Cefepime-induced encephalopathy in an older patient with polypharmacy and renal insufficiency: a case report.

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.

Metronidazole-Induced Encephalopathy With Probable Crohn Encephalitis: A Case Report.

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.

The incidence and predictors of antibiotic-associated encephalopathy: a multicenter hospital-based study.

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 m2 had significantly higher incidence rates of AAE compared to those with GFRs ≥ 90 mL/min/1.73 m2 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.

A rare case of daratumumab-associated encephalopathy in multiple myeloma.

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.

Daratumumab is a drug. It is used to treat multiple myeloma. Many patients use this drug. It has many side effects. But consciousness disorder is rare. A 57-year-old male was diagnosed with multiple myeloma. He was treated with daratumumab. He became unconscious after this treatment. Steroids helped his recovery.

Hyperammonemic encephalopathy after tyrosine kinase inhibitors: A literature review and a case example.

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.

Unusual case of sodium valproate-induced hyperammonaemia encephalopathy.

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.

[A case of irreversible metronidazole encephalopathy during liver abscess treatment].

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.

Acute Toxic Encephalopathy in Occupational Exposure with Polyvinyl Chloride (PVC) Fumes: A Case Series.

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.

A Case of Encephalopathy Caused by Drug Interaction between Ifosfamide and Aprepitant.

A 72-year-old man with a malignant retroperitoneal soft tissue tumor was treated with ifosfamide (IFO) for 5 consecutive days (1.8 g/m2/d×5 d, expected dose 9 g/m2). The patient developed neurological symptoms such as mild somnolence, seizures, and inability to write from Day 1, and became delirious on Day 3, so IFO was discontinued on Day 4 (dose: 7.2 g/m2). Since there are reports of drug interactions that increase the frequency of encephalopathy when combined with aprepitant (Apr), Dexamethasone was increased and IFO was administered without the use of Apr after the second course, and there was no recurrence of encephalopathy in the second and third courses. IFO-induced encephalopathy is considered to occur due to an increase in blood concentration of IFOs caused by high dosage, decreased renal function, or other factors. In this case, encephalopathy was observed even though the dose of IFO was reduced due to the patient's advanced age and impaired renal function. The combination use of Apr with IFO should be considered with caution for the occurrence of adverse events, including encephalopathy, and if possible, control of gastrointestinal toxicity with other antiemetic agents should be considered.

Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial.

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/m2, 80 mg/m2, 135 mg/m2, 175 mg/m2, 215 mg/m2, and 260 mg/m2) 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/m2), and 12 patients were treated at dose level 6 (260 mg/m2). 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/m2, 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/m2 in the case of the grade 3 encephalopathy, and to 215 mg/m2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m2 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.

Flow diagram of the differential diagnosis and clinical decision making in a rare case of contrast-induced encephalopathy following cardiac catheterization: a case report.

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.

The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms.

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 PM2.5 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 PM2.5 pollution on the brain. The paper also highlights quercetin's potential health benefits and anti-inflammatory and neuroprotective properties.

Ifosfamide - History, efficacy, toxicity and encephalopathy.

In this review we trace the passage of fundamental ideas through 20th 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.

Methotrexate-induced Subacute Encephalopathy That Showed No Abnormalities on Magnetic Resonance Imaging Soon after Symptom Appearance.

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.

Correlation of magnetic resonance images with neuropathology of irreversible metronidazole-induced encephalopathy: an autopsy case report.

BACKGROUND: Neurological symptoms and radiographic abnormalities may remain in a small proportion of patients with metronidazole-induced encephalopathy (MIE). Although experimental animal models of MIE have suggested a Wernicke's encephalopathy-like pathology, little is known about the histopathological features of MIE. Here we report the first autopsy case of irreversible MIE. CASE PRESENTATION: A 72-year-old Japanese woman with pancreatic neuroendocrine tumour and metastatic tumours in the liver developed intraabdominal bleeding from a hepatic abscess. She was administered metronidazole for 79 days (1.5 g/day), which caused dysarthria followed by hand tremor and altered mental status. Brain magnetic resonance imaging at the time of onset revealed hyperintensities in the deep white matter of the bilateral parietal lobes and splenium of the corpus callosum on diffusion-weighted imaging (DWI) with reduced apparent diffusion coefficient (ADC) values. Despite the improvement of dysarthria and hand tremor, her cognition remained affected even after the withdrawal of metronidazole. She died of pancreatic neuroendocrine tumour at the age of 74 years. Histopathological examinations of the brain confirmed a combination of severe demyelination and moderate axonal degeneration, which corresponded to the regions showing abnormal signal intensities on DWI with reduced ADC values. There were no pathological findings suggestive of Wernicke's encephalopathy in the brain. CONCLUSION: We have demonstrated the clinical, radiographic and histopathological aspects of irreversible MIE. Hyperintensities on DWI with reduced ADC values in affected regions may indicate a poor clinical prognosis due to irreversible pathological damage.

[Clinical characteristics and prognosis of seizures in 75 children with acute lymphoblastic leukemia].

OBJECTIVE: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. METHODS: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. RESULTS: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. CONCLUSION: Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.

Idiopathic hyperammonemic encephalopathy secondary to gemcitabine-cisplatin treatment.

Idiopathic hyperammonemic encephalopathy is a rare complication of chemotherapy, which has previously mainly been associated with L-asparaginase, cytarabine and 5-FU. We present a case following treatment with gemcitabine-cisplatin in a patient with cholangiocarcinoma. The etiology of chemotherapy-induced idiopathic hyperammonemic encephalopathy remains unclear and existing theories differ per chemotherapeutic agent. Physicians treating patients with gemcitabine-cisplatin should be aware of the possibility of this complication, especially because it is treatable when recognized early.

Cefepime-induced neurotoxicity: systematic review.

BACKGROUND: Cefepime-induced neurotoxicity (CIN) has been well acknowledged among clinicians, although there are no clear diagnostic criteria or specific laboratory testing to help with its diagnosis. We aimed to summarize the existing evidence regarding CIN and provide future agendas for research. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and Embase for all peer-reviewed articles using keywords including 'cefepime', 'neurotoxicity', 'encephalopathy' and 'seizure', from their inception to 20 January 2022. RESULTS: We included 92 articles, including 23 observational studies and 69 cases from case reports and case series, in the systematic review. Among 119 patients with CIN, 23.5% were in the ICU at the time of diagnosis and nearly 90% of the cases showed renal dysfunction.Cefepime overdoses were described in 41%. The median latency period of developing CIN from cefepime initiation was 4 days, and about 12% developed CIN during empirical treatment. CIN patients commonly manifested altered mental status (93%), myoclonus (37%) and non-convulsive seizure epilepticus (28%). A serum cefepime trough level of >20 mg/L would put patients at risk for CIN. CIN-related symptoms were ameliorated in 97.5% by dose reduction or discontinuation of cefepime, with median time to improvement of 3 days. No CIN-associated deaths were reported. CONCLUSIONS: This systematic review summarizes the current evidence and characteristics of CIN. In the current situation where there are no CIN diagnostic criteria and the drug monitoring platform is not routinely available, candidates for cefepime should be carefully selected. Also, based on these findings, it needs to be appropriately dosed to avoid the development of CIN.

Ifosfamide-induced Encephalopathy With Rapid Response to Thiamine: A Pediatric Case.

Ifosfamide is an important chemotherapeutic agent used in the therapeutic protocols of many malignant tumors. Central nervous system toxicity of ifosfamide manifests with encephalopathy in 10% to 30% of patients treated with ifosfamide. Thiamine and methylene blue have been reported beneficial in the treatment and prevention of ifosfamide-induced encephalopathy (IIE). We describe an episode of encephalopathy developed at the third cycle of ifosfamide treatment in a child with Ewing sarcoma. With the administration of thiamin, the encephalopathy resolved and no episode was noted during subsequent courses of ifosfamide. Previous use of cisplatin, concomitant use of opioids, low levels of serum albumin and hemoglobin, and elevated levels of serum creatinine are potential risk factors for IIE. The current case illustrates the possibility of IIE even in the absence of such additional risk factors, treated successfully with thiamin and draws attention to the need for close neurological monitorization of patients treated with ifosfamide.

Multiple cycles of granulocyte colony-stimulating factor in decompensated cirrhosis: a double-blind RCT.

BACKGROUND: Liver transplant, the definitive treatment of decompensated cirrhosis (DC), is constrained by donor shortage and long-term complications. Granulocyte colony-stimulating factor (G-CSF) has been explored as an alternative option in open-label studies. This double-blind, randomized, placebo-controlled trial was designed to elucidate the efficacy of G-CSF in DC. METHODS: Seventy patients were randomized to either G-CSF plus standard medical therapy (group A, n = 35) or placebo plus standard medical therapy (group B, n = 35). Primary outcome was 12-month overall survival in patients who received at least one cycle of intervention. Secondary outcomes were mobilization of CD34+ cells at day 6, improvement in Child-Turcotte-Pugh (CTP), and model for end-stage liver disease (MELD), liver stiffness measurement, quality of life, nutrition, hepatic decompensation, infection, hospitalization, and acute kidney injury. RESULTS: Survival in group A was higher than that in Group B although the difference was not statistically significant (87.9% vs 66.7%; p = 0.053). CD34+ cells at day 6 were significantly higher in group A as compared to baseline (p < 0.001). Ascites control (p = 0.03) and CTP score improvement (p = 0.02) were better in group A at 12-months. Encephalopathy episodes (p = 0.005), infections (p = 0.005) were fewer in group A than group B at 12 months. Other secondary outcomes did not improve post-therapy. There were no treatment-related discontinuations or severe adverse events. CONCLUSIONS: G-CSF therapy is safe. The improvement in survival at 12 months is not statistically significant. Better control of ascites, improvement of CTP score, fewer encephalopathy episodes and decreased rate of infections were observed with G-CSF therapy (NCT03911037). Trials Registration NCT03911037.