BACKGROUND:Mutations in the NMDA receptor are known to disrupt glutamatergic signaling crucial for early neurodevelopment, often leading to severe global developmental delay/intellectual disability, epileptic encephalopathy, and cerebral palsy phenotypes. Both seizures and movement disorders can be highly treatment-refractory.RESULTS:We describe a targeted ABA n-of-1 treatment trial with intrathecal MgSO4, rationally designed based on the electrophysiologic properties of this gain of function mutation in the GRIN1 NMDA subunit.CONCLUSION:Although the invasive nature of the trial necessitated a short-term, non-randomized, unblinded intervention, quantitative longitudinal neurophysiologic monitoring indicated benefit, providing class II evidence in support of intrathecal MgSO4 for select forms of GRIN disorders.

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 (P = .024) and early treatment (R2 = .57, P = .030) were associated with improved outcomes (ie, decreased mRS). Higher ANE-SS (R2 = .79, P = .011), higher age (R2 = .62, P = .038), and presence of brainstem lesions (P = .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.

Objective: Regional differences were investigated in quantitative EEG (QEEG) characteristics and associations of QEEG to hemodynamics after pediatric acute stroke. Methods: Quantitative EEG was analyzed, including power in delta, theta, alpha, and beta bands, alpha-delta power ratio, total power, and spectral edge frequency from 11 children with unilateral, anterior circulation strokes during the first 24 hours of continuous EEG recording. Differences between injured and uninjured hemispheres were assessed using multivariate dynamic structural equations modeling. Dynamic structural equations modeling was applied to six children with hemorrhagic stroke undergoing arterial blood pressure, heart rate, and cerebral oximetry monitoring to investigate associations between hemodynamics with QEEG adjacent to anterior circulation regions. Results: All patients with acute ischemic stroke (n = 5) had lower alpha and beta power and spectral edge frequency on injured compared with uninjured regions. This was not consistent after hemorrhagic stroke (n = 6). All hemorrhagic stroke patients demonstrated negative association of total power with arterial blood pressure within injured regions. No consistency was observed for direction or strength of association in other QEEG measures to arterial blood pressure nor were such consistent relationships observed for any QEEG measure studied in relation to heart rate or cerebral oximetry. Conclusions: After pediatric anterior circulation acute ischemic stroke, reduced spectral edge frequency and alpha and beta power can be observed on injured as compared with noninjured regions. After pediatric anterior circulation hemorrhagic stroke, total power can be negatively associated with arterial blood pressure within injured regions. Larger studies are needed to understand conditions in which QEEG patterns manifest and relate to hemodynamics and brain penumbra.

OBJECTIVES:Electroencephalography is used in neurocritical care for detection of seizures and assessment of cortical function. Due to limited resolution from scalp electroencephalography, important abnormalities may not be readily detectable. We aimed to identify whether intracranial electroencephalography allows for improved methods of monitoring cortical function in children with severe traumatic brain injury.DESIGN:This is a retrospective cohort study from a prospectively collected clinical database. We investigated the occurrence rate of epileptiform abnormalities detected on intracranial electroencephalography when compared with scalp electroencephalography. We also investigated the strength of association of quantitative electroencephalographic parameters and cerebral perfusion pressure between both intracranial and scalp electroencephalography.SETTING:This is a single-institution study performed in the Phoenix Children's Hospital PICU.PATIENTS:Eleven children with severe traumatic brain injury requiring invasive neuromonitoring underwent implantation of a six-contact intracranial electrode as well as continuous surface electroencephalography.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Visual detection of epileptiform abnormalities was performed by pediatric epileptologists. Association of intracranial and scalp electroencephalography total power, alpha percentage, and alpha-delta power ratio to cerebral perfusion pressure was performed using univariate dynamic structural equations modeling. Demographic data were assessed by retrospective analysis. Intracranial and scalp electroencephalography was performed in 11 children. Three of 11 children had observed epileptiform abnormalities on intracranial electroencephalography. Two patients had epileptiform abnormalities identified exclusively on intracranial electroencephalography, and one patient had seizures initiating on intracranial electroencephalography before arising on scalp electroencephalography. Identification of epileptiform abnormalities was associated with subsequent identification of stroke or malignant cerebral edema. We observed statistically significant positive associations between intracranial alpha-delta power ratio to cerebral perfusion pressure in nine of 11 patients with increased strength of association on intracranial compared with scalp recordings.CONCLUSIONS:These findings suggest that intracranial electroencephalography may be useful for detection of secondary insult development in children with traumatic brain injury.

Whole-brain analysis of resting-state functional MRI by independent component analysis may aid in accurate diagnosis of disorders of consciousness, prognosis of coma following an acute brain injury, as well as provide an opportunity for early therapeutic intervention of subclinical seizures.