Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children.

BACKGROUND AND OBJECTIVES: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children. METHODS: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with p < 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE. RESULTS: We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes [IQR 5-45]; rESE 18 minutes [IQR 6-44], p = 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes; p = 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70, p = 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53, p = 0.0012) was associated with decreased odds of RSE. DISCUSSION: Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures.

Parent-reported measure of repetitive behavior in Phelan-McDermid syndrome.

BACKGROUND: Phelan McDermid syndrome (PMS) is a neurogenetic condition associated with a high prevalence of intellectual disability (ID) and autism spectrum disorder (ASD). This study provides a more comprehensive and quantitative profile of repetitive behaviors within the context of ID seen with the condition. METHODS: Individuals age 3-21 years with a confirmed PMS diagnosis participated in a multicenter observational study evaluating the phenotype and natural history of the disorder. We evaluated data collected from this study pertaining to repetitive behaviors from the Repetitive Behavior Scales-Revised (RBS-R). RESULTS: There were n = 90 participants who were part of this analysis. Forty-seven percent (n = 42/90) were female, and the average age at baseline evaluation was 8.88 ± 4.72 years. The mean best estimate IQ of the cohort was 26.08 ± 17.67 (range = 3.4-88), with n = 8 with mild ID (or no ID), n = 20 with moderate ID, and n = 62 with severe-profound ID. The RBS-R total overall score was 16.46 ± 13.9 (compared to 33.14 ± 20.60 reported in previous studies of ASD) (Lam and Aman, 2007), and the total number of items endorsed was 10.40 ± 6.81 (range = 0-29). After statistical correction for multiple comparisons, IQ correlated with the RBS-R stereotypic behavior subscale score (rs = - 0.33, unadjusted p = 0.0014, adjusted p = 0.01) and RBS-R stereotypic behavior total number of endorsed items (rs = - 0.32, unadjusted p = 0.0019, adjusted p = 0.01). IQ did not correlate with any other RBS-R subscale scores. CONCLUSIONS: The RBS-R total overall score in a PMS cohort appears milder compared to individuals with ASD characterized in previous studies. Stereotypic behavior in PMS may reflect cognitive functioning.

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

OBJECTIVE: This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE). METHODS: This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non-BZD ASM. RESULTS: We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997-.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73-3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40-6.03, p < .0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01-2.06, p = .04). Forty-seven percent of patients (n = 94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival. SIGNIFICANCE: Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings.

Factors associated with long-term outcomes in pediatric refractory status epilepticus.

OBJECTIVE: This study was undertaken to describe long-term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE. METHODS: We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients. RESULTS: Follow-up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow-up duration was 1.6 (.9-2.7) years. The in-hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty-six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1-134.5] h vs. 4 [1.6-16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008-1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale-Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion. SIGNIFICANCE: About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow-up, with longer electroclinical RSE duration as a predictor.

Estimating myofiber cross-sectional area and connective tissue deposition with electrical impedance myography: A study in D2-mdx mice.

INTRODUCTION: Surface electrical impedance myography (sEIM) has the potential for providing information on muscle composition and structure noninvasively. We sought to evaluate its use to predict myofiber size and connective tissue deposition in the D2-mdx model of Duchenne muscular dystrophy (DMD). METHODS: We applied a prediction algorithm, the least absolute shrinkage and selection operator, to select specific EIM measurements obtained with surface and ex vivo EIM data from D2-mdx and wild-type (WT) mice (analyzed together or separately). We assessed myofiber cross-sectional area histologically and hydroxyproline (HP), a surrogate measure for connective tissue content, biochemically. RESULTS: Using WT and D2-mdx impedance values together in the algorithm, sEIM gave average root-mean-square errors (RMSEs) of 26.6% for CSA and 45.8% for HP, which translate into mean errors of ±363 µm2 for a mean CSA of 1365 µm2 and of ±1.44 µg HP/mg muscle for a mean HP content of 3.15 µg HP/mg muscle. Stronger predictions were obtained by analyzing sEIM data from D2-mdx animals alone (RMSEs of 15.3% for CSA and 34.1% for HP content). Predictions made using ex vivo EIM data from D2-mdx animals alone were nearly equivalent to those obtained with sEIM data (RMSE of 16.59% for CSA), and slightly more accurate for HP (RMSE of 26.7%). DISCUSSION: Surface EIM combined with a predictive algorithm can provide estimates of muscle pathology comparable to values obtained using ex vivo EIM, and can be used as a surrogate measure of disease severity and progression and response to therapy.

Predicting myofiber cross-sectional area and triglyceride content with electrical impedance myography: A study in db/db mice.

BACKGROUND: Electrical impedance myography (EIM) provides insight into muscle composition and structure. We sought to evaluate its use in a mouse obesity model characterized by myofiber atrophy. METHODS: We applied a prediction algorithm, ie, the least absolute shrinkage and selection operator (LASSO), to surface, needle array, and ex vivo EIM data from db/db and wild-type mice and assessed myofiber cross-sectional area (CSA) histologically and triglyceride (TG) content biochemically. RESULTS: EIM data from all three modalities provided acceptable predictions of myofiber CSA with average root mean square error (RMSE) of 15% in CSA (ie, ±209 µm2 for a mean CSA of 1439 µm2 ) and TG content with RMSE of 30% in TG content (ie, ±7.3 nmol TG/mg muscle for a mean TG content of 25.4 nmol TG/mg muscle). CONCLUSIONS: EIM combined with a predictive algorithm provides reasonable estimates of myofiber CSA and TG content without the need for biopsy.

Visual field outcomes in children treated for neurofibromatosis type 1-associated optic pathway gliomas: a multicenter retrospective study.

BACKGROUND: Optic pathway gliomas associated with neurofibromatosis type 1 (NF1-OPGs) may adversely affect visual acuity, but data regarding visual field (VF) outcomes after treatment in children are limited. The purpose of this study was to investigate the effects of NF1-OPGs on VF function in a large cohort of children after treatment with chemotherapy. METHODS: We performed a retrospective, international, multicenter study of VF outcomes in patients treated with chemotherapy for NF1-OPGs. RESULTS: A total of 25 participants underwent VF testing using formal perimetric techniques. At the end of treatment, 19 participants (76%) had persistent VF deficits. Formal VF testing was available for 16 participants (64%) at initiation and completion of treatment. Of the 16 children who underwent VF testing at initiation and completion of treatment, 7 (44%) showed stability of VF changes, 3 (19%) showed improvement of VF function, and 6 (38%) had worsening of VFs. Improvement or worsening of VF outcome did not always correlate with visual acuity outcome. Posterior tumor location involving the optic tracts and radiations was associated with more frequent and more profound VF defects. CONCLUSIONS: In our study cohort, children undergoing initial chemotherapy for NF1-OPGs had a high prevalence of VF loss, which could be independent of visual acuity loss. A larger, prospective study is necessary to fully determine the prevalence of VF loss and the effects of chemotherapy on VF outcomes in children with NF1-OPGs.

First-line medication dosing in pediatric refractory status epilepticus.

OBJECTIVE: To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation. METHODS: This was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation. RESULTS: We included 289 patients (55.7% male) with a median age of 4.3 (1.3-9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio [OR] 2, 95% confidence interval [CI] 1.18-3.49; p = 0.012), older age (OR 1.1, 95% CI 1.05-1.17; p < 0.001), no prior diagnosis of epilepsy (OR 2.1, 95% CI 1.23-3.69; p = 0.008), and delayed BZD treatment (OR 2.2, 95% CI 1.24-3.94; p = 0.007) were associated with low total BZD dose. Patients who received low total BZD dosing were less likely to achieve seizure cessation (hazard ratio 0.7, 95% CI 0.57-0.95). CONCLUSION: BZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation.

Use of longitudinal EEG measures in estimating language development in infants with and without familial risk for autism spectrum disorder.

Language development in children with autism spectrum disorder (ASD) varies greatly among affected individuals and is a strong predictor of later outcomes. Younger siblings of children with ASD have increased risk of ASD, but also language delay. Identifying neural markers of language outcomes in infant siblings could facilitate earlier intervention and improved outcomes. This study aimed to determine whether EEG measures from the first 2-years of life can explain heterogeneity in language development in children at low- and high-risk for ASD, and to determine whether associations between EEG measures and language development are different depending on ASD risk status or later ASD diagnosis. In this prospective longitudinal study EEG measures collected between 3-24 months were used in a multivariate linear regression model to estimate participants' 24-month language development. Individual baseline longitudinal EEG measures included (1) the slope of EEG power across 3-12 months or 3-24 months of life for 6 canonical frequency bands, (2) estimated EEG power at age 6-months for the same frequency bands, and (3) terms representing the interaction between ASD risk status and EEG power measures. Modeled 24-month language scores using EEG data from either the first 2-years (Pearson R = 0.70, 95% CI 0.595-0.783, P=1x10-18) or the first year of life (Pearson R=0.66, 95% CI 0.540-0.761, P=2.5x10-14) were highly correlated with observed scores. All models included significant interaction effects of risk on EEG measures, suggesting that EEG-language associations are different depending on risk status, and that different brain mechanisms effect language development in low-versus high-risk infants.

IQ predictors in pediatric opsoclonus myoclonus syndrome: a large international cohort study.

AIM: To determine predictors of full-scale IQ (FSIQ) in an international pediatric opsoclonus myoclonus syndrome (OMS) cohort. METHOD: In this retrospective and prospective cohort study at three academic medical centers (2006-2013), the primary outcome measure, FSIQ, was categorized based on z-score: above average (≥+1), average (+1 to -1), mildly impaired (-1 to -2), and impaired (<-2). Univariate analysis and multivariable linear regression modeling using stepwise selection with Akaike's information criterion was performed to understand the relationship between exposures and FSIQ. RESULTS: Of 81 participants, 37 with sufficient data had mean FSIQ 84.38 (SD 20.55) and median 90 (40-114) at latest available evaluation (mean age 8y 5mo). Twenty (54%), nine (24.3%), and eight (21.6%) had normal, mildly impaired, and impaired FSIQ respectively. The final multivariable linear regression model included 34 participants with evaluable data: number of relapses occurring before neuropsychological testing (p<0.001) and OMS severity score at last follow-up (p<0.001) predicted FSIQ (adjusted R2 =0.64). There was a mean decrease of 2.4 FSIQ points per OMS relapse. INTERPRETATION: Number of relapses negatively correlates with FSIQ in pediatric OMS. Demographic and clinical measures available at OMS onset did not predict FSIQ. Strategies to reduce OMS relapses may improve intellectual outcomes.

Photoplethysmography: A measure for the function of the autonomic nervous system in focal impaired awareness seizures.

OBJECTIVES: Photoplethysmography (PPG) reflects variations of blood perfusion in tissues, which may signify seizure-related autonomic changes. The aim of this study is to assess the variability of PPG signals and their value in detecting peri-ictal changes in patients with focal impaired awareness seizures (FIASs). METHODS: PPG data were recorded using a wearable sensor placed on the wrist or ankle of children with epilepsy admitted for long-term video-electroencephalographic monitoring. We analyzed PPG data in four different periods: seizure-free, preictal, ictal, and postictal. Multiple features were automatically extracted from the PPG signal-frequency, duration, amplitude, increasing and decreasing slopes, smoothness, and area under the curve (AUC)-and were used to identify preictal, ictal, or postictal changes by comparing them with seizure-free periods and with each other using a linear mixed-effects model. RESULTS: We studied PPG in 11 patients (18 FIASs), including seizure-free, preictal, and postictal periods, and a subset of eight patients (12 FIASs) including the ictal period. Compared to the seizure-free period, we found significant changes in PPG (1) during the ictal period across all features; (2) during the preictal period in amplitude, duration, increasing slope, and AUC; and (3) during the postictal period in decreasing slope. SIGNIFICANCE: Specific PPG changes can be seen before, during, and after FIASs. The peri-ictal changes in the PPG features of patients with FIASs suggest potential applications of PPG monitoring for seizure detection.

Photoplethysmographic evaluation of generalized tonic-clonic seizures.

OBJECTIVE: Photoplethysmography (PPG) is an optical technique measuring variations of blood perfusion in peripheral tissues. We evaluated alterations in PPG signals in relationship to the occurrence of generalized tonic-clonic seizures (GTCSs) in patients with epilepsy to evaluate the feasibility of seizure detection. METHODS: During electroencephalographic (EEG) long-term monitoring, patients wore portable wristband sensor(s) on their wrists or ankles recording PPG signals. We analyzed PPG signals during three time periods, which were defined with respect to seizures detected on EEG: (1) baseline (>30 minutes prior to seizure), (2) preseizure period, and (3) postseizure period. Furthermore, we selected five random control segments during seizure-free periods. PPG features, including frequency, amplitude, duration, slope, smoothness, and area under the curve, were automatically calculated. We used a linear mixed-effect model to evaluate changes in PPG features between different time periods in an attempt to identify signal changes that detect seizures. RESULTS: We prospectively enrolled 174 patients from the epilepsy monitoring unit at Boston Children's Hospital. Twenty-five GTCSs were recorded from 13 patients. Data from the first recorded GTCS of each patient were included in the analysis. We observed an increase in PPG frequency during pre- and postseizure periods that was higher than the changes during seizure-free periods (frequency increase: preseizure = 0.22 Hz, postseizure = 0.58 Hz vs changes during seizure-free period = 0.05 Hz). The PPG slope decreased significantly by 56.71 nW/s during preseizure periods compared to seizure-free periods. Additionally, the smoothness increased significantly by 0.22 nW/s during the postseizure period compared to seizure-free periods. SIGNIFICANCE: Monitoring of PPG signals may assist in the detection of GTCSs in patients with epilepsy. PPG may serve as a promising biomarker for future seizure detection systems and may contribute to future seizure prediction systems.

Prevalence of Symptoms of Anxiety, Depression, and Post-traumatic Stress Disorder in Parents and Children Following Pediatric Stroke.

Post-traumatic stress disorder (PTSD), anxiety, and depression are seen in parents and children following critical illness. Whether this exists in parents and children following pediatric stroke has not been thoroughly studied. We examined emotional outcomes in 54 mothers, 27 fathers, and 17 children with stroke. Parents of children 0-18 years and children 7-18 years who were within 2 years of stroke occurrence were asked to complete questionnaires to determine their emotional outcomes. Of participating mothers, 28% reported PTSD, 26% depression, and 4% anxiety; in fathers, 15% reported PTSD, 24% depression, and none reported anxiety. Further, children reported significant emotional difficulty, with 24% having depression, 14% anxiety, and 6% PTSD by self-report ratings. Maternal PTSD, anxiety and depression, and paternal anxiety were all negatively associated with the child's functional outcome. Clinically significant anxiety (based on clinical thresholds) was not found in fathers; however, continuous scores were still analyzed for association between subclinical anxiety and functional outcome, which revealed a statistically significant association between more reported symptoms and higher Recovery and Recurrence Questionnaire scores. Prevalence of PTSD and depression are greater in parents compared to the general population in this preliminary study.

Diffusion Tensor Imaging Abnormalities in the Uncinate Fasciculus and Inferior Longitudinal Fasciculus in Phelan-McDermid Syndrome.

BACKGROUND: This cohort study utilized diffusion tensor imaging tractography to compare the uncinate fasciculus and inferior longitudinal fasciculus in children with Phelan-McDermid syndrome with age-matched controls and investigated trends between autism spectrum diagnosis and the integrity of the uncinate fasciculus and inferior longitudinal fasciculus white matter tracts. METHODS: This research was conducted under a longitudinal study that aims to map the genotype, phenotype, and natural history of Phelan-McDermid syndrome and identify biomarkers using neuroimaging (ClinicalTrial NCT02461420). Patients were aged three to 21 years and underwent longitudinal neuropsychologic assessment over 24 months. MRI processing and analyses were completed using previously validated image analysis software distributed as the Computational Radiology Kit (http://crl.med.harvard.edu/). Whole-brain connectivity was generated for each subject using a stochastic streamline tractography algorithm, and automatically defined regions of interest were used to map the uncinate fasciculus and inferior longitudinal fasciculus. RESULTS: There were 10 participants (50% male; mean age 11.17 years) with Phelan-McDermid syndrome (n = 8 with autism). Age-matched controls, enrolled in a separate longitudinal study (NIH R01 NS079788), underwent the same neuroimaging protocol. There was a statistically significant decrease in the uncinate fasciculus fractional anisotropy measure and a statistically significant increase in uncinate fasciculus mean diffusivity measure, in the patient group versus controls in both right and left tracts (P ≤ 0.024). CONCLUSION: Because the uncinate fasciculus plays a critical role in social and emotional interaction, this tract may underlie some deficits seen in the Phelan-McDermid syndrome population. These findings need to be replicated in a larger cohort.

School start time change and motor vehicle crashes in adolescent drivers.

STUDY OBJECTIVES: The aim of this study was to examine the association between a 50-minute delay (7:20 am to 8:10 am) in high school start times in Fairfax County (FC) Virginia and changes in rates of adolescent motor vehicle crashes. Crash rates in FC were also compared to those in the rest of the state during the same time period. METHODS: Virginia Department of Motor Vehicles crash data in drivers age 16 to 18 years old between September and June of each year in FC versus the rest of the state were compared in the combined 2-year periods preceding (2013-2014 and 2014-2015; T1) and following (2015-2016 and 2016-2017; T2) school start time change in the fall of 2015. RESULTS: The crash rate per 1000 in 16- to 18-year-old licensed drivers in FC during T1 was significantly higher compared to T2, 31.63 versus 29.59 accidents per 1,000 (95% confidence interval, 1.0-1.14, odds ratio 1.07, P = .03). In contrast, adolescent crash rates in the rest of Virginia were not statistically significantly different at T1 versus T2. With regard to subtypes of crashes, there was a trend toward significance in distraction-related crashes per 1,000 in FC at T1 compared to T2 at 7.01 versus 6.13 (95% confidence interval, 0.99-1.31, odds ratio 1.14, P = .05), but were not significantly different in the remainder of the state. CONCLUSIONS: The results of this study suggest that school start time delay is associated with decreased adolescent motor vehicle crash risk, with significant implications for public health and safety.

Natural History and Management of Incidentally Discovered Focal Brain Lesions Indeterminate for Tumor in Children.

BACKGROUND: The incidental discovery of brain lesions in children has increased due to greater utilization of neuroimaging. Standardized surveillance and management guidelines following the discovery of such lesions remain nonexistent. OBJECTIVE: To study the natural history and management of incidental brain lesions in children. METHODS: A retrospective analysis of pediatric patients who were treated at our institution between 2000 and 2016 with incidentally detected brain lesions that were indeterminate for neoplasm on MRI. RESULTS: We identified 445 patients with incidental brain abnormalities of whom 144 had lesions indeterminate for neoplasm. Average age at diagnosis was 11.2 (SD = 4.14) yr and average follow-up was 3.8 yr (range 1-13.2 yr). Lesions showed no progression in 112 patients (77.8%), whereas progression was detected in 31 patients (21.5%). Mean time to progression was 32.3 months (SD = 24.4). A change in management was made in 13/144 patients (9%), which included surgical resection (n = 11), biopsy (n = 1), and lumbar puncture (n = 1). Lesion size, location, multiplicity, new-onset symptoms, associated contrast enhancement, or edema were not predictive of radiologic progression. Larger lesions and those with contrast enhancement or edema were significantly more likely to undergo surgery (P < .001 each). Median geometric diameter of lesions that did not undergo surgery was 6.5 mm, whereas that of surgically resected lesions was 12.5 mm (P < .001). CONCLUSION: Most incidental brain lesions indeterminate for neoplasm have an indolent, benign course. For asymptomatic patients with radiologically stable lesions, we recommend conservative management with MRI and clinical surveillance at 6, 12, 24, 36, and 60 mo after detection.

The Connectivity Fingerprint of the Fusiform Gyrus Captures the Risk of Developing Autism in Infants with Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors throughout the body; it is generally diagnosed early in life and has a high prevalence of autism spectrum disorder (ASD), making it uniquely valuable in studying the early development of autism, before neuropsychiatric symptoms become apparent. One well-documented deficit in ASD is an impairment in face processing. In this work, we assessed whether anatomical connectivity patterns of the fusiform gyrus, a central structure in face processing, capture the risk of developing autism early in life. We longitudinally imaged TSC patients at 1, 2, and 3 years of age with diffusion compartment imaging. We evaluated whether the anatomical connectivity fingerprint of the fusiform gyrus was associated with the risk of developing autism measured by the Autism Observation Scale for Infants (AOSI). Our findings suggest that the fusiform gyrus connectivity captures the risk of developing autism as early as 1 year of age and provides evidence that abnormal fusiform gyrus connectivity increases with age. Moreover, the identified connections that best capture the risk of developing autism involved the fusiform gyrus and limbic and paralimbic regions that were consistent with the ASD phenotype, involving an increased number of left-lateralized structures with increasing age.

Electrical impedance myography for reducing sample size in Duchenne muscular dystrophy trials.

OBJECTIVE: To evaluate the sensitivity of electrical impedance myography (EIM) to disease progression in both ambulatory and non-ambulatory boys with DMD. METHODS AND PARTICIPANTS: A non-blinded, longitudinal cohort study of 29 ambulatory and 15 non-ambulatory boys with DMD and age-similar healthy boys. Subjects were followed for up to 1 year and assessed using the Myolex® mViewTM EIM system as part of a multicenter study. RESULTS: In the ambulatory group, EIM 100 kHz resistance values showed significant change compared to the healthy boys. For example, in lower extremity muscles, the average change in EIM 100 kHz resistance values over 12 months led to an estimated effect size of 1.58. Based on these results, 26 DMD patients/arm would be needed for a 12-month clinical trial assuming a 50% treatment effect. In non-ambulatory boys, EIM changes were greater in upper limb muscles. For example, biceps at 100kHz resistance gave an estimated effect size of 1.92 at 12 months. Based on these results, 18 non-ambulatory DMD patients/arm would be needed for a 12-month clinical trial assuming a 50% treatment effect. Longitudinal changes in the 100 kHz resistance values for the ambulatory boys correlated with the longitudinal changes in the timed supine-to-stand test. EIM was well-tolerated throughout the study. INTERPRETATION: This study supports that EIM 100 kHz resistance is sensitive to DMD progression in both ambulatory and non-ambulatory boys. Given the technology's ease of use and broad age range of utility it should be employed as an exploratory endpoint in future clinical therapeutic trials in DMD. TRIAL REGISTRATION: Clincialtrials.gov registration #NCT02340923.

A Stroke Alert Protocol Decreases the Time to Diagnosis of Brain Attack Symptoms in a Pediatric Emergency Department.

OBJECTIVE: To determine whether a stroke alert system decreases the time to diagnosis of children presenting to the emergency department (ED) with acute-onset focal neurologic deficits. STUDY DESIGN: We performed a retrospective comparison of clinical and demographic information for patients who presented to the ED of a tertiary children's hospital with acute-onset focal neurologic deficits during the 2.5 years before (n = 14) and after (n = 65) the implementation of a stroke alert system. The primary outcome was the median time to neuroimaging analyzed using a Wilcoxon rank-sum test. RESULTS: The median time from ED arrival to neuroimaging for patients with acute-onset focal neurologic deficits decreased significantly after implementation of a stroke alert system (196 minutes; IQR, 85-230 minutes before [n = 14] vs 82 minutes; IQR, 54-123 minutes after [n = 65]; P < .01). Potential intravenous tissue plasminogen activator candidates experienced the shortest time to neuroimaging after implementation of a stroke alert system (54 minutes; IQR, 34-66 minutes [n = 13] for intravenous tissue plasminogen activator candidates vs 89.5 minutes; IQR, 62-126.5 minutes [n = 52] for non-intravenous tissue plasminogen activator candidates; P < .01). CONCLUSIONS: A stroke alert system decreases the median time to diagnosis by neuroimaging of children presenting to the ED with acute-onset focal neurologic deficits by more than one-half. Such a protocol constitutes an important step in ensuring that a greater proportion of children with arterial ischemic stroke are diagnosed in a time frame that enables hyperacute treatment.