing interest The authors declare no competing interests at the time of manuscript preparation and submission. Subsequent to manuscript finalization, author MAA has initiated employment with Novo Nordisk., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To review the evidence of uncommon but fatal adverse event of hyperammonemic encephalopathy by tyrosine kinase inhibitors (TKI) and the possible mechanisms underlying this condition and to describe the case of a patient that developed drug-induced hyperammonemic encephalopathy related to TKI., Data Sources: Literature search of different databases was performed for studies published from 1 January 1992 to 7 May 2023. The search terms utilized were hyperammonemic encephalopathy, TKI, apatinib, pazopanib, sunitinib, imatinib, sorafenib, regorafenib, trametinib, urea cycle regulation, sorafenib, carbamoyl-phosphate synthetase 1, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, arginase 1, Mitogen activated protein kinases (MAPK) pathway and mTOR pathway, were used individually search or combined., Data Summary: Thirty-seven articles were included. The articles primarily focused in hyperammonemic encephalopathy case reports, management of hyperammonemic encephalopathy, urea cycle regulation, autophagy, mTOR and MAPK pathways, and TKI., Conclusion: Eighteen cases of hyperammonemic encephalopathy were reported in the literature from various multitargeted TKI. The mechanism of this event is not well-understood but some authors have hypothesized vascular causes since some of TKI are antiangiogenic, however our literature review shows a possible relationship between the urea cycle and the molecular inhibition exerted by TKI. More preclinical evidence is required to unveil the biochemical mechanisms responsible involved in this process and clinical studies are necessary to shed light on the prevalence, risk factors, management and prevention of this adverse event. It is important to monitor neurological symptoms and to measure ammonia levels when manifestations are detected., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: Daratumumab, a CD38 monoclonal antibody, has been widely used in patients with multiple myeloma. Although a variety of adverse events have been reported, consciousness impairment has not been reported yet. We report a case of encephalopathy associated with daratumumab. Case presentation: A 57-year-old male, diagnosed with relapsed multiple myeloma, was treated with daratumumab. He developed a loss of consciousness after the first administration. Cerebral spinal fluid and magnetic resonance imaging of the brain suggested encephalopathy. Conclusion: It is recommended to be aware of rare but life threatening side effects of daratumumab. We present a case of rare encephalopathy characterized by consciousness disorder associated with daratumumab, which was successfully resolved on prompt institution of steroids, although the mechanism was unknown.

Background: The recreational use of nitrous oxide (N 2 O) has gained popularity over recent years. We present a case series of excessive N 2 O users with neurological complications., Methods: In this retrospective three-centre study, we used a text mining algorithm to search for patients who used N 2 O recreationally and visited a neurologist., Results: We identified 251 patients. The median duration of N 2 O use was 11 months (interquartile range [IQR], 3-24) and the median amount of N 2 O used per occasion 1.6 kg (IQR 0.5-4.0). Clinically, polyneuropathy (78%), myelopathy (41%), and encephalopathy (14%) were the most common diagnoses. An absolute vitamin B12 deficiency of < 150 pmol/L was found in 40% of cases. In 90%, at least one indicator of functional vitamin B12 status (vitamin B12, homocysteine, or methylmalonic acid) was abnormal. MRI showed signs of myelopathy in 30/55 (55%) of cases. In 28/44 (64%) of those who underwent electromyography, evidence of axonal polyneuropathy was found. Most (83%) patients were treated with vitamin B12 supplementation, and 23% were admitted to the hospital. Only 41% had follow-up for ≥ 30 days, and 79% of those showed partial or complete recovery., Conclusions: In this case series of excessive N 2 O users, we describe a high prevalence of polyneuropathy, myelopathy, and encephalopathy. Stepwise testing for serum levels of vitamin B12, homocysteine, and methylmalonic acid may support the clinical diagnosis. Due to low sensitivity, MRI of the spinal cord and electromyography have limited value. Effective treatment should incorporate supplementation of vitamin B12 and strategies to prevent relapses in N 2 O use., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Valproate (VPA) is broad-spectrum antiepileptic drug. Several adverse reactions including hepatotoxicity, fetal risk and pancreatitis are well known and labelled as boxed warnings in the USA. One adverse reaction that is less well known but clinically significant for its severe morbidity is hyperammonemic encephalopathy. We present a case of woman with hyperammonemic encephalopathy following the initiation of VPA therapy; she had a favourable outcome with discontinuation of the drug and prompt treatment with lactulose and L-carnitine., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Ceftriaxone-induced encephalopathy is an exceptionally rare adverse effect of this commonly used cephalosporin and is generally observed in patients undergoing haemodialysis or suffering from severe renal failure. We present a case of a fit woman in her mid-80s with a normal renal function who developed severe fluctuating neurological symptoms (aphasia, loss of contact, chorea-like tongue movements) while being treated with ceftriaxone for a urinary tract infection with bacteraemia. The symptoms began on day 4 of treatment and an adverse drug reaction was suspected on day 7, after exhaustive investigations failed to reveal another cause. A complete recovery was observed 3 days after discontinuing ceftriaxone. Our case highlights the need to consider the diagnosis of ceftriaxone encephalopathy, even if the traditional risk factors are lacking. In this article, we also provide a brief overview of the pathophysiology as well as a literature review concerning the subject., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Cefepime is a fourth-generation cephalosporin with extended antimicrobial coverage. Concerns have been raised about the side effects of cefepime including myoclonus, encephalopathy, and seizures, especially when renal impairment is present. There have been reports of cases of adverse neurological consequences despite appropriate renal adjustment. Here, we present a case of a 69-year-old patient initially diagnosed with pneumonia and treated with cefepime. The patient later developed altered mental status, leading to differential diagnoses including stroke, drug overdose, or non-convulsive seizures. Following a comprehensive workup, it was determined that she had cefepime-induced encephalopathy, despite having normal kidney function, which resolved completely after discontinuing the medication. In addition, we include similar cases retrieved from PubMed up to the present date, to the best of our knowledge., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Few reports have described acyclovir (ACV) encephalopathy without acute kidney injury (AKI)., Objective: This study clarified the clinical features of ACV encephalopathy without AKI compared to that with AKI., Methods: Creatinine (Cre) levels were measured on admission. After admission, Cre was measured in a timely manner for the first seven hospital days. The minimum Cre level in these measurements was then determined. ACV encephalopathy was defined when two criteria were met: 1) neurological symptoms appeared after valacyclovir (VACV) administration, and 2) neurological symptoms improved after VACV discontinuation. AKI was defined when the Cre level on admission was >1.5 times higher than the minimum Cre level. The subjects were divided into AKI and non-AKI groups based on these findings., Results: Eighteen patients had ACV encephalopathy (5 males, mean age 81.3±5.5 years old). All patients were prescribed VACV 3,000 mg/day. The minimum Cre was 1.93±1.76 mg/dL. AKI occurred in 10 (56.6%) patients. VACV was discontinued in all patients, and emergency hemodialysis treatment was administered in 10 (55.6%) patients. All patients recovered. Compared to the AKI group, the non-AKI group had a lower history of taking a Ca-blocker (33.3% vs 80.0%, p=0.092), a lower rate of emergency dialysis (16.9% vs 70.0%, p=0.059) and a longer time to clinical improvement (3.67±1.86 vs 2.20±0.63 days, p=0.073)., Conclusion: ACV encephalopathy without AKI is characterized by a low rate of emergency dialysis, which may be linked to a prolonged duration of symptoms.

There is limited information about sodium valproate-induced hyperammonaemia encephalopathy (VPAIHE). The aim of this case report is to provide medical practitioners with a greater awareness of the possible development of hyperammonaemia due to sodium valproate use and its associated complications.This paper describes a middle-aged man with a history of bipolar affective disorder who was admitted with a manic relapse secondary to medication non-compliance. His admission was complicated by an intensive care unit admission to manage medical compromise in the context of sodium VPAIHE., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Contrast-induced encephalopathy can result from neurotoxicity of contrast medium in the affected area. The development of intermediate catheters has allowed guidance of catheters to more distal arteries. This study focused on the association between contrast-induced encephalopathy and contrast injection from an intermediate catheter guided into a distal intradural artery during neurointervention for cerebral aneurysms., Materials and Methods: We retrospectively reviewed 420 consecutive aneurysms in 396 patients who underwent neurointervention for extracranial aneurysms and unruptured intracranial aneurysms at our institution from February 2012 to January 2023. Patients were divided into a group with contrast-induced encephalopathy and a group without. To identify risk factors for contrast-induced encephalopathy, we compared clinical, anatomic, and procedural factors between groups by multivariate logistic regression analysis and stepwise selection., Results: Among the 396 patients who underwent neurointervention for cerebral aneurysms, 14 (3.5%) developed contrast-induced encephalopathy. Compared with the group without contrast-induced encephalopathy, the group with contrast-induced encephalopathy showed significantly higher rates of patients on hemodialysis, previously treated aneurysms, intradural placement of a catheter for angiography, nonionic contrast medium, and flow-diversion procedures in univariate analyses. Stepwise multivariate logistic regression analysis revealed intradural placement of a catheter for angiography (OR = 40.4; 95% CI, 8.63-189) and previously treated aneurysms (OR = 8.20; 95% CI, 2.26-29.6) as independent predictors of contrast-induced encephalopathy., Conclusions: Contrast injection from an intradural artery and retreatment of recurrent aneurysms were major risk factors for contrast-induced encephalopathy. Attention should be paid to the location of the intermediate catheter for angiography to avoid developing contrast-induced encephalopathy., (© 2023 by American Journal of Neuroradiology.)

Background: Valproate-induced encephalopathy (VIE) affects between 0.1% and 2.5% of patients under long-term epilepsy treatment. Its frequency and characteristics in adults with status epilepticus (SE) is, however, unknown., Objective: The aim of this study was to characterize the frequency and the clinico-biological characteristics of VIE in adult SE patients., Methods: We reviewed all patients included in our institutional SE registry who were treated for an SE episode between November 2021 and February 2023 and identified 39 patients who received valproate for their SE treatment. Acute VIE was defined by worsening of consciousness having led to the discontinuation of valproate, and improvement of consciousness within 96 hours after discontinuation of valproate during acute hospital treatment., Results: Patients had a mean valproate intravenous loading dose of 34.5 mg/kg and a mean maintenance dose of 15.3 mg/kg/d (1078 mg/d). Four out of 29 patients with measured ammonium had hyperammonemia. We identified four (10%) patients fulfilling acute VIE criteria. Median time from administration of valproate to the occurrence of VIE, and to resolution of VIE after cessation of valproate treatment, was 2 days for each. Three of the four VIE patients had no associated hyperammonemia. Patients who developed VIE more frequently had a history of liver disease (p = 0.023), and tended to be younger, but other clinical variables did not differ significantly from patients without VIE, including valproate loading or maintenance doses, SE cause, duration or severity, other concomitant antiseizure medications (none received topiramate, phenobarbital, or primidone)., Conclusion: Pending larger studies, VIE in SE seems relatively frequent and difficult to foresee; clinical alertness to symptoms is mandatory, even without hyperammonemia, and valproate withdrawal should be considered in suspected cases., (© 2023. The Author(s).)

A 21-year-old woman was diagnosed with acute lymphoblastic leukemia. After the administration of intrathecal methotrexate (MTX), the patient experienced dysarthria and paralysis for one hour. Magnetic resonance imaging (MRI) performed one hour from the onset and just before symptoms disappeared revealed no abnormalities. The next day, the symptoms appeared again, and diffusion-weighed MRI revealed a high-intensity area in the left frontal lobe. The patient was diagnosed with MTX-induced encephalopathy. This case suggested that MRI performed as soon as symptoms appear might show normal findings in MTX-induced encephalopathy.

Rationale: Iodinated contrast agents are extensively employed in clinical settings, with allergic reactions and renal impairment being the most prevalent adverse events. Contrast-induced encephalopathy (CIE) can present with heterogeneous clinical features, making diagnosis challenging. Prior studies on CIE have primarily documented rapid recovery within several days. However, this paper describes a case of CIE in a patient whose clinical symptoms took 3 months to fully abate., Patient Concerns: A female patient, aged 54 years, received drug-coated balloon therapy for stenosis in a branch of the anterior descending coronary artery. Unfortunately, the patient developed CIE, which initially manifested as visual disturbances and subsequently progressed to gastrointestinal and limb movement issues, as well as an altered mental status, all of which occurred within a 24-hour period during hospitalization., Diagnoses: The patient was diagnosed with CIE after cerebral hemorrhage, and cerebral edema was ruled out based on the history of contrast medium administration and radiographic exams., Interventions and Outcomes: Dexamethasone (10 mg/d), mannitol (100 mL/d), betahistine (500 mL), trazodone (25 mg), and hydration supplementation were given to treat CIE-related symptoms. Aspirin and clopidogrel were administered for the management of the cardiovascular ailment. The neurologist prescribed neurotrophic agents, namely, cytarabine and methylcobalamin, based on the cerebral magnetic resonance imaging findings. Despite the treatment, the patient's ocular symptoms, including blurry vision, diplopia, and impaired intraocular retraction, persisted. Furthermore, the patient's mental state was altered, and she continued to exhibit a depressive state during her 1-month follow-up visit., Lessons: CIE is a comparatively infrequent ailment, and its prompt identification and management are of paramount importance. Although the treatments for CIE are primarily symptomatic, it is crucial to acknowledge that the symptoms may not always subside quickly within a short duration. In conjunction with pharmacotherapy, counseling should be offered to address patients' mental health., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Encephalopathy can occur from a non-fatal toxic drug event (overdose) which results in a partial or complete loss of oxygen to the brain, or due to long-term substance use issues. It can be categorized as a non-traumatic acquired brain injury or toxic encephalopathy. In the context of the drug toxicity crisis in British Columbia (BC), Canada, measuring the co-occurrence of encephalopathy and drug toxicity is challenging due to lack of standardized screening. We aimed to estimate the prevalence of encephalopathy among people who experienced a toxic drug event and examine the association between toxic drug events and encephalopathy., Methods: Using a 20% random sample of BC residents from administrative health data, we conducted a cross-sectional analysis. Toxic drug events were identified using the BC Provincial Overdose Cohort definition and encephalopathy was identified using ICD codes from hospitalization, emergency department, and primary care records between January 1st 2015 and December 31st 2019. Unadjusted and adjusted log-binomial regression models were employed to estimate the risk of encephalopathy among people who had a toxic drug event compared to people who did not experience a toxic drug event., Results: Among people with encephalopathy, 14.6% (n = 54) had one or more drug toxicity events between 2015 and 2019. After adjusting for sex, age, and mental illness, people who experienced drug toxicity were 15.3 times (95% CI = 11.3, 20.7) more likely to have encephalopathy compared to people who did not experience a drug toxicity event. People who were 40 years and older, male, and had a mental illness were at increased risk of encephalopathy., Conclusions: There is a need for collaboration between community members, health care providers, and key stakeholders to develop a standardized approach to define, screen, and detect neurocognitive injury related to drug toxicity., (© 2023. The Author(s).)

Background: Butane is an aliphatic hydrocarbon used in various commercial products. While numerous reports of sudden cardiac-related deaths from butane inhalation have been described, butane-associated acute encephalopathy has rarely been reported., Case Presentation: A 38-year-old man presented with cognitive dysfunction after butane gas inhalation. Neuropsychological test results showed impairments in verbal and visual memory, and frontal executive function. Diffusion weighted MRI revealed symmetric high-signal changes in the bilateral hippocampus and globus pallidus. FDG-PET demonstrated decreased glucose metabolism in the bilateral precuneus and occipital areas and the left temporal region. At the 8-month follow-up, he showed still significant deficits in memory and frontal functions. Diffuse cortical atrophy with white matter hyperintensities and extensive glucose hypometabolism were detected on follow-up MRI and FDG-PET, respectively. Brain autopsy demonstrated necrosis and cavitary lesions in the globus pallidus., Conclusions: Only a few cases of butane encephalopathy have been reported to date. Brain lesions associated with butane encephalopathy include lesions in the bilateral thalamus, insula, putamen, and cerebellum. To the best of our knowledge, this is the first report on bilateral hippocampal and globus pallidal involvement in acute butane encephalopathy. The pathophysiology of central nervous system complications induced by butane intoxication is not yet fully understood. However, the direct toxic effects of butane or anoxic injury secondary to cardiac arrest or respiratory depression have been suggested as possible mechanisms of edematous changes in the brain after butane intoxication., (© 2023. The Author(s).)

Background: Contrast-induced encephalopathy (CIE) is considered as an uncommon complication following cardiac catheterization. Due to the varied manifestations, CIE has no formal diagnostic criteria. In fact, the incidence of CIE may be greatly underestimated because of the difficulty in its differential diagnosis with other cerebrovascular complications. Thus, making a flow diagram according to patients' clinical symptoms and examinations after cardiac catheterization to help clinicians diagnose CIE is important and needed., Case Presentation: In this report, we describe a case of probable CIE in a 66-year-old Chinese man with hypertension who underwent cardiac catheterization with stents placement in the bifurcation lesion, during which 80 ml iopromide contrast was used. About 2 h following the procedure, the patient lost his consciousness suddenly and suffered from a status epilepticus. Malignant arrhythmias were not found through continuous electrocardiogram monitoring, but mild ST-segment elevation was displayed in leads I and aVL. The echocardiography, plasma glucose and electrolyte levels were normal. Emergency re-angiography with percutaneous transluminal coronary angioplasty was performed in the culprit lesion, which involved 60 ml iopromide contrast. However, the patient remained unconsciousness and epilepticus. Non-contrast computed tomography (CT) of the head showed cortical and subarachnoid enhancement as well as prolonged retention of contrast media in the middle cerebral artery. With supportive treatment of intravenous hydration, sedative and dehydrant, the patient recovered 3 h later and finally discharged without any neurological deficits., Conclusions: CIE is an acute reversible encephalopathy induced by contrast media. It is exceptionally challenging to make the diagnosis of CIE following cardiac catheterization since there is a lack of consensus on the definition of CIE. Via this case we reviewed the related literatures, through which a flow diagram of the differential diagnosis and clinical decision making was given, which could help to differentiate CIE from other neurological complications following cardiac catheterization., (© 2023. The Author(s).)

Purpose: The purpose of this case report is to describe spasticity and encephalopathy that developed in a multiple sclerosis patient following carbapenem administration. Summary: A 55-year-old female with multiple sclerosis developed spasticity and encephalopathy within 24 hours of meropenem and ertapenem administration. This was the second time that she had developed encephalopathy following carbapenem administration. The patient gradually recovered over four days following discontinuation of carbapenem therapy. Conclusion: Carbapenem neurotoxicity, a well-documented adverse effect, has been linked to several risk factors, including central nervous system lesions. Despite this, there is little evidence describing the risk of neurotoxicity in patients with multiple sclerosis. It is important to understand the potential adverse effects of carbapenems in specific patient populations to help guide appropriate treatment of infections.

A 63-year-old man developed reduced consciousness and dysphagia progressively. Examination and parameters were normal, except for a Glasgow Coma Scale score of seven, and his grading on the swallow water test increased from grade 1 to grade 5. Brain imaging and blood tests were unexplainable except by high plasma ammonia. His past medical history included cerebral infarction, hypertension and epilepsy induced by cerebral hyperperfusion syndrome. He was rceiving antiepileptic treatment of continuously intravenously pumped sodium valproate of 64 mg/h for 4 days, which overlapped for 12 hours with taking 500 mg sustained release tablets. Sodium valproate was stopped; testing demonstrated normal plasma concentrations of sodium valproate and elevated concentrations of ammonia. Ornithine aspartate was administrated. The patient's level of responsiveness and ammonia levels gradually improved. The patient was also being treated with ceftriaxone sodium for a hypostatic pneumonia and with desmopressin for diabetes insipidus. There is an association between sodium valproate and hyperammonaemia and encephalopathy. Immediate recognition of the serious but uncommon adverse effects is essential. To our knowledge this is the first report of ornithine aspartate being used in this disorder., (© Royal College of Physicians 2023. All rights reserved.)

Objective: To quantify the risk of encephalopathy associated with oral baclofen compared with other muscle relaxants-tizanidine or cyclobenzaprine., Patients and Methods: We conducted a new-user, active-comparator study of 2 pairwise cohorts using tertiary health system data from Geisinger Health in Pennsylvania (January 1, 2005, through December 31, 2018). Adults (aged ≥18 years) newly treated with baclofen or tizanidine were included in cohort 1. Adults newly treated with baclofen or cyclobenzaprine were included in cohort 2. Propensity score-based inverse probability of treatment weighting (IPTW) was used to balance the respective cohorts on 45 patient characteristics. Fine-Gray competing risk regression was used to estimate the risk of encephalopathy., Results: Cohort 1 included 16,192 new baclofen users and 9782 new tizanidine users. The 30-day risk of encephalopathy was higher in patients treated with baclofen vs tizanidine (IPTW incidence rate, 64.7 vs 28.3 per 1000 person-years) with an IPTW subdistribution hazard ratio (SHR) of 2.29 (95% CI, 1.43 to 3.67). This risk persisted through 1 year (SHR, 1.32 [95% CI, 1.07 to 1.64]). Similarly in cohort 2, baclofen vs cyclobenzaprine was associated with a greater risk of encephalopathy at 30 days (SHR, 2.35 [95% CI, 1.59 to 3.48]) that persisted through the first year of treatment (SHR, 1.94 [95% CI, 1.56 to 2.40])., Conclusion: The risk of encephalopathy was greater with baclofen vs tizanidine or cyclobenzaprine use. The elevated risk was apparent as early as 30 days and persisted through the first year of treatment. Our findings from routine care settings may inform shared treatment decisions between patients and prescribers., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Toxic encephalopathy is a spectrum of central nervous system disorders caused by exposure to toxins, especially from occupational workplace. Polyvinylchloride (PVC) is a synthetic chemical polymer that is used widely in daily activities of living. PVC is produced by polymerization of monomer units of vinyl chloride. Its manufacturing requires multiple procedures and additives for heat and light stabilization involving heavy metals., Objective: In this novel case series, we present the diverse clinical presentation of 10 patients, working in plastic recycling factory having inhalational exposure to PVC fumes, manifesting as acute toxic encephalopathy., Materials and Methods: All the patients were screened for the causes of acute encephalopathy including heavy metals, methanol poisoning, and organotins along with arterial blood gas analysis, brain imaging, and electroencephalogram. Memory loss, confusion, vertigo, headache, and nausea were complained in all the patients while seizure occurred in three patients. Neurocognitive status was grossly impaired in all the patients. Metabolic acidosis in presence of hyponatremia and/or hypokalemia was observed in nine cases. Five of the patients were having evidence of white matter involvement in brain imaging. The screening for heavy metal, methanol, and organotin were negative. Hemodialysis was done in six patients. Recovery was good in everyone and the average discharge was by 10.8 days (range: 2-25 days). All the patients were symptom-free at 3-months follow-up., Conclusion: Early suspicion and aggressive management can have favorable outcome in PVC toxic encephalopathy. Occupational hazards due to PVC toxicity are increasing in the present industrial era but it is very less identified., Competing Interests: None

Background: Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood-brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma., Methods: We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m 2 , 80 mg/m 2 , 135 mg/m 2 , 175 mg/m 2 , 215 mg/m 2 , and 260 mg/m 2 ) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood-brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov, NCT04528680, and a phase 2 trial is currently open for accrual., Findings: 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. As of data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12-12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40-215 mg/m 2 ), and 12 patients were treated at dose level 6 (260 mg/m 2 ). A total of 68 cycles of LIPU-MB-based blood-brain barrier opening were done (median 3 cycles per patient [range 2-6]). At a dose of 260 mg/m 2 , encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m 2 in the case of the grade 3 encephalopathy, and to 215 mg/m 2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m 2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood-brain barrier opening was most commonly associated with immediate yet transient grade 1-2 headache (12 [71%] of 17 patients). The most common grade 3-4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood-brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 μM [95% CI 0·022-0·063] in non-sonicated brain to 0·139 μM [0·083-0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 μM [0·562-1·747] in non-sonicated brain to 5·878 μM [3·462-9·980] μM in sonicated brain [5·9-times increase], p=0·0001)., Interpretation: LIPU-MB using a skull-implantable ultrasound device transiently opens the blood-brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing., Funding: National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family., Competing Interests: Declaration of interests AMS and RS have received in-kind (drug) support from Bristol-Myers Squibb, in-kind (ultrasound devices) and research support from and Carthera, and in-kind (drug) and research support from Agenus. AMS, DYZ, VAA, and RS are co-authors of intellectual property filed by Northwestern University related to therapeutic ultrasound. RS has acted or is acting as a scientific advisor or has served on advisory boards for the following companies: Alpheus Medical, AstraZeneca, Boston Scientific, Carthera, Celularity, GT Medical, Insightec, Lockwood (BlackDiamond), Northwest Biotherapeutics, Novocure, Syneos Health (Boston Biomedical), TriAct Therapeutics, and Varian Medical Systems. RVL is on the scientific advisory board and speakers’ bureau for Merck and on the speakers’ bureau for Novocure; has obtained research support from Bristol-Myers Squibb; and has received honoraria for editing from EBSCO INFORMATION services, Medlink, Neurology, and Elsevier. PK participates in advisory boards for Novocure, Janssen, SDP Oncology, Affinia, Sintetica, Mirati; has done consulting for Biocept, Enclear Therapies, Affinia Therapeutics and Bioclinica; and has received research support from Genentech and Novocure. MC, CD, GB, and AC are employees of Carthera, inventors of patents related to the technology, or have stock ownership in Carthera. AC has received funding support from Horizon 2020 European Innovation Council; is a paid consultant of Carthera; and is part of the Board of Directors of Carthera. JB is vice chair of the Neuro Education Track Subcommittee from the American Society of Anesthesiologists., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Neuroinflammation is a critical factor in developing and progressing numerous brain diseases, including neurodegenerative diseases. Chronic or excessive neuroinflammation can lead to neurotoxicity, causing brain damage and contributing to the onset and progression of various brain diseases. Therefore, understanding neuroinflammation mechanisms and developing strategies to control them is crucial for treating brain diseases. Studies have shown that neuroinflammation plays a vital role in the progression of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD), and stroke. Additionally, the effects of PM 2.5 pollution on the brain, including neuroinflammation and neurotoxicity, are well-documented. Quercetin is a flavonoid, a plant pigment in many fruits, vegetables, and grains. Quercetin has been studied for its potential health benefits, including its anti-inflammatory, antioxidant, and anti-cancer properties. Quercetin may also have a positive impact on immune function and allergy symptoms. In addition, quercetin has been shown to have anti-inflammatory and neuroprotective properties and can activate AMP-activated protein kinase (AMPK), a cellular energy sensor that modulates inflammation and oxidative stress. By reducing inflammation and protecting against neuroinflammatory toxicity, quercetin holds promise as a safe and effective adjunctive therapy for treating neurodegenerative diseases and other brain disorders. Understanding and controlling the mechanisms of NF-κB and NLRP3 inflammasome pathways are crucial for preventing and treating conditions, and quercetin may be a promising tool in this effort. This review article aims to discuss the role of neuroinflammation in the development and progression of various brain disorders, including neurodegenerative diseases and stroke, and the impact of PM 2.5 pollution on the brain. The paper also highlights quercetin's potential health benefits and anti-inflammatory and neuroprotective properties.

Background: Common adverse effects of valproate include sedation, tremor, gastrointestinal effects, and weight gain. Valproate-associated hyperammonemic encephalopathy (VHE) is an uncommon adverse effect of valproate therapy, which includes symptoms such as tremors, ataxia, seizures, confusion, sedation and coma. We report clinical features and management of 10 cases of VHE in a tertiary care center., Methods: In a retrospective chart review of case records from January 2018 to June 2021, 10 patients with VHE were identified and included in this case series. The data collected include demographic information, psychiatric diagnosis, comorbidities, liver function tests, serum ammonia and serum valproate levels, dosages and duration of valproate, management of hyperammonemia including dosage variations, discontinuation, adjuvant drugs used, and whether rechallenge was done., Results: The most common indication of starting valproate was bipolar disorder (n = 5). All the patients had more than one physical comorbidity and risk factors for developing hyperammonemia. Seven patients received valproate at a dose higher than 20 mg/kg. The duration of valproate use varied from 1 week to 19 years before developing VHE. Dose reduction or discontinuation and lactulose were the most common management strategies used. All 10 patients improved. Among the 7 patients in whom valproate was discontinued, for 2 patients valproate was reinitiated in inpatient care with careful monitoring and was found to be well tolerated., Conclusions: This case series highlights the need for a high index of suspicion for VHE as it is frequently associated with a delayed diagnosis and recovery in psychiatric settings. Screening for risk factors and serial monitoring may allow earlier diagnosis and management., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In this review we trace the passage of fundamental ideas through 20 th century cancer research that began with observations on mustard gas toxicity in World War I. The transmutation of these ideas across scientific and national boundaries, was channeled from chemical carcinogenesis labs in London via Yale and Chicago, then ultimately to the pharmaceutical industry in Bielefeld, Germany. These first efforts to checkmate cancer with chemicals led eventually to the creation of one of the most successful groups of cancer chemotherapeutic drugs, the oxazaphosphorines, first cyclophosphamide (CP) in 1958 and soon thereafter its isomer ifosfamide (IFO). The giant contributions of Professor Sir Alexander Haddow, Dr. Alfred Z. Gilman & Dr. Louis S. Goodman, Dr. George Gomori and Dr. Norbert Brock step by step led to this breakthrough in cancer chemotherapy. A developing understanding of the metabolic disposition of ifosfamide directed efforts to ameliorate its side-effects, in particular, ifosfamide-induced encephalopathy (IIE). This has resulted in several candidates for the encephalopathic metabolite, including 2-chloroacetaldehyde, 2-chloroacetic acid, acrolein, 3-hydroxypropionic acid and S-carboxymethyl-L-cysteine. The pros and cons for each of these, together with other IFO metabolites, are discussed in detail. It is concluded that IFO produces encephalopathy in susceptible patients, but CP does not, by a "perfect storm," involving all of these five metabolites. Methylene blue (MB) administration appears to be generally effective in the prevention and treatment of IIE, in all probability by the inhibition of monoamine oxidase in brain potentiating serotonin levels that modulate the effects of IFO on GABAergic and glutamatergic systems. This review represents the authors' analysis of a large body of published research., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose.

Metronidazole (MNZ) is a widely used drug for protozoan and anaerobic infections. The continuous use of MNZ causes various neurological symptoms, such as cerebellar ataxia, visual disturbance, vestibulocochlear symptoms, gait disturbance, dysarthria, and epileptic seizures of unknown cause, named MNZ-induced encephalopathy (MIE), in rare cases. MIE is a reversible disease that often improves within a few days of MNZ discontinuation, but irreversible neurological symptoms rarely remain. Herein, we report a case of MIE that developed during MNZ administration for a liver abscess, causing prolonged unconsciousness and death even after drug discontinuation. An 85-year-old female patient complained of fever, elevated liver enzymes, and a multifocal abscess in the right hepatic lobe, as seen on computed tomography. Percutaneous transhepatic abscess drainage and antibiotic therapy were initiated. The causative agent of the liver abscess could not be identified, thus meropenem was started, which demonstrated no inflammation improvement, thus oral MNZ was added. The inflammation recurred when MNZ was discontinued, and the patient continued taking MNZ. Vomiting, upper limb tremors, consciousness disturbance, and convulsions appeared on day 46 (total dose of MNZ 73.5mg), and the patient was hospitalized. T2-weighted, diffusion-weighted, and FLAIR head magnetic resonance imaging (MRI) revealed symmetrical abnormal high-signal areas in the cerebellar dentate nucleus, corpus callosum, cerebral white matter, and periventricular areas. MIE was diagnosed based on the patient's course and MRI images, and MNZ was discontinued. The patient continued to suffer from impaired consciousness and convulsions after MNZ discontinuation and died due to aspiration pneumonia. Suggestively, MIE development is related to long-term MNZ administration, poor nutrition, liver disease, underlying diseases (such as advanced cancer), and serious complications. A systematic review of MIE cases revealed that 4.8-5.9% of the patients demonstrated little improvement of symptoms after MNZ discontinuation, and some deaths were reported. Patients with poor prognosis were often suffering from impaired consciousness and convulsions. Furthermore, impaired consciousness was the most common residual symptom. Abnormal signals in characteristic areas, such as the dentate nucleus cerebri and corpus callosum, on head MRI are useful for MIE diagnosis, especially in patients with abnormal findings in the cerebral white matter, which is associated with a poor prognosis. We should pay close attention to the onset of MIE when MNZ is administered.