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The intrauterine environment strongly influences development. Neurodevelopmental effects of in utero exposure to maternal SARS-CoV-2 infection are widely speculated but currently unknown. The COVID-19 Mother Baby Outcomes (COMBO) initiative was established at Columbia University Irving Medical Center (CUIMC) in New York City to prospectively study the health and wellbeing of infants with and without in utero exposure to maternal SARS-CoV-2 infection. We report findings on 6-month neurodevelopmental outcomes using the parental-report Ages & Stages Questionnaire, 3rd Edition (ASQ-3), from 107 in utero exposed and 131 unexposed full-term infants born between March and December, 2020. We compare these infants to a historical cohort comprised of 62 infants born at CUIMC at least two months prior to the onset of the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with differences on any ASQ-3 subdomain regardless of infection timing or severity, however, infants born during the pandemic had significantly lower scores on gross motor, fine motor, and personal-social subdomains when compared to the historical cohort. Infants born to women who were in the first trimester of pregnancy during the peak of the pandemic in NYC had the lowest personal-social scores. Birth during the pandemic, but not maternal SARS-CoV-2 infection, was associated with differences in neurodevelopmental outcomes at 6-months. These early findings suggest significantly higher public health impact for the generation born during the COVID-19 pandemic than previously anticipated.

Objective This study aimed to assess the clinical outcome and outcome predictive factors in pediatric epilepsy patients evaluated with stereo-electroencephalography (SEEG). Methods Thirty-eight patients who underwent SEEG implantation at the Pediatric Epilepsy Center in New York Presbyterian Hospital between June 2014 and December 2019 were enrolled for retrospective chart review. Postoperative seizure outcomes were evaluated in patients with at least 12-months follow up. Meta-analysis was conducted via electronic literature search of data reported from 2000 to 2020 to evaluate significant surgical outcome predictors for SEEG evaluation in the pediatric population. Results In the current case series of 25 postsurgical patients with long-term follow up, 16 patients (64.0%) were seizure free. An additional 7 patients (28.0%) showed significant seizure improvement and 2 patients (8.0%) showed no change in seizure activity. Patients with nonlesional magnetic resonance imaging (MRI) achieved seizure freedom in 50% (5/10) of cases. By comparison, 73% (11/15) of patients with lesional MRI achieved seizure freedom. Out of 12 studies, 158 pediatric patients were identified for inclusion in a meta-analysis of the effectiveness of SEEG. Seizure freedom was reported 54.4% (n =86/158) of patients at last follow up. Among patients with nonlesional MRI, 45% (n = 24) achieved seizure freedom compared with patients with lesional MRI findings (61.2%, n:= 60) (p = 0.02). The risk for seizure recurrence was 2.15 times higher [95% confidence interval [CI] 1.06–4.37, p = 0.033] in patients diagnosed with nonlesional focal epilepsy compared to those with lesional epilepsy [ 1.49 (95% CI 1.06–2.114, p = 0.021]. Conclusion Evaluation by SEEG implantation in pediatric epilepsy is effective in localizing the epileptogenic zone with favorable outcome. Presence of a non-lesional brain MRI was associated with lower chances of seizure freedom. Further research is warranted to improve the efficacy of SEEG in localizing the epileptogenic zone in pediatric patients with non-lesional brain MRI.

Aims We aimed to classify ictal onset patterns (IOPs) in pediatric patients undergoing intracranial electroencephalography (IEEG) to guide surgery for refractory epilepsy. We aimed to determine if morphology of IOPs can predict surgical outcome. Materials and Methods We performed a retrospective review of pediatric patients who underwent epilepsy surgery guided by subdural IEEG from 2007 to 2016. IEEG seizures were reviewed by a blinded epileptologist. Data was collected on outcomes. Results Twenty-three patients with 784 seizures were included. Age at seizure onset was 0.2–11 (mean 4.3, standard deviation 3.2) years. Age at time of IEEG was 4–20 (mean 13.5, standard deviation 4.4) years. Five distinct IOPs were seen at seizure onset: A) Low voltage fast activity (LVFA) with spread to adjacent electrodes (n = 7 patients, 30%), B) Burst of LVFA followed by electrodecrement (n = 12 patients, 52%), C) Burst of rhythmic spike waves (RSW) followed by electrodecrement (n = 9 patients, 39%), D) RSW followed by LVFA (n = 7 patients, 30%), E) Rhythmic spikes alone (n = 10 patients, 43%). Twelve patients (52%) had the same IOP type with all seizures. When the area of the IOP was resected, 14 patients (61%) had Engel I outcomes. Patients who had LVFA seen within their predominant IOP type were more likely to have good surgical outcomes (odds ratio 7.50, 95% confidence interval 1.02–55.0, p = 0.05). Patients who had only one IOP type were more likely to have good outcomes than patients who had multiple IOP types (odds ratio 12.6, 95% confidence interval 1.19–134, p = 0.04). Patients who had LVFA in their predominant IOP type were older than patients who did not have LVFA (mean age 15.0 vs. 9.9 years, p = 0.02). Conclusions LVFA at ictal onset and all seizures having the same IOP morphology are associated with increased likelihood of surgical success in children, but LVFA is less common in children who are younger at the time of IEEG.

Advanced techniques in neuroimaging and genetics, as well as the publication of longer-term prognostic studies, have led to fetal neurology becoming an essential part of prenatal obstetric care. A multidisciplinary approach to providing prenatal counseling is now commonly used in most academic medical centers. Common conditions seen are ventriculomegaly, agenesis of the corpus callosum and other midline abnormalities, and posterior fossa anomalies. The prognosis frequently depends on the severity of the condition and the presence of other anomalies. Certain pathologic processes, such as myelomeningocele, can be treated surgically in the prenatal period, and there is ongoing research regarding potential treatments of other conditions such as tuberous sclerosis. Acquired conditions such as hemorrhage, tumor, and ischemic stroke can also be seen prenatally, and their early diagnosis may inform postnatal care.

Advanced techniques in neuroimaging and genetics, as well as the publication of longer-term prognostic studies, have led to fetal neurology becoming an essential part of prenatal obstetric care. A multidisciplinary approach to providing prenatal counseling is now commonly used in most academic medical centers. Common conditions seen are ventriculomegaly, agenesis of the corpus callosum and other midline abnormalities, and posterior fossa anomalies. The prognosis frequently depends on the severity of the condition and the presence of other anomalies. Certain pathologic processes, such as myelomeningocele, can be treated surgically in the prenatal period, and there is ongoing research regarding potential treatments of other conditions such as tuberous sclerosis. Acquired conditions such as hemorrhage, tumor, and ischemic stroke can also be seen prenatally, and their early diagnosis may inform postnatal care.

OBJECTIVEPatients with medically refractory localization-related epilepsy (LRE) may be candidates for surgical intervention if the seizure onset zone (SOZ) can be well localized. Stereoelectroencephalography (SEEG) offers an attractive alternative to subdural grid and strip electrode implantation for seizure lateralization and localization; yet there are few series reporting the safety and efficacy of SEEG in pediatric patients.METHODSThe authors review their initial 3-year consecutive experience with SEEG in pediatric patients with LRE. SEEG coverage, SOZ localization, complications, and preliminary seizure outcomes following subsequent surgical treatments are assessed.RESULTSTwenty-five pediatric patients underwent 30 SEEG implantations, with a total of 342 electrodes placed. Ten had prior resections or ablations. Seven had no MRI abnormalities, and 8 had multiple lesions on MRI. Based on preimplantation hypotheses, 7 investigations were extratemporal (ET), 1 was only temporal-limbic (TL), and 22 were combined ET/TL investigations. Fourteen patients underwent bilateral investigations. On average, patients were monitored for 8 days postimplant (range 3–19 days). Nearly all patients were discharged home on the day following electrode explantation.There were no major complications. Minor complications included 1 electrode deflection into the subdural space, resulting in a minor asymptomatic extraaxial hemorrhage; and 1 in-house and 1 delayed electrode superficial scalp infection, both treated with local wound care and oral antibiotics.SEEG localized the hypothetical SOZ in 23 of 25 patients (92%). To date, 18 patients have undergone definitive surgical intervention. In 2 patients, SEEG localized the SOZ near eloquent cortex and subdural grids were used to further delineate the seizure focus relative to mapped motor function just prior to resection. At last follow-up (average 21 months), 8 of 15 patients with at least 6 months of follow-up (53%) were Engel class I, and an additional 6 patients (40%) were Engel class II or III. Only 1 patient was Engel class IV.CONCLUSIONSSEEG is a safe and effective technique for invasive SOZ localization in medically refractory LRE in the pediatric population. SEEG permits bilateral and multilobar investigations while avoiding large craniotomies. It is conducive to deep, 3D, and perilesional investigations, particularly in cases of prior resections. Patients who are not found to have focally localizable seizures are spared craniotomies.

The mediators of tissue damage in systemic lupus erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood-brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will acquire tissue damage slowly and not at the same rate as other organs. On the basis of these assumptions, we wished to determine if duration of disease correlated with brain injury, as measured with functional magnetic resonance imaging (fMRI), and if this was independent of degree of tissue damage in other organs. We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short-term [ST]) or ≥10 years (long-term [LT]). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for one and two shape recall; however, both groups did poorly with three shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the two shape retention phase of the working memory task (P < 0.001) and increased amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to the fearful faces paradigm. In conclusion, analysis of activation patterns stratified by performance accuracy, differences in co-morbid disease, corticosteroid doses or disease activity suggests that these observed differences are attributable to SLE effects on the central nervous system exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the Systemic Lupus International Collaborating Clinics (SLICC) damage index.

SummaryRationaleThe diagnosis of non-epileptic spells (NES) in children can be challenging, even for experienced clinicians. Our objective was to describe the characteristics of such events.MethodsThis was a retrospective study conducted from January 2004 to December 2006. Inclusion criteria were age >1 month and

A 2-year-old girl from a consanguineous marriage was evaluated for refractory seizures that had presented at birth. Since her presentation, she had been treated with pyridoxine and antiepileptic medications. Because she did not manifest the expected clinical response, pyridoxine was discontinued, which led to an increase in clinical events. Cerebrospinal fluid neurotransmitter metabolite chromatography and an assay of serum biomarkers, including pipecolic acid and α-aminoadipic semialdehyde, confirmed the diagnosis of pyridoxine-dependent epilepsy, and genetic testing identified a homozygous mutation in our patient, and in a first cousin with epilepsy. The reintroduction of pyridoxine and addition of folinic acid eventually led to control of her seizures. Early testing of biomarkers may prevent delays in diagnosing pyridoxine-dependent epilepsy. We recommend that all patients presenting with cryptogenic seizures before age 18 months undergo this evaluation.

Model-free parameters obtained from nuclear magnetic resonance (NMR) relaxation experiments and molecular dynamics (MD) simulations commonly are used to describe the intramolecular dynamical properties of proteins. To assess the relative accuracy and precision of experimental and simulated model-free parameters, three independent data sets derived from backbone 15N NMR relaxation experiments and two independent data sets derived from MD simulations of Escherichia coli ribonuclease HI are compared. The widths of the distributions of the differences between the order parameters for pairs of NMR data sets are congruent with the uncertainties derived from statistical analyses of individual data sets; thus, current protocols for analyzing NMR data encapsulate random uncertainties appropriately. Large differences in order parameters for certain residues are attributed to systematic differences between samples for intralaboratory comparisons and unknown, possibly magnetic field-dependent, experimental effects for interlaboratory comparisons. The widths of distributions of the differences between the order parameters for two NMR sets are similar to widths of distributions for an NMR and an MD set or for two MD sets. The linear correlations between the order parameters for an MD set and an NMR set are within the range of correlations observed between pairs of NMR sets. These comparisons suggest that the NMR and MD generalized order parameters for the backbone amide N—H bond vectors are of comparable accuracy for residues exhibiting motions on a fast time scale (

Ribonuclease H is an endonuclease that hydrolyzes the RNA moiety of RNA–DNA duplex molecules.Escherichia coliribonuclease H is involved in DNA replication, and retroviral ribonuclease H is essential for reverse transcription of the viral genome. To characterize the intramolcular dynamical properties ofE. coliribonuclease H, spin-lattic relaxation rate constants, spin-spin relaxation rate constants and steady state nuclear Overhauser effects for the15N nuclear spins were measured by using proton-detected heteronuclear NMR spectroscopy. The relaxation data were analyzed by using a series of dynamical models in conjunction with a statistical model selection protocol. Ribonuclease H exhibits a complex array of dynamical features, most notably in the parallel β-strands of the principal five-stranded β-sheet, the coiled-coil helical interface, the active site, and the loop regions surrounding the active site. The dynamical properties are correlated with local structural environments of the15N spins and suggest possible relationships to the functional properties of ribonuclease H. Results forE. coliribonuclease H are compared to previously reported results for the human immunodeficiancy virus type 1 ribonuclease H domain of reverse transcriptase.