The Pediatric Neuroradiologist's Practical Guide to Capture and Evaluate Pre- and Postoperative Velopharyngeal Insufficiency.

Up to 30% of children with cleft palate will develop a severe speech disorder known as velopharyngeal insufficiency. Management of velopharyngeal insufficiency typically involves structural and functional assessment of the velum and pharynx by endoscopy and/or videofluoroscopy. These methods cannot provide direct evaluation of underlying velopharyngeal musculature. MR imaging offers an ideal imaging method, providing noninvasive, high-contrast, high-resolution imaging of soft-tissue anatomy. Furthermore, focused-speech MR imaging techniques can evaluate the function of the velum and pharynx during sustained speech production, providing critical physiologic information that supplements anatomic findings. The use of MR imaging for velopharyngeal evaluation is relatively novel, with limited literature describing its use in clinical radiology. Here we provide a practical approach to perform and interpret velopharyngeal MR imaging examinations. This article discusses the velopharyngeal MR imaging protocol, methods for interpreting velopharyngeal anatomy, and examples illustrating its clinical applications. This knowledge will provide radiologists with a new, noninvasive tool to offer to referring specialists.

Neonatal Aneurysm Rupture in a Child with a De Novo Variant to ANKRD17.

Ankyrin repeat domain 17 (ANKRD17) is postulated to play a role in the integrity of blood vessels and has been reported to be associated with developmental delays, epilepsy, and growth restriction. Whereas ANKRD17-deficient mice have been demonstrated to experience catastrophic hemorrhages, vascular malformations have not been reported in human patients with pathogenic variants to ANKRD17. We report a term male neonate with a heterozygous de novo variant to ANKRD17 (ANKRD17; c6988 C > G, P.[P2330a]) who experienced subarachnoid hemorrhage from a ruptured aneurysm involving the left middle cerebral artery. He experienced acute symptomatic seizures and required clipping of his aneurysm at 35 days of life, later progressing to developing multifocal drug-resistant epilepsy. To our knowledge, this case represents the first report of a cerebrovascular malformation from a patient with ANKRD17. Further work is needed to investigate whether pathogenic variants to ANKRD17 can lead to cerebral aneurysms or other cerebrovascular malformations in children.

Association of Cerebral and Systemic Physiology With Quantitative Electroencephalographic Characteristics of Early Posttraumatic Seizures.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Acute physiologic prediction of pediatric post-traumatic epilepsy.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Evaluation of axial gradient Echo spiral MRI of the spine at 1.5 T.

Axial gradient echo T2*-weighed MRI of the spine is a valuable diagnostic tool with several advantages over axial T2-weighted TSE MRI, but it suffers from a low signal-to-noise ratio (SNR) and inconsistent image quality. This work investigates the potential of spiral MRI to reduce artifacts and produce improved SNR and image quality in axial T2*-weighted gradient echo MRI of the spine of pediatric patients. For the purposes of image quality evaluation, 15 pediatric patients were recruited among those scheduled for a routine spine or brain exam at 1.5 T. Pediatric spine images were rated by three pediatric neuroradiologists on a subjective scale of 1-5 using four image quality criteria. Image quality scores were evaluated using non-parametric Wilcoxon signed-rank testing and a mixed effects logistic regression model. Significant differences were found in the image quality scores in favor of spiral MRI. The odds of spiral images receiving an overall image quality score higher than 3 was 16.3 times greater than the odds of Cartesian images receiving a score higher than 3 (p < 0.001, 95% CI of 4.6 to 86) as calculated using a mixed effects logistic regression model. A quantitative comparison was also performed on a single volunteer to illustrate the SNR benefit of spiral MRI. In conclusion, spiral MRI was found to provide equal or better image quality than Cartesian MRI in axial T2*-weighted gradient echo MRI in the spine of a small cohort of pediatric patients at 1.5 T.

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.

Physiologic Characteristics of Hyperosmolar Therapy After Pediatric Traumatic Brain Injury.

All work was performed at the Barrow Neurological Institute at Phoenix Children's Hospital. Objective: Investigate injury severity, neuroimaging, physiology, and outcomes with bolus hyperosmolar therapy (HT) of 3% hypertonic saline or mannitol. Methods: Retrospective cohort analysis was performed. Physiologic variables included intracranial pressure (ICP), arterial blood pressure (ABP), and heart rate (HR). Volume-pressure compensation (PVC) indices included ICP pulse amplitude (AMP) and correlation of AMP and ICP (RAP). Cerebrovascular pressure reactivity (CVPR) indices included pressure reactivity index (PRx), pulse amplitude index (PAx), wavelet PRx (wPRx), and correlation of AMP and cerebral perfusion pressure (RAC). Heart rate variability (HRV) indices included heart rate standard deviation (HRsd), heart rate root mean square of successive differences (HRrmssd) and low-high frequency ratio (LHF). Outcome was assessed using Glasgow Outcomes Scale Extended Pediatrics, 12-months post-injury. Generalized estimating equations was applied to investigate associations of physiologic changes and pre-treatment indices with HT efficacy. Repeated measures analysis of variance was applied to investigate changes after HT without intracranial hypertension (ICH). Wilcoxon rank-sum was applied to investigate HT responsiveness with age, injury severity, neuroimaging, and outcomes. Results: Thirty children received bolus HT. ICH reduction after HT was associated with reduced ICP (p = 0.0064), ABP (p = 0.0126), PRx (p = 0.0063), increased HRsd (p = 0.0408), and decreased pretreatment RAC (p = 0.0115) and wPRx (p = 0.0072). HT-responsive patients were older and had improved outcomes (p = 0.0394). HT without ICH was associated with increased ICP (P < 0.0001) and ABP (P < 0.0001), increases in all HRV indices and decreases in all PVC indices. Conclusion: After pediatric TBI, efficacious HT is associated with decreased ICP and ABP, pre-treatment indices suggesting efficient CVPR, and potentially improved outcomes.

Improving the image quality of 3D FLAIR with a spiral MRI technique.

PURPOSE: Fluid-attenuated inversion recovery (FLAIR) nulls the CSF signal and is widely used in neuro MRI exams. A 3D scan can provide high SNR, contiguous coverage, and reduced sensitivity to through-plane CSF flow. In this work, a 3D spiral FLAIR technique is proposed to improve the image quality of conventional 3D Cartesian FLAIR. METHODS: The 3D spiral FLAIR sequence incorporated a spiral-in/out readout to preserve higher scan efficiency and eliminate off resonance-induced artifacts observed with a commonly implemented spiral-out readout, a compensation approach to minimize phase errors due to the concomitant fields accompanying the spiral gradient, and an adapted variable flip angle scheme to preserve scan efficiency and maintain a long and stable echo train. 3D Cartesian and spiral FLAIR (~6 min each) were acquired on a 3 Tesla scanner from 6 subjects (age range: 31-64 years; mean: 39.5). Two neuroradiologists rated the images in a blinded fashion on a 5-point scale. The noise performance was assessed quantitatively. RESULTS: Compared to 3D Cartesian FLAIR, 3D spiral FLAIR exhibits greater reduction of artifacts from CSF, especially anterior to the brain stem (rated better in 4 cases), artifacts attributed to blood/flow in the deep brain (better or much better in all 6 cases), and superior overall image quality (much better in 5 cases) despite residual susceptibility artifacts near the nasal cavity. Quantitative assessment demonstrates ~1.5× higher average SNR than Cartesian data. CONCLUSION: 3D spiral FLAIR achieves higher SNR, reduced CSF, and blood/flow artifacts, providing an alternative to 3D Cartesian FLAIR for neurological exams.