Seizures after initiation of rewarming in cooled infants with hypoxic ischaemic encephalopathy.

BACKGROUND: Seizures after initiation of rewarming from therapeutic hypothermia for neonatal encephalopathy are well recognised but not easy to predict. METHODS: A secondary analysis was performed of NEOLEV2 trial data, a multicentre randomised trial of levetiracetam versus phenobarbital for neonatal seizures. Enrolled infants underwent continuous video EEG (cEEG) monitoring. The trial data were reviewed for 42 infants with seizures during therapeutic hypothermia and 118 infants who received therapeutic hypothermia but had no seizures on cEEG. RESULTS: Overall, 112 of 160 (70%) had cEEG monitoring continued until rewarming was completed. Of the 42 infants with prior seizures, there were 30 infants with valid cEEG available and seizures occurred following the initiation of rewarming in 8 (26.6%). For the 118 seizure-naive infants, 82 (69.5%) continued cEEG until either rewarming was completed or 90 h of age and none had documented seizures. CONCLUSION: Overall, just over a quarter of infants with prior seizures had cEEG evidence of at least one seizure in the 24 h after initiation of rewarming but no seizure-naive infant had cEEG evidence of seizure(s) on rewarming. Critically, by reporting the two groups separately, the data can provide guidance on the duration of EEG monitoring. IMPACT: Infants with hypoxic ischaemic encephalopathy who have cEEG evidence of seizures during therapeutic hypothermia have a significant risk of further seizures on rewarming. For infants with hypoxic ischaemic encephalopathy but no cEEG evidence of seizures during therapeutic hypothermia, there is very little risk of de novo seizures. Ongoing work utilising large cohorts may generate EEG criteria that refine estimates of risk for rewarming seizures. Based on current experience, if seizures have occurred during therapeutic hypothermia for hypoxic ischaemic encephalopathy, the EEG monitoring should be continued during rewarming and for 12 h thereafter to minimise the risk of missing an event.

Indications and prescribing patterns of antiseizure medications in children in New Zealand.

AIM: To determine indications and prescribing patterns for antiseizure medications (ASMs) in children by age, sex, and socioeconomic status. METHOD: This retrospective study searched the New Zealand database of ASM prescriptions dispensed to individuals aged 18 years or under during 2015 in three regions of New Zealand (48% paediatric population). Medical records were reviewed by a paediatric neurologist for indication. ASMs were grouped into old or new (1993 onwards). RESULTS: In total, 2594 children (0 to 18 years, mean age 11 years 2 months, median 12 years; 51% male) were dispensed 3557 ASMs for seizures (76%), pain (6%), headache (5%), mental health (3%), and movement disorders (2%). After 10 years of age, lamotrigine was more likely and valproate less likely to be prescribed in females than males. No sex difference was observed for valproate prescriptions for non-seizure indications. Topiramate prescriptions increased in adolescent females. Prescriptions for non-seizure indications increased from 7% in children aged 6 years or under to 31% in 16- to 18-year-olds. The proportion of children receiving a new ASM compared to an old ASM was greater in children from higher than lower socioeconomic areas. INTERPRETATION: Our results highlight a need for focused ASM teratogenicity messaging to clinicians prescribing ASMs for non-seizure indications. In addition, to improve equity of epilepsy care, it is critical for health policies to consider socioeconomic factors that impact on ASM prescribing.

PIGN encephalopathy: Characterizing the epileptology.

OBJECTIVE: Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy. METHODS: We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment. Seizure and epilepsy types were classified. RESULTS: Twenty six patients (13 female) from 26 families were identified, with mean age 7 years (range = 1 month to 21 years; three deceased). Abnormal development at seizure onset was present in 25 of 26. Developmental outcome was most frequently profound (14/26) or severe (11/26). Patients presented with focal motor (12/26), unknown onset motor (5/26), focal impaired awareness (1/26), absence (2/26), myoclonic (2/26), myoclonic-atonic (1/26), and generalized tonic-clonic (2/26) seizures. Twenty of 26 were classified as developmental and epileptic encephalopathy (DEE): 55% (11/20) focal DEE, 30% (6/20) generalized DEE, and 15% (3/20) combined DEE. Six had intellectual disability and epilepsy (ID+E): two generalized and four focal epilepsy. Mean age at seizure onset was 13 months (birth to 10 years), with a lower mean onset in DEE (7 months) compared with ID+E (33 months). Patients with DEE had drug-resistant epilepsy, compared to 4/6 ID+E patients, who were seizure-free. Hyperkinetic movement disorder occurred in 13 of 26 patients. Twenty-seven of 34 variants were novel. Variants were truncating (n = 7), intronic and predicted to affect splicing (n = 7), and missense or inframe indels (n = 20, of which 11 were predicted to affect splicing). Seven variants were recurrent, including p.Leu311Trp in 10 unrelated patients, nine with generalized seizures, accounting for nine of the 11 patients in this cohort with generalized seizures. SIGNIFICANCE: PIGN encephalopathy is a complex autosomal recessive disorder associated with a wide spectrum of epilepsy phenotypes, typically with substantial profound to severe developmental impairment.

Status epilepticus in Auckland, New Zealand: Incidence, etiology, and outcomes.

OBJECTIVE: To determine the incidence, etiology, and outcome of status epilepticus (SE) in Auckland, New Zealand, using the latest International League Against Epilepsy (ILAE) SE semiological classification. METHODS: We prospectively identified patients presenting to the public or major private hospitals in Auckland (population = 1.61 million) between April 6, 2015 and April 5, 2016 with a seizure lasting 10 minutes or longer, with retrospective review to confirm completeness of data capture. Information was recorded in the EpiNet database. RESULTS: A total of 477 episodes of SE occurred in 367 patients. Fifty-one percent of patients were aged <15 years. SE with prominent motor symptoms comprised 81% of episodes (387/477). Eighty-four episodes (18%) were nonconvulsive SE. Four hundred fifty episodes occurred in 345 patients who were resident in Auckland. The age-adjusted incidence of 10-minute SE episodes and patients was 29.25 (95% confidence interval [CI] = 27.34-31.27) and 22.22 (95% CI = 20.57-23.99)/100 000/year, respectively. SE lasted 30 minutes or longer in 250 (56%) episodes; age-adjusted incidence was 15.95 (95% CI = 14.56-17.45) SE episodes/100 000/year and 12.92 (95% CI = 11.67-14.27) patients/100 000/year. Age-adjusted incidence (10-minute SE) was 25.54 (95% CI = 23.06-28.24) patients/100 000/year for males and 19.07 (95% CI = 16.91-21.46) patients/100 000/year for females. The age-adjusted incidence of 10-minute SE was higher in Maori (29.31 [95% CI = 23.52-37.14]/100 000/year) and Pacific Islanders (26.55 [95% CI = 22.05-31.99]/100 000/year) than in patients of European (19.13 [95% CI = 17.09-21.37]/100 000/year) or Asian/other descent (17.76 [95% CI = 14.73-21.38]/100 000/year). Seventeen of 367 patients in the study died within 30 days of the episode of SE; 30-day mortality was 4.6%. SIGNIFICANCE: In this population-based study, incidence and mortality of SE in Auckland lie in the lower range when compared to North America and Europe. For pragmatic reasons, we only included convulsive SE if episodes lasted 10 minutes or longer, although the 2015 ILAE SE classification was otherwise practical and easy to use.

The epileptology of GNB5 encephalopathy.

Pathogenic variants in GNB5 cause an autosomal recessive neurodevelopmental disorder with neonatal sinus bradycardia. Seizures or epilepsy occurred in 10 of 22 previously reported cases, including 6 children from one family. We delineate the epileptology of GNB5 encephalopathy. Our nine patients, including five new patients, were from seven families. Epileptic spasms were the most frequent seizure type, occurring in eight of nine patients, and began at a median age of 3 months (2 months to 3 years). Focal seizures preceded spasms in three children, with onset at 7 days, 11 days, and 4 months. One child presented with convulsive status epilepticus at 6 months. Three children had burst suppression on electroencephalography (EEG), three had hypsarrhythmia, and one evolved from burst suppression to hypsarrhythmia. Background slowing was present in all after age 3 years. Magnetic resonance imaging (MRI) showed cerebral atrophy in one child and cerebellar atrophy in another. All nine had abnormal development prior to seizure onset and ultimately had profound impairment without regression. Hypotonia was present in all, with contractures developing in two older patients. All individuals had biallelic pathogenic variants in GNB5, predicted by in silico tools to result in protein truncation and loss-of-function. GNB5 developmental and epileptic encephalopathy is characterized by epileptic spasms, focal seizures, and profound impairment.

Use of the EpiNet database for observational study of status epilepticus in Auckland, New Zealand.

The EpiNet project has been established to facilitate investigator-initiated clinical research in epilepsy, to undertake epidemiological studies, and to simultaneously improve the care of patients who have records created within the EpiNet database. The EpiNet database has recently been adapted to collect detailed information regarding status epilepticus. An incidence study is now underway in Auckland, New Zealand in which the incidence of status epilepticus in the greater Auckland area (population: 1.5 million) will be calculated. The form that has been developed for this study can be used in the future to collect information for randomized controlled trials in status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus".

Acute Colonic Pseudo-Obstruction (Ogilvie's Syndrome) Following Total Laparoscopic Hysterectomy.

Rapid identification of acute colonic pseudo-obstruction (ACPO), or Ogilvie's syndrome, is paramount in the management of this condition, which, if unresolved, can progress to bowel ischemia and perforation with significant morbidity and mortality. We present the first case report, to our knowledge, of ACPO following total laparoscopic hysterectomy. We describe the presentation and management of ACPO in a patient who underwent uncomplicated total laparoscopic hysterectomy to treat menorrhagia and dysmenorrhea after declining conservative treatment. Following initial conservative management, the patient rapidly deteriorated and required laparotomy for clinically suspected cecal ischemia. Cecal resection, colonic decompression, and end ileostomy formation were performed. A brief review of the current literature is presented with respect to the case report.

Informed substitution of hazardous chemicals through the lens of California's Safer Consumer Products Alternatives Analysis: Best practices, challenges, and opportunities.

California adopted the Safer Consumer Products (SCP) regulations in 2013, which mandate that companies that manufacture specific products containing designated chemicals of concern complete an Alternatives Analysis. Alternatives Analysis is a process to avoid regrettable substitution by identifying, comparing, and selecting safer alternatives based on technical functions, hazards, exposure pathways, life-cycle multimedia impacts, and economic impacts. The SCP Alternatives Analysis builds upon and expands existing frameworks for alternatives assessments (AAs). The aim of this study was to identify practices from AA that facilitate the robust assessment of alternatives and that align with SCP requirements and identify gaps in the practice. We evaluated completed AAs for methods regarding transparency and careful documentation of information sources, data gaps, uncertainty, criteria, and justification for decision-making. The AAs in this review demonstrate some of the challenges in the field. Most AAs have a constrained scope and only consider chemical substitutes rather than a broad array of functional alternatives. Their scopes were also limited in the hazard endpoints that were evaluated. This was most noted with ecotoxicity endpoints, which were generally confined to aquatic toxicity. The majority of AAs do not explicitly explain their decision-making methods or adequately discuss tradeoffs across the adverse impacts. The AAs also lack the analysis in the exposure, life-cycle impacts, and economic impacts that are required in the SCP Alternatives Analysis process. Further, we recommend strategies and research opportunities to address these challenges and strengthen the practice of AAs. Integr Environ Assess Manag 2022;18:1007-1019. © 2021 SETAC.

Optical Flow Estimation Improves Automated Seizure Detection in Neonatal EEG.

PURPOSE: Existing automated seizure detection algorithms report sensitivities between 43% and 77% and specificities between 56% and 90%. The algorithms suffer from false alarms when applied to neonatal EEG because of the high degree of nurse handling and rhythmic patting used to soothe neonates. Computer vision technology that quantifies movement in real time could distinguish artifactual motion and improve automated neonatal seizure detection algorithms. METHODS: The authors used video EEG recordings from 43 neonates undergoing monitoring for seizures as part of the NEOLEV2 clinical trial. The Persyst neonatal automated seizure detection algorithm ran in real time during study EEG acquisitions. Computer vision algorithms were applied to extract detailed accounts of artifactual movement of the neonate or people near the neonate though dense optical flow estimation. RESULTS: Using the methods mentioned above, 197 periods of patting activity were identified and quantified, of which 45 generated false-positive automated seizure detection events. A binary patting detection algorithm was trained with a subset of 470 event videos. This supervised detection algorithm was applied to a testing subset of 187 event videos with 8 false-positive events, which resulted in a 24% reduction in false-positive automated seizure detections and a 50% reduction in false-positive events caused by neonatal care patting, while maintaining 11 of 12 true-positive seizure detection events. CONCLUSIONS: This work presents a novel approach to improving automated seizure detection algorithms used during neonatal video EEG monitoring. This artifact detection mechanism can improve the ability of a seizure detector algorithm to distinguish between artifact and true seizure activity.

Infantile-onset myoclonic developmental and epileptic encephalopathy: A new RARS2 phenotype.

Recessive variants in RARS2, a nuclear gene encoding a mitochondrial protein, were initially reported in pontocerebellar hypoplasia. Subsequently, a recessive RARS2 early-infantile (<12 weeks) developmental and epileptic encephalopathy was described with hypoglycaemia and lactic acidosis. Here, we describe two unrelated patients with a novel RARS2 phenotype and reanalyse the published RARS2 epilepsy phenotypes and variants. Our novel cases had infantile-onset myoclonic developmental and epileptic encephalopathy, presenting with a progressive movement disorder from 9 months on a background of normal development. Development plateaued and regressed thereafter, with mild to profound impairment. Multiple drug-resistant generalized and focal seizures occurred with episodes of non-convulsive status epilepticus. Seizure types included absence, atonic, myoclonic, and focal seizures. Electroencephalograms showed diffuse slowing, multifocal, and generalised spike-wave activity, activated by sleep. Both patients had compound heterozygous RARS2 variants with likely impact on splicing and transcription. Remarkably, of the now 52 RARS2 variants reported in 54 patients, our reanalysis found that 44 (85%) have been shown to or are predicted to affect splicing or gene expression leading to protein truncation or nonsense-mediated decay. We expand the RARS2 phenotypic spectrum to include infantile encephalopathy and suggest this gene is enriched for pathogenic variants that disrupt splicing.

Failure of the Milwaukee protocol in a child with rabies.

Rabies has the highest case-fatality rate of all infectious diseases, with 50,000 cases occurring annually worldwide. In 2004 an unvaccinated adolescent survived after novel therapy. We report the management of a child with rabies. Although the implementation of this same therapeutic protocol was successful, the child died after 1 month of hospitalization.

Epidemiology of Treated Epilepsy in New Zealand Children: A Focus on Ethnicity.

BACKGROUND AND OBJECTIVES: To determine the period prevalence and incidence of treated epilepsy in a New Zealand pediatric cohort with a focus on ethnicity and socioeconomic status. METHODS: This was a retrospective cohort study. The New Zealand Pharmaceutical Collection database was searched for individuals ≤18 years of age dispensed an antiseizure medication (ASM) in 2015 from areas capturing 48% of the New Zealand pediatric population. Medical records of identified cases were reviewed to ascertain the indication for the ASM prescription. Population data were derived from the New Zealand 2013 Census. RESULTS: A total of 3,557 ASMs were prescribed during 2015 in 2,594 children, of whom 1,717 (66%) children had epilepsy. An indication for prescription was ascertained for 3,332/3,557 (94%) ASMs. The period prevalence of treated epilepsy was 3.4 per 1,000 children. Children in the most deprived areas had 1.9 times the rate of treated epilepsy (95% confidence interval [CI] 1.6-2.2) as those from the least deprived areas. Prevalence was similar for most ethnic groups (European/other: 3.7, 95% CI 3.4-3.9; Pacific Peoples: 3.6, 95% CI 3.2-4.1; Maori: 3.4, 95% CI 3.1-3.8) apart from Asians, who had a lower prevalence of 2.3 per 1,000 (95% CI 2.0-2.6). However, when adjusted for socioeconomic deprivation, the prevalence of epilepsy was highest in European and similar in Maori, Pacific, and Asian children. DISCUSSION: This is the largest pediatric epidemiology epilepsy study where diagnosis of epilepsy was confirmed by case review. This is the first study to provide epidemiologic information for pediatric epilepsy in Maori and Pacific children.

Does the first hour of continuous electroencephalography predict neonatal seizures?

OBJECTIVE: Prolonged continuous video-electroencephalography (cEEG) is recommended for neonates at risk of seizures. The cost and expertise required to provide a real-time response to detected seizures often limits its utility. We hypothesised that the first hour of cEEG could predict subsequent seizures. DESIGN AND SETTING: Retrospective multicentre diagnostic accuracy study. PATIENTS: 266 term neonates at risk of seizure or with suspected seizures. INTERVENTION: The first hour of cEEG was graded by expert and novice interpreters as normal, mildly, moderately or severely abnormal; seizures were identified. MAIN OUTCOME MEASURES: Association between abnormalities in the first hour of cEEG and the presence of seizures during total cEEG monitoring. RESULTS: 50/98 (51%) of neonates who developed seizures had their first seizure in the first hour of cEEG monitoring. The 'time-to-event' risk of seizure from 0 to 96 hours was 0.38 (95% CI 0.32 to 0.44) while the risk in the first hour was 0.19 (95% CI 0.15 to 0.24). cEEG background was normal in 48% of neonates, mildly abnormal in 30%, moderately abnormal in 13% and severely abnormal in 9%. Inter-rater agreement for determination of background was very good (weighted kappa=0.81, 95% CI 0.72 to 0.91). When neonates with seizures during the first hour were excluded, an abnormal background resulted in 2.4 times increased risk of seizures during the subsequent monitoring period (95% CI 1.3 to 4.4, p<0.003) while a severely abnormal background resulted in a sevenfold increased risk (95% CI 3.4 to 14.3, p<0.0001). CONCLUSIONS: The first hour of cEEG in at-risk neonates is useful in identifying and predicting whether seizures occur during cEEG monitoring up to 96 hours. This finding enables identification of high-risk neonates who require closer observation.

Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures. METHODS: The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists. RESULTS: Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam (P < .001; relative risk 0.35 [95% confidence interval: 0.22-0.56]; modified intention-to-treat population). A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. More adverse effects were seen in subjects randomly assigned to phenobarbital (not statistically significant). CONCLUSIONS: In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.

Assessment of biodegradation in ancient archaeological wood from the Middle Cemetery at Abydos, Egypt.

Abydos is a large, complex archaeological site located approximately 500 km south of Cairo in Upper Egypt. The site has served as a cemetery for thousands of years and is where most of the Early Dynastic royal tombs are located. North Abydos includes the Middle Cemetery and the North Cemetery, which are separated from each other by a wadi. The Middle Cemetery was the burial ground for important Sixth Dynasty (2407-2260 BC) officials and over time for thousands of elite and non-elite individuals as well. Excavations at the core area of the Old Kingdom mortuary landscape have revealed many culturally important wooden objects but these are often found with extensive deterioration that can compromise their preservation. The objectives of this study were to characterize the biodegradation that has taken place in excavated wooden objects, elucidate the type of wood degradation present, obtain information on soil properties at the site and identify fungi currently associated with the wood and soils. Light and scanning electron microscopy studies were used to observe the micromorphological characteristics of the wood, and culturing on different media was done to isolate fungi. Identification of the fungi was done by examining morphological characteristics and extracting rDNA from pure cultures and sequencing the ITS region. Wooden objects, made from Cedrus, Juniperus and Acacia as well as several unidentified hardwoods, were found with extensive degradation and were exceedingly fragile. Termite damage was evident and frass from the subterranean termites along with sand particles were present in most woods. Evidence of soft rot attack was found in sections of wood that remained. Fungi isolated from wood and soils were identified as species of Aspergillus, Chaetomium, Cladosporium, Fusarium, Penicillium, Stemphylium Talaromyces and Trichoderma. Results provide important information on the current condition of the wood and gives insights to the identity of the fungi in wood and soils at the site. These results provide needed information to help develop conservation plans to preserve these degraded and fragile wooden objects.

Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected With Continuous Long-Term Neonatal Electroencephalography Monitoring.

PURPOSE: Continuous video electroencephalography (cEEG) monitoring is the recommended gold standard of care for at-risk neonates but is not available in many Neonatal Intensive Care Units (NICUs). To conduct a randomized treatment trial of levetiracetam for the first-line treatment of neonatal seizures (the NEOLEV2 trial), we developed a monitoring infrastructure at five NICUs, implementing recent technological advancements to provide continuous video EEG monitoring and real-time response to seizure detection. Here, we report on the feasibility of providing this level of care. METHODS: Twenty-five key informant interviews were conducted with study neurologists, neonatologists, coordinators, and EEG technicians from the commercial EEG monitoring company Corticare. A general inductive approach was used to analyze these qualitative data. RESULTS: A robust infrastructure for continuous video EEG monitoring, remote review, and real-time seizure detection was established at all sites. At the time of this survey, 260 babies had been recruited and monitored for 2 to 6 days. The EEG technician review by the commercial EEG monitoring company was reassuring to families and neonatologists and led to earlier detection of seizures but did not reduce work load for neurologists. Neurologists found the automated neonatal seizure detector algorithm provided by the EEG software company Persyst useful, but the accuracy of the algorithm was not such that it could be used without review by human expert. Placement of EEG electrodes to initiate monitoring, especially after hours, remains problematic. CONCLUSIONS: Technological advancements have made it possible to provide at-risk neonates with continuous video EEG monitoring, real-time detection of and response to seizures. However, this standard of care remains unfeasible in usual clinical practice. Chief obstacles remain starting a recording and resourcing the real-time specialist review of suspect seizures.

The carotid chemoreceptors are a major determinant of ventilatory CO2 sensitivity and of PaCO2 during eupneic breathing.

Both carotid and intracranial chemoreceptors are critical to a normal ventilatory CO2-H+ chemosensitivity. At low levels of hypercapnia, the carotid contribution is probably greater than the central contribution but, at high levels, the intracranial chemoreceptors are dominant. The carotid chemoreceptors are also critical to maintaining a stable and normal eupneic PaCO2, but lesion-induced attenuation of intracranial CO2-H+ chemosensitivity does not consistently alter eupneic PaCO2. A major unanswered question is why do intracranial chemoreceptors in carotid body denervation (CBD) animals tolerate an acidosis during eupnea which prior to CBD elicits a marked increase in breathing.

Fracture of a Broviac catheter in a low-birth-weight infant.

Central venous catheters are widely used in children, particularly in very-low-birth-weight infants in whom long-term access to the venous system is required. This may be achieved by using peripherally inserted central catheters or tunnelled central venous lines (eg Broviac or Hickman lines). Previous case reports of fractured central catheters in premature neonates have involved peripherally inserted silastic catheters. Fractures and embolisation of Broviac central venous fragments have not been previously reported in preterm neonates. We describe a premature neonate with this rare complication along with the retrieval technique used.

Chimeric antigen receptor T-cell therapy - assessment and management of toxicities.

Immunotherapy using T cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.