Predictors of intellectual functioning after epilepsy surgery in childhood: The role of socioeconomic status

ObjectiveThe objective of this study was to evaluate the association between socioeconomic status and intellectual functioning in children with medically refractory epilepsy, before and after resective epilepsy surgery. Family environment is a strong contributor to cognitive development in children and has been recently shown to play a significant role in intellectual outcome after surgery in children with epilepsy.MethodsOne hundred children who had undergone resective epilepsy surgery and completed preoperative and postoperative assessments of IQ as part of clinical care were included in the study. We evaluated the impact of epilepsy-related variables, income quintile, and residence location on IQ.ResultsGreater improvements in IQ after surgery were associated with an older age at surgery (β = .235, p = .018). Higher IQ scores at follow-up were associated with an older age of seizure onset (β = .371, p < .001), older age at surgery (β = .356, p < .001), unilobar epileptogenic focus (β = .394, p < .001), and mesial temporal sclerosis (β = .338, p = .001) or tumor (β = .457, p < .001) in comparison with malformation of cortical development; age at seizure onset did not remain as a significant predictor in multivariable regression analysis. Income quintile, residence location, seizure control, and antiepileptic medication use were not significant predictors.ConclusionsEpilepsy-related variables were the strongest predictors of IQ and postoperative change in IQ. We were unable to identify a significant association between IQ and socioeconomic status. Future research should evaluate the impact of multiple aspects of family environment.     

Effect of successful epilepsy surgery on subjective and objective sleep parameters – a prospective study

ObjectiveTo evaluate the effect of surgery on subjective and objective measures of sleep quality among patients with medically refractory focal epilepsy.MethodsIn a prospective cohort study, patients with medically refractory epilepsy undergoing epilepsy surgery were recruited. All patients were assessed seven days pre- and three months post-surgery in terms of history pertaining to epilepsy and sleep, Epworth sleepiness score (ESS), one week sleep log and over night polysomnography (PSG).ResultsAmong 17 patients (mean age 18, 11 males), seizure frequency had reduced (p = 0.04) and self reported sleep parameters had significantly improved (reduced total duration of night time sleep, regularity on one week sleep log and ESS (p < 0.05)) three months following epilepsy surgery. Patients with good surgical outcome (n = 12) showed reduced seizure frequency (p = 0.01) and reduced ESS with corresponding reduction in arousal index (AI) (p = 0.02) and increase in total sleep time (p = 0.03), postoperatively. Three patients in the good surgical outcome group showed reduction in apnea–hypopnea index (AHI) from more than five to less than five. There was no significant change either in seizure frequency, self reported clinical parameters or PSG parameters among patients with poor surgical outcome.ConclusionEpilepsy surgery improves subjective sleep parameters in patients with medically refractory epilepsy during the early post operative period. Successful epilepsy surgery may improve objective (PSG documented) sleep quality, sleep architecture and obstructive sleep apnea with resultant reduction in excessive daytime sleepiness.     

Is reoperation an option for patients with temporal lobe epilepsy after failure of surgery?

PurposeEpilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe.MethodsWe systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies.ResultsOverall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60 months, range 12–72); six patients (35.3%) were seizure free at least 12 month before observation points (median duration 120.5 months, range 35–155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI (p = 0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery (p = 0.116) and before reoperation (p = 0.622) was not poorer compared to patients with congruent Video-EEG results.ConclusionsReoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries.     

Clinical relevance of source location in frontal lobe epilepsy and prediction of postoperative long-term outcome

PurposeTo evaluate the value of magnetoencephalography (MEG) source localization in localization of epileptic activities and predicting surgical outcome in frontal lobe epilepsies (FLE).MethodsForty-six patients with presurgical MEG evaluation and intractable FLE surgery (28 male patients) were analyzed retrospectively with a mean follow-up of 5 years. Dipole analysis was performed for MEG source imaging (MSI). The localization of dipole clusters in relation to the dominant hemisphere, lesions, resection cavity and functional cortex were analyzed. The predictive value of MSI in respect to clinical outcome with long-term postoperative follow up was evaluated.ResultsInterictal focal epileptic activities were found in 82.6% (38/46) patients with monofocal activity 81.6% (31/38) and multifocal activities 18.4% (7/38). Seizure free rate was 47.9% at the mean follow-up of 5.0 ± 4.0 years (median 11.5, range 2–57). Seizure recurrence mainly occurred in the first 1 year after surgery. In the monofocal epileptic activity group, 58.1% (18/31) of the patients were seizure free, predicitng postoperative seizure freedom better than multifocal localization 0% (0/7) (p = 0.028). Dipole clusters were completely resected in 70.9% of monofocal activity patients, which had higher seizure free rates compared to partial resection (p = 0.002). In patients with surgery in the dominant hemisphere, seizure control was less likely (p = 0.006).ConclusionMSI contributes to the clinical prediction of postoperative outcome in FLE patients. MSI may non-invasively disclose early epileptogenic lesions, pointing to a resectable lesion, and it then facilitates shortcut route of presurgical evaluation.     

Stability and change of cognitive attributes in children with uneven/delayed cognitive development from preschool through childhood

As part of an ongoing clinical service program for children with developmental delay in an Asian developing country, we analyzed the cognitive attributes of 362 Taiwanese children (average age 48.5 ± 12.9 month-old) with uneven/delayed cognitive development as they were assessed repeatedly with average duration of 39.7 ± 22.6 months from preschool through early childhood. The objectives were to determine the stability and related factors in cognitive scores of these 362 children belonging to three diagnostic subgroups: 181 children with non-autistic mental retardation (MR), 95 children with autism spectrum disorder (ASD) and 64 children with mixed type developmental language disorder (DLD); and to contribute to the accumulation of data on cognitive outcome in preschool children with developmental delay. Analysis revealed that mean initial cognitive score (IQ1) was 64.9 ± 16.9 while mean cognitive measure at follow-up (IQ2) was 72.2 ± 19.7. Whole group analysis showed the correlation between IQ1 and IQ2 was moderate (r = 0.73, p < 0.001). Analysis by a general linear model showed only male gender (β = 4.95, p = 0.02, C.I. = 0.8–9.1) and IQ1 (β = 0.79, p < 0.001, C.I. = 0.68–0.90) to be significant predictors of IQ2. There were differences among three groups in IQ1 (p < 0.001), IQ2 (p < 0.001) and IQ change (p < 0.001). Correlation coefficients of IQ1 and IQ2 were 0.6 for ASD group, 0.7 for MR group and 0.4 for DLD group respectively. The greatest proportion of children remained within the same cognitive range for both assessment points, however, it is noted that a substantial minority of children changed IQ ranges drastically from preschool through early childhood. Our results suggest that measurements of cognitive function at preschool age for children with developmental delay were valid in the context of a developing country, and the observed change in cognitive scores during follow-up emphasized the need to interpret the initial results of cognitive tests with caution.     

Preoperative IQ predicts seizure outcomes after anterior temporal lobectomy

PurposeIQ tests are frequently used in the preoperative neuropsychological assessment of candidates for anterior temporal lobectomy (ATL). We reviewed IQ test results and surgery outcomes to evaluate the roles of IQ tests in the preoperative work-up.MethodsA total of 205 adult patients who had undergone ATL and whose seizure outcomes were followed for 2 years after surgery were included. The short form WAIS-R was used to estimate intelligence. Multiple linear regression and logistic regression analyses were used to examine the variables for IQ and seizure outcomes.ResultsEducation, duration of epilepsy and gender were factors that accounted for 24.6% of the variance in the full-scale IQ (FSIQ) scores. The verbal IQ and performance IQ discrepancies at various magnitudes could not lateralize the seizure foci. Freedom of seizure was noted in 128 (62.4%) of the patients. Seizure outcomes, however, correlated with the preoperative FSIQ. After adjustment for variables that affect seizure outcomes, the FSIQ was an independent predictor of postoperative seizure outcomes (OR 1.04, 95% CI 1.01–1.06, p = 0.003). Of patients who had FSIQ lower than 70, 50% became free from seizures by 2 years after surgery.ConclusionsIn our study, IQ tests were unable to lateralize seizure foci but may serve as an independent predictor of postoperative seizure outcomes. Since a longer duration of epilepsy had deleterious effects on intelligence, earlier surgical intervention might better preserve neuropsychological function and, consequently, allow better seizure control after ATL. Nonetheless, patients with lower IQ scores could still benefit from ATL.     

Socioeconomic status influences time to surgery and surgical outcome in pediatric epilepsy surgery

The aims of this study were to evaluate the influence of socioeconomic status (SES) on time-to-surgery (TTS) and surgical outcome in children with treatment-resistant epilepsy in a universal health care system. The cohort consisted of children who had undergone resective epilepsy surgery between 2001 and 2013 in Canada. The patients' postal codes were linked to Statistics Canada National Household Survey data to obtain dissemination area income, which was used to infer SES. Time-to-surgery was defined as the interval from date of epilepsy onset to date of surgery. Seizure outcome was classified using ILAE classification. The associations between SES and TTS, as well as SES and surgical outcome, were assessed. Two hundred eighty-four children who had epilepsy surgery were included. Patients in the lowest income quintile had a significantly higher TTS relative to the highest income quintile (β = 0.121, p = 0.044). There were no significant associations between income quintiles and seizure-free surgical outcome (odds ratio (OR) = 0.746–1.494, all p > 0.05). However, patients in the lowest income quintile had a significantly lower odds of an improvement in seizure frequency relative to the highest income quintile (OR = 0.262, p = 0.046). The TTS was not uniform across SES in spite of the existence of a universal health care system. This finding highlights the need to address social and economic barriers for epilepsy surgery to improve access to this potentially curative treatment. Those with lower SES had lower likelihood of improvement in seizure control following epilepsy surgery and may require additional support including social and financial support to mitigate the discrepancies in seizure control following surgery between SES levels.     

Increased hair cortisol and antecedent somatic complaints in children with a first epileptic seizure

ObjectiveStress is the most frequent seizure-precipitating factor reported by patients with epilepsy, while stressful life events may increase seizure susceptibility in humans. In this study, we investigated the relations between both biological and behavioral measures of stress in children with a first epileptic seizure (hereafter called seizure). We hypothesized that hair cortisol, a biomarker of chronic stress reflecting approximately 3 months of preceding exposure, might be increased in children with a first seizure. We also employed standardized questionnaires to examine presence of stress-related behavioral markers.MethodsThis was a cross-sectional clinical study investigating stress-related parameters in children with a first seizure (First Epileptic Seizure Group (FESG), n = 22) in comparison to healthy children without seizures (Control Group, n = 29). Within 24 h after a first seizure, hair samples were collected from children for the determination of cortisol. In parallel, perceived stress and anxiety and depressive symptoms were examined with appropriate self- and parent-completed questionnaires, and history of stressful life events during the past year was recorded. Emotional and behavioral problems were also assessed by parent-reported validated and widely-used questionnaires.ResultsHigher hair cortisol measurements were observed in the FESG than control children (7.5 versus 5.0 pg/mg respectively, p = 0.001). The former were more likely to complain of somatic problems than the latter (59.8 vs. 55.4 according to DSM-oriented Scale, p = 0.021); however, there were no differences in perceived stress and anxiety or depressive symptoms between the two groups. Using ROC analysis of hair cortisol measurements for predicting disease status, the maximum sensitivity and specificity were observed for a cut-off point of 5.25 pg/mg.SignificanceIncreased hair cortisol indicates chronic hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis prior to the first seizure. This might have contributed to the epileptogenesis process and may help explain the higher incidence of antecedent somatic complaints in the first seizure group.     

Socioeconomic deprivation is an independent risk factor for behavioral problems in children with epilepsy

AimThe aim of this study was to examine whether socioeconomic deprivation in children with epilepsy (CWE) increases risk for behavioral problems independent of seizure factors.MethodsA cross-sectional study was done in which parents of children attending a specialist epilepsy clinic were invited to complete a child behavior checklist (CBCL) questionnaire about their child. Medical and sociodemographic data on CWE were obtained through their pediatric neurologists. Home postal code was used to obtain quintiles of Scottish Index of Multiple Deprivation 2012 (SIMD2012) scores for individuals. Lower (1–3) quintiles correspond to higher socioeconomic deprivation. Regression analysis was used to investigate whether a lower quintile was an independent risk factor for scores > 63 (significant behavioral problem).ResultsParents of 87 children (42 male, mean age of 10.5 years) were enrolled. Fifty-nine percent had total scores > 63. A higher proportion of children from quintiles 1–3 compared to those from quintiles 4–5 had externalizing (49% vs. 25%, p = 0.02) and total (54% vs. 30%, p = 0.02) scores > 63. Adjusted OR of quintiles 1–3 vs. 4–5 for scores > 63 = 14.8, 95% CI = 3.0, 68.0. Fewer children with scores > 63 and from quintiles 1–3 were known to the child and adolescent mental health service (CAMHS) compared to those in quintiles 4–5 (p = 0.01).InterpretationSocioeconomic deprivation was an independent risk factor for behavioral problems in CWE. Children with epilepsy and behavioral problems who lived in socioeconomically deprived areas received less help.     

Long-term outcome and tolerability of the ketogenic diet in drug-resistant childhood epilepsy—The Austrian experience

PurposeTo evaluate the long-term efficacy/tolerability of the ketogenic diet (KD) in paediatric drug-resistant epilepsies.MethodsData from children who were treated between 1999 and 2008 and had continuous follow-up of at least 6 months after initiation of the KD were analysed retrospectively. Response was defined as ≥50% seizure reduction. Treatment effects on EEG, developmental outcome and the “outcome-predictive” value of various clinical factors were also assessed.Results50 children (22 boys; mean age 4.5 years ± 3.55) were included. Mean follow-up was 3.93 ± 2.95. 50% of the patients were responders, 48% of them became seizure free. 50% were non-responders, 20% of them deteriorated. In responders, EEG background activity improved significantly (p = 0.014) and a significantly lower rate of epileptic discharges (p = 0.009) was seen after 6 months. In addition, neurological examination findings demonstrated significant developmental progress (p = 0.038).Favourable treatment outcome was associated with a shorter disease duration (p = 0.025) and generalised tonic clonic seizures (p = 0.059). No further significant outcome predictors were detected. However, response was 44% in patients with infantile spasms, 62.5% in those with Dravet syndrome and 50% in Lennox-Gastaut-syndrome.Side effects occurred in 28%, but discontinuation of the KD was not required in any case. They most often observed with concomitant topiramate (p = 0.001) and valproate (p = 0.046).ConclusionDespite the retrospective nature of the study and the inhomogeneous patient sample, we found good long-term effects of the KD on seizure frequency, EEG and neurological development.     

Seizure severity in children with epilepsy is associated with their parents' perception of stigma

AimsTo develop and implement interventions to improve the quality of life (QOL) in children with epilepsy, it is important for clinicians and researchers to understand the effects of the children's parents' perception of stigma. The purpose of this study was to identify a relationship between patient clinical characteristics and perception of stigma in the parents of children with epilepsy.MethodsParents of children with epilepsy were recruited from our university hospital between April 1, 2005 and March 31, 2012. Items for the Parent Stigma Scale were developed from the literature and open-ended interviews with parents of children with epilepsy about their concerns and fears, including those related to stigma. Parents were asked to respond to five items, each on a 5-point scale from 1 (strongly disagree) to 5 (strongly agree). Assessments were performed for each clinical characteristic, such as child's sex, age at seizure onset, family history of epilepsy, seizure frequency, presence of status epilepticus (SE), presence of treatment-related adverse events, and the scores of each scale.ResultsA total of 52 parents of children with epilepsy and 10 parents of healthy children were enrolled in the study. Parents of children with epilepsy showed significantly higher scores on the questionnaire than parents of healthy children. In multiple regression analysis, greater perceptions of stigma were associated with a seizure frequency of more than one per month (p = 0.0036, B = 1.104, β = 0.402). In contrast, the presence of prior febrile seizures (p = 0.0034, B = − 1.297, β = − 0.308) and family history of epilepsy (p = 0.0066, B = − 1.613, β = − 0.277) were associated with lower perceptions of stigma. Greater parental perceptions of stigma were seen with the presence of monthly seizures.ConclusionsParents of children with epilepsy are at risk of significant perceptions of stigma. Seizure severity, indicated by the presence of monthly seizures, was associated with greater perceptions of stigma in parents. In addition, the presence of prior febrile seizures and family history of epilepsy were associated with fewer perceptions of stigma. The findings of this study emphasize the importance of acknowledging and addressing parental perceptions of stigma.     

Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis

ObjectiveThe objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield.MethodsThe hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36).ResultsThere were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p = 0.048). The groups with HS presented different memory performance — the right HS were worse in visual memory test [Complex Rey Figure, immediate (p = 0.001) and delayed (p = 0.009)], but better in one verbal task [RAVLT delayed (p = 0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p = 0.050) and Logical Memory and RAVLT delayed recalls (p = 0.004 and p = 0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p = 0.006) and epilepsy duration (p = 0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p < 0.001).SignificanceCornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS.     

Acute postoperative seizures and long-term outcome following pediatric epilepsy surgery

PurposeAcute post-operative seizures (APOS) after epilepsy surgery, previously believed to be benign, are increasingly associated with poor long-term prognosis. Prior literature has focused primarily on adult temporal lobe epilepsy. This retrospective study aimed to identify the prevalence, prognostic significance and risk factors for APOS in pediatric epilepsy surgery at a single center.MethodRetrospective chart review of all children aged 0–21 years undergoing resective surgery for epilepsy between 2009 and 2012 at a single center. APOS were defined as seizures within 30 days of resection. Surgical outcome was determined, using a minimum of 12 months postoperative follow-up for inclusion.ResultsAPOS, defined as a seizure within 30 days of resection, were identified in 50/112 (44%) of patients. APOS were a significant predictor of poor postoperative seizure outcome (ILAE 4–6); only 26% of those with APOS had a good outcome (ILAE 1–3), compared to 76% without APOS. Timing of postoperative seizure was not correlated with outcome. Most (54%) with APOS and good outcome had continued seizures between 14-30 days postoperatively. Patients with APOS after temporal (p = 0.05) and extratemporal (p < 0.001) resections had a significantly worse prognosis. APOS after hemispherectomy were not associated with a worse prognosis (p = 0.22). Key risk factors for APOS include lack of ictal EEG lateralization to operated hemisphere/side of MRI abnormality.ConclusionThis study shows an association between APOS and poor outcome in both temporal and extratemporal pediatric epilepsy surgery. Findings support the expansion of APOS duration to 30 days.     

Evaluation of developmental profiles of children with hydrocephalus

ObjectiveThe objective of this study was to compare the developmental characteristics of children with hydrocephalus with those of healthy children.Material and methodsA total of 109 children aged between 2 and 46 months were included in the study, 54 patients diagnosed with hydrocephalus and 55 healthy children were evaluated with demographic data forms and Denver Developmental Screening Test II.ResultsThe mean personal–social (p < 0.001), fine motor-adaptive (p < 0.001), language (p < 0.001), and gross motor subscale scores were significantly lower in children with hydrocephalus than in the control group. Personal–social (p = 0.002) and gross motor (p = 0.029) subscale scores were significantly lower in children with obstructive hydrocephalus than communicating hydrocephalus. There was a significant negative correlation between language scores and ages of the children with hydrocephalus (r = ?0.350, p = 0.009). It was found that children with obstructive hydrocephalus carry a 6.7 folds higher risk of experiencing problems in terms of personal–social development compared to those with communicating hydrocephalus (p = 0.011).ConclusionWe found that patients with hydrocephalus were developmentally retarded compared to the healthy control subjects. Retardation was the most prominent in the obstructive group. Our results showed that neurodevelopmental follow-up should be carried-out regularly in pediatric patients with hydrocephalus, and early intervention should be started in necessary cases.     

The neuropsychological outcome of pediatric patients with refractory epilepsy treated with VNS — A 24-month follow-up in Taiwan

ObjectivesMultiple studies have reported the benefits of vagus nerve stimulation (VNS) on neuropsychological outcomes. The aim of this study was to investigate how VNS affects cognition and psychosocial adjustment in children with refractory epilepsy (RE), and to determine the efficacy of VNS in a Taiwanese population.MethodsWe conducted a one-group pretest–posttest study on pediatric patients with RE. The study comprised 19 males and 18 females, all aged < 18 years. We recorded seizure frequency at 3, 12, and 24 months after VNS device implantation. Intelligence quotients (IQ) were assessed using the Wechsler Intelligence Scale for Children — IV. The Parental Stress Index (PSI) scores were evaluated by a pediatric psychologist.ResultsVagus nerve stimulation device implantation significantly reduced seizure frequency at 3, 12 and 24 months, especially in young children (< 12 years). No significant improvement in IQ test performance was observed, though there were significant improvements in the PSI, especially in young children.ConclusionsVagus nerve stimulation device implantation does not significantly improve cognition function, but it does significantly reduce seizure frequency and stress in parent–child relationships, especially in young children (< 12 years). These findings suggest that VNS should be considered as an alternative therapy for patients proven to have seizures that are medically refractory, especially those younger than 12 years of age.     

Gender and age influence in daytime and nighttime seizure occurrence in epilepsy associated with mesial temporal sclerosis

ObjectivesThe aim of this study was to analyze the daytime and nighttime seizure distribution during video-EEG monitoring in patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS) and the role of gender, age, and lesion side on 24-hour seizure distribution.MethodsWe studied 167 consecutive adult (age ≥ 16 years) patients with epilepsy associated with unilateral mesial temporal sclerosis that had three or more recorded seizures during continuous video-EEG monitoring with a minimum recording time period of 24 h. Seizure onset time was classified according to occurrence in six 4-hour periods.ResultsSeven hundred thirty-five seizures were evaluated. We observed two higher seizure occurrence periods: 08:01–12:00 (p = 0.001) and 16:01–20:00 (p = 0.03). Significantly fewer seizures were observed between 0:01 and 4:00 (p = 0.01). Nonuniform seizure distribution was noted in women (p < 0.0001), in young patients (less than 45 years of age) (p < 0.0001), and in both patients with left (p = 0.03) and patients with right mesial temporal sclerosis (p = 0.008). Men presented uniform seizure occurrence distribution (p = 0.15). Women had fewer seizures than expected and fewer seizures than men between 0:01–04:00 (p < 0.0001 and p = 0.0015, respectively) and 04:01–08:00 (p = 0.01 and p = 0.03, respectively). Young patients (age < 45 years) had two seizure occurrence peaks, 08:01–12:00 (p = 0.016) and 16:01–20:00 (p = 0.004). Middle-aged/old patients (≥ 45 years) had only one seizure occurrence peak, 08:01–12:00 (p = 0.012). Young patients had more seizures than middle-aged/old patients between 16:01–20:00 (p = 0.04). No differences were noted between left and right MTS.SignificanceWe observed two seizure occurrence peaks: morning and late afternoon/evening. We encountered variations in daytime and nighttime seizure distribution according to gender and age, but not according to side of MTS. Future studies are needed to confirm these findings and to unravel the neurobiological substrate underlying daytime and nighttime variations of seizure occurrence in different age groups and between genders.     

Cognitive functions in children exposed to antiepileptic drugs in utero - Study in Georgia

ObjectiveThe cognitive teratogenicity of antiepileptic drugs (AEDs) has gained increasing attention in the last decade. The objective of the current study was to assess the effects of AED fetal exposure on the cognitive development of children of mothers with epilepsy from Georgia in a controlled study taking into consideration major confounding factors.MethodsA prospective cohort group was formed from children and mothers registered in the Georgian National AED-Pregnancy Registry. The study group's age- and gender-matched control children without fetal AED exposure were selected retrospectively. The Intelligence Quotient (IQ) using the Wechsler Adult Intelligence Scale – revised (WAIS-R) was assessed in mothers. The Wechsler Preschool and Primary Scale of Intelligence (WPPSI-4) were used to assess intellectual functioning for children of both study and control groups. Linear regression analysis was performed to detect association of AED exposure on the cognitive performance of children.ResultsIn total, 100 children aged 36 to 72 months were evaluated. The IQ of WWE was significantly lower compared to women without epilepsy in all modalities. Exposure to valproate (VPA) (n = 18) was associated with lowest cognitive performance regarding Full Scale IQ (FSIQ) (β, − 12.04; p = 0.006) and verbal comprehension (VCI) (β, − 8.89; p = 0.019). Maternal FSIQ, maternal performance IQ (PIQ), and child's age at first phrases were independent factors associated with the cognitive development of children.ConclusionsMultivariate analysis showed VPA to be an independent predictor for decreased cognitive performance. Maternal FSIQ, PIQ, and child developmental achievements were significant confounders for cognitive performance in children.     

Inattention and hyperactivity in association with autism spectrum disorders in the CHARGE study

BackgroundAttention deficits in young children with autism spectrum disorder (ASD) are not well understood. This study sought to determine: 1) the prevalence of ADHD symptoms in young children with ASD, typical development (TD), and developmental delay (DD) and 2) the association between ADHD symptoms and cognitive and behavioral functioning in children with ASD.MethodADHD symptoms, defined according to Aberrant Behavior Checklist (ABC) hyperactivity subscale scores, were compared across children aged 2–5 from a large case-control study with ASD (n = 548), TD (n = 423), and DD (n = 180). Inattention and hyperactivity items within this subscale were also explored. Within the ASD group, linear and logistic regression were used to examine how ADHD symptoms were associated with cognition as assessed by the Mullen Scales of Early Learning and adaptive functioning as assessed by the Vineland Adaptive Behavior Scales.ResultsMean hyperactivity subscale scores were lowest in children with TD (mean = 3.19), higher in children with DD (12.3), and highest in children with ASD (18.2; between-group p < 0.001). Among children with ASD, significant associations were observed with higher ADHD symptoms and poorer adaptive and cognitive functioning (adjusted beta for hyperactivity score in association with: Vineland composite = −5.63, p = 0.0005; Mullen visual reception scale = −2.94, p = 0.02; for the highest vs. lowest quartile of hyperactivity score, odds of lowest quintile of these scores was approximately doubled). Exploratory analyses highlighted associations with inattention-related items specifically.ConclusionThese results suggest ADHD symptoms may play a key role in the functioning of young children with ASD.     

Surgical versus conservative treatment in patients with cerebral cavernomas and non refractory epilepsy

PurposeThe optimal therapy of patients with cerebral cavernoma (CCs) and new onset epilepsy, sporadic seizures, or non well established refractory epilepsy is still not clear. The aim of this study was to compare the incidence of seizures in patients with CCs both operated and non operated, in order to obtain more information on the correct management of these patients.Materials and methodsWe studied retrospectively 43 patients with non refractory epilepsy secondary to CCs. Twenty-six of them (60.5%) underwent surgery and made up the surgical group, and 17 patients were treated medically and constituted the medical group. Seizure frequency and other clinical variables were compared between both groups.ResultsAt two years, out of the 26 operated patients, 19 (73%) remained seizure free, 4 (15%) had less than a seizure per month, and one patient (4%) had more than one seizure per month. At five years, 15 patients of the surgical group remained for analysis. Of them, 11 (73.3%) were seizure free, and 4 (26.7%) had less than one seizure a month. In the medical group, 12 out of 17 patients were seizure free (70.6%). There were no significant differences between the two groups (p = 0.2 and p = 0.3, respectively). Seven patients had postoperative neurological sequelae.ConclusionSurgical treatment of patients with non refractory epilepsy due to CCs did not significantly reduce the likelihood of seizures when compared to medical treatment. It must also be considered that surgery carries serious risks. A prospective and randomized study must be carried out to further clarify our findings.     

Childhood trauma in patients with self-reported stress-precipitated seizures

ObjectiveStress is the most commonly reported precipitant of epileptic seizures, but the mechanism by which stress precipitates seizures and the risk factors for stress as a seizure precipitant are poorly understood. Previously, we observed higher levels of anxiety symptoms in patients with epilepsy who reported stress as a seizure precipitant. Given that childhood trauma increases the risk of general psychiatric symptom burden, including anxiety symptoms, we sought to examine the relationship between childhood adversity and stress as a seizure precipitant.MethodsSequential outpatients (N = 236) evaluated at the Epilepsy Center of the University of Cincinnati Neuroscience Institute who had previously enrolled in an earlier study of stress and seizures were enrolled. Subjects either endorsed stress as a seizure precipitant [Stress (+)] or not [Stress (−)]. The Childhood Trauma Questionnaire Short Form (CTQ-SF), a 28-question scale that evaluates 5 domains of childhood adversity (physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse) was sent via mail and returned on paper or electronically from participants. Total CTQ-SF score and CTQ-SF domain scores were compared between Stress (+) and Stress (−) groups using Wilcoxon rank sum test. Spearman's rank correlation between CTQ-SF scores with depression and anxiety was also determined, and these analyses were followed by a multivariate analysis to identify the association of childhood trauma with other factors including anxiety and depression.ResultsA total of 119 out of 236 CTQ-SFs that were sent out were completed. Response rates were 91/195 for Stress (+) and 28/41 for Stress (−). The Stress (+) group reported higher scores in emotional abuse compared with the Stress (−) group (p = 0.029); CTQ-SF total scores were higher in the Stress (+) group compared with the Stress (−) group (p = 0.08), and sexual abuse scores were higher in Stress (+) group (p = 0.07), but there were no statistically significant differences for other types of trauma. Depression and anxiety scores were higher in the Stress (+) group, but anxiety was the only independent factor associated with the Stress (+) group in the multivariate analysis (p = 0.0021).ConclusionPatients with epilepsy who report stress as a seizure precipitant are more likely to endorse a history of childhood traumatic experiences, particularly emotional abuse, compared with those who do not perceive stress as a precipitant. Further study is needed to identify how childhood trauma interacts with anxiety in modulating stress response in patients with epilepsy.