Add-On Deep Brain Stimulation versus Continued Vagus Nerve Stimulation for Childhood Epilepsy (ADVANCE): A Partially Randomized Patient Preference Trial.

Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug-resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non-blinded, randomized patient preference trial of 18 children (aged 8-17 years) who did not respond to VNS after at least 1 year, add-on DBS resulted in greater seizure reduction compared with an additional year of VNS optimization (51.9% vs. 12.3%, p = 0.047). Add-on DBS also resulted in less bothersome seizures (p = 0.03), but no change in quality of life. DBS may be considered earlier for childhood epilepsy after non-response to VNS. ANN NEUROL 2024;96:405-411.

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people.

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.

Identification of brain cell types underlying genetic association with word reading and correlated traits.

Neuroimaging studies implicate multiple cortical regions in reading ability/disability. However, the neural cell types integral to the reading process are unknown. To contribute to this gap in knowledge, we integrated genetic results from genome-wide association studies for word reading (n = 5054) with gene expression datasets from adult/fetal human brain. Linkage disequilibrium score regression (LDSC) suggested that variants associated with word reading were enriched in genes expressed in adult excitatory neurons, specifically layer 5 and 6 FEZF2 expressing neurons and intratelencephalic (IT) neurons, which express the marker genes LINC00507, THEMIS, or RORB. Inhibitory neurons (VIP, SST, and PVALB) were also found. This finding was interesting as neurometabolite studies previously implicated excitatory-inhibitory imbalances in the etiology of reading disabilities (RD). We also tested traits that shared genetic etiology with word reading (previously determined by polygenic risk scores): attention-deficit/hyperactivity disorder (ADHD), educational attainment, and cognitive ability. For ADHD, we identified enrichment in L4 IT adult excitatory neurons. For educational attainment and cognitive ability, we confirmed previous studies identifying multiple subclasses of adult cortical excitatory and inhibitory neurons, as well as astrocytes and oligodendrocytes. For educational attainment and cognitive ability, we also identified enrichment in multiple fetal cortical excitatory and inhibitory neurons, intermediate progenitor cells, and radial glial cells. In summary, this study supports a role of excitatory and inhibitory neurons in reading and excitatory neurons in ADHD and contributes new information on fetal cell types enriched in educational attainment and cognitive ability, thereby improving our understanding of the neurobiological basis of reading/correlated traits.

Longitudinal point-of-care assessment of psychomotor vigilance in children in the epilepsy monitoring unit.

The epilepsy monitoring unit (EMU) is a complex and dynamic operational environment, where the cognitive and behavioural consequences of medical and environmental changes often go unnoticed. The psychomotor vigilance task (PVT) has been used to detect changes in cognition and behaviour in numerous contexts, including among astronauts on spaceflight missions, pilots, and commercial drivers. Here, we piloted serial point-of-care administration of the PVT in children undergoing invasive monitoring in the EMU. Seven children completed the PVT throughout their hospital admission and their performance was associated with daily seizure counts, interictal epileptiform discharges, number of antiseizure medications (ASMs) administered, and sleep quality metrics. Using mixed-effects models, we found that PVT reaction time and accuracy were adversely affected by greater number of ASMs and interictal epileptiform activity. We show that serial point-of-care PVT is simple and feasible in the EMU and may enable greater understanding of individual patient responses to medical and environmental alterations, inform clinical decision-making, and support quality-improvement and research initiatives.

Lay healthcare worker financial toxicity intervention: a pilot financial toxicity screening and referral program.

PURPOSE: Financial toxicity is a source of significant distress for patients with urologic cancers, yet few studies have addressed financial burden in this patient population. METHODS: We developed a financial toxicity screening program using a lay health worker (LHW) and social worker (SW) to assess and mitigate financial toxicity in a single academic medical clinic. As part of a quality improvement project, the LHW screened all newly diagnosed patients with advanced stages of prostate, kidney, or urothelial cancer for financial burden using three COST tool questions and referred patients who had significant financial burden to an SW who provided personalized recommendations. The primary outcome was feasibility defined as 80% of patients with financial burden completing the SW consult. Secondary outcomes were patient satisfaction, change in COST Tool responses, and qualitative assessment of financial resources utilized. RESULTS: The LHW screened a total of 185 patients for financial toxicity; 82% (n = 152) were male, 65% (n = 120) White, and 75% (n = 139) reported annual household income >$100,000 US Dollars; 60% (n = 114) had prostate cancer. A total of 18 (9.7%) participants screened positive for significant financial burden and were referred to the SW for consultation. All participants (100%) completed and reported satisfaction with the SW consultation and had 0.83 mean lower scores on the COST Tool post-intervention assessment compared to pre-intervention (95% confidence interval [0.26, 1.41]). CONCLUSION: This multidisciplinary financial toxicity intervention using an LHW and SW was feasible, acceptable, and associated with reduced financial burden among patients with advanced stages of urologic cancers. Future work should evaluate the effect of this intervention among cancer patients in diverse settings.

Which is more deleterious to cognitive performance? Interictal epileptiform discharges vs anti-seizure medication.

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (ß ± SE = 49.91 ± 16.55 ms, p = .003) and number of IEDs (ß ± SE = 49.84 ± 12.51 ms, p < .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p = .009) and improved task performance (ß ± SE = -107.43 ± 39.54 ms, p = .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function.

Language and reading impairments are associated with increased prevalence of non-right-handedness.

Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6-19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases  = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06-1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.

Epilepsy disrupts hippocampal phase precision and impairs working memory.

OBJECTIVE: Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy. METHODS: Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory-related networks of children with drug-resistant epilepsy during a 1-back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared. RESULTS: Twelve children (mean age = 14.3 ± 2.8 years) with drug-resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z-score = 9, Rayleigh z-score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p = .01, p = .03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory-related networks were enhanced (phase difference derivative [PDD] z-scores = 6-11). During retrieval trials with pre-encoding or pre-retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z-score = 5, Rayleigh z-score = 1), interregional connectivity was altered (PDD z-scores = 1-3), and reaction times were prolonged (p = .01, p = .03). SIGNIFICANCE: This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population.

Interictal discharges delay target-directed eye movements and impair attentional set-shifting in children with epilepsy.

OBJECTIVE: The theory of transient cognitive impairment in epilepsy posits that lapses in attention result from ephemeral disruption of attentional circuitry by interictal events. Eye movements are intimately associated with human attention and can be monitored in real time using eye-tracking technologies. Here, we sought to characterize the associations between interictal epileptiform discharges (IEDs), gaze, and attentional behavior in children with epilepsy. METHODS: Eleven consecutive children undergoing invasive monitoring with stereotactic electrodes for localization-related epilepsy performed an attentional set-shifting task while tandem intracranial electroencephalographic signals and eye-tracking data were recorded. Using an established algorithm, IEDs were detected across all intracranial electrodes on a trial-by-trial basis. Hierarchical mixed-effects modeling was performed to delineate associations between trial reaction time (RT), eye movements, and IEDs. RESULTS: Hierarchical mixed-effects modeling revealed that both the presence of an IED (ß ± SE = 72.74 ± 24.21 ms, p = .003) and the frequency of epileptiform events (ß ± SE = 67.54 ± 17.30 ms, p < .001) were associated with prolonged RT on the attentional set-shifting task. IED occurrence at the time of stimulus presentation was associated with delays in gaze initiation toward the visual targets (p = .017). SIGNIFICANCE: The occurrence of epileptiform activity in close temporal association with stimulus presentation is associated with delays in target-directed gaze and prolonged response time, hallmarks of momentary lapses in attention. These findings provide novel insights into the mechanisms of transient impairments in children and support the use of visual tracking as a correlate of higher order attentional behavior.

Phase Resetting in the Anterior Cingulate Cortex Subserves Childhood Attention and Is Impaired by Epilepsy.

The neural mechanisms that underlie selective attention in children are poorly understood. By administering a set-shifting task to children with intracranial electrodes stereotactically implanted within anterior cingulate cortex (ACC) for epilepsy monitoring, we demonstrate that selective attention in a set-shifting task is dependent upon theta-band phase resetting immediately following stimulus onset and that the preferred theta phase angle is predictive of reaction time during attentional shift. We also observe selective enhancement of oscillatory coupling between the ACC and the dorsal attention network and decoupling with the default mode network during task performance. When transient focal epileptic activity occurs around the time of stimulus onset, phase resetting is impaired, connectivity changes with attentional and default mode networks are abolished, and reaction times are prolonged. The results of the present work highlight the fundamental mechanistic role of oscillatory phase in ACC in supporting attentional circuitry and present novel opportunities to remediate attention deficits in children with epilepsy.

Spectral changes following resective epilepsy surgery and neurocognitive function in children with epilepsy.

Decelerated resting cortical oscillations, high-frequency activity, and enhanced cross-frequency interactions are features of focal epilepsy. The association between electrophysiological signal properties and neurocognitive function, particularly following resective surgery, is, however, unclear. In the current report, we studied intraoperative recordings from intracranial electrodes implanted in seven children with focal epilepsy and analyzed the spectral dynamics both before and after surgical resection of the hypothesized seizure focus. The associations between electrophysiological spectral signatures and each child's neurocognitive profiles were characterized using a partial least squares analysis. We find that extent of spectral alteration at the periphery of surgical resection, as indexed by slowed resting frequency and its acceleration following surgery, is associated with baseline cognitive deficits in children. The current report provides evidence supporting the relationship between altered spectral properties in focal epilepsy and neuropsychological deficits in children. In particular, these findings suggest a critical role of disrupted thalamocortical rhythms, which are believed to underlie the spectral alterations we describe, in both epileptogenicity and neurocognitive function.NEW & NOTEWORTHY Spectral alterations marked by decelerated resting oscillations and ectopic high-frequency activity have been noted in focal epilepsy. We leveraged intraoperative recordings from chronically implanted electrodes pre- and postresection to understand the association between these electrophysiological phenomena and neuropsychological function. We find that the extent of spectral alteration, indexed by slowed resting frequency and its acceleration following resection, is associated with baseline cognitive deficits. These findings provide novel insights into neurocognitive impairments in focal epilepsy.

Brief video enhances teacher trainees' knowledge of epilepsy.

OBJECTIVE: Relative to the general population, children with epilepsy (CWE) demonstrate difficulties in aspects of cognition and mental health. Previous studies have found that teachers have poor knowledge about epilepsy, which may lead to inadequate management of CWE's comorbidities and seizures, potentially impacting CWE's school performance, social development, and safety. The current study aimed to evaluate whether a brief training program improves teachers' epilepsy knowledge. METHOD: Participants included pre-service teachers enrolled in the Faculty of Education at Western University (London, Ontario, Canada). There were no exclusion criteria. Pre-service teachers completed a questionnaire evaluating their experiences and knowledge of epilepsy prior to, and two weeks following, the training program. The training program consisted of a 10.5-min video and booklet that described the characteristics of seizures, seizure first aid, and the cognitive, psychological, and social consequences of epilepsy. RESULTS: Pre-service teachers' knowledge about epilepsy, seizure safety, and common comorbidities associated with epilepsy significantly improved after participating in the training program. Furthermore, pre-service teachers indicated greater self-reported knowledge about epilepsy and greater preparedness to handle a seizure in the classroom. CONCLUSION: The results of the current study demonstrated that a brief, cost-effective training program significantly enhances teachers' knowledge about epilepsy, seizure safety, and the comorbidities associated with epilepsy. Enhancing teachers' knowledge about epilepsy has the potential to improve children's academic and social success in school.

Prospective Evaluation of Xpert® Xpress Strep A Automated PCR Assay vs. Solana® Group A Streptococcal Nucleic Acid Amplification Testing vs. Conventional Throat Culture.

In our laboratory, the negative rapid group A streptococcal (GAS) antigen assays are backed up by the Solana® GAS Assay by Quidel instead of a Group A streptococcal throat culture. Another FDA cleared RT-PCR assay is the Xpert® Xpress Strep A, which detects Streptococcus pyogenes DNA, and is performed on the Cepheid GeneXpert instrument. Three hundred seventy-five positive and negative specimens were randomly selected from 5489 throat specimens that had been tested by the Solana® GAS Assay during January 2018 and were tested with the Xpress Strep A assay. A throat culture was also set up (sheep blood agar at 35 °C in 5% CO2). All beta-hemolytic streptococci were purified and identified by MALDI-TOF mass spectrometry. Of the 375 samples, 185 were positive by Solana® GAS Assay, and 187 were positive by the Xpress Strep A. The total agreement between the Solana® GAS Assay and the Xpert® Xpress Strep A was 99.5%. The agreement of the Xpert® Xpress Strep A assay with culture was 90.1%. The sensitivity and specificity for Xpress Strep A versus culture were 100% and 83.5%, respectively. The Xpert® Xpress Strep A assay's performance was equivalent to the Solana® GAS Assay, and was highly sensitive. The lower specificity was likely due to the Xpress Strep A assay having higher sensitivity as compared to throat culture.

Primary care providers' role in newborn screening result notification for cystic fibrosis.

OBJECTIVE: To explore primary care providers' (PCPs') role in result notification for newborn screening (NBS) for cystic fibrosis (CF), given that expanded NBS has increased the number of positive screening test results, drawing attention to the role of PCPs in supporting families. DESIGN: Cross-sectional survey and qualitative interviews. SETTING: Ontario. PARTICIPANTS: Primary care providers (FPs, pediatricians, and midwives) who received a positive CF NBS result for an infant in their practice in the 6 months before the study. MAIN OUTCOME MEASURES: Whether the PCP notified the family of the initial positive CF screening result. RESULTS: Data from 321 PCP surveys (response rate of 51%) are reported, including 208 FPs, 68 pediatricians, and 45 midwives. Interviews were completed with 34 PCPs. Most (65%) surveyed PCPs reported notifying the infant's family of the initial positive screening result; 81% agreed that they have an important role to play in NBS; and 88% said it was important for PCPs, rather than the NBS centre, to notify families of initial positive results. With support and information from NBS centres, 68% would be extremely or very confident in doing so; this dropped to 54% when reflecting on their recent reporting experience. More than half (58%) of all PCPs said written point-of-care information from the NBS centre was the most helpful format. Adjusted for relevant factors, written educational information was associated with a lower rate of notifying families than written plus verbal information (risk ratio of 0.79; 95% CI 0.69 to 0.92). In the interviews, PCPs emphasized the challenge of balancing required content knowledge with the desire for the news to come from a familiar provider. CONCLUSION: Most PCPs notify families of NBS results and value this role. These data are relevant as NBS programs and other genomic services expand and consider ways of keeping PCPs confident and actively involved.

Newborn screening for cystic fibrosis: Role of primary care providers in caring for infants with positive screening results.

OBJECTIVE: To explore primary care providers' (PCPs') preferred roles and confidence in caring for infants receiving a positive cystic fibrosis (CF) newborn screening (NBS) result, as well as management of CF family planning issues, given that expanded NBS has resulted in an increase in positive results. DESIGN: Mailed questionnaire. SETTING: Ontario. PARTICIPANTS: Ontario FPs, pediatricians, and midwives identified by Newborn Screening Ontario as having had an infant with a positive CF NBS result in their practice in the previous 6 months. MAIN OUTCOME MEASURE: Primary care providers' preferred roles in providing well-baby care for infants with positive CF screening results. RESULTS: Overall, 321 of 628 (51%) completed surveys (208 FPs, 68 pediatricians, 45 midwives). For well-baby care for infants confirmed to have CF, 77% of PCPs indicated they would not provide total care (ie, 68% would share care with other specialists and 9% would refer to specialists completely); for infants with an inconclusive CF diagnosis, 50% of PCPs would provide total care, 45% would provide shared care, and 5% would refer to a specialist; for CF carriers, 89% of PCPs would provide total care, 9% would provide shared care, and 2% would refer. Half (54%) of PCPs were extremely or very confident in providing reassurance about CF carriers' health. Only 25% knew how to order parents' CF carrier testing; 67% knew how to refer for prenatal diagnosis. Confidence in reassuring parents about the health of CF carrier children was associated with providing total well-baby care for CF carriers (risk ratio of 1.50; 95% CI 1.14 to 1.97) and infants with an inconclusive diagnosis (risk ratio of 3.30; 95% CI 1.34 to 8.16). CONCLUSION: Most PCPs indicated willingness to treat infants with a range of CF NBS results in some capacity. It is concerning that some indicated CF carriers should have specialist involvement and only half were extremely or very confident about reassuring families about carrier status. This raises issues about possible medicalization of those with carrier status, prompting the need for PCP education about genetic disorders and the meaning of genetic test results.

Memory outcomes following hemispherectomy in children.

OBJECTIVE: A vast proportion of children with epilepsy exhibit memory impairments. Although numerous studies have examined memory performance following pediatric resective epilepsy surgery, little is known about the memory outcomes following hemispherectomy. The few studies that report on memory performance typically include restricted measures, consist of case reports, or do not report on preoperative performance. Given the current limitations, the aim of this study was to delineate pre- and postoperative memory functioning in youth who underwent a hemispherectomy. METHOD: Participants included patients who had undergone a hemispherectomy at the Hospital for Sick Children, between 1999 and 2016. Standardized neuropsychological assessments of verbal (digit span, word list recall, word pair recall, stories) and visual (faces, dot locations) memory abilities prior to and after surgery were reviewed. A Wilcoxon signed rank test and effect sizes was completed to compare patients' memory performance to population norms and to assess pre- to postoperative difference scores. RESULTS: Thirteen participants were included in the study: five patients completed preoperative assessments only and eight patients completed pre- and postoperative assessments. Preoperatively, patients performed substantially worse relative to population norms as indicated by large effect sizes (r: 0.5-0.9). Postoperatively, effect sizes were large for the majority of the memory tests, demonstrating considerable differences in patients' memory scores over time. When clinically meaningful changes were examined, stable performance was evident on 63% of the memory tasks. CONCLUSION: Overall, the results highlight that youth who are eligible for hemispherectomy demonstrate profound memory deficits prior to surgery. In addition, undergoing hemispherectomy was not necessarily associated with declined memory performance, with the majority of patients showing stable scores.

A secondary benefit: the reproductive impact of carrier results from newborn screening for cystic fibrosis.

PURPOSE: Newborn screening (NBS) for cystic fibrosis (CF) can identify carriers, which is considered a benefit that enables reproductive planning. We examined the reproductive impact of carrier result disclosure of NBS for CF. METHODS: We surveyed mothers of carrier infants after NBS (Time 1) and 1 year later (Time 2) to ascertain intended and reported communication of their infants' carrier results to relatives, carrier testing for themselves/other children, and reproductive decisions. A sub-sample of mothers was also interviewed at Time 1 and Time 2. RESULTS: The response rate was 54%. A little more than half (55%) of mothers underwent carrier testing at Time 1; another 40% of those who intended to undergo testing at Time 1 underwent testing at Time 2. Carrier result communication to relatives was high (92%), but a majority of participants did not expect the results to influence family planning (65%). All interviewed mothers valued learning their infants' carrier results. Some underwent carrier testing and then shared results with family. Others did not use the results or used them in unintended ways. CONCLUSION: Although mothers valued learning carrier results from NBS, they reported moderate uptake of carrier testing and limited influence on family planning. Our study highlights the secondary nature of the benefit of disclosing carrier results of NBS.Genet Med 19 4, 403-411.

Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis.

OBJECTIVE: To explore the psychosocial implications of diagnostic uncertainty that result from inconclusive results generated by newborn bloodspot screening (NBS) for cystic fibrosis (CF). STUDY DESIGN: Using a mixed methods prospective cohort study of children who received NBS for CF, we compared psychosocial outcomes of parents whose children who received persistently inconclusive results with those whose children received true positive or screen-negative results. RESULTS: Mothers of infants who received inconclusive results (n = 17), diagnoses of CF (n = 15), and screen-negative results (n = 411) were surveyed; 23 parent interviews were completed. Compared with mothers of infants with true positive/screen-negative results, mothers of infants with inconclusive results reported greater perceived uncertainty (P < .006) but no differences in anxiety or vulnerability (P > .05). Qualitatively, parents valued being connected to experts but struggled with the meaning of an uncertain diagnosis, worried about their infant's health-related vulnerability, and had mixed views about surveillance. CONCLUSION: Inconclusive CF NBS results were not associated with anxiety or vulnerability but led to health-related uncertainty and qualitative concerns. Findings should be considered alongside efforts to optimize protocols for CF screening and surveillance. Educational and psychosocial supports are warranted for these families.

Maintenance effects of working memory intervention (Cogmed) in children with symptomatic epilepsy.

PURPOSE: To extend previous research documenting the benefits of working memory (WM) intervention (Cogmed) immediately post-intervention in children with epilepsy by assessing the 3-month maintenance effects. METHODS: Participants involved in a previous randomized clinical trial (RCT) were invited to participate if they completed Cogmed within the last 3months (n=15) and additional participants (n=13) were prospectively recruited. Standardized assessments of near-transfer effects (i.e., visual and auditory attention and WM) were completed prior to and immediately after intervention and at 3-month follow-up. An additional measure assessing the far-transfer effect of fluid reasoning was administered prior to intervention and at 3-month follow-up. RESULTS: Participants exhibited gains in auditory and visual attention and WM immediately following intervention and gains were generally sustained at 3-month follow-up. Intervention did not improve visual-verbal WM or fluid reasoning. The clinical variables studied (i.e., age of seizure onset, seizure frequency, epilepsy duration, and overall intellectual functioning) did not elucidate reliable relationships with intervention. CONCLUSIONS: Working memory training is possibly efficacious in improving related skills which are maintained for 3months in children with active epilepsy. No transfer to fluid reasoning was documented. Further investigation by means of a large-scale RCT which includes a placebo and both objective and subjective measures of the impact of training on daily functioning is warranted.

Near-transfer effects following working memory intervention (Cogmed) in children with symptomatic epilepsy: An open randomized clinical trial.

OBJECTIVE: Limited research exists regarding the effectiveness of educational and psychological interventions for improving commonly presenting cognitive impairments experienced by children with epilepsy. We evaluated the efficacy of a commercially available, computerized, working memory (WM) program (Cogmed) using a well-defined population of children with epilepsy. METHODS: In this controlled trial, 77 children with symptomatic epilepsy (ages 6.5-15.5 years; 100% taking medication) with estimated intellectual ability greater than the 2nd percentile were randomly assigned to an intervention (n = 42) or waitlist-control (n = 35) group. Standardized assessments of attention and WM were administered pre- and posttraining or waitlist interval, 7 weeks apart. RESULTS: Without intervention, participants displayed significant weaknesses in intelligence, attention, and WM compared to normative samples. After controlling for preintervention scores and intelligence, we found that significant treatment effects for the intervention group were evident for visual attention span, auditory WM, and visual-verbal WM. Intention-to-treat analyses (all participants) and sensitivity analyses (n = 37 and n = 21 for the intervention and waitlist-control groups, respectively) were highly similar, providing confidence to the results. Effect sizes for significant outcomes were large (greater than or equal to two thirds of the standard deviation of the normative-data). The clinical/demographic and functional factors studied did not elucidate who most benefits from training. SIGNIFICANCE: This is the first study to evaluate the effectiveness of intervention to ameliorate WM deficits commonly experienced by children with symptomatic epilepsy. Results support group improvement on some untrained tasks immediately postintervention, demonstrating preliminary usefulness of Cogmed as a treatment option.