Association of Prenatal Exposure to Antiseizure Medications With Creative and Executive Function at Age 4.5 Years.

BACKGROUND AND OBJECTIVES: Neurodevelopmental effects of fetal antiseizure medication (ASM) exposure on creativity and executive functions are poorly understood. We previously found fetal valproate exposure to adversely affect measures of creativity and executive functions. In this study, we examine fetal exposure of newer ASMs on these functions in children of women with epilepsy (WWE) compared with children of healthy women (HW). METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational cohort study of WWE and HW enrolled in pregnancy and their offsprings. This report examines blindly assessed creativity and executive functions in 4.5-year-old children of WWE vs HW. In addition, exposure-dependent ASM effects during the third trimester were examined in children of WWE, using a ratio of maximum observed ASM concentrations and ratio of defined daily dose (ratio DDD). For polytherapy, ratios were summed across ASMs. Linear regression models adjusted for multiple potential confounding factors were conducted for all analyses. The primary outcome for 4.5-year-old children was the Torrance Test of Creative Thinking-Figural Creativity Index. Secondary outcomes included the Global Executive Composite Score from the Behavior Rating Inventory of Executive Function-Preschool Version and subscales and other indexes of both measures. RESULTS: The primary analysis included 251 children of WWE and 73 of HW. No differences in creativity or executive function were found between children of WWE vs HW. No ASM exposure-dependent effects were found for the creativity measures, but exposure-dependent effects for executive function were present for ratio ASM concentration and ratio DDD. DISCUSSION: Our findings at 4.5 years show no differences in creative thinking between children of WWE vs HW (-3.2 [-9.0 to 2.7], p = 0.286) or associations with fetal exposure to ASMs (-2.6 [-11.0 to 5.7], p = 0.530). Secondary analyses revealed fetal exposure-dependent effects for executive function in children of WWE (7.0 [2.9-11.2], p = 0.001), which are most marked for levetiracetam (12.9 [4.2-21.6], p = 0.004). Our findings suggest that even for relatively safe ASMs, dosing needs to be adjusted to concentrations that prevent seizures, but balance risks to the fetus that high concentrations may pose. TRIAL REGISTRATION INFORMATION: The study is registered at ClinicalTrials.gov as NCT01730170.

The Korean Version of the Oxford Cognitive Screen (K-OCS) Normative Study.

OBJECTIVE: To generate a Korean version of the Oxford Cognitive Screen (K-OCS) and obtain cutoff scores that determine the impairment of each subdomain. Post-stroke cognitive impairment (PSCI) negatively impacts the rehabilitation process and independence in daily life. Its obscure manifestations require effective screening for appropriate rehabilitation. However, in most rehabilitation clinics, psychological evaluation tools for Alzheimer's dementia have been used without such considerations. The OCS is a screening assessment tool for PSCI and vascular dementia that can evaluate the cognitive domains most often affected by stroke, including language, attention, memory, praxis, and numerical cognition. It comprises 10 subtasks and enables quick and effective cognitive evaluation. METHODS: The K-OCS, which considers Korea's unique cultural and linguistic characteristics, was developed with the approval and cooperation of the original author. Enrollment of participants without disabilities was announced at Duksung Women's University, Yongin Sevrance Hospital, CHA Bundang Medical Center. The study was conducted between September 2020 and March 2022 on 97 male and female participants aged ≥30 years. RESULTS: All the 97 participants completed the task. In this study, the 5th percentile score was presumed to be the cutoff value for each score, and the values are provided here. The cutoff score for each OCS subtask was similar to that of the original British version. CONCLUSION: We suggest the usability of the K-OCS as a screening tool for PSCI by providing the cutoff value of each subtask.

Behavioral Outcomes and Neurodevelopmental Disorders Among Children of Women With Epilepsy.

Importance: The association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated. Objective: To examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age. Design, Setting, and Participants: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023. Exposures: Exposures included mother's epilepsy status as well as mother's ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen. Main Outcomes and Measures: The primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures. Results: Primary analysis included 302 children of women with epilepsy (143 boys [47.4%]) and 84 children of women without epilepsy (45 boys [53.6%]). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate [PE], 0.4 [95% CI, -2.5 to 3.4]; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, -7.8 [95% CI, -12.6 to -3.1]; P = .001). This decrease in functioning was evident for levetiracetam (PE, -18.9 [95% CI, -26.8 to -10.9]; P < .001) and lamotrigine (PE, -12.0 [95% CI, -23.7 to -0.3]; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose. Conclusions and Relevance: This study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings.

Leveraging a smartphone to perform time-gated luminescence measurements.

Empowered by advanced on-board sensors, high-performance optics packages and ever-increasing computational power, smartphones have democratized data generation, collection, and analysis. Building on this capacity, many platforms have been developed to enable its use as an optical sensing platform for colorimetric and fluorescence measurements. In this paper, we report the ability to enable a smartphone to perform laboratory quality time-resolved analysis of luminescent samples via the exploitation of the rolling shutter mechanism of the native CMOS imager. We achieve this by leveraging the smartphone's standard image capture applications, commercially available image analysis software, and housing the device within a UV-LED containing case. These low-cost modifications enable us to demonstrate the smartphone's analytical potential by performing tasks ranging from authentication and encryption to the interrogation of packaging, compounds, and physical phenomena. This approach underscores the power of repurposing existing technologies to extend the reach and inclusivity of scientific exploration, opening new avenues for data collection and analysis.

Initiation and Duration of Breastfeeding in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study.

BACKGROUND AND OBJECTIVES: Breastfeeding has important health benefits for both mother and child. We characterize breastfeeding initiation and duration in mothers with epilepsy relative to control mothers in a large prospective cohort. METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a prospective, multicenter observational, US cohort study. Pregnant individuals with and without epilepsy, aged 14-45 years, were enrolled between December 19, 2012, and February 11, 2016. Exclusion criteria included intelligence quotient (IQ) <70, and gestational age >20 weeks at enrollment. Breastfeeding was assessed through electronic diary and at study visits until 2 years postpartum. Odds of initiating breastfeeding was compared between cohorts using unadjusted and adjusted logistic regression models. Duration of breastfeeding was compared between cohorts using the log-rank test. RESULTS: Three hundred fifty-one pregnant individuals with epilepsy and 105 pregnant controls were enrolled. Breastfeeding data were available for 325 mothers with epilepsy and 98 controls. Study cohorts were similar demographically except race (p = 0.008); 84.9% of mothers with epilepsy and 71.4% of controls were White. The mean IQ was lower in mothers with epilepsy compared with that in controls (97.7 vs 104.2, p < 0.001). Breastfeeding was initiated by 74.8% mothers with epilepsy and 88.8% controls; this difference was significant in unadjusted logistic regression (odds ratio [OR] 0.4 [95% CI 0.2, 0.7], p = 0.004), but not in adjusted model (OR 0.5 [95% CI 0.2, 1.0], p = 0.051). Factors associated with breastfeeding were higher maternal education and IQ. There was no difference in duration of breastfeeding between mothers with and without epilepsy (median duration 8.5 months vs 9.9 months, p = 0.793). Among mothers with epilepsy, both convulsive seizures and all seizures that impair awareness during pregnancy were associated with lower breastfeeding initiation (OR 0.4 [95% CI 0.2, 0.8], p = 0.013) and (OR 0.4 [95% CI 0.2, 0.8], p = 0.003, respectively). Any peripartum seizures were associated with shorter breastfeeding duration (median 6 months vs 9.7 months, [p = 0.040]). DISCUSSION: Mothers with epilepsy were less likely to initiate breastfeeding compared with controls; however, this difference was not significant when controlling for maternal IQ and education level. Continuation of breastfeeding once initiated was not different between mothers with and without epilepsy. Seizure control was associated with breastfeeding initiation and duration in mothers with epilepsy. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier NCT01730170.

Cognitive outcomes at age 3 years in children with fetal exposure to antiseizure medications (MONEAD study) in the USA: a prospective, observational cohort study.

BACKGROUND: The neurodevelopmental effects of fetal exposure to most antiseizure medications are unclear. We aimed to investigate the effects of fetal exposure to commonly used antiseizure medications on neuropsychological outcomes at age 3 years. METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicentre cohort study at 20 specialty epilepsy centres in the USA. We have investigated pregnancy outcomes in women (aged 14-45 years) with and without epilepsy who were enrolled during pregnancy (≤20 weeks' gestational age), and their children. The primary outcome for children at age 3 years was a blindly assessed Verbal Index score, which was calculated by averaging scores on the Naming Vocabulary and Verbal Comprehension subtests of Differential Ability Scales-II, Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale-5, and Peabody Picture Vocabulary Test-4. Children of women with and without epilepsy were compared, and the associations of medication exposures to outcomes in exposed children were assessed. The MONEAD study is registered with ClinicalTrials.gov, NCT0730170, and is ongoing. FINDINGS: Between Dec 19, 2012, and Jan 13, 2016, 456 pregnant women (351 with epilepsy and 105 without epilepsy) were enrolled into the study. 345 children were born to women with epilepsy and 106 children were born to women without epilepsy. Verbal Index scores at age 3 years did not differ for children of women with epilepsy (n=284; adjusted least-square mean 102·7, 95% CI 101·4 to 103·9) versus those without epilepsy (n=87; 102·3, 99·8 to 104·7). Significant risk factors for reduced Verbal Index scores included maternal intelligence quotient, maternal education, post-birth anxiety, gestational age at enrolment, child's sex, and child's ethnicity. For Verbal Index scores, antiseizure medication exposure effects were not seen for maximum third trimester blood concentrations (n=258; adjusted parameter estimate -2·9, 95% CI -6·7 to 1·0). However, in secondary analyses, exposure-dependent effects were present on multiple cognitive measures, which varied by medication. INTERPRETATION: We found no difference in neurodevelopmental outcomes between children with fetal exposure to newer antiseizure medications compared with unexposed children. However, some exposure-dependent antiseizure medication effects were seen in secondary analyses. The adverse effects of maternal post-birth anxiety emphasise the importance of screening mothers during pregnancy and postpartum and implementing interventions. Additional studies are needed to clarify the exposure-dependent effects. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Institute of Child Health and Development.

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice.

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. Exposures: Genetic test results. Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

EEG Abnormalities and Their Radiographic Correlates in a COVID-19 Inpatient Cohort.

Background and Objectives: To identify the prevalence of EEG abnormalities in patients with coronavirus disease 2019 (COVID-19) with neurologic changes, their associated neuroimaging abnormalities, and rates of mortality. Methods: A retrospective case series of 192 adult COVID-19-positive inpatients with EEG performed between March and June 2020 at 4 hospitals: 161 undergoing continuous, 24 routine, and 7 reduced montage EEG. Study indication, epilepsy history, intubation status, administration of sedatives or antiseizure medications (ASMs), metabolic abnormalities, neuroimaging pathology associated with epileptiform abnormalities, and in-hospital mortality were analyzed. Results: EEG indications included encephalopathy (54.7%), seizure (18.2%), coma (17.2%), focal deficit (5.2%), and abnormal movements (4.6%). Epileptiform abnormalities occurred in 39.6% of patients: focal intermittent epileptiform discharges in 25.0%, lateralized periodic discharges in 6.3%, and generalized periodic discharges in 19.3%. Seizures were recorded in 8 patients, 3 with status epilepticus. ASM administration, epilepsy history, and older age were associated with epileptiform abnormalities. Only 26.3% of patients presented with any epileptiform abnormality, 37.5% with electrographic seizures, and 25.7% patients with clinical seizures had known epilepsy. Background findings included generalized slowing (88.5%), focal slowing (15.6%), burst suppression (3.6%), attenuation (3.1%), and normal EEG (3.1%). Neuroimaging pathology was identified in 67.1% of patients with epileptiform abnormalities, over two-thirds acute. In-hospital mortality was 39.5% for patients with epileptiform abnormalities and 36.2% for those without. Risk factors for mortality were coma and ventilator support at time of EEG. Discussion: This article highlights the range of EEG abnormalities frequently associated with acute neuroimaging abnormalities in COVID-19. Mortality rates were high, particularly for patients in coma requiring mechanical ventilation. These findings may guide the prognosis and management of patients with COVID-19 and neurologic changes.

The Effect of Epilepsy on Sleep Quality During Pregnancy and Postpartum.

OBJECTIVE: This study seeks to understand how sleep is affected in pregnant women with epilepsy (WWE) relative to healthy pregnant women during pregnancy and postpartum and to non-pregnant WWE during comparative time periods. BACKGROUND: Sleep impacts maternal health and mood during pregnancy. Maternal sleep disturbances are related to poor fetal growth and increased fetal deaths. Epilepsy is the most common neurologic condition in pregnancy. Sleep disruption can worsen epileptic seizures. The interplay between epilepsy, pregnancy, and sleep is poorly understood. DESIGN: /Methods: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter study, enrolling women from December 2012 through January 2016. Sleep quality was assessed utilizing the average Pittsburgh Sleep Quality Index collected during pregnancy; postpartum; or analogous time periods. Sleep scores range from 0 to 21 with higher scores indicating worse sleep quality; scores > 5 are associated with poor sleep quality. RESULTS: Of 351 pregnant WWE, 105 healthy pregnant women, and 109 non-pregnant WWE enrolled in MONEAD, data from 241 pregnant WWE, 74 healthy pregnant women, and 84 non-pregnant WWE were analyzed. Pregnant WWE had worse sleep (higher mean sleep score) during pregnancy compared to healthy pregnant women in unadjusted analysis (p=0.006), but no longer significant in adjusted analysis (p=0.062), pregnant WWE (least square mean sleep score (95% CI) = 5.8 (5.5, 6.1)) vs. healthy pregnant women (5.1 (4.6, 5.7)). During postpartum, pregnant WWE (5.6 (5.4, 5.9)) had similarly impaired sleep compared to healthy pregnant women (5.7 (5.2, 6.2); adjusted p=0.838). Sleep was significantly worse in pregnant WWE vs non-pregnant WWE (for comparable time period) in pregnancy and postpartum in unadjusted and adjusted analyses. Adjusted scores for pregnant WWE in pregnancy (5.7 (5.4, 6.0)) and postpartum (5.7 (5.4, 6.0)) compared to non-pregnant WWE (4.7 (4.2, 5.3); p=0.002) and (4.1 (3.6, 4.7); p<0.001), respectively. Sleep quality between pregnancy and postpartum varied only in healthy pregnant women (change in mean score = 0.8 (0.2, 1.3); p=0.01), whose sleep was worse in postpartum. CONCLUSIONS: Pregnant WWE had worse sleep during pregnancy and postpartum than non-pregnant WWE during comparable periods in the adjusted analysis.The study is registered at clinicaltrials.gov as NCT01730170.

Multigene Panel Testing in a Large Cohort of Adults With Epilepsy: Diagnostic Yield and Clinically Actionable Genetic Findings.

BACKGROUND AND OBJECTIVES: Although genetic testing among children with epilepsy has demonstrated clinical utility and become a part of routine testing, studies in adults are limited. This study reports the diagnostic yield of genetic testing in adults with epilepsy. METHODS: Unrelated individuals aged 18 years and older who underwent diagnostic genetic testing for epilepsy using a comprehensive, next-generation sequencing-based, targeted gene panel (range 89-189 genes) were included in this cross-sectional study. Clinical information, provided at the discretion of the ordering clinician, was reviewed and analyzed. Diagnostic yield was calculated for all individuals including by age at seizure onset and comorbidities based on clinician-reported information. The proportion of individuals with clinically actionable genetic findings, including instances when a specific treatment would be indicated or contraindicated due to a diagnostic finding, was calculated. RESULTS: Among 2,008 individuals, a diagnostic finding was returned for 218 adults (10.9%), with clinically actionable findings in 55.5% of diagnoses. The highest diagnostic yield was in adults with seizure onset during infancy (29.6%, 0-1 year), followed by in early childhood (13.6%, 2-4 years), late childhood (7.0%, 5-10 years), adolescence (2.4%, 11-17 years), and adulthood (3.7%, ≥18 years). Comorbid intellectual disability (ID) or developmental delay resulted in a high diagnostic yield (16.0%), most notably for females (19.6% in females vs 12.3% in males). Among individuals with pharmacoresistant epilepsy, 13.5% had a diagnostic finding, and of these, 57.4% were clinically actionable genetic findings. DISCUSSION: These data reinforce the utility of genetic testing for adults with epilepsy, particularly for those with childhood-onset seizures, ID, and pharmacoresistance. This is an important consideration due to longer survival and the complexity of the transition from pediatric to adult care. In addition, more than half of diagnostic findings in this study were considered clinically actionable, suggesting that genetic testing could have a direct impact on clinical management and outcomes.

Intracranial EEG Biomarkers for Seizure Lateralization in Rapidly-Bisynchronous Epilepsy After Laser Corpus Callosotomy.

Objective: It has been asserted that high-frequency analysis of intracranial EEG (iEEG) data may yield information useful in localizing epileptogenic foci. Methods: We tested whether proposed biomarkers could predict lateralization based on iEEG data collected prior to corpus callosotomy (CC) in three patients with bisynchronous epilepsy, whose seizures lateralized definitively post-CC. Lateralization data derived from algorithmically-computed ictal phase-locked high gamma (PLHG), high gamma amplitude (HGA), and low-frequency (filtered) line length (LFLL), as well as interictal high-frequency oscillation (HFO) and interictal epileptiform discharge (IED) rate metrics were compared against ground-truth lateralization from post-CC ictal iEEG. Results: Pre-CC unilateral IEDs were more frequent on the more-pathologic side in all subjects. HFO rate predicted lateralization in one subject, but was sensitive to detection threshold. On pre-CC data, no ictal metric showed better predictive power than any other. All post-corpus callosotomy seizures lateralized to the pathological hemisphere using PLHG, HGA, and LFLL metrics. Conclusions: While quantitative metrics of IED rate and ictal HGA, PHLG, and LFLL all accurately lateralize based on post-CC iEEG, only IED rate consistently did so based on pre-CC data. Significance: Quantitative analysis of IEDs may be useful in lateralizing seizure pathology. More work is needed to develop reliable techniques for high-frequency iEEG analysis.

Two-Year-Old Cognitive Outcomes in Children of Pregnant Women With Epilepsy in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study.

Importance: The neurodevelopmental risks of fetal exposure are uncertain for many antiseizure medications (ASMs). Objective: To compare children at 2 years of age who were born to women with epilepsy (WWE) vs healthy women and assess the association of maximum ASM exposure in the third trimester and subsequent cognitive abilities among children of WWE. Design, Setting, and Participants: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicenter investigation of pregnancy outcomes that enrolled women from December 19, 2012, to January 13, 2016, at 20 US epilepsy centers. Children are followed up from birth to 6 years of age, with assessment at 2 years of age for this study. Of 1123 pregnant women assessed, 456 were enrolled; 426 did not meet criteria, and 241 chose not to participate. Data were analyzed from February 20 to December 4, 2020. Main Outcomes and Measures: Language domain score according to the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), which incorporates 5 domain scores (language, motor, cognitive, social-emotional, and general adaptive), and association between BSID-III language domain and ASM blood levels in the third trimester in children of WWE. Analyses were adjusted for multiple potential confounding factors, and measures of ASM exposure were assessed. Results: The BSID-III assessments were analyzed in 292 children of WWE (median age, 2.1 [range, 1.9-2.5] years; 155 female [53.1%] and 137 male [46.9%]) and 90 children of healthy women (median age, 2.1 [range, 2.0-2.4] years; 43 female [47.8%] and 47 male [52.2%]). No differences were found between groups on the primary outcome of language domain (-0.5; 95% CI, -4.1 to 3.2). None of the other 4 BSID-III domains differed between children of WWE vs healthy women. Most WWE were taking lamotrigine and/or levetiracetam. Exposure to ASMs in children of WWE showed no association with the language domain. However, secondary analyses revealed that higher maximum observed ASM levels in the third trimester were associated with lower BSID-III scores for the motor domain (-5.6; 95% CI, -10.7 to -0.5), and higher maximum ASM doses in the third trimester were associated with lower scores in the general adaptive domain (-1.4; 95% CI, -2.8 to -0.05). Conclusions and Relevance: Outcomes of children at 2 years of age did not differ between children of WWE taking ASMs and children of healthy women. Trial Registration: ClinicalTrials.gov Identifier: NCT01730170.

Heterogeneous Growth of UiO-66-NH2 on Oxidized Single-Walled Carbon Nanotubes to Form "Beads-on-a-String" Composites.

In this work, we demonstrate a facile synthesis of UiO-66-NH2 metal-organic framework (MOF)/oxidized single-walled carbon nanotubes (ox-SWCNTs) composite at room temperature. Acetic acid (HAc) was used as a modulator to manipulate the morphology of the MOF in these composites. With a zirconium oxide cluster (Zr) to 2-aminoteraphthalate linker (ATA) 1:1.42 ratio and acetic acid modulator, we achieved predominately heterogeneous MOF growth on the sidewalls of CNTs. Understanding the growth mechanism of these composites was facilitated by conducting DFT calculations to investigate the interactions between ox-SWCNTs and the MOF precursors. The synthesized composites combine both microporosity of the MOF and electrical conductivity of the SWCNTs. Gas sensing tests demonstrated higher response for UiO-66-NH2/ox-SWCNT hybrid toward dry air saturated with dimethyl methylphosphonate (DMMP) vapor compared to oxidized single-walled carbon nanotubes (ox-SWCNTs) alone.

Breath Acetone Sensing Based on Single-Walled Carbon Nanotube-Titanium Dioxide Hybrids Enabled by a Custom-Built Dehumidifier.

Acetone is a metabolic byproduct found in the exhaled breath and can be measured to monitor the metabolic degree of ketosis. In this state, the body uses free fatty acids as its main source of fuel because there is limited access to glucose. Monitoring ketosis is important for type I diabetes patients to prevent ketoacidosis, a potentially fatal condition, and individuals adjusting to a low-carbohydrate diet. Here, we demonstrate that a chemiresistor fabricated from oxidized single-walled carbon nanotubes functionalized with titanium dioxide (SWCNT@TiO2) can be used to detect acetone in dried breath samples. Initially, due to the high cross sensitivity of the acetone sensor to water vapor, the acetone sensor was unable to detect acetone in humid gas samples. To resolve this cross-sensitivity issue, a dehumidifier was designed and fabricated to dehydrate the breath samples. Sensor response to the acetone in dried breath samples from three volunteers was shown to be linearly correlated with the two other ketone bodies, acetoacetic acid in urine and ß-hydroxybutyric acid in the blood. The breath sampling and analysis methodology had a calculated acetone detection limit of 1.6 ppm and capable of detecting up to at least 100 ppm of acetone, which is the dynamic range of breath acetone for someone with ketosis. Finally, the application of the sensor as a breath acetone detector was studied by incorporating the sensor into a handheld prototype breathalyzer.

Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy.

BACKGROUND: Among women with epilepsy, studies regarding changes in seizure frequency during pregnancy have been limited by the lack of an appropriate nonpregnant comparator group to provide data on the natural course of seizure frequency in both groups. METHODS: In this prospective, observational, multicenter cohort study, we compared the frequency of seizures during pregnancy through the peripartum period (the first 6 weeks after birth) (epoch 1) with the frequency during the postpartum period (the following 7.5 months after pregnancy) (epoch 2). Nonpregnant women with epilepsy were enrolled as controls and had similar follow-up during an 18-month period. The primary outcome was the percentage of women who had a higher frequency of seizures that impaired awareness during epoch 1 than during epoch 2. We also compared changes in the doses of antiepileptic drugs that were administered in the two groups during the first 9 months of epoch 1. RESULTS: We enrolled 351 pregnant women and 109 controls with epilepsy. Among the 299 pregnant women and 93 controls who had a history of seizures that impaired awareness and who had available data for the two epochs, seizure frequency was higher during epoch 1 than during epoch 2 in 70 pregnant women (23%) and in 23 controls (25%) (odds ratio, 0.93; 95% confidence interval [CI], 0.54 to 1.60). During pregnancy, the dose of an antiepileptic drug was changed at least once in 74% of pregnant women and in 31% of controls (odds ratio, 6.36; 95% CI, 3.82 to 10.59). CONCLUSIONS: Among women with epilepsy, the percentage who had a higher incidence of seizures during pregnancy than during the postpartum period was similar to that in women who were not pregnant during the corresponding epochs. Changes in doses of antiepileptic drugs occurred more frequently in pregnant women than in nonpregnant women during similar time periods. (Funded by the National Institutes of Health; MONEAD ClinicalTrials.gov number, NCT01730170.).

Acute Seizures Occurring in Association With SARS-CoV-2.

Seizures are an infrequent and serious neurological complication of SARS-CoV-2 infection, with limited data describing the etiology and the clinical context in which these occur or the associated electrographic and imaging findings. This series details four cases of seizures occurring in patients with COVID-19 with distinct time points, underlying pathology, and proposed physiological mechanisms. An enhanced understanding of seizure manifestations in COVID-19 and their clinical course may allow for earlier detection and improved patient management.

Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy.

OBJECTIVE: To examine occurrence of severe adverse fetal outcomes (SAO), including fetal loss and major congenital malformations (MCMs), in pregnant women with epilepsy (PWWE) vs healthy pregnant women (HPW). METHODS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women December 2012 through January 2016. RESULTS: The 351 PWWE had 365 conceptions, and 105 HPW had 109 conceptions. SAOs occurred more often in PWWE (7.9%) vs HPW (1.9%) (p = 0.025) with odds ratio (OR) 4.45 (95% confidence intervals [CI] 1.04-19.01). There were no significant differences for fetal loss (2.8% vs 0%, p = 0.126) or MCMs (5.2% vs 1.9%, p = 0.185; OR 2.86, 95% CI 0.65-12.53) individually. No fetal losses in PWWE appeared to be related to acute seizures. Outcomes were not affected by periconceptional folate, unplanned/unwanted pregnancies, prior maternal pregnancy history, or antiepileptic drug (AED) blood levels, except for an AED level effect for fetal loss that appeared to be due to polytherapy. Combined maternal or paternal family history of MCM was marginally associated with increased SAOs (p = 0.046). CONCLUSIONS: The findings provide additional information on risks of SAOs in PWWE, assessing effects of both AED levels and periconceptional folate. Group differences in average enrollment gestational age could have affected fetal loss results. Analyses are limited by small sample sizes as the MONEAD study was not powered for these secondary outcomes. The large majority of pregnancies in women with epilepsy do not have SOAs.

Modification of Carbon Nitride/Reduced Graphene Oxide van der Waals Heterostructure with Copper Nanoparticles To Improve CO2 Sensitivity.

Carbon nitride/reduced graphene oxide (rGO) van der Waals heterostructures (vdWH) have previously shown exceptional oxygen sensitivity via a photoredox mechanism, making it a potential material candidate for various applications such as oxygen reduction reaction catalysis and oxygen sensing. In this work, the electronic structure of a carbon nitride/rGO composite is modified through the introduction of copper nanoparticles (NPs). When incorporated into a chemiresistor device, this vdWH displayed a newfound CO2 sensitivity. The effects of humidity and light were investigated and found to be crucial components for the CO2 sensitivity. Density functional theory calculations performed on a carbon nitride/copper NP@rGO model system found an enhanced stabilization of CO2 caused by H-bonds between the carbon nitride layer and chemisorbed CO2 on copper, pointing to the important role played by humidity. The synergetic effect between the carbon nitride layer interfaced with CuNP@rGO, in combination with humidity and light (395 nm) irradiation, is found to be responsible for the newfound sensitivity toward CO2.

Painful Seizures: a Review of Epileptic Ictal Pain.

PURPOSE OF REVIEW: To summarize the literature regarding the prevalence, pathophysiology, and anatomic networks involved with painful seizures, which are a rare but striking clinical presentation of epilepsy. RECENT FINDINGS: Several recent large case series have explored the prevalence of the main cephalgic, somatosensory, and abdominal variants of this rare disorder. Research studies including the use of electrical stimulation and functional neuroimaging have demonstrated the networks underlying painful somatosensory or visceral seizures. Improved understanding of some of the overlapping mechanisms between migraines and seizures has elucidated their common pathophysiology. The current literature reflects a widening range of awareness and understanding of painful seizures, despite their rarity.