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Iliana Manjón

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2 papers

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YNICL Journal 2022 Journal Article

Association of network connectivity via resting state functional MRI with consciousness, mortality, and outcomes in neonatal acute brain injury

Varina L. Boerwinkle
Bethany L. Sussman
Iliana Manjón
Lucia Mirea
Saher Suleman
Sarah N. Wyckoff
Alexandra Bonnell
Andrew Orgill

BACKGROUND: An accurate and comprehensive test of integrated brain network function is needed for neonates during the acute brain injury period to inform on morbidity. This retrospective cohort study assessed whether integrated brain network function acquired by resting state functional MRI during the acute period in neonates with brain injury, is associated with acute exam, neonatal mortality, and 6-month outcomes. METHODS: Study subjects included 40 consecutive neonates with resting state functional MRI acquired within 31 days after suspected brain insult from March 2018 to July 2019 at Phoenix Children's Hospital. Acute-period exam and test results were assigned ordinal scores based on severity as documented by respective treating specialists. Analyses (Fisher exact, Wilcoxon-rank sum test, ordinal/multinomial logistic regression) examined association of resting state networks with demographics, presentation, neurological exam, electroencephalogram, anatomical MRI, magnetic resonance spectroscopy, passive task functional MRI, and outcomes of discharge condition, outpatient development, motor tone, seizure, and mortality. RESULTS: Subjects had a mean (standard deviation) gestational age of 37.8 (2.6) weeks, a majority were male (63%), with a diagnosis of hypoxic ischemic encephalopathy (68%). Findings at birth included mild distress (48%), moderately abnormal neurological exam (33%), and consciousness characterized as awake but irritable (40%). Significant associations after multiple testing corrections were detected for resting state networks: basal ganglia with outpatient developmental delay (odds ratio [OR], 14.5; 99.4% confidence interval [CI], 2.00-105; P < .001) and motor tone/weakness (OR, 9.98; 99.4% CI, 1.72-57.9; P < .001); language/frontoparietal network with discharge condition (OR, 5.13; 99.4% CI, 1.22-21.5; P = .002) and outpatient developmental delay (OR, 4.77; 99.4% CI, 1.21-18.7; P=.002); default mode network with discharge condition (OR, 3.72; 99.4% CI, 1.01-13.78; P=.006) and neurological exam (P = .002 (FE); OR, 11.8; 99.4% CI, 0.73-191; P = .01 (OLR)); and seizure onset zone with motor tone/weakness (OR, 3.31; 99.4% CI, 1.08-10.1; P=.003). Resting state networks were not detected in three neonates, who died prior to discharge. CONCLUSIONS: This study provides level 3 evidence (OCEBM Levels of Evidence Working Group) demonstrating that in neonatal acute brain injury, the degree of abnormality of resting state networks is associated with acute exam and outcomes. Total lack of brain network detection was only found in patients who did not survive.

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YNICL Journal 2022 Journal Article

Discerning Seizure-Onset v. Propagation Zone: Pre-and-Post-Operative Resting-State fMRI Directionality and Boerwinkle Neuroplasticity Index

Varina L. Boerwinkle
Bethany L. Sussman
Sarah N. Wyckoff
Iliana Manjón
Justin M. Fine
P. David Adelson

The goal of this study was to determine resting state fMRI (rs-fMRI) effective connectivity (RSEC) capacity, agnostic of epileptogenic events, in distinguishing seizure onset zones (SOZ) from propagation zones (pZ). Consecutive patients (2.1-18.2 years old), with epilepsy and hypothalamic hamartoma, pre-operative rs-fMRI-directed surgery, post-operative imaging, and Engel class I outcomes were collected. Cross-spectral dynamic causal modelling (DCM) was used to estimate RSEC between the ablated rs-fMRI-SOZ to its region of highest connectivity outside the HH, defined as the propagation zone (pZ). Pre-operatively, RSEC from the SOZ and PZ was expected to be positive (excitatory), and pZ to SOZ negative (inhibitory), and post-operatively to be either diminished or non-existent. Sensitivity, accuracy, positive predictive value were determined for node-to-node connections. A Parametric Empirical Bayes (PEB) group analysis on pre-operative data was performed to identify group effects and effects of Engel class outcome and age. Pre-operative RSEC strength was also evaluated for correlation with percent seizure frequency improvement, sex, and region of interest size. Of the SOZ's RSEC, only 3.6% had no connection of significance to the pZ when patient models were individually reduced. Among remaining, 96% were in expected (excitatory signal found from SOZ → pZ and inhibitory signal found from pZ → SOZ) versus 3.6% reversed polarities. Both pre-operative polarity signals were equivalently as expected, with one false signal direction out of 26 each (3.7% total). Sensitivity of 95%, specificity 73%, accuracy of 88%, negative predictive value 88%, and positive predictive value of 88% in identifying and differentiating the SOZ and pZ. Groupwise PEB analysis confirmed SOZ → pZ EC was excitatory, and pZ → SOZ EC was inhibitory. Patients with better outcomes (Engel Ia vs. Ib) showed stronger inhibitory signal (pZ → SOZ). Age was negatively associated with absolute RSEC bidirectionally but had no relationship with Directionality SOZ identification performance. In an additional hierarchical PEB analysis identifying changes from pre-to-post surgery, SOZ → pZ modulation became less excitatory and pZ → SOZ modulation became less inhibitory. This study demonstrates the accuracy of Directionality to identify the origin of excitatory and inhibitory signal between the surgically confirmed SOZ and the region of hypothesized propagation zone in children with DRE due to a HH. Thus, this method validation study in a homogenous DRE population may have potential in narrowing the SOZ-candidates for epileptogenicity in other DRE populations and utility in other neurological disorders.

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