Multivariate Prediction of Stroke in Children Requiring Mechanical Circulatory Support

This is a prospective observational study at Phoenix Children's to investigate for physiologic biomarkers from multimodality monitoring data that predict stroke and acute brain injuries in children requiring mechanical circulatory support

Approaches to Multimodality Monitoring in Pediatric Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children. Improved methods of monitoring real-time cerebral physiology are needed to better understand when secondary brain injury develops and what treatment strategies may alleviate or prevent such injury. In this review, we discuss emerging technologies that exist to better understand intracranial pressure (ICP), cerebral blood flow, metabolism, oxygenation and electrical activity. We also discuss approaches to integrating these data as part of a multimodality monitoring strategy to improve patient care

Clinical trials for pediatric traumatic brain injury: definition of insanity?

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children both in the United States and throughout the world. Despite valiant efforts and multiple clinical trials completed over the last few decades, there are no high-level recommendations for pediatric TBI available in current guidelines. In this review, the authors explore key findings from the major pediatric clinical trials in children with TBI that have shaped present-day recommendations and the insights gained from them. The authors also offer a perspective on potential efforts to improve the efficacy of future clinical trials in children following TBI

Carbon Dioxide Reactivity of Brain Tissue Oxygenation after Pediatric Traumatic Brain Injury

Background: We investigated how changes in partial pressure of brain tissue oxygenation (PbtO2) relate to end-tidal carbon dioxide (EtCO2) after pediatric traumatic brain injury (TBI). Methods: Dynamic structural equation modeling (DSEM) was used to investigate associations between EtCO2 and PbtO2, with positive associations indicating intact CO2 reactivity of PbtO2, and negative associations indicating impaired reactivity. Sub-analyses were performed to investigate associations of PbtO2 to intracranial pressure (ICP), arterial blood pressure (ABP) and cerebral regional oximetry (rSO2). Results: Among 14 patients, a positive association between PbtO2 and EtCO2 was demonstrated (SRC 0.05, 95% CI [0.04, 0.06]), with 9 patients demonstrating intact CO2 reactivity and 5 patients demonstrating impaired reactivity. Patients demonstrating intact CO2 reactivity had positive associations between PbtO2 and ICP (0.22 [0.21, 0.23]), whereas patients with impaired reactivity had negative associations (−0.28 [−0.29, −0.28]). Patients demonstrating intact CO2 reactivity had negative associations between PbtO2 and rSO2 (−0.08 [−0.09, −0.08]), whereas patients with impaired reactivity had positive associations (−0.15 [0.14, 0.16]). Compared to patients with intact CO2 reactivity, those with impaired reactivity had increased ICP (p < 0.0000), lower PbtO2 (p < 0.0000) and higher PRx (p = 0.0134). Conclusion: After TBI, CO2 reactivity of PbtO2 can be heterogenous, necessitating further work investigating factors contributing toward impaired reactivity

Changes in autonomic function and cerebral and somatic oxygenation with arterial flow pulsatility for children requiring veno-arterial extracorporeal membrane oxygenation

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) carries variability in arterial flow pulsatility (AFP). Research question: What changes in cerebral and somatic oxygenation, hemodynamics, and autonomic function are associated with AFP during VA-ECMO? Methods: This is a prospective study of children on VA-ECMO undergoing neuromonitoring. AFP was quantified by arterial blood pressure pulse amplitude and subcategorized: no pulsatility (<1 mmHg), minimal pulsatility (1 to <5 mmHg), moderate pulsatility (5 to <15 mmHg) and high pulsatility (≥15 mmHg). CVPR was assessed using the cerebral oximetry index (COx). Cerebral and somatic oxygenation was assessed using cerebral regional oximetry (rSO2) or peripheral oxygen saturation (SpO2). Autonomic function was assessed using baroreflex sensitivity (BRs), low-frequency high-frequency (LF/HF) ratio and standard deviation of heart rate R–R intervals (HRsd). Differences were assessed across AFP categories using linear mixed effects models with Tukey pairwise comparisons. Univariate logistic regression was used to explore risk of AFP with brain injuries. Results: Among fifty-three children, comparisons of moderate to high pulsatility were associated with reductions in rSO2 (p < 0.001), SpO 2 (p = 0.005), LF/HF ratio (p = 0.028) and an increase in HRsd (p < 0.001). Reductions in BRs were observed across comparisons of none to minimal (P < 0.001) and minimal to moderate pulsatility (p = 0.004). Comparisons of no to low pulsatility were associated with reductions in BRs (p < 0.001) and ABP (p < 0.001) with increases in SpO2 (p < 0.001) and HR (p < 0.001). Arterial ischemic stroke was associated with higher pulsatility (p = 0.0384). Conclusion: During VA-ECMO support, changes toward high AFP are associated with autonomic dysregulation and compromised cerebral and somatic tissue oxygenation

Association of Outcomes with Model-Based Indices of Cerebral Autoregulation After Pediatric Traumatic Brain Injury

BACKGROUND: We investigated whether model-based indices of cerebral autoregulation (CA) are associated with outcomes after pediatric traumatic brain injury. METHODS: This was a retrospective analysis of a prospective clinical database of 56 pediatric patients with traumatic brain injury undergoing intracranial pressure monitoring. CA indices were calculated, including pressure reactivity index (PRx), wavelet pressure reactivity index (wPRx), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Each CA index was used to compute optimal cerebral perfusion pressure (CPP). Time of CPP below lower limit of autoregulation (LLA) or above upper limit of autoregulation (ULA) were computed for each index. Demographic, physiologic, and neuroimaging data were collected. Primary outcome was determined using Pediatric Glasgow Outcome Scale Extended (GOSE-Peds) at 12 months, with higher scores being suggestive of unfavorable outcome. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that can best explain the variability of GOSE-Peds scores, and the best fit model was applied to the age strata. We hypothesized that higher GOSE-Peds scores were associated with higher CA values and more time below LLA or above ULA for each index. RESULTS: At the univariate level, CPP, dose of intracranial hypertension, PRx, PAx, wPRx, RAC, percent time more than ULA derived for PAx, and percent time less than LLA derived for PRx, PAx, wPRx, and RAC were all associated with GOSE-Peds scores. The best subset model selection on all pediatric patients identified that when accounting for CPP, increased dose of intracranial hypertension and percent time less than LLA derived for wPRx were independently associated with higher GOSE-Peds scores. Age stratification of the best fit model identified that in children less than 2 years of age or 8 years of age or more, percent time less than LLA derived for wPRx represented the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and dose of intracranial hypertension. For children 2 years or younger to less than 8 years of age, dose of intracranial hypertension was identified as the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and percent time less than LLA derived for wPRx. CONCLUSIONS: Increased dose of intracranial hypertension, PRx, wPRx, PAx, and RAC values and increased percentage time less than LLA based on PRx, wPRx, PAx, and RAC are associated with higher GOSE-Peds scores, suggestive of unfavorable outcome. Reducing intracranial hypertension and maintaining CPP more than LLA based on wPRx may improve outcomes and warrants prospective investigation

Shift in electrocorticography electrode locations after surgical implantation in children

Interpreting electrocorticography (ECoG) in the context of neuroimaging requires that multimodal information be integrated accurately. However, the implantation of ECoG electrodes can shift the brain impacting the spatial interpretation of electrode locations in the context of pre-implant imaging. We characterized the amount of shift in ECoG electrode locations immediately after implant in a pediatric population. Electrode-shift was quantified as the difference in the electrode locations immediately after surgery (via post-operation CT) compared to the brain surface before the operation (pre-implant T1 MRI). A total of 1140 ECoG contracts were assessed across 18 patients ranging from 3 to 19 (12.1 ± 4.8) years of age who underwent intracranial monitoring in preparation for epilepsy resection surgery. Patients had an average of 63 channels assessed with an average of 5.64 ± 3.27 mm shift from the pre-implant brain surface within 24 h of implant. This shift significantly increased with estimated intracranial volume, but not age. Shift also varied significantly depending of the lobe the contact was over; where contacts on the temporal and frontal lobe had less shift than the parietal. Furthermore, contacts on strips had significantly less shift than those on grids. The shift in the brain surface due to ECoG implantation could lead to a misinterpretation of contact location particularly in patients with larger intracranial volume and for grid contacts over the parietal lobes

Pediatric Acute Stroke Protocols in the United States and Canada

OBJECTIVE: To describe existing pediatric acute stroke protocols to better understand how pediatric centers might implement such pathways within the context of institution-specific structures. STUDY DESIGN: We administered an Internet-based survey of pediatric stroke specialists. The survey included questions about hospital demographics, child neurology and pediatric stroke demographics, acute stroke response, imaging, and hyperacute treatment. RESULTS: Forty-seven surveys were analyzed. Most respondents practiced at a large, freestanding children\u27s hospital with a moderate-sized neurology department and at least 1 neurologist with expertise in pediatric stroke. Although there was variability in how the hospitals deployed stroke protocols, particularly in regard to staffing, the majority of institutions had an acute stroke pathway, and almost all included activation of a stroke alert page. Most institutions preferred magnetic resonance imaging (MRI) over computed tomography (CT) and used abbreviated MRI protocols for acute stroke imaging. Most institutions also had either CT-based or magnetic resonance-based perfusion imaging available. At least 1 patient was treated with intravenous tissue plasminogen activator (IV-tPA) or mechanical thrombectomy at the majority of institutions during the year before our survey. CONCLUSIONS: An acute stroke protocol is utilized in at least 41 pediatric centers in the US and Canada. Most acute stroke response teams are multidisciplinary, prefer abbreviated MRI over CT for diagnosis, and have experience providing IV-tPA and mechanical thrombectomy. Further studies are needed to standardize practices of pediatric acute stroke diagnosis and hyperacute management

Multimodal Assessment of Cerebral Autoregulation and Autonomic Function After Pediatric Cerebral Arteriovenous Malformation Rupture

BACKGROUND: Management after cerebral arteriovenous malformation (AVM) rupture aims toward preventing hemorrhagic expansion while maintaining cerebral perfusion to avoid secondary injury. We investigated associations of model-based indices of cerebral autoregulation (CA) and autonomic function (AF) with outcomes after pediatric cerebral AVM rupture. METHODS: Multimodal neurologic monitoring data from the initial 3 days after cerebral AVM rupture were retrospectively analyzed in children (\u3c 18 years). AF indices included standard deviation of heart rate (HRsd), root-mean-square of successive differences in heart rate (HRrmssd), low-high frequency ratio (LHF), and baroreflex sensitivity (BRS). CA indices include pressure reactivity index (PRx), wavelet pressure reactivity indices (wPRx and wPRx-thr), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Percent time of cerebral perfusion pressure (CPP) below lower limits of autoregulation (LLA) was also computed for each CA index. Primary outcomes were determined using Pediatric Glasgow Outcome Score Extended-Pediatrics (GOSE-PEDs) at 12 months and acquired epilepsy. Association of biomarkers with outcomes was investigated using linear regression, Wilcoxon signed-rank, or Chi-square. RESULTS: Fourteen children were analyzed. Lower AF indices were associated with poor outcomes (BRS [p = 0.04], HRsd [p = 0.04], and HRrmssd [p = 0.00]; and acquired epilepsy (LHF [p = 0.027]). Higher CA indices were associated with poor outcomes (PRx [p = 0.00], wPRx [p = 0.00], and wPRx-thr [p = 0.01]), and acquired epilepsy (PRx [p = 0.02] and wPRx [p = 0.00]). Increased time below LLA was associated with poor outcome (percent time below LLA based on PRx [p = 0.00], PAx [p = 0.04], wPRx-thr [p = 0.03], and RAC [p = 0.01]; and acquired epilepsy (PRx [p = 0.00], PAx [p = 0.00], wPRx-thr [p = 0.03], and RAC [p = 0.01]). CONCLUSIONS: After pediatric cerebral AVM rupture, poor outcomes are associated with AF and CA when applying various neurophysiologic model-based indices. Prospective work is needed to assess these indices of CA and AF in clinical decision support

Treatment Timing, EEG, Neuroimaging, and Outcomes After Acute Necrotizing Encephalopathy in Children

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare condition associated with rapid progression to coma and high incidence of morbidity and mortality. METHODS: Clinical, electroencephalographic (EEG), and brain magnetic resonance imaging (MRI) characteristics and immunomodulatory therapy timing were retrospectively analyzed in children with ANE. ANE severity scores (ANE-SS) and MRI scores were also assessed. The associations of patient characteristics with 6-month modified Rankin scale (mRS) and length of hospitalization were determined using either univariate linear regression or one-way analysis of variance. RESULTS: 7 children were retrospectively evaluated. Normal EEG sleep spindles ( = .024) and early treatment ( = .57, = .030) were associated with improved outcomes (ie, decreased mRS). Higher ANE-SS ( = .79, = .011), higher age ( = .62, = .038), and presence of brainstem lesions ( = .015) were associated with longer length of hospitalization. Other patient characteristics were not significantly associated with mRS or length of hospitalization. CONCLUSION: Early immunomodulatory therapy and normal sleep spindles are associated with better functional outcome in children with ANE