Forehead location and large segmental pattern of facial port-wine stains predict risk of Sturge-Weber syndrome.

BACKGROUND: Children with forehead port-wine stains (PWSs) are at risk of Sturge-Weber syndrome (SWS). However, most will not develop neurologic manifestations. OBJECTIVE: To identify children at greatest risk of SWS. METHOD: In this retrospective cohort study of children with a forehead PWS, PWSs were classified as "large segmental" (half or more of a contiguous area of the hemiforehead or median pattern) or "trace/small segmental" (less than half of the hemiforehead). The outcome measure was a diagnosis of SWS. RESULTS: Ninety-six children had a forehead PWS. Fifty-one had a large segmental PWS, and 45 had a trace/small segmental PWS. All 21 children with SWS had large segmental forehead PWSs. Large segmental forehead PWSs had a higher specificity (0.71 vs 0.27, P < .0001) and a higher positive predictive value (0.41 vs 0.22, P < .0001) for SWS than any forehead involvement by a PWS. LIMITATIONS: Retrospective study at a referral center. CONCLUSION: Children with large segmental forehead PWSs are at highest risk of SWS.

Structural MRI and tract-based spatial statistical analysis of diffusion tensor imaging in children with hemimegalencephaly.

PURPOSE: To investigate the gross white matter abnormalities in the structural brain MR imaging as well as white matter microstructural alterations using tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) in both affected and contralateral cerebral hemispheres of children with hemimegalencephaly (HMEG). METHODS: From 2003 to 2019, we retrospectively reviewed brain MR images in 20 children (11 boys, 2 days-16.5 years) with HMEG, focusing on gross white matter abnormalities. DTI was evaluated in 12 patients (8 boys, 3 months-16.5 years) with HMEG and 12 age-, sex-, and magnetic field strength-matched control subjects. TBSS analysis was performed to analyze main white matter tracts. Regions of significant differences in fractional anisotropy (FA) were determined between HMEG and control subjects and between affected and contralateral hemispheres of HMEG. RESULTS: Gross white matter abnormalities were noted in both affected (n = 20, 100%) and contralateral hemisphere (n = 4, 20%) of HMEG. FA values were significantly decreased in both hemispheres of HMEG, compared with control subjects (P < 0.05). Contralateral hemispheres of HMEG showed regions with significantly decreased FA values compared with affected hemispheres (P < 0.05). CONCLUSIONS: In addition to gross white matter abnormalities particularly evident in affected hemispheres, DTI analysis detected widespread microstructural alterations in both affected and contralateral hemispheres in HMEG suggesting HMEG may involve broader abnormalities in neuronal networks.

Phenotypes and Genotypes in Patients with SMC1A-Related Developmental and Epileptic Encephalopathy.

The X-linked SMC1A gene encodes a core subunit of the cohesin complex that plays a pivotal role in genome organization and gene regulation. Pathogenic variants in SMC1A are often dominant-negative and cause Cornelia de Lange syndrome (CdLS) with growth retardation and typical facial features; however, rare SMC1A variants cause a developmental and epileptic encephalopathy (DEE) with intractable early-onset epilepsy that is absent in CdLS. Unlike the male-to-female ratio of 1:2 in those with CdLS associated with dominant-negative SMC1A variants, SMC1A-DEE loss-of-function (LOF) variants are found exclusively in females due to presumed lethality in males. It is unclear how different SMC1A variants cause CdLS or DEE. Here, we report on phenotypes and genotypes of three females with DEE and de novo SMC1A variants, including a novel splice-site variant. We also summarize 41 known SMC1A-DEE variants to characterize common and patient-specific features. Interestingly, compared to 33 LOFs detected throughout the gene, 7/8 non-LOFs are specifically located in the N/C-terminal ATPase head or the central hinge domain, both of which are predicted to affect cohesin assembly, thus mimicking LOFs. Along with the characterization of X-chromosome inactivation (XCI) and SMC1A transcription, these variants strongly suggest that a differential SMC1A dosage effect of SMC1A-DEE variants is closely associated with the manifestation of DEE phenotypes.

Retrospective Evaluation of First-line Levetiracetam use for Neonatal Seizures after Congenital Heart Defect repair with or without Extracorporeal Membrane Oxygenation.

OBJECTIVE: Levetiracetam (LEV) efficacy for neonatal seizures is debated. We evaluated LEV as a first line anti-seizure medicine (ASM) in neonates following neonatal congenital heart defect (CHD) repair who did not require extracorporeal membrane oxygenation (ECMO) vs neonates who required ECMO. METHODS: A single center retrospective review of neonates with CHD from 2015 to 2020 was conducted. Neonates were included if seizures were present on continuous EEG after CHD repair either on or off ECMO, and they received LEV as a first line ASM. Primary outcomes were seizure resolution with LEV, adverse events and response to subsequent ASM. RESULTS: Eighteen total neonates were evaluated, 10 with seizures post-CHD repair who did not require ECMO and 8 who required ECMO. In the non-ECMO cohort, nine of ten were successfully treated with LEV monotherapy with no adverse events. In comparison, the eight neonates who required ECMO had a higher initial seizure burden (1.6% vs 17%, p=0.003), were more likely to have injury on neuroimaging (12.5 vs 75%, p= 0.04), and all neonates required multiple ASMs. Seizure burden did not decrease with LEV, but significantly decreased with phenobarbital and fosphenytoin (14.4% and 10.5%, p = 0.024). CONCLUSIONS: Neonates with CHD and seizures on and off ECMO demonstrated divergent seizure characteristics including seizure burden and response to LEV. LEV may reduce neonatal seizure burden after uncomplicated CHD repair. However, in neonates requiring ECMO, multiple ASMs were required. A prospective evaluation of ASM efficacy and safety in this high-risk population is urgently needed.

Current Status of Continuous Electroencephalographic Monitoring in Critically Ill Children.

The utilization of continuous electroencephalographic monitoring in critical care units has increased significantly, and several consensus statements and guidelines have been published. The use of critical care electroencephalographic monitoring has become a standard of care in many centers in the United States and other countries. The most common indication is to detect electrographic seizures and status epilepticus. Other indications include monitoring treatment efficacy in patients with electrographic seizures and status epilepticus, evaluating the degree of disturbance of function in patients with encephalopathy, monitoring brain function in patients treated with sedation and neuromuscular blocking agents, and event characterization. The urgent initiation of critical care electroencephalographic monitoring is recommended in certain clinical populations, but varies among institutions. The consensus among neurologists is to start treatment after identifying electrographic seizures or electrographic status epilepticus with or without clinical signs. However, the optimal treatment of nonconvulsive and electrographic-only seizures remains controversial. Critical care electroencephalographic monitoring has significant impact on clinical management, but there is lack of clear evidence that treatment guided by critical care electroencephalographic monitoring leads to improvement of clinical and neurodevelopmental outcome. There are substantial discrepancies among institutions on personnel and technical support used for critical care electroencephalographic monitoring. The optimal critical care electroencephalographic monitoring team should include electroencephalographers with experience in critical care electroencephalographic monitoring interpretation and appropriately trained technologists certified in electroencephalography by the American Board of Registration of Electroencephalographic and Evoked Potential Technologists specializing in critical care electroencephalographic monitoring or long-term monitoring.