Ictal-Interictal Continuum in the Pediatric Intensive Care Unit.

BACKGROUND: The ictal-interictal continuum (IIC) consists of several electroencephalogram (EEG) patterns that are common in critically ill adults. Studies focused on the IIC are limited in critically ill children and have focused primarily on associations with electrographic seizures (ESs). We report the incidence of the IIC in the pediatric intensive care unit (PICU). We then compare IIC patterns to rhythmic and periodic patterns (RPP) not meeting IIC criteria looking for associations with acute cerebral abnormalities, ES, and in-hospital mortality. METHODS: This was a retrospective review of prospectively collected data for patients admitted to the PICU at Children's National Hospital from July 2021 to January 2023 with continuous EEG. We excluded patients with known epilepsy and cerebral injury prior to presentation. All patients were screened for RPP. The American Clinical Neurophysiology Society standardized Critical Care EEG terminology for the IIC was applied to each RPP. Associations between IIC and RPP not meeting IIC criteria, with clinical and EEG variables, were calculated using odds ratios (ORs). RESULTS: Of 201 patients, 21% (42/201) had RPP and 12% (24/201) met IIC criteria. Among patients with an IIC pattern, the median age was 3.4 years (interquartile range (IQR) 0.6-12 years). Sixty-seven percent (16/24) of patients met a single IIC criterion, whereas the remainder met two criteria. ESs were identified in 83% (20/24) of patients and cerebral injury was identified in 96% (23/24) of patients with IIC patterns. When comparing patients with IIC patterns with those with RPP not qualifying as an IIC pattern, both patterns were associated with acute cerebral abnormalities (IIC OR 26 [95% confidence interval {CI} 3.4-197], p = 0.0016 vs. RPP OR 3.5 [95% CI 1.1-11], p = 0.03), however, only the IIC was associated with ES (OR 121 [95% CI 33-451], p < 0.0001) versus RPP (OR 1.3 [0.4-5], p = 0.7). CONCLUSIONS: Rhythmic and periodic patterns and subsequently the IIC are commonly seen in the PICU and carry a high association with cerebral injury. Additionally, the IIC, seen in more than 10% of critically ill children, is associated with ES. The independent impact of RPP and IIC patterns on secondary brain injury and need for treatment of these patterns independent of ES requires further study.

Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

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.

Bilateral Retinal and Lateral Geniculate Nucleus Infarction in an Adolescent With Influenza.

We describe a 13-year-old female with influenza complicated by bilateral vision loss due to retinal and lateral geniculate nucleus (LGN) infarctions. She continues to have near-total vision loss in her left eye 3.5 years later. This is the second reported case of bilateral retinal and LGN infarctions in the setting of influenza. The mechanism of infarction remains to be determined, but it is important to recognize this entity and counsel patients appropriately as visual recovery may be poor.

Case Report: Successful Anterior Circulation Thrombectomy After 24 Hours in an Adolescent.

BACKGROUND: Arterial ischemic stroke in children comes with the potential for morbidity and mortality and can result in high cost of care and decreased quality of life among survivors. Children with arterial ischemic stroke are increasingly being treated with mechanical thrombectomy, but little is known about the risks and benefits 24 hours after a patient's last known well (LKW) time. METHODS: A 16-year-old female presented with acute onset of dysarthria and right hemiparesis with LKW time 22 hours prior. Pediatric National Institutes of Health Stroke Scale score was 12. Magnetic resonance imaging showed diffusion restriction and T2 hyperintensity primarily in the left basal ganglia. Magnetic resonance angiography revealed left M1 occlusion. Arterial spin labeling showed a large apparent perfusion deficit. She underwent thrombectomy with TICI3 recanalization 29.5 hours after LKW time. RESULTS: At 2-month follow-up, her examination showed moderate right-hand weakness and mild diminished sensation of the right arm. CONCLUSIONS: Adult thrombectomy trials include patients up to 24 hours from their LKW time and suggest that some patients maintain a favorable perfusion profile for over 24 hours. Without intervention many go on to experience infarct expansion. The persistence of a favorable perfusion profile likely reflects robust collateral circulation. We hypothesized our patient was relying on collateral circulation to maintain the noninfarcted areas of her left middle cerebral artery territory. Owing to concern for eventual collateral failure, thrombectomy outside of the 24-hour window was performed. This case serves as a call to action to better understand the impact of collateral circulation on cerebral perfusion in children with large vessel occlusions and delineate which children may benefit from thrombectomy in a delayed time window.

Neuromonitoring in Children with Cerebrovascular Disorders.

BACKGROUND: Cerebrovascular disorders are an important cause of morbidity and mortality in children. The acute care of a child with an ischemic or hemorrhagic stroke or cerebral sinus venous thrombosis focuses on stabilizing the patient, determining the cause of the insult, and preventing secondary injury. Here, we review the use of both invasive and noninvasive neuromonitoring modalities in the care of pediatric patients with arterial ischemic stroke, nontraumatic intracranial hemorrhage, and cerebral sinus venous thrombosis. METHODS: Narrative review of the literature on neuromonitoring in children with cerebrovascular disorders. RESULTS: Neuroimaging, near-infrared spectroscopy, transcranial Doppler ultrasonography, continuous and quantitative electroencephalography, invasive intracranial pressure monitoring, and multimodal neuromonitoring may augment the acute care of children with cerebrovascular disorders. Neuromonitoring can play an essential role in the early identification of evolving injury in the aftermath of arterial ischemic stroke, intracranial hemorrhage, or sinus venous thrombosis, including recurrent infarction or infarct expansion, new or recurrent hemorrhage, vasospasm and delayed cerebral ischemia, status epilepticus, and intracranial hypertension, among others, and this, is turn, can facilitate real-time adjustments to treatment plans. CONCLUSIONS: Our understanding of pediatric cerebrovascular disorders has increased dramatically over the past several years, in part due to advances in the neuromonitoring modalities that allow us to better understand these conditions. We are now poised, as a field, to take advantage of advances in neuromonitoring capabilities to determine how best to manage and treat acute cerebrovascular disorders in children.

The Spectrum of Quantitative EEG Utilization Across North America: A Cross-Sectional Survey.

BACKGROUND: Continuous electroencephalography (cEEG) is commonly used for neuromonitoring in pediatric intensive care units (PICU); however, there are barriers to real-time interpretation of EEG data. Quantitative EEG (qEEG) transforms the EEG signal into time-compressed graphs, which can be displayed at the bedside. A survey was designed to understand current PICU qEEG use. METHODS: An electronic survey was sent to the Pediatric Neurocritical Care Research Group and Pediatric Status Epilepticus Research Group, and intensivists in 16 Canadian PICUs. Questions addressed demographics, qEEG acquisition and storage, clinical use, and education. RESULTS: Fifty respondents from 39 institutions completed the survey (response rate 53% [39 of 74 institutions]), 76% (37 of 50) from the United States and 24% (12 of 50) from Canada. Over half of the institutions (22 of 39 [56%]) utilize qEEG in their ICUs. qEEG use was associated with having a neurocritical care (NCC) service, ≥200 NCC consults/year, ≥1500 ICU admissions/year, and ≥4 ICU EEGs/day (P < 0.05 for all). Nearly all users (92% [24 of 26]) endorsed that qEEG enhanced care of children with acute neurological injury. Lack of training in qEEG was identified as a common barrier [85% (22 of 26)]. Reviewing and reporting of qEEG was not standard at most institutions. Training was required by 14% (three of 22) of institutions, and 32% (seven of 22) had established curricula. CONCLUSIONS: ICU qEEG was used at more than half of the institutions surveyed, but review, reporting, and application of this tool remained highly variable. Although providers identify qEEG as a useful tool in patient management, further studies are needed to define clinically meaningful pediatric trends, standardize reporting, and enhance educate bedside providers.

Theta-Alpha Variability on Admission EEG Is Associated With Outcome in Pediatric Cerebral Malaria.

PURPOSE: Pediatric cerebral malaria has high rates of mortality and neurologic morbidity. Although several biomarkers, including EEG, are associated with survival or morbidity, many are resource intensive or require skilled interpretation for clinical use. Automation of quantitative interpretation of EEG may be preferable in resource-limited settings, where trained interpreters are rare. As currently used quantitative EEG factors do not adequately describe the spectrum of variability seen in studies from children with cerebral malaria, the authors developed and validated a new quantitative EEG variable, theta-alpha variability (TAV). METHODS: The authors developed TAV, a new quantitative variable, as a composite of multiple automated EEG outputs. EEG records from 194 children (6 months to 14 years old) with cerebral malaria were analyzed. Independent EEG interpreters performed standard quantitative and qualitative analyses, with the addition of the newly created variable. The associations of TAV with other quantitative EEG factors, a qualitative assessment of variability, and outcomes were assessed. RESULTS: Theta-alpha variability was not highly correlated with alpha, theta, or delta power and was not associated with qualitative measures of variability. Children whose EEGs had higher values of TAV had a lower risk of death (odds ratio = 0.934, 95% confidence interval = 0.902-0.966) or neurologic sequelae (odds ratio = 0.960, 95% confidence interval = 0.932-0.990) compared with those with lower values. Receiver operating characteristic analysis in predicting death at a TAV threshold of 0.244 yielded a sensitivity of 74% and specificity of 70% for an area under the receiver operating characteristic curve of 0.755. CONCLUSIONS: Theta-alpha variability is independently associated with outcome in pediatric cerebral malaria and can predict death with high sensitivity and specificity. Automated determination of this newly created EEG factor holds promise as a potential method to increase the clinical utility of EEG in resource-limited settings by allowing interventions to be targeted to those at higher risk of death or disability.

Seizures, Epilepsy, and Electroencephalography Findings in Pediatric Moyamoya Arteriopathy: A Scoping Review.

BACKGROUND: Although seizures are known to occur in children with moyamoya arteriopathy, data regarding characteristics, prevalence, and predictive factors for their development are less established. This study aimed to systematically review literature addressing seizures, epilepsy, and electroencephalography findings in the pediatric moyamoya population. METHODS: A scoping review was performed by searching PubMed and Ovid:Embase databases for articles that described seizures, epilepsy, and electroencephalography findings in patients aged 0 to 21 years with moyamoya arteriopathy. RESULTS: The search yielded 43 total articles that addressed the following topics in childhood moyamoya: seizures as the presenting symptom, epilepsy characteristics and management, characteristic electroencephalography findings including rebuildup with discussion of proposed mechanisms, and potential predictive clinical factors for the development of seizures preoperatively and the persistence of epilepsy postoperatively. In the reviewed literature, 9% to 19% of children with moyamoya had epilepsy, with over half of the cases lacking radiographic evidence of ischemia. Young age was the most consistent clinical factor associated with both seizures as the presenting symptom and with moyamoya-related epilepsy. Multiple studies report that seizures, electroencephalographic background abnormalities, and the rebuildup phenomenon improve after successful revascularization surgery. CONCLUSIONS: This scoping review provides a thorough investigation of the literature available to date on the clinical features of seizures in the pediatric moyamoya population. Literature on this topic is scarce and further studies assessing predictive factors for the development of epilepsy, prognosis as a result of having seizures, and seizure management in this population will help to fill existing knowledge gaps.

Acute Hospital Management of Pediatric Stroke.

The field of pediatric stroke has historically been hampered by limited evidence and small patient cohorts. However the landscape of childhood stroke is rapidly changing due in part to increasing awareness of the importance of pediatric stroke and the emergence of dedicated pediatric stroke centers, care pathways, and alert systems. Acute pediatric stroke management hinges on timely diagnosis confirmed by neuroimaging, appropriate consideration of recanalization therapies, implementation of neuroprotective measures, and attention to secondary prevention. Because pediatric stroke is highly heterogenous in etiology, management strategies must be individualized. Determining a child's underlying stroke etiology is essential to appropriately tailoring hyperacute stroke management and determining best approach to secondary prevention. Herein, we review the methods of recognition, diagnosis, management, current knowledge gaps and promising research for pediatric stroke.

Cerebral Sinus Venous Thrombosis in Infants after Surgery for Congenital Heart Disease.

OBJECTIVE: To determine the prevalence of and risk factors for cerebral sinus venous thrombosis (CSVT) in neonates undergoing congenital heart disease (CHD) repair. STUDY DESIGN: Neonates who had CHD repair with cardiopulmonary bypass and postoperative brain magnetic resonance imaging (MRI) between 2013 and 2019 at a single tertiary care center were identified from institutional databases. Demographic, clinical, and surgical data were abstracted from these databases and from the medical record; 278 neonates with CHD had cardiopulmonary bypass, 184 of whom had a postoperative brain MRI. RESULTS: Eight patients (4.3%) had a CSVT. Transposition of the great arteries with an intact ventricular septum (P < .01) and interrupted aortic arch (P = .02) were associated with an increased risk for CSVT. Other risk factors for CSVT included cross-clamp time (98 [IQR, 77.5-120] minutes vs 67 [IQR, 44-102] minutes; P = .03), units of platelets (3.63 [IQR, 3-4] vs 2.17 [IQR, 1-4]; P < .01) and packed red blood cells (0.81 [IQR, 0.25-1] vs 1.21 [IQR, 1-1]; P = .03) transfused intraoperatively, and time between surgery and MRI (10 [IQR, 7-12.5] days vs 20 [IQR, 12-35] days; P < .01). Five patients (62.5%) were treated with anticoagulation. All patients had complete or partial resolution of their CSVT, regardless of treatment. CONCLUSIONS: Brain MRI after cardiopulmonary bypass in neonates revealed a low prevalence of CSVT (4.3%). Further studies are needed to establish best practices for surveillance, prevention, and treatment of CSVT in this population.

Zebras Seize the Day: Rare Causes of Status Epilepticus Across the Continuum of Critical Care.

Status epilepticus (SE) is a common neurologic emergency and is associated with a high risk of morbidity and mortality. The management of SE in the intensive care unit centers on stabilization and treatment, as well as identifying and treating the underlying etiology. Numerous etiologies of SE are amenable to treatment, including certain genetic and metabolic disorders, autoimmune encephalitis and other inflammatory disorders, intracranial infections, and toxic/metabolic derangements. This article highlights rare but important causes of SE across the continuum of care from neonates to adults.

International Prevalence and Mechanisms of SARS-CoV-2 in Childhood Arterial Ischemic Stroke During the COVID-19 Pandemic.

BACKGROUND: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2. METHODS: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients <18 years, numbers of incident AIS cases among children (29 days to <18 years), frequency of SARS-CoV-2 testing for children with AIS, and numbers of childhood AIS cases positive for SARS-CoV-2 June 1 to December 31, 2020. Two stroke neurologists with 1 neuroradiologist determined whether SARS-CoV-2 was the main stroke risk factor, contributory, or incidental. RESULTS: Sixty-one centers from 21 countries provided AIS data. Forty-eight centers (78.7%) provided SARS-CoV-2 hospitalization data. SARS-CoV-2 testing was performed in 335/373 acute AIS cases (89.8%) compared with 99/166 (59.6%) in March to May 2020, P<0.0001. Twenty-three of 335 AIS cases tested (6.9%) were positive for SARS-CoV-2 compared with 6/99 tested (6.1%) in March to May 2020, P=0.78. Of the 22 of 23 AIS cases with SARS-CoV-2 in whom we could collect additional data, SARS-CoV-2 was the main stroke risk factor in 6 (3 with arteritis/vasculitis, 3 with focal cerebral arteriopathy), a contributory factor in 13, and incidental in 3. Elevated inflammatory markers were common, occurring in 17 (77.3%). From centers with SARS-CoV-2 hospitalization data, of 7231 pediatric patients hospitalized with SARS-CoV-2, 23 had AIS (0.32%) compared with 6/971 (0.62%) from March to May 2020, P=0.14. CONCLUSIONS: The risk of AIS among children hospitalized with SARS-CoV-2 appeared stable compared with our earlier estimate. Among children in whom SARS-CoV-2 was considered the main stroke risk factor, inflammatory arteriopathies were the stroke mechanism.

Pediatric Critical Care Neurologists in the United States and Canada: A Survey of Clinical Practice Experience.

OBJECTIVE: To describe the characteristics of pediatric intensive care neurologists and their practice in the United States and Canada. METHODS: We performed a survey-based study of child neurologists who self-identify as 'intensive care neurologists'. The survey included questions about demographics, training, pediatric neurocritical care service and job structure, teaching, academics, challenges, and views on the future of pediatric neurocritical care. RESULTS: We analyzed 55 surveys. Most respondents were 31-50 years of age with ≤10 years of practice experience. Fifty-four percent identified as female. Most completed subspecialty training after child neurology residency. The majority practice at highly resourced centers with >45 intensive care unit beds. Respondents cover a variety of inpatient (critical and noncritical care) services, at times simultaneously, for a median of 19.5 weeks/y and work >70 hours/wk when on service for pediatric neurocritical care. The top 3 challenges reported were competing demands for time, excess volume, and communication with critical care medicine. Top priorities for the "ideal pediatric neurocritical care service" were attendings with training in pediatric neurocritical care or a related field and joint rounding with critical care medicine. CONCLUSION: We report a survey-based analysis of the demographics and scope of practice of pediatric critical care neurologists. We highlight challenges faced and provide a framework for the further development of this rapidly growing field.