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.

Intracranial investigation of piriform cortex epilepsy during odor presentation.

The piriform cortex (PC) is part of the olfactory system, principally receiving input from the lateral olfactory tract and projecting to downstream components of the olfactory network, including the amygdala. Based on preclinical studies, PC is vulnerable to injury and can be easily kindled as an onset site for seizures. While the role of PC in human epilepsy has been studied indirectly and the subject of speculation, cases of demonstrated PC seizure onset from direct intracranial recording are rare. We present a pediatric patient with drug-resistant focal reflex epilepsy and right mesial temporal sclerosis with habitual seizures triggered by coconut aroma. The patient underwent stereoelectroencephalography with implantation of olfactory cortices including PC, through which we identified PC seizure onset, mapped high-frequency activity associated with presentation of olfactory stimuli and performance on cognitive tasks, and reproduced habitual seizures via cortical stimulation of PC. Coconut odor did not trigger seizures in our work with the patient. Surgical workup resulted in resection of the patient's right amygdala, PC, and mesial temporal pole, following which she has been seizure free for 20 months without functional decline in cognition or smell. Histological findings from resected tissue showed astrogliosis and subpial gliosis.

Interventions for ADHD in children & adolescents with epilepsy: A review and decision tree to guide clinicians.

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common pediatric epilepsy comorbidities. Treating ADHD in the context of epilepsy can be overwhelming for parents and clinicians. Current frontline treatment for ADHD is stimulant medication. However, some parents of pediatric patients with epilepsy have concerns about adding additional medication to their child's epilepsy regimen and/or about adverse effects of stimulant medication. Non-medication ADHD treatments including psychosocial interventions and ketogenic diet have also shown success in improving ADHD symptoms. Our focused review provides an easy-to-use guide for clinicians on ADHD interventions and combinations of interventions for pediatric patients with epilepsy and ADHD. Our guide includes information from 8 electronic databases for peer-reviewed, English language studies of psychosocial treatments for youth with epilepsy and ADHD. One hundred eight studies were selected based on inclusion criteria (21 systematic reviews, 12 meta-analyses, 8 literature reviews, 6 population surveys, 31 clinical trials, 20 cross-sectional studies, and 10 retrospective reviews). Results indicated that stimulant medication is a frontline treatment for ADHD symptoms in youth with epilepsy, with important caveats and alternatives.

Longitudinal Changes in Resting State Connectivity and White Matter Integrity in Adolescents With Sports-Related Concussion.

OBJECTIVES: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. METHODS: We assessed male high school football players (ages 14-18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. RESULTS: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. CONCLUSIONS: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781-792).

Assessment of Sleep Quantity and Sleep Disturbances During Recovery From Sports-Related Concussion in Youth Athletes.

OBJECTIVE: To determine the relation between sleep quantity and sleep disturbances on symptoms and neurocognitive ability during the acute phase (<7d) and after sports-related concussion (SRC; >21d). DESIGN: Prospective inception cohort study. SETTING: General community setting of regional middle and high schools. PARTICIPANTS: A sample (N=971) including youth athletes with SRC (n=528) and controls (n=443) (age, 10-18y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Athletes completed the Immediate Post-Concussion Assessment and Cognitive Testing battery. Partial correlation analyses and independent t tests were conducted to assess sleep quantity the night before testing. Multivariate analysis of covariance was used to assess sleep disturbances and their interaction with age. RESULTS: Less sleep quantity was correlated with greater report of cognitive (P=.001) and neuropsychological (P=.024) symptoms specific to prolonged recovery from SRC. Sleep disturbances significantly affect each migraine, cognitive, and neuropsychological symptoms (P<.001). A significant interaction was found between sleep disturbances and age (P=.04) at >21 days post-SRC. CONCLUSIONS: Findings emphasize that the continued presence of low sleep quantity and sleep disturbances in youth athletes with SRC should be a specific indicator to health professionals that these athletes are at an increased risk of protracted recovery. Further research should identify additional factors that may interact with sleep to increase the risk of protracted recovery.

Quality Improvement in Concussion Care: Influence of Guideline-Based Education.

OBJECTIVE: To evaluate the potential impact of a concussion management education program on community-practicing pediatricians. STUDY DESIGN: We prospectively surveyed 210 pediatricians before and 18 months after participation in an evidence-based, concussion education program. Pediatricians were part of a network of 38 clinically integrated practices in metro-Atlanta. Participation was mandatory for at least 1 pediatrician in each practice. We assessed pediatricians' self-reported concussion knowledge, use of guidelines, and comfort level, as well as self-reported referral patterns for computed tomography (CT) and/or emergency department (ED) evaluation of children who sustained concussion. RESULTS: Based on responses from 120 pediatricians participating in the 2 surveys and intervention (response rate, 57.1%), the program had significant positive effects from pre- to postintervention on knowledge of concussions (-0.26 to 0.56 on -3 to +1 scale; P < .001), guideline use (0.73-.06 on 0-6 scale; P < .01), and comfort level in managing concussions (3.76-4.16 on 1-5 scale; P < .01). Posteducation, pediatricians were significantly less likely to self-report referral for CT (1.64-1.07; P < .001) and CT/ED (4.73-3.97; P < .01), but not ED referral alone (3.07-3.09; P = ns). CONCLUSIONS: Adoption of a multifaceted, evidence-based, education program translated into a positive modification of self-reported practice behavior for youth concussion case management. Given the surging demand for community-based youth concussion care, this program can serve as a model for improving the quality of pediatric concussion management.

Methylphenidate treatment for cognitive symptoms associated with ADHD in a pediatric epilepsy patient following resection of a left frontal cortical dysplasia.

We present data on a 10-year-old patient with drug-resistant epilepsy who was treated with methylphenidate for symptoms of attention deficit hyperactivity disorder (ADHD) that developed after she underwent surgical resection of a left frontal cortical dysplasia. . The patient's parents reported methylphenidate was helpful in improving their child's reading performance. Based on parents' report, we examined benefits of methylphenidate on our patient's cognitive problems in a controlled setting. The patient underwent a neuropsychological evaluation completed in three sessions over a five-day period. Methylphenidate was administered prior to the second testing session only and was associated with improvements in the patient's attention, executive function, processing speed, and short-term memory performances. In comparison, word-reading performance, a task less susceptible to neurological impairment, was stable over the three sessions. The patient remained seizure-free after surgery and use of methylphenidate did not reduce seizure threshold. These findings support the use of methylphenidate in treating targeted cognitive problems associated with ADHD emerging after epilepsy surgery in children.

Cognitive and behavioral outcome of stereotactic laser amydalohippocampotomy in a pediatric setting.

We present neuropsychological and functional outcome data in a teenager undergoing stereotactic laser amygdalohippocampotomy (SLAH) who had drug-resistant mesial temporal lobe epilepsy due to left hippocampal sclerosis. Given strong baseline cognitive performance, there was concern for post-operative declines in language and verbal memory were this patient to undergo open resection. She was evaluated pre- and post-ablation with clinical and experimental neuropsychological measures including semantic memory, category-specific object/face recognition and naming, spatial learning, and socio-emotional processing. The patient became seizure-free following SLAH and experienced significant improvements in school performance and social engagement. She experienced improvement in recognition and naming of multiple object categories, memory functions, and verbal fluency. In contrast, the patient declined significantly in her ability to recognize emotional tone from facial expressions, a socio-emotional process that had been normal prior to surgery. We believe this decline was related to surgical disruption of the limbic system, an area highly involved in emotional processing, and suspect such deficits are an under-assessed and unrecognized risk for all surgeries involving the amygdalohippocampal complex and broader limbic system regions. We hope this positive SLAH outcome will serve as impetus for group level research to establish its safety and efficacy in the pediatric setting.

Effects of Developmental Age on Symptom Reporting and Neurocognitive Performance in Youth After Sports-Related Concussion Compared to Control Athletes.

There is increased necessity to focus research on school-aged athletes with sports-related concussion (SRC). This study assessed differences in symptom reporting and neurocognitive performance in youth athletes who sustained a sports-related concussion. A total of 1345 concussed and 3529 nonconcussed athletes (ages 8-21) completed the Immediate Post-concussive Assessment and Cognitive Testing (ImPACT). Analyses of covariance were conducted in order to assess differences in neurocognitive performance and symptom reporting between the sports-related concussion and control groups across age ranges. Longitudinal hierarchical linear modeling was employed to examine age and its relationship with rates of sports-related concussion recovery in neurocognitive performance. Results revealed athletes aged 13 to 15 had significantly lower neurocognitive performance scores compared to same-aged athletes without a history of sports-related concussion. With respect to the hierarchical linear modeling results, age was identified as a unique predictor of symptom recovery, particularly for ages 8 to 12. Results provide a better understanding of typical symptom reporting and neurocognitive outcomes for younger athletes across different ages.

Neurocognitive functioning in adults with congenital heart disease.

OBJECTIVE: Adults with congenital heart disease (CHD) are at increased risk of psychological disorders and cognitive deficiencies due to structural/acquired neurological abnormalities and neurodevelopmental disorders as children. However, limited information is known about the neuropsychological functioning of adults with CHD. This study screened neuropsychological abilities and explored group differences related to cardiac disease severity and neurological risk factors in adults with CHD. DESIGN: Participants completed brief neuropsychological testing. Information about neurobehavioral and psychological symptoms, employment, education, and disability were also collected from the patient and a family member. RESULTS: Forty-eight participants with adult CHD completed neuropsychological testing. Visuospatial skills and working memory were worse than expected compared to the typical population. Frequency of neurological comorbidities (e.g., stroke, seizures) was higher in those with more severe heart disease (e.g., single ventricle or cyanotic disease), and executive functioning was weaker in those with neurological comorbidities. Those with more severe heart disease were more likely to be unemployed and to receive disability benefits, but educational attainment did not differ. Those who received disability performed worse on tasks of executive functioning. CONCLUSIONS: Findings suggest concerns about neuropsychological functioning that need to be more comprehensively assessed in adults with CHD. Understanding the cognitive limitations of this aging population can help guide access to resources, transition of care, and medical care engagement, thus improving quality of care and quality of life.

Sex-Based Differences as a Predictor of Recovery Trajectories in Young Athletes After a Sports-Related Concussion.

BACKGROUND: To date, few studies have delineated clear sex-based differences in symptom resolution after a sports-related concussion (SRC), and equivocal results have been identified in sex-based differences on baseline assessments. PURPOSE: To assess whether female athletes displayed prolonged recovery and more symptoms at baseline and after an SRC compared with male athletes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The current study assessed 135 male and 41 female athletes (10-18 years old) who participated in high-impact sports in metropolitan Atlanta middle and high schools. All athletes completed a baseline assessment and at least 1 postconcussion assessment from the Immediate Post-Concussion Assessment and Cognitive Testing battery. Longitudinal hierarchical linear modeling was employed to examine individual-level variables and their associations with adolescents' rates of recovery in concussive symptoms after controlling for age and number of prior concussions. RESULTS: Aggregate symptoms were rated as higher in female athletes compared with male athletes at baseline (mean ± SD: females, 13.49 ± 11.20; males, 4.88 ± 8.74; F(1,175) = 10.59, P < .001) and immediately after a concussion (females: 16.75 ± 18.08; males: 10.58 ± 14.21; F(1,175) = 3.99, P = .05). There were no group differences in the slope of recovery between male and female athletes, indicating generally similar trajectories of change for both groups. Post hoc analyses revealed higher baseline levels of migraine and neuropsychological symptoms in female athletes. CONCLUSION: Although female athletes in the current study reported increased symptoms, identical recovery patterns were observed in both sexes, suggesting that sex-based differences in concussion recovery are better explained by increased symptom frequency among female athletes when compared with their male counterparts.

The costs and benefits of self-monitoring for higher functioning children and adolescents with autism.

The ability to regulate behaviors and emotions depends in part on the ability to flexibly monitor one's own progress toward a goal. Atypical patterns of response monitoring have been reported in individuals with autism spectrum disorders (ASD). In the current study we examined the error related negativity (ERN), an electrophysiological index of response monitoring, in relation to behavioral, social cognitive, and emotional presentation in higher functioning children (8-16 years) diagnosed with autism (HFA: N = 38) and an age- and IQ-matched sample of children without autism (COM: N = 36). Both HFA and COM participants displayed larger amplitude responses to error compared to correct response trials and these amplitudes did not differ by diagnostic group. For participants with HFA, larger ERN amplitudes were associated with more parent-reported autistic symptoms and more self-reported internalizing problems. However, across the full sample, larger ERN amplitudes were associated with better performance on theory of mind tasks. The results are discussed in terms of the utility of electrophysiological measures for understanding essential moderating processes that contribute to the spectrum of behavioral expression in the development of ASD.

The effects of eszopiclone on sleep spindles and memory consolidation in schizophrenia: a randomized placebo-controlled trial.

STUDY OBJECTIVES: In schizophrenia there is a dramatic reduction of sleep spindles that predicts deficient sleep-dependent memory consolidation. Eszopiclone (Lunesta), a non-benzodiazepine hypnotic, acts on γ-aminobutyric acid (GABA) neurons in the thalamic reticular nucleus where spindles are generated. We investigated whether eszopiclone could increase spindles and thereby improve memory consolidation in schizophrenia. DESIGN: In a double-blind design, patients were randomly assigned to receive either placebo or 3 mg of eszopiclone. Patients completed Baseline and Treatment visits, each consisting of two consecutive nights of polysomnography. On the second night of each visit, patients were trained on the motor sequence task (MST) at bedtime and tested the following morning. SETTING: Academic research center. PARTICIPANTS: Twenty-one chronic, medicated schizophrenia outpatients. MEASUREMENTS AND RESULTS: We compared the effects of two nights of eszopiclone vs. placebo on stage 2 sleep spindles and overnight changes in MST performance. Eszopiclone increased the number and density of spindles over baseline levels significantly more than placebo, but did not significantly enhance overnight MST improvement. In the combined eszopiclone and placebo groups, spindle number and density predicted overnight MST improvement. CONCLUSION: Eszopiclone significantly increased sleep spindles, which correlated with overnight motor sequence task improvement. These findings provide partial support for the hypothesis that the spindle deficit in schizophrenia impairs sleep-dependent memory consolidation and may be ameliorated by eszopiclone. Larger samples may be needed to detect a significant effect on memory. Given the general role of sleep spindles in cognition, they offer a promising novel potential target for treating cognitive deficits in schizophrenia.

Reduced sleep spindles and spindle coherence in schizophrenia: mechanisms of impaired memory consolidation?

BACKGROUND: Sleep spindles are thought to induce synaptic changes and thereby contribute to memory consolidation during sleep. Patients with schizophrenia show dramatic reductions of both spindles and sleep-dependent memory consolidation, which may be causally related. METHODS: To examine the relations of sleep spindle activity to sleep-dependent consolidation of motor procedural memory, 21 chronic, medicated schizophrenia outpatients and 17 healthy volunteers underwent polysomnography on two consecutive nights. On the second night, participants were trained on the finger-tapping motor sequence task (MST) at bedtime and tested the following morning. The number, density, frequency, duration, amplitude, spectral content, and coherence of stage 2 sleep spindles were compared between groups and examined in relation to overnight changes in MST performance. RESULTS: Patients failed to show overnight improvement on the MST and differed significantly from control participants who did improve. Patients also exhibited marked reductions in the density (reduced 38% relative to control participants), number (reduced 36%), and coherence (reduced 19%) of sleep spindles but showed no abnormalities in the morphology of individual spindles or of sleep architecture. In patients, reduced spindle number and density predicted less overnight improvement on the MST. In addition, reduced amplitude and sigma power of individual spindles correlated with greater severity of positive symptoms. CONCLUSIONS: The observed sleep spindle abnormalities implicate thalamocortical network dysfunction in schizophrenia. In addition, the findings suggest that abnormal spindle generation impairs sleep-dependent memory consolidation in schizophrenia, contributes to positive symptoms, and is a promising novel target for the treatment of cognitive deficits in schizophrenia.