Individualized Care Delivery for Children With Autism and Related Disabilities Undergoing Overnight Video Electroencephalography (EEG): One Hospital's Experience With a Coordinated Team Approach.

Background and Purpose: Children with developmental disabilities have increased risk of epilepsy and need for overnight video electroencephalographic (EEG) monitoring. However, video EEGs have historically been considered difficult to complete for this population. An autism support service at a pediatric tertiary care hospital implemented a coordinated team approach to help children with developmental disability tolerate overnight video EEGs. The project included completion of a caregiver-report preprocedure questionnaire that then was shared with the multidisciplinary team and used to create individualized care plans. The current study aims to describe rates of video EEG completion and need for lead placement under general anesthesia among children with autism and related disabilities who received these supports. Methods: Rates of video EEG completion and general anesthesia use were analyzed for children referred to the support service between April 2019 and November 2021. Results: A total of 182 children with developmental disability (mean age = 10.3 years, 54.9% diagnosed with autism) met inclusion criteria. 92.9% (n = 169) of children successfully completed EEG (leads on ≥12 hours). Only 19.2% (n = 35) required general anesthesia for video EEG lead placement. The majority (80.2%) of parents (n = 146) completed the preprocedure questionnaire. Video EEG outcomes did not differ based on completion of the questionnaire. Parent-reported challenges with communication and cooperation were associated with shorter video EEG duration and greater use of general anesthesia. Conclusions: These findings suggest that most children with developmental disability can complete video EEG with sufficient support. Preprocedure planning can identify children who would benefit from additional accommodations. Further research is necessary to clarify which supports are most helpful.

Glial Fibrillary Acidic Protein (GFAP) Astrocytopathy: An Emerging Cause of Meningoencephalomyelitis in Children and Adolescents.

Introduction: We describe 5 children with GFAP astrocytopathy with the goal of further characterizing this rare form of meningoencephalomyelitis. Methods: Retrospective chart review of patients diagnosed with GFAP astrocytopathy between 2019 and 2021. Results: Patients were 8-17 years old, and all were male. Fever, headache, and vomiting were common presenting symptoms, and weakness, tremor, and ataxia were common initial examination findings. Initial magnetic resonance imaging (MRI) showed spinal cord abnormalities in 2 patients and leptomeningeal enhancement in 1. Most patients had cerebral spinal fluid pleocytosis, and all screened negative for malignancy. Three patients progressed to coma, and all were treated with immunosuppressant therapy. By discharge, all patients had improved over their clinical nadir, although none had returned to baseline. Discussion: GFAP astrocytopathy is a recently recognized cause of meningoencephalomyelitis in children. Here, we expand our understanding of this entity with the goal of aiding those treating children with GFAP astrocytopathy.

Chimeric Viruses Containing Select Agents: The Biology Behind Their Creation, Attenuation, and Exclusion From Regulation.

The US Centers for Disease Control and Prevention (CDC), as part of the Federal Select Agent Program, and under the purview of 42 CFR §73.3, has the ability to regulate chimeric viruses that contain portions of pathogens that are part of the select agents and toxins list. In addition, the CDC is responsible for excluding pathogens from regulation, including chimeric viruses, that are sufficiently attenuated. Since 2003, the CDC has excluded over 20 chimeric viruses that contain portions of select agents. But in late 2021, the CDC proposed a regulatory first-the addition of a chimeric virus to the select agents and toxins list. To better understand the importance and applicability of this action, we surveyed the landscape of previous exclusions from select agent regulation. First, we reviewed the exclusion criteria used by the Intragovernmental Select Agents and Toxins Technical Advisory Committee in their advisement of the Federal Select Agent Program. We then reviewed the literature on chimeric viruses that contain portions of select agents and that have been excluded from regulation due to sufficient attenuation, focusing on chimeric alphaviruses and chimeric avian influenza viruses. By analyzing biological commonalities and patterns in the structure and methodology of the development of previously excluded chimeric viruses, we provide insight into how the CDC has used exclusion criteria in the past to regulate chimeric viruses. We conclude by contrasting previous exclusions with the recent addition of SARS-CoV-1/SARS-CoV-2 chimeric viruses to the select agents and toxins list, demonstrating that this addition strays from established, effective regulatory processes, and is thus a regulatory misstep.

Regulating Select Agent Chimeras: Defining the Problem(s) Through the Lens of SARS-CoV-1/SARS-CoV-2 Chimeric Viruses.

In late 2021, the US Centers for Disease Control and Prevention (CDC) posted an interim final rule (86 FR 64075) to the federal register regulating the possession, use, and transfer of SARS-CoV-1/SARS-CoV-2 chimeric viruses. In doing so, the CDC provided the reasoning that viral chimeras combining the transmissibility of SARS-CoV-2 with the pathogenicity and lethality of SARS-CoV-1 pose a significant risk to public health and should thus be placed on the select agents and toxins list. However, 86 FR 64075 lacked clarity in its definitions and scope, some of which the CDC addressed in response to public comments in the final rule, 88 FR 13322, in early 2023. To evaluate these regulatory actions, we reviewed the existing select agent regulations to understand the landscape of chimeric virus regulation. Based on our findings, we first present clear definitions for the terms "chimeric virus," "viral chimera," and "virulence factor" and provide a list of SARS-CoV-1 virulence factors in an effort to aid researchers and federal rulemaking for these agents moving forward. We then provide suggestions for a combination of similarity and functional characteristic cutoffs that the government could use to enable researchers to distinguish between regulated and nonregulated chimeras. Finally, we discuss current select agent regulations and their overlaps with 86 FR 64075 and 88 FR 13322 and make suggestions for how to address chimera concerns within and/or without these regulations. Collectively, we believe that our findings fill important gaps in current federal regulations and provide forward-looking philosophical and practical analysis that can guide future decisionmaking.

Clinical outcomes and safety of anakinra in the treatment of multisystem inflammatory syndrome in children: a single center observational study.

BACKGROUND AND OBJECTIVE: Evidence for the treatment of multisystem inflammatory syndrome in children (MIS-C) is lacking. Anakinra, which targets IL-1-mediated inflammation, is reserved for refractory cases of MIS-C; however, its use in the treatment of MIS-C is not clearly established. PATIENTS AND METHODS: To examine a role for anakinra in MIS-C, we performed a single center observational cohort study of all MIS-C patients diagnosed at our children's hospital from May 15 to November 15, 2020. Demographics, clinical features, diagnostic testing, and cardiac function parameters were compared between MIS-C patients treated with intravenous immunoglobulin (IVIG) monotherapy and IVIG with anakinra (IVIG + anakinra). RESULTS: Among 46 patients with confirmed MIS-C, 32 (70%) were in the IVIG + anakinra group, of which 9 (28%) were also given corticosteroids (CS). No patients were treated with anakinra alone. MIS-C patients in the IVIG + anakinra group were enriched in a CV shock phenotype (p = 0.02), and those with CV shock were treated with higher doses of anakinra for a longer duration. Furthermore, MIS-C patients in the IVIG + anakinra group exhibited improvements in fever and cardiac function with or without CS. No significant adverse events were observed, and no differences in IL-1ß levels were found among MIS-C patients in the IVIG + anakinra group. CONCLUSIONS: Anakinra treatment, which was co-administered with IVIG primarily in patients with severe MIS-C, was associated with improvements in fever and cardiac function, and demonstrated a favorable side-effect profile. These findings suggest a role for adjunctive anakinra in the treatment of severe MIS-C.

Post-intubation analgesia and sedation following succinylcholine vs. rocuronium in the emergency department.

BACKGROUND: Succinylcholine and rocuronium are the most commonly utilized neuromuscular blocker agents (NMBAs) for rapid sequence intubation (RSI) in the emergency department (ED). The duration of action of rocuronium is significantly longer (∼30 min) compared to succinylcholine (∼10 min) and previous studies have shown that patients receiving rocuronium are more likely to have longer time to sedation initiation following RSI. Furthermore, patients receiving rocuronium may be more likely to experience awareness with paralysis than those receiving succinylcholine. The primary goal for this study was to evaluate the association between NMBA use during RSI and post-intubation sedation and analgesia practices in the ED. METHODS: This was a retrospective, multicenter cohort study including patients 18 years and older that received succinylcholine or rocuronium during RSI in the ED between September 1, 2020 and August 31, 2021. Patients were excluded if they were intubated prior to ED arrival, experienced an out-of-hospital or in ED cardiac arrest, or received sugammadex within 60 min of rocuronium administration. Patients were screened in reverse chronological order until the targeted sample size was achieved and all data was abstracted from the electronic health record. The primary outcome was the time to initiation of analgesia or sedation. Secondary outcomes included dose of sedatives or analgesia administered at 30- and 60 min, and medications administered for post-intubation sedation or analgesia. FINDINGS: A total of 200 ED patients were included of which 100 received succinylcholine and 100 received rocuronium. There was no difference in the median time to initiation of analgesia or sedation between the succinylcholine and rocuronium groups (10 vs 8.5 min, p = 0.82) or in Kaplan-Meier cumulative probabilities (p = 0.17). At 60 min post-RSI, those receiving succinylcholine received significantly higher median doses of propofol (20 µg/kg/min vs. 10 µg/kg/min; p = 0.02) and fentanyl [100 µg vs. 84.2 µg; p = 0.02]. CONCLUSION: While no differences were observed in the time to initiation of post-intubation sedation or analgesia in ED patients receiving succinylcholine compared to rocuronium, differences in the intensity of post-intubation regimens was observed. Further investigation is needed to evaluate the adequacy of sedation following RSI in the ED.

The State of Inpatient Child Neurology: A Survey of North American Academic Programs.

BACKGROUND AND OBJECTIVES: Inpatient child neurology programs provide essential services for children. We sought to understand the current structure and challenges of inpatient pediatric neurologic care delivery in academic programs in North America. METHODS: We identified a single child neurologist from 39 of the first 40 programs on the 2019-2020 US News and World Report ranking and 3 large Canadian programs to be invited to participate in an inpatient focused survey. In October 2020, these 42 child neurologists were invited to complete an anonymous on-line survey including 37 questions about the structure, workload, and challenges of their inpatient program. Data was analyzed descriptively. RESULTS: We received responses from 30/42 (71%) invited child neurologists from unique programs. The majority (25/30, 83%) were Child Neurology Program Directors, Inpatient Directors, and/or Division Chiefs. Two-thirds (20/30, 67%) reported a total of 2-4 inpatient services. Two-thirds (20/30, 67%) reported a primary neurology admitting service. Nearly two-thirds (19/30, 63%) reported a separate ICU service, and about one-third (11/30, 37%) reported a separate stroke/vascular service. Half of respondents (15/30, 50%) reported some attendings whose primary clinical effort is in the inpatient setting. Over half (17/30, 57%) reported having trainees interested in inpatient-focused careers. About half (16/30, 53%) reported a full-time equivalent metric for inpatient time, and under half (13/30, 43%) reported use of critical-care billing. Most respondents (26/30, 87%) endorsed that inpatient attendings frequently complete documentation/sign notes outside of normal daytime hours. During night call, attendings commonly spend 30 minutes-2 hours on patient care-related phone calls between 5pm-10pm (24/30, 80%) and receive 1-3 patient care-related phone calls after 10pm (21/30, 70%). Faculty burnout was the biggest inpatient-specific challenge before the COVID-19 pandemic (25/30, 83%), and concern about faculty well-being during the COVID-19 pandemic was reported in nearly all respondents (28/30, 93%). DISCUSSION: Academic child neurology programs in North America implement varied models for inpatient care delivery and face common challenges. The information presented in this study serves to stimulate discussion, help optimize operations, and encourage novel approaches to accomplish work and advance careers in academic inpatient child neurology.

A randomized clinical trial evaluating the impact of counselor training and patient feedback on substance use disorder patients' sexual risk behavior.

INTRODUCTION: High risk sex-such as sex with multiple partners, condomless sex, or transactional or commercial sex-is a risk factor in individuals with substance use disorders (SUDs). SUD treatment can reduce sexual risk behavior, but interventions to reduce such behavior in this context have not been consistently effective. This study sought to determine if the impact of treatment on sexual risk behavior can be increased. METHODS: In a nested 2 × 2 factorial repeated measures design, we examined outcomes of two interventions: training for counselors in talking to patients about sexual risk; and availability to both counselors and patients of a personalized feedback report based on patient self-report of sexual behavior. Counselors received either a brief, information-based, Basic Training, or a multi-session, skills-based Enhanced Training. Their patients completed an audio-assisted computerized assessment of sexual behavior and received either No Feedback or a Personalized Feedback Report (PFR). Four hundred seventy six patients participated. Patient follow-up occurred 3- and 6-months postbaseline. Primary patient outcome measures were Number of Unsafe Sex Occasions (USO) and whether patients reported talking about sex in counseling sessions (Discussed Sex), both in the past 90 days. Secondary outcomes included Number of Sexual Partners, Sex Under the Influence of Substances, and Perceived Condom Barriers. RESULTS: Patients of Enhanced-condition counselors compared to those of Basic-condition counselors were more likely to report talking about sex with their counselor at 6-month follow-up. Personalized feedback also increased the likelihood of reporting counselor discussions at 6-month follow-up. Neither the training nor the feedback condition affected USO, Number of Partners, or Sex Under the Influence. DISCUSSION: We discuss why these two interventions apparently altered counselor-patient communication about sexual risk behavior without affecting the behavior itself.

Multicenter Study of the Impact of COVID-19 Shelter-In-Place on Tertiary Hospital-based Care for Pediatric Neurologic Disease.

Objective: To describe changes in hospital-based care for children with neurologic diagnoses during the initial 6 weeks following regional Coronavirus 2019 Shelter-in-Place orders. Methods: This retrospective cross-sectional study of 7 US and Canadian pediatric tertiary care institutions included emergency and inpatient encounters with a neurologic primary discharge diagnosis code in the initial 6 weeks of Shelter-in-Place (COVID-SiP), compared to the same period during the prior 3 years (Pre-COVID). Patient demographics, encounter length, and neuroimaging and electroencephalography use were extracted from the medical record. Results: 27,900 encounters over 4 years were included. Compared to Pre-COVID, there was a 54% reduction in encounters during Shelter-in-Place. COVID-SiP patients were younger (median 5 years vs 7 years). The incidence of encounters for migraine fell by 72%, and encounters for acute diagnoses of status epilepticus, infantile spasms, and traumatic brain injury dropped by 53%, 55%, and 56%, respectively. There was an increase in hospital length of stay, relative utilization of intensive care, and diagnostic testing (long-term electroencephalography, brain MRI, and head CT (all P<.01)). Conclusion: During the initial 6 weeks of SiP, there was a significant decrease in neurologic hospital-based encounters. Those admitted required a high level of care. Hospital-based neurologic services are needed to care for acutely ill patients. Precise factors causing these shifts are unknown and raise concern for changes in care seeking of patients with serious neurologic conditions. Impacts of potentially delayed diagnosis or treatment require further investigation.

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis.

Importance: Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear. Objective: To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. Data Sources: Systematic search in PubMed from inception to January 1, 2019. Study Selection: Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data. Data Extraction and Synthesis: Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models. Main Outcomes and Measures: The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset). Results: Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05). Conclusions and Relevance: Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

OBJECTIVE: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE). METHODS: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement). RESULTS: Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided. CONCLUSION: These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients.

Multisystem Inflammatory Syndrome of Children: Subphenotypes, Risk Factors, Biomarkers, Cytokine Profiles, and Viral Sequencing.

OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. CONCLUSIONS: This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.

Differential activation of neuroinflammatory pathways in children with seizures: A cross-sectional study.

PURPOSE: Inflammation plays a crucial role in epileptogenesis. We analyzed inflammatory cytokines in plasma and saliva from children with seizures and healthy controls and measured their associations with HHV6 and EBV infection. METHODS: We analyzed plasma from 36 children within 24 h of seizures (cases) and 43 healthy controls and saliva from 44 cases and 44 controls with a multiplex immunoassay. Saliva from all controls and 65 cases and blood from 26 controls and 35 cases were also analyzed by PCR for viral DNA. Primary outcome was cytokine levels in cases vs. controls. Secondary outcomes included detection of HHV-6 and EBV viral DNA in cases vs. controls and viral loads in cases vs. controls. Statistical analysis included the Wilcoxon Rank Sum test, Fisher's exact test, ANOVA, and Spearman correlation. RESULTS: Compared to controls, patients had higher levels of CCL11 (p = 0.0018), CCL26 (p<0.001), IL10 (p = 0.044), IL6 (p<0.001), IL8 (p = 0.018), and MIP1ß (p = 0.0012). CCL11 was higher with 3 or more seizures (p = 0.01), seizures longer than 10 min (p = 0.001), and when EEG showed focal slowing (p = 0.02). In saliva, febrile seizures had higher levels of IL-1ß (n = 7, p = 0.04) and new onset seizures had higher IL-6 (n = 15, p = 0.02). Plasma and saliva cytokine levels did not show a correlation. The frequency of HHV-6 and EBV detection was similar across groups and not different than controls. We found no correlation between viral load and cytokine levels. CONCLUSIONS: We showed differential activation of neuroinflammatory pathways in plasma from different seizure etiologies compared to controls, unrelated to viral infection.

Management considerations for stroke-like episodes in MELAS with concurrent COVID-19 infection.

There have been considerations since the beginning of the Coronavirus pandemic that COVID-19 infection, like any other viral illness, can trigger neurological and metabolic decompensation in patients with mitochondrial diseases. At the time of writing, there were no published reports reviewing experiences and guidelines about management of COVID-19 infection in this patient population. We present a challenging case of an adult patient with a known diagnosis of Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes (MELAS) complicated by COVID-19 infection. She initially presented with altered mental status and vomiting and went on to develop a stroke-like episode, pancreatitis, and pneumatosis intestinalis. We review salient features of her hospitalization, including initiation of thromboprophylaxis in relation to intravenous arginine therapy, caution regarding medications such as remdesivir, and the incidence of gastrointestinal complications.

Proposal to optimize evaluation and treatment of Febrile infection-related epilepsy syndrome (FIRES): A Report from FIRES workshop.

Febrile infection-related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL-1 receptor antagonist that blocks biologic activity of IL-1ß) are recommended.

Cerebral vasculopathy and strokes in a child with COVID-19 antibodies: illustrative case.

BACKGROUND: The ability of coronavirus disease 2019 (COVID-19) to cause neurological insults in afflicted adults is becoming increasingly understood by way of an ever-growing amount of international data. By contrast, the pandemic illness's neurological effects in the pediatric population are both poorly understood and sparsely reported. OBSERVATIONS: In this case, the authors reported their experience with a preschool-age child with hydrocephalus who suffered multiterritory strokes presumed secondary to immune-mediated cerebral vasculopathy as a result of asymptomatic COVID-19 infection. LESSONS: Growing evidence indicates that COVID-19 can cause neurological sequelae such as encephalitis and strokes. In this case report, the authors discussed a case of cerebral vasculopathy and strokes in a pediatric patient who was positive for COVID-19.

Acute flaccid myelitis: cause, diagnosis, and management.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy.

Vincristine is a core chemotherapeutic drug administered to pediatric acute lymphoblastic leukemia patients. Despite its efficacy in treating leukemia, it can lead to severe peripheral neuropathy in a subgroup of the patients. Peripheral neuropathy is a debilitating and painful side-effect that can severely impact an individual's quality of life. Currently, there are no established predictors of peripheral neuropathy incidence during the early stage of chemotherapeutic treatment. As a result, patients who are not susceptible to peripheral neuropathy may receive sub-therapeutic treatment due to an empirical upper cap on the dose, while others may experience severe neuropathy at the same dose. Contrary to previous genomics based approaches, we employed a metabolomics approach to identify small sets of metabolites that can be used to predict a patient's susceptibility to peripheral neuropathy at different time points during the treatment. Using those identified metabolites, we developed a novel strategy to predict peripheral neuropathy and subsequently adjust the vincristine dose accordingly. In accordance with this novel strategy, we created a free user-friendly tool, VIPNp, for physicians to easily implement our prediction strategy. Our results showed that focusing on metabolites, which encompasses both genotypic and phenotypic variations, can enable early prediction of peripheral neuropathy in pediatric leukemia patients.