We aimed to investigate model-based indices of cerebrovascular dynamics after pediatric traumatic brain injury (TBI) using transcranial Doppler ultrasound (TCD) integrated into multimodality ...neurologic monitoring (MMM).
We performed a retrospective analysis of pediatric TBI patients undergoing TCD integrated into MMM. Classic TCD characteristics included pulsatility indices and systolic, diastolic and mean flow velocities of the bilateral middle cerebral arteries. Model-based indices of cerebrovascular dynamics included the mean velocity index (Mx), compliance of the cerebrovascular bed (Ca), compliance of the cerebrospinal space (Ci), arterial time constant (TAU), critical closing pressure (CrCP) and diastolic closing margin (DCM). Classic TCD characteristics and model-based indices of cerebrovascular dynamics were investigated in relation to functional outcomes and intracranial pressure (ICP) using generalized estimating equations with repeated measures. Functional outcomes were assessed using the Glasgow Outcome Scale-Extended Pediatrics score (GOSE-Peds) at 12 months, post-injury.
Seventy-two separate TCD studies were performed on twenty-five pediatric TBI patients. We identified that reduced Ci (estimate -5.986,
= 0.0309), increased CrCP (estimate 0.081,
< 0.0001) and reduced DCM (estimate -0.057,
= 0.0179) were associated with higher GOSE-Peds scores, suggestive of unfavorable outcome. We identified that increased CrCP (estimate 0.900,
< 0.001) and reduced DCM (estimate -0.549,
< 0.0001) were associated with increased ICP.
In an exploratory analysis of pediatric TBI patients, increased CrCP and reduced DCM and Ci are associated with unfavorable outcomes, and increased CrCP and reduced DCM are associated with increased ICP. Prospective work with larger cohorts is needed to further validate the clinical utility of these features.
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.
Early posttraumatic seizures (EPTS) occur after pediatric traumatic brain injury and have been associated with unfavorable outcomes. We aimed to characterize the relationship among quantitative EEG ...characteristics of early posttraumatic seizures, cerebral and somatic physiologic measures.
Differences in baseline physiologic, neuroimaging, and demographic characteristics between those with and without early posttraumatic seizures were investigated using Mann-Whitney U test or Fisher exact test. Multivariable dynamic structural equations modeling was used to investigate time series associations between ictal quantitative EEG characteristics with intracranial pressure, arterial blood pressure, heart rate (HR), and cerebral regional oximetry. Quantitative EEG characteristics included amplitude, total power, spectral edge frequency, peak value frequency, complexity, and periodicity.
Among 72 children, 146 seizures were identified from 19 patients. Early posttraumatic seizures were associated with younger age ( P = 0.0034), increased HR ( P = 0.0018), and increased Glasgow Outcome Scale-Extended scores ( P = 0.0377). Group dynamic structural equations modeling analysis of the first seizure for patients demonstrated that intracranial pressure is negatively associated with spectral edge frequency (standardized regression coefficient -0.12, 99% credible interval -0.21 to -0.04), and HR is positively associated with peak value frequency (standardized regression coefficient 0.16, 0.00-0.31). Among nine patients with seizures arising over the frontal lobe regions, HR was positively associated with peak value frequency (standardized regression coefficient 0.26 0.02-0.50) and complexity (standardized regression coefficient 0.14 0.03-0.26). Variation in strength and direction of associations was observed between subjects for relationships that were significant during group analysis.
Quantitative EEG characteristics of pediatric early posttraumatic seizures are associated with variable changes in cerebral and systemic physiology, with spectral edge frequency negatively associated with intracranial pressure and peak value frequency positively associated with HR.
Brain tissue hypoxia is associated with poor outcomes after pediatric traumatic brain injury. Although invasive brain oxygenation (PbtO 2 ) monitoring is available, noninvasive methods assessing ...correlates to brain tissue hypoxia are needed. We investigated EEG characteristics associated with brain tissue hypoxia.
We performed a retrospective analysis of 19 pediatric traumatic brain injury patients undergoing multimodality neuromonitoring that included PbtO 2 and quantitative electroencephalography(QEEG). Quantitative electroencephalography characteristics were analyzed over electrodes adjacent to PbtO 2 monitoring and over the entire scalp, and included power in alpha and beta frequencies and the alpha-delta power ratio. To investigate relationships of PbtO 2 to quantitative electroencephalography features using time series data, we fit linear mixed effects models with a random intercept for each subject and one fixed effect, and an auto-regressive order of 1 to model between-subject variation and correlation for within-subject observations. Least squares (LS) means were used to investigate for fixed effects of quantitative electroencephalography features to changes in PbtO 2 across thresholds of 10, 15, 20, and 25 mm Hg.
Within the region of PbtO 2 monitoring, changes in PbtO 2 < 10 mm Hg were associated with reductions of alpha-delta power ratio (LS mean difference -0.01, 95% confidence interval (CI) -0.02, -0.00, p = 0.0362). Changes in PbtO 2 < 25 mm Hg were associated with increases in alpha power (LS mean difference 0.04, 95% CI 0.01, 0.07, p = 0.0222).
Alpha-delta power ratio changes are observed across a PbtO 2 threshold of 10 mm Hg within regions of PbtO 2 monitoring, which may reflect an EEG signature of brain tissue hypoxia after pediatric traumatic brain injury.
Background
We investigated whether early electroencephalographic features predicted intracranial pressure (ICP), cerebrovascular pressure reactivity, brain tissue oxygenation, and functional outcomes ...in patients with pediatric traumatic brain injury (TBI).
Methods
This was a retrospective analysis of a prospective data set of 63 patients with pediatric TBI. Electroencephalographic features were collected in the first 24 h of recording to predict values of ICP, pressure reactivity index (PRx), and brain tissue oxygenation (PbtO
2
) through the initial 7 days of critical care monitoring, in addition to Glasgow Outcome Scale Extended–Pediatric Revision (GOSE-Peds) scores at 12 months. Electroencephalographic features were averaged over all surface electrodes and included seizures, interictal epileptiform discharges, suppression percentage, complexity, the alpha/delta power ratio, and both absolute asymmetry indices and power in beta (13–20 Hz), alpha (8–13 Hz), theta (4–7 Hz) and delta (0–4 Hz) bands. Demographic data and injury severity scores, such as the Glasgow Coma Scale (GCS) and Pediatric Risk of Mortality III (PRISM III) scores, at presentation were also assessed. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that best explain variability in ICP, PRx, PbtO
2
, and GOSE-Peds values, and best fit models were applied to pediatric age strata. We hypothesized that suppression percentage and the alpha/delta power ratio in the first 24 h of recording predict ICP, PRx, PbtO
2
, and GOSE-Peds values.
Results
Best subset model selection identified that increased suppression percentage and PRISM III scores predicted increased ICP (
R
2
= 79%, Akaike information criterion AIC = 332.30, root mean square error RMSE = 6.62), with suppression percentages < 5% (slope = − 5687.0,
p
= 0.0001) and ≥ 45% (slope = 9825.9,
p
= 0.0000) being predictive of dose of intracranial hypertension. When accounting for age and GCS score, increased suppression percentage predicted increased PRx values, suggestive of inefficient cerebrovascular pressure reactivity (
R
2
= 53%, AIC = 3.93, RMSE = 0.23), with suppression percentages ≥ 5% (
p
= 0.0033) and ≥ 45% (
p
= 0.0027) being predictive of median PRx values ≥ 0.3. Lower GCS scores, the presence of seizures, and increased suppression percentages each were independently associated with higher GOSE-Peds scores (
R
2
= 52%, AIC = 194.04, RMSE = 1.58), suggestive of unfavorable outcomes, with suppression percentages ≥ 5% (
p
= 0.0005) and ≥ 45% (
p
= 0.0000) being predictive of GOSE-Peds scores ≥ 5. At the univariate level, no electroencephalographic or clinical feature was associated with differences in PbtO
2
values.
Conclusions
Increased electroencephalographic suppression percentage on the initial day of monitoring may identify patients with pediatric TBI at risk of increased ICP, inefficient cerebrovascular pressure reactivity, and unfavorable outcomes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Post-traumatic epilepsy (PTE) is a known complication of traumatic brain injury (TBI). Limited physiologic biomarkers have been investigated in relation to pediatric PTE. Our aim is to identify ...clinical, physiologic and neuroimaging biomarkers predictive of pediatric PTE arising during the acute care phase after injury.
We performed a retrospective analysis from a prospectively collected clinical database of pediatric patients who underwent multimodality neurologic monitoring that included continuous electroencephalography and intracranial pressure (ICP) monitoring. Biomarkers included hemodynamic vital signs, model-based indices of cerebrovascular pressure reactivity (CVPR) and autonomic function (AF), electroencephalographic abnormalities, and neuroimaging abnormalities on the initial CT scan on day of imaging. Our primary outcome, PTE, was classified as the presence of unprovoked seizures 2 months post-injury or the continued need for antiseizure medications at 12-month post-injury. We utilized univariate logistic regression to identify biomarkers associated with PTE.
61 surviving patients were included in this study, among which 10 (16.4%) developed PTE. We identified that PTE was associated with increased ICP (odds ratio OR 1.25, 95% confidence interval CI 1.02–1.52), increased pressure reactivity indices (92.53, 2.84->999.99), increased wavelet pressure reactivity indices (121.76, 2.84->999.99), increased CT Marshall scores (1.76, 1.13–2.74), decreased HRsd (0.54, 0.33–0.87) and the presence of epileptiform discharges (8.06, 1.85–35.17), and abnormal sleep spindles (4.88, 1.18–20.00). Whereas early post-traumatic seizures within the first 7 days post-injury were associated with PTE development (7.58, 1.81–39.68), this association was significant for such seizures occurring between 24 and 168 h post-injury (21.47, 4.18–110.38), and not for seizures occurring within 24 h post-injury. Among patients experiencing early post-traumatic seizures, increased time with seizures on surface electroencephalography was associated with PTE development (7.28, 2.05–73.14). We also identified that development of PTE was associated with worsened functional outcomes identified by increased Glasgow Outcome Scale – Extended Pediatric (GOSE-PEDs) scores (3.18, 1.68–8.01).
Pediatric PTE development is associated with increased ICP, impaired CVPR, low heart rate variability, worsened neuroimaging findings, and electroencephalographic abnormalities identified during intensive care. Further studies are needed to investigate strategies to mitigate pediatric PTE development.
•Higher intracranial pressure is associated with pediatric post-traumatic epilepsy.•Worse cerebrovascular pressure reactivity associates with post-traumatic epilepsy.•Higher early post-traumatic seizure burden associates with post-traumatic epilepsy.•Decreased heart rate variability associates with pediatric post-traumatic epilepsy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•KD achieved EEG seizure resolution in 71% of patients with RSE within 7 days.•79% of RSE patients could be weaned off their infusion treatments within 14 days.•KD is under-utilized (only 7% of ...patients from 11 centers) for treatment of RSE.•KD is used late (median 13 days after onset) for the treatment of RSE.
To describe the efficacy and safety of ketogenic diet (KD) for convulsive refractory status epilepticus (RSE).
RSE patients treated with KD at the 6/11 participating institutions of the pediatric Status Epilepticus Research Group from January-2011 to December-2016 were included. Patients receiving KD prior to the index RSE episode were excluded. RSE was defined as failure of ≥2 anti-seizure medications, including at least one non-benzodiazepine drug. Ketosis was defined as serum beta-hydroxybutyrate levels >20 mg/dl (1.9 mmol/l). Outcomes included proportion of patients with electrographic (EEG) seizure resolution within 7 days of starting KD, defined as absence of seizures and ≥50% suppression below 10 μV on longitudinal bipolar montage (suppression-burst ratio ≥50%); time to start KD after onset of RSE; time to achieve ketosis after starting KD; and the proportion of patients weaned off continuous infusions 2 weeks after KD initiation. Treatment-emergent adverse effects (TEAEs) were also recorded.
Fourteen patients received KD for treatment of RSE (median age 4.7 years, interquartile range IQR 5.6). KD was started via enteral route in 11/14 (78.6%) patients. KD was initiated a median of 13 days (IQR 12.5) after the onset of RSE, at 4:1 ratio in 8/14 (57.1%) patients. Ketosis was achieved within a median of 2 days (IQR 2.0) after starting KD.
EEG seizure resolution was achieved within 7 days of starting KD in 10/14 (71.4%) patients. Also, 11/14 (78.6%) patients were weaned off their continuous infusions within 2 weeks of starting KD. TEAEs, potentially attributable to KD, occurred in 3/14 (21.4%) patients, including gastro-intestinal paresis and hypertriglyceridemia. Three month outcomes were available for 12/14 (85.7%) patients, with 4 patients being seizure-free, and 3 others with decreased seizure frequency compared to pre-RSE baseline.
This series suggests efficacy and safety of KD for treatment of pediatric RSE.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background/Objective
Multimodality neurologic monitoring (MMM) is an emerging technique for management of traumatic brain injury (TBI). An increasing array of MMM-derived biomarkers now exist that ...are associated with injury severity and functional outcomes after TBI. A standardized MMM reporting process has not been well described, and a paucity of evidence exists relating MMM reporting in TBI management with functional outcomes or adverse events.
Methods
Prospective implementation of standardized MMM reporting at a single pediatric intensive care unit (PICU) is described that included monitoring of intracranial pressure (ICP), cerebral oxygenation and electroencephalography (EEG). The incidence of clinical decisions made using MMM reporting is described, including timing of neuroimaging, ICP monitoring discontinuation, use of paralytic, hyperosmolar and pentobarbital therapies, neurosurgical interventions, ventilator and CPP adjustments and neurologic prognostication discussions. Retrospective analysis was performed on the association of MMM reporting with initial Glasgow Coma Scale (GCS) and Pediatric Risk of Mortality III (PRISM III) scores, duration of total hospitalization and PICU hospitalization, duration of mechanical ventilation and invasive ICP monitoring, inpatient complications, time with ICP > 20 mmHg, time with cerebral perfusion pressure (CPP) < 40 mmHg and 12-month Glasgow Outcome Scale—Extended Pediatrics (GOSE-Peds) scores. Association of outcomes with MMM reporting was investigated using the Wilcoxon rank-sum test or Fisher’s exact test, as appropriate.
Results
Eighty-five children with TBI underwent MMM over 6 years, among which 18 underwent daily MMM reporting over a 21-month period. Clinical decision-making influenced by MMM reporting included timing of neuroimaging (100.0%), ICP monitoring discontinuation (100.0%), timing of extubation trials of surviving patients (100.0%), body repositioning (11.1%), paralytic therapy (16.7%), hyperosmolar therapy (22.2%), pentobarbital therapy (33.3%), provocative cerebral autoregulation testing (16.7%), adjustments in CPP thresholds (16.7%), adjustments in PaCO2 thresholds (11.1%), neurosurgical interventions (16.7%) and neurologic prognostication discussions (11.1%). The implementation of MMM reporting was associated with a reduction in ICP monitoring duration (p = 0.0017) and mechanical ventilator duration (p = 0.0018). No significant differences were observed in initial GCS or PRISM III scores, total hospitalization length, PICU hospitalization length, total complications, time with ICP > 20 mmHg, time with CPP < 40 mmHg, use of tier 2 therapy, or 12-month GOS-E Peds scores.
Conclusion
Implementation of MMM reporting in pediatric TBI management is feasible and can be impactful in tailoring clinical decisions. Prospective work is needed to understand the impact of MMM and MMM reporting systems on functional outcomes and clinical care efficacy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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