The changing landscape of electrical stimulation language mapping with subdural electrodes and stereoelectroencephalography for pediatric epilepsy: A literature review and commentary.

Electrical stimulation mapping (ESM) is used to locate the brain areas supporting language directly within the human cortex to minimize the risk of functional decline following epilepsy surgery. ESM is completed by utilizing subdural grid or depth electrodes (stereo-electroencephalography [sEEG]) in combination with behavioral evaluation of language. Despite technological advances, there is no standardized method of assessing language during pediatric ESM. To identify current clinical practices for pediatric ESM of language, we surveyed neuropsychologists in the Pediatric Epilepsy Research Consortium. Results indicated that sEEG is used for functional mapping at >80% of participating epilepsy surgery centers (n = 13/16) in the United States. However, >65% of sites did not report a standardized protocol to map language. Survey results indicated a clear need for practice recommendations regarding ESM of language. We then utilized PubMed/Medline and PsychInfo to identify 42 articles that reported on ESM of language, of which 18 met inclusion criteria, which included use of ESM/signal recording to localize language regions in children (<21 years) and a detailed account of the procedure and language measures used, and region-specific language localization outcomes. Articles were grouped based on the language domain assessed, language measures used, and the brain regions involved. Our review revealed the need for evidence-based clinical guidelines for pediatric language paradigms during ESM and a standardized language mapping protocol as well as standardized reporting of brain regions in research. Relevant limitations and future directions are discussed with a focus on considerations for pediatric language mapping.

Leveraging expertise and optimizing clinical research: Initial success of a pediatric epilepsy surgery collaborative.

OBJECTIVE: Improve data-driven research to inform clinical decision-making with pediatric epilepsy surgery patients by expanding the Pediatric Epilepsy Research Consortium Epilepsy Surgery (PERC-Surgery) Workgroup to include neuropsychological data. This article reports on the process and initial success of this effort and characterizes the cognitive functioning of the largest multi-site pediatric epilepsy surgery cohort in the United States. METHODS: Pediatric neuropsychologists from 18 institutions completed surveys regarding neuropsychological practice and the impact of involvement in the collaborative. Neuropsychological data were entered through an online database. Descriptive analyses examined the survey responses and cognitive functioning of the cohort. Statistical analyses examined which patients were evaluated and if composite scores differed by domain, demographics, measures used, or epilepsy characteristics. RESULTS: Positive impact of participation was evident by attendance, survey responses, and the neuropsychological data entry of 534 presurgical epilepsy patients. This cohort, ages 6 months to 21 years, were majority White and non-Hispanic, and more likely to have private insurance. Mean intelligence quotient (IQ) scores were below to low average, with weaknesses in working memory and processing speed. Full-scale IQ (FSIQ) was lowest for patients with younger age at seizure onset, daily seizures, and magnetic resonance imaging (MRI) abnormalities. SIGNIFICANCE: We established a collaborative network and fundamental infrastructure to address questions outlined by the Epilepsy Research Benchmarks. There is a wide range in the age and IQ of patients considered for pediatric epilepsy surgery, yet it appears that social determinants of health impact access to care. Consistent with other national cohorts, this US cohort has a downward shift in IQ associated with seizure severity.

Hydroxyurea Use Associated with Nonverbal and Executive Skills in Sickle Cell Anemia.

OBJECTIVE: Hydroxyurea (HU) is used in children with sickle cell disease (SCD) to increase fetal hemoglobin (HF), contributing to a decrease in physical symptoms and potential protection against cerebral microvasculopathy. There has been minimal investigation into the association between HU use and cognition in this population. This study examined the relationship between HU status and cognition in children with SCD. METHODS: Thirty-seven children with SCD HbSS or HbS/ß0 thalassaemia (sickle cell anemia; SCA) ages 4:0-11 years with no history of overt stroke or chronic transfusion completed a neuropsychological test battery. Other medical, laboratory, and demographic data were obtained. Neuropsychological function across 3 domains (verbal, nonverbal, and attention/executive) was compared for children on HU (n = 9) to those not taking HU (n = 28). RESULTS: Children on HU performed significantly better than children not taking HU on standardized measures of attention/executive functioning and nonverbal skills. Performance on verbal measures was similar between groups. CONCLUSIONS: These results suggest that treatment with HU may not only reduce physical symptoms, but may also provide potential benefit to cognition in children with SCA, particularly in regard to attention/executive functioning and nonverbal skills. Replication with larger samples and longitudinal studies are warranted.

Concussion Symptom Treatment and Education Program: A Feasibility Study.

OBJECTIVE: To evaluate the feasibility and potential benefits of a manualized, brief cognitive-behavioral therapy-based intervention program for children and adolescents with persistent postconcussive symptoms. SETTING: Two outpatient pediatric concussion programs in the United States. PARTICIPANTS: Patients aged 8 to 17 years who sustained concussions between 2 and 12 months prior to enrollment. DESIGN: Pre-/postretrospective study. MAIN MEASURES: SCAT-3; HBI; PedsQL 4.0 Generic Core Scales; and RCADS. RESULTS: Thirty children and adolescents completed the treatment program. Self- and parent-reported postconcussive symptoms, quality of life, and internalizing symptoms significantly improved with treatment. Mixed-effects models revealed a significant decline in self-reported postconcussive symptoms across treatment sessions, a = -2.07, SE = 0.25, P < .001. The largest change occurred between sessions 2 and 3, following the session focusing on concussion psychoeducation and sleep hygiene (estimated mean change between sessions 2 and 3 = -4.72, P < .0001). CONCLUSIONS: Our findings indicate that a 6-session manualized cognitive behavioral intervention is feasible to initiate in an outpatient clinic 1 to 12 months following a pediatric mild traumatic brain injury. With a manualized format, clinicians at most levels of training should be able to implement this treatment manual and flexibly adapt as needed when working with children and adolescents who are experiencing delayed symptom recovery following concussion.

Sleep Differences by Race in Preschool Children: The Roles of Parenting Behaviors and Socioeconomic Status.

BACKGROUND AND OBJECTIVE: This study aimed to examine whether socioeconomic variables (SES) and parenting behaviors mediate differences in sleep problems between Black and White preschool-aged children. METHOD: Parents of 191 preschool-aged children (53% male; 77% White) completed questionnaires regarding SES and sleep behaviors. Parenting behaviors and SES were analyzed as mediators of differences in sleep problems between Black and White children. RESULTS: Parent behaviors related to bedtime routine and independence mediated the relationship between race and parent-reported bedtime difficulty, parent confidence managing sleep, and sleep onset latency. SES mediated the relationship between race and sleep onset latency. CONCLUSIONS: Sleep differences between Black and White preschool children were primarily mediated by parent behaviors rather than socioeconomic variables. Results may reflect differences in cultural practices and provide important information for treatment and parent-directed intervention regarding improving sleep in young children.

Driving characteristics of young adults prior to and following concussion.

OBJECTIVES: This study sought to examine whether young adults who sustain concussions have different driving histories and pre-injury driving styles than uninjured peers. In addition, we assessed whether modifications were made to driving behavior in the acute period following concussion. METHODS: Self-reported driving and demographic information was collected from 102 16- to 25-year-old drivers. Half of the sample had recently sustained concussions and the other half comprised a matched comparison group. RESULTS: The groups reported similar pre-injury driving behaviors and styles. However, the recently injured group had more driving citations, higher rates of psychiatric disorders, and greater likelihood of having sustained a prior concussion. Self-reported driving habits postconcussion suggested that most drivers did not modify their driving behavior following concussion, though they were less likely to drive at night or with others in the car. CONCLUSION: Results highlight the need for postconcussion driving guidelines and support for returning to driving safely.

Cognitive Impairment and Driving Skills in Youth After Concussion.

Abstract Concussions can impact cognitive processes necessary for driving. Young adults, a group who are more likely to engage in risky behaviors, have limited driving experience and a higher rate of motor vehicle collisions; they may be at higher risk for driving impairment after concussion. There are no clear guidelines for return-to-driving following a concussion. We sought to examine the simulated driving performance of young drivers after receiving medical care following a concussion, compared with a similar control population, to examine the association of driving performance with performance on neuropsychological tests. We evaluated 47 drivers, 16- to 25-year-old, within 3 weeks of sustaining a concussion and 50 drivers with similar characteristics who had not sustained concussions. Participants completed demographic questionnaires, the Sport Concussion Assessment Tool-5 (SCAT-5), and a brief set of neurocognitive tests, including the National Institutes of Health (NIH) Toolbox Cognition Battery and the Trail Making Test, and a simulated driving assessment. At various times during simulated driving, participants were asked to respond to tactile stimuli using the tactile detection response task (TDRT), a validated method of testing cognitive load during simulated driving. The concussion group reported significantly higher symptoms on the SCAT-5 than the comparison group. Performance on crystallized neurocognitive skills was similar between groups. Performance on fluid neurocognitive skills was significantly lower in the concussion than comparison group, although scores were in the normal range for both groups. Simulated driving was similar between groups, although there was a small but significant difference in variation in speed as well as TDRT miss rate, with worse performance by the concussion group. Symptom report on the SCAT-5 was significantly associated with TDRT miss rate. In addition, neurocognitive test scores significantly predicted TDRT reaction time and miss count with medium to large effect sizes. Results suggest that neurocognitive screening may be a useful tool for predicting capacity to return to drive. However, further research is needed to determine guidelines for how neuropsychological tests can be used to make return to driving recommendations and to evaluate effects of concussion on real world driving.

A Multidisciplinary Pediatric Neurology Clinic for Systematic Follow-up of Children with Neurologic Sequelae of COVID-19.

Clinical guidance on outpatient follow-up of children hospitalized with acute neurologic complications of SARS-CoV2 infection is needed. We describe the clinical infrastructure of our pediatric neurology post-Covid clinic, including our clinical evaluation and cognitive testing battery specific to this patient population, and a case series of our initial patient cohort. Our findings demonstrate cognitive sequelae in all 4 of our patients months following acute SARS-CoV2 infection with neurologic complications including acute disseminated encephalomyelitis, posterior reversible encephalopathy syndrome, viral encephalitis, and gait difficulties. Verbal and executive function domains were predominantly affected in our cohort, even in patients who did not endorse symptomatic or academic complaints at follow-up. Our recommendations include systematic clinical follow-up for children following hospitalization with SARS-CoV2 infection with a comprehensive cognitive battery to monitor for cognitive sequalae and to assist with developing an individualized education plan for the child as they return to school.

Concordance of functional MRI memory task and resting-state functional MRI connectivity used in surgical planning for pediatric temporal lobe epilepsy.

OBJECTIVE: Assessing memory is often critical in surgical evaluation, although difficult to assess in young children and in patients with variable task abilities. While obtaining interpretable data from task-based functional MRI (fMRI) measures is common in compliant and awake patients, it is not known whether functional connectivity MRI (fcMRI) data show equivalent results. If this were the case, it would have substantial clinical and research generalizability. To evaluate this possibility, the authors evaluated the concordance between fMRI and fcMRI data collected in a presurgical epilepsy cohort. METHODS: Task-based fMRI data for autobiographical memory tasks and resting-state fcMRI data were collected in patients with epilepsy evaluated at Seattle Children's Hospital between 2010 and 2017. To assess memory-related activation and laterality, signal change in task-based measures was computed as a percentage of the average blood oxygen level-dependent signal over the defined regions of interest. An fcMRI data analysis was performed using 1000 Functional Connectomes Project scripts based on Analysis of Functional NeuroImages and FSL (Functional Magnetic Resonance Imaging of the Brain Software Library) software packages. Lateralization indices (LIs) were estimated for activation and connectivity measures. The concordance between these two measures was evaluated using correlation and regression analysis. RESULTS: In this epilepsy cohort studied, the authors observed concordance between fMRI activation and fcMRI connectivity, with an LI regression coefficient of 0.470 (R2 = 0.221, p = 0.00076). CONCLUSIONS: Previously published studies have demonstrated fMRI and fcMRI overlap between measures of vision, attention, and language. In the authors' clinical sample, task-based measures of memory and analogous resting-state mapping were similarly linked in pattern and strength. These results support the use of fcMRI methods as a proxy for task-based memory performance in presurgical patients, perhaps including those who are more limited in their behavioral compliance. Future investigations to extend these results will be helpful to explore how the magnitudes of effect are associated with neuropsychological performance and postsurgical behavioral changes.

Homoplasmy of the m. 8993 T>G variant in a patient without MRI findings of Leigh syndrome, ataxia or retinal abnormalities.

Leigh syndrome is a progressive neurodegenerative syndrome caused by multiple mitochondrial DNA and nuclear DNA pathological variants. Patients with Leigh syndrome consistently have distinct brain lesions found on MRI scanning involving abnormal signal in the basal ganglia, brainstem and/or cerebellum. Other clinical findings vary depending on the genetic etiology and epigenetic factors. Mitochondrial DNA-derived Leigh syndrome phenotype is thought to be modulated by heteroplasmy level. The classic example is the clinical expression of the pathological variant, m. 8993 T>G. At heteroplasmy levels above 90%, the resulting phenotype is Leigh syndrome, but at levels 70-90% patients present with a syndrome of neuropathy, ataxia and retinitis pigmentosa. We describe a 15-year old girl with homoplasmic variant in m.8993 T>G and clinical and biochemical findings consistent with Leigh syndrome but with normal brain MRI findings and without retinal abnormalities or ataxia.

Executive function "drives" differences in simulated driving performance between young adults with and without autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) may experience greater difficulty learning to drive than peers who do not have ASD, but reasons for those differences are unclear. This study examined how diagnostic symptoms of ASD and commonly co-morbid executive dysfunction relate to differences in simulated driving performance between young, inexperienced drivers with and without ASD. Participants included 98 young adults, ages 16-26 years, half of which were diagnosed with ASD. Participants with ASD completed the Autism Diagnostic Observation Schedule (ADOS-2) and self- and parent-report versions of the Social Responsiveness Scale (SRS-2) to confirm diagnosis and assess the severity of ASD symptoms. All participants completed neuropsychological tests measuring executive functioning. Driving behaviors, including speed and lane positioning, were assessed on a virtual reality driving simulator. Analyses were conducted to first examine relationships between autism severity and driving behaviors, and then to examine whether neurocognitive performance mediated differences in driving behaviors between young adults with and without ASD. Controlling for age, gender, and licensure status, ASD symptom severity was not significantly related to driving. Neurocognitive variables were grouped into three factors: Speed of Information Processing, Auditory Attention and Working Memory, and Selective and Divided Attention. Speed of Information Processing significantly mediated group driving differences. Results suggest that assessment of executive functions such as processing speed may be more useful than the diagnostic assessment of ASD symptoms for evaluation of driving readiness.

Brief cognitive behavioral intervention for children and adolescents with persistent post-concussive symptoms: A pilot study.

This study aims to evaluate the efficacy of a brief cognitive behavioral intervention program for children and adolescents experiencing persistent post-concussion symptoms. A total of 31 patients aged 10 to 18 years participated in the intervention. The median time since injury at treatment onset was 95 days though the range was large (23-720 days). Treatment was on average four sessions in duration. Sessions included concussion education, activity scheduling, sleep hygiene relaxation training, and cognitive restructuring. Outcomes were measured using symptom reports on the Sports Concussion Assessment Tool - Third Edition (SCAT-3) and parent-reported quality of life on the Pediatric Quality of Life Inventory (PedsQL). Mixed-effects models revealed that symptom reports did not decrease prior to the initiation of this treatment, though significant symptom improvement occurred following treatment. Quality of life scores significantly improved across domains, with the largest gains made in the emotional and school domains. Participant characteristics including age, sex, maternal education, and previous mental health problems were not found to be significantly related to treatment outcomes. Contrary to predictions, length of time since injury was not related to symptom changes. The primary limitation of this study is that it lacks randomization and an experimental control group. The results suggest that brief cognitive behavioral intervention may be a promising treatment for children and adolescents experiencing persistent post-concussive symptoms and warrants further investigation.

Driving Comparisons Between Young Adults with Autism Spectrum Disorder and Typical Development.

OBJECTIVE: Many individuals with autism spectrum disorder (ASD) are reluctant to pursue driving because of concerns about their ability to drive safely. This study aimed to assess differences in simulated driving performance in young adults with ASD and typical development, examining relationships between driving performance and the level of experience (none, driver's permit, licensed) across increasingly difficult driving environments. METHOD: Participants included 50 English-speaking young adults (16-26 years old) with ASD matched for sex, age, and licensure with 50 typically-developing (TD) peers. Participants completed a structured driving assessment using a virtual-reality simulator that included increasingly complex environmental demands. Differences in mean speed and speed and lane variability by diagnostic group and driving experience were analyzed using multilevel linear modeling. RESULTS: Young adults with ASD demonstrated increased variability in speed and lane positioning compared with controls, even during low demand tasks. When driving demands became more complex, group differences were moderated by driving experience such that licensed drivers with ASD drove similarly to TD licensed drivers for most tasks, whereas unlicensed drivers with ASD had more difficulty with speed and lane management than TD drivers. CONCLUSION: Findings suggest that young adults with ASD may have more difficulty with basic driving skills than peers, particularly in the early stages of driver training. Increased difficulty compared with peers increases as driving demands become more complex, suggesting that individuals with ASD may benefit from a slow and gradual approach to driver training. Future studies should evaluate predictors of driving performance, on-road driving, and ASD-specific driving interventions.

Differences in Sleep Patterns and Problems by Race in a Clinical Sample of Black and White Preschoolers.

STUDY OBJECTIVES: Community-based research indicates that Black preschoolers tend to have more bedtime difficulties and are at higher risk for obstructive sleep apnea (OSA) compared to White preschoolers. This study examined differences in sleep patterns and problems by race among a clinical sample of Black and White preschoolers at an outpatient sleep clinic. METHODS: Data were collected from electronic medical records for 125 children ages 2-5 years (mean = 3.37 years, 64.0% White, 36.0% Black; 59.2% male) presenting at a pediatric sleep clinic in an academic medical center. Neighborhood income data were based on ZIP codes entered into the United States Census Bureau's American Fact Finder. RESULTS: Black patients (51.1%) were significantly more likely than White patients (20.0%) to bed-share with a caregiver (χ2 = 12.99, P ≤ .001). There were no other significant differences in presenting sleep patterns (bed/wake times, sleep onset latency, naps, night awakenings, or sleep opportunity). Logistic regressions showed that White patients were more likely to present with difficulty falling/staying asleep and receive an insomnia diagnosis, and Black patients were more likely to present with OSA-related concerns and receive a diagnosis of suspected OSA, even when controlling for relevant sociodemographic covariates. CONCLUSIONS: In contrast to community-based research, Black and White children showed similar sleep patterns. However, there were differences by race in referral questions and diagnoses. Findings suggest the need to consider caregiver perceptions and other sociocultural factors that may contribute to differential rates of presentation for sleep services, as well as potential health disparities in this regard.

Individual and socio-demographic factors related to presenting problem and diagnostic impressions at a pediatric sleep clinic.

OBJECTIVE: Individual and socio-demographic factors have been found to be associated with sleep disturbances in children. Few studies have examined these factors among children presenting for care at pediatric sleep clinics. This study examined individual and socio-demographic factors in association with presenting problems and diagnostic impressions for new patients at an interdisciplinary pediatric sleep clinic. METHODS: Data were collected from electronic medical records of 207 consecutive patients (54% male, 59% White, Meanage = 7.73, SD = 5.62). RESULTS: Older age, female gender, and White race were associated with higher likelihood of presenting with difficulty falling asleep; younger age, male gender, and Black race were associated with higher likelihood of presenting with obstructive sleep apnea (OSA)-related concerns. Older age was associated with diagnostic impressions of inadequate sleep hygiene, insufficient sleep, circadian rhythm disorder/delayed sleep phase disorder, periodic limb movement disorder/restless legs syndrome, and insomnia, while younger age was associated with provisional OSA and behavioral insomnia of childhood (BIC) diagnoses. Male gender was associated with provisional OSA. White race was associated with BIC. Age-based analyses were also conducted to further understand the findings within a developmental context. CONCLUSIONS: Age- and gender-related findings converged with prevalence literature on pediatric sleep disorders. Race was only associated with presenting concern and BIC, and one association for neighborhood disadvantage was found within the age-based analysis. Results suggest a potential service delivery gap, with racial/ethnic minority youth being less likely to present for sleep services, despite prevalence data on the increased likelihood of sleep disturbances among these youth.

Cortical Changes Across the Autism Lifespan.

Although it is widely accepted that autism spectrum disorder (ASD) involves neuroanatomical abnormalities and atypical neurodevelopmental patterns, there is little consensus regarding the precise pattern of neuroanatomical differences or how these differences relate to autism symptomology. Furthermore, there is limited research related to neuroanatomical correlates of autism symptomology in individuals with ASD and the studies that do exist primarily include small samples. This study was the first to investigate gray matter (GM) changes throughout the ASD lifespan, using voxel-based morphometry to determine whether significant differences exist in the GM volumes of a large sample of individuals with ASD compared to age- and IQ-matched typical controls. We examined GM volume across the lifespan in 531 individuals diagnosed with ASD and 571 neurotypical controls, aged 7-64. We compared groups and correlated GM with age and autism severity in the ASD group. Findings suggest bilateral decreased GM volume for individuals with ASD in regions extending from the thalamus to the cerebellum, anterior medial temporal lobes, and orbitofrontal regions. Higher autism severity was associated with decreased GM volumes in prefrontal cortex, inferior parietal and temporal regions, and temporal poles. Similar relationships were found between GM volume and age. ASD diagnosis and severity were not associated with increased GM volumes in any region.

Driving behaviors in adults with autism spectrum disorders.

This pilot study investigated driving history and driving behaviors between adults diagnosed with autism spectrum disorders (ASD) as compared to non-ASD adult drivers. Seventy-eight licensed drivers with ASD and 94 non-ASD comparison participants completed the Driver Behavior Questionnaire. Drivers with ASD endorsed significantly lower ratings of their ability to drive, and higher numbers of traffic accidents and citations relative to non-ASD drivers. Drivers with ASD also endorsed significantly greater numbers of difficulties on the following subscales: intentional violations, F(1, 162) = 6.15, p = .01, η p (2)  = .04; mistakes, F(1, 162) = 10.15, p = .002, η p (2)  = .06; and slips/lapses, F(1, 162) = 11.33, p = .001, η p (2)  = .07. These findings suggest that individuals with ASD who are current drivers may experience more difficulties in driving behaviors and engage in more problematic driving behaviors relative to non-ASD drivers.

Clinical utility of the Colorado Learning Difficulties Questionnaire.

BACKGROUND AND OBJECTIVE: Behavioral disorders are highly comorbid with childhood learning disabilities (LDs), and accurate identification of LDs is vital for guiding appropriate interventions. However, it is difficult to conduct comprehensive assessment of academic skills within the context of primary care visits, lending utility to screening of academic skills via informant reports. The current study evaluated the clinical utility of a parent-reported screening measure in identifying children with learning difficulties. METHODS: Participants included 440 children (66.7% male), ages 5.25 to 17.83 years (mean = 10.32 years, SD = 3.06 years), referred for neuropsychological assessment. Academic difficulties were screened by parent report using the Colorado Learning Difficulties Questionnaire (CLDQ). Reading and math skills were assessed via individually administered academic achievement measures. Sensitivity, specificity, classification accuracy, and conditional probabilities were calculated to evaluate the efficacy of the CLDQ in predicting academic impairment. RESULTS: Correlations between the CLDQ reading scale and reading achievement measures ranged from -0.35 to -0.65 and from -0.24 to -0.46 between the CLDQ math scale and math achievement measures (all P < .01). Sensitivity was good for both reading and math scales, whereas specificity was low. Taking into account the high base rate of reading and math LDs within our sample, the conditional probability of true negatives (96.2% reading, 85.1% math) was higher than for true positives (40.5% reading, 37.9% math). CONCLUSIONS: Overall, the CLDQ may more accurately predict children without LDs than children with LDs. As such, the absence of parent-reported difficulties may be adequate to rule out an overt LD, whereas elevated scores likely indicate the need for more comprehensive assessment.