Resection of Temporal Neocortex During Multiple Hippocampal Transections for Mesial Temporal Lobe Epilepsy Does not Affect Seizure or Memory Outcome.

BACKGROUND: Multiple hippocampal transection (MHT) is a surgical treatment for mesial temporal lobe epilepsy associated with improved postoperative neuropsychological outcomes compared with lobectomy. OBJECTIVE: To determine whether resection of the amygdala and anterior temporal neocortex during MHT affects postoperative seizure/memory outcome. METHODS: Seventeen patients with normal magnetic resonance imaging and stereo-electroencephalogram-proven drug-resistant dominant mesial temporal lobe epilepsy were treated with MHT. Nine patients underwent MHT alone (MHT-) and 8 patients underwent MHT plus removal of the amygdala and anterior 4.5 cm of temporal neocortex lateral to the fusiform gyrus (MHT+). Verbal and visual-spatial memory were assessed in all patients preoperatively and in 14 patients postoperatively using the Wechsler Memory Scale. Postoperative seizure control was assessed at 12 months for all patients. RESULTS: Overall, 11 of 17 patients (64.7%) were Engel class 1 at 1 year (6/9 MHT-, 5/8 MHT+, P = .38), and 10 of 14 patients (71.4%) had no significant postoperative decline in either verbal or visual memory (6/8 MHT-, 4/6 MHT+, P = .42). Verbal memory declined in 2 of 8 MHT- and 1 of 6 MHT+ patients, and visual memory declined in 1 of 8 MHT- and 2 of 6 MHT+ patients. Two patients had improved visual memory postoperatively, both in the MHT+ group. CONCLUSION: MHT on the dominant side is associated with high rates of seizure freedom and favorable memory preservation outcomes regardless of the extent of neocortical resection. Preservation of the temporal neocortex and amygdala during MHT does not appear to decrease the risk of postoperative memory decline, nor does it alter seizure outcome.

Temporal lobe epilepsy in patients with nonlesional MRI and normal memory: an SEEG study.

OBJECT: Temporal lobe epilepsy (TLE) in the absence of MRI abnormalities and memory deficits is often presumed to have an extramesial or even extratemporal source. In this paper the authors report the results of a comprehensive stereoelectroencephalography (SEEG) analysis in patients with TLE with normal MRI images and memory scores. METHODS: Eighteen patients with medically refractory epilepsy who also had unremarkable MR images and normal verbal and visual memory scores on neuropsychological testing were included in the study. All patients had seizure semiology and video electroencephalography (EEG) findings suggestive of TLE. A standardized SEEG investigation was performed for each patient with electrodes implanted into the mesial and lateral temporal lobe, temporal tip, posterior temporal neocortex, orbitomesiobasal frontal lobe, posterior cingulate gyrus, and insula. This information was used to plan subsequent surgical management. RESULTS: Interictal SEEG abnormalities were observed in the mesial temporal structures in 17 patients (94%) and in the temporal tip in 6 (33%). Seizure onset was exclusively from mesial structures in 13 (72%), exclusively from lateral temporal cortex and/or temporal tip structures in 2 (11%), and independently from mesial and neocortical foci in 3 (17%). No seizure activity was observed arising from any extratemporal location. All patients underwent surgical intervention targeting the temporal lobe and tailored to the SEEG findings, and all experienced significant improvement in seizure frequency with a postoperative follow-up observation period of at least 1 year. CONCLUSIONS: This study demonstrates 3 important findings: 1) normal memory does not preclude mesial temporal seizure onset; 2) onset of seizures exclusively from mesial temporal structures without early neocortical involvement is common, even in the absence of memory deficits; and 3) extratemporal seizure onset is rare when video EEG and semiology are consistent with focal TLE.

Visual-spatial memory may be enhanced with theta burst deep brain stimulation of the fornix: a preliminary investigation with four cases.

Memory loss after brain injury can be a source of considerable morbidity, but there are presently few therapeutic options for restoring memory function. We have previously demonstrated that burst stimulation of the fornix is able to significantly improve memory in a rodent model of traumatic brain injury. The present study is a preliminary investigation with a small group of cases to explore whether theta burst stimulation of the fornix might improve memory in humans. Four individuals undergoing stereo-electroencephalography evaluation for drug-resistant epilepsy were enrolled. All participants were implanted with an electrode into the proximal fornix and dorsal hippocampal commissure on the language dominant (n = 3) or language non-dominant (n = 1) side, and stimulation of this electrode reliably produced a diffuse evoked potential in the head and body of the ipsilateral hippocampus. Each participant underwent testing of verbal memory (Rey Auditory-Verbal Learning Test), visual-spatial memory (Medical College of Georgia Complex Figure Test), and visual confrontational naming (Boston Naming Test Short Form) once per day over at least two consecutive days using novel test forms each day. For 50% of the trials, the fornix electrode was continuously stimulated using a burst pattern (200 Hz in 100 ms trains, five trains per second, 100 µs, 7 mA) and was compared with sham stimulation. Participants and examiners were blinded to whether stimulation was active or not, and the order of stimulation was randomized. The small sample size precluded use of inferential statistics; therefore, data were analysed using descriptive statistics and graphic analysis. Burst stimulation of the fornix was not perceived by any of the participants but was associated with a robust reversible improvement in immediate and delayed performance on the Medical College of Georgia Complex Figure Test. There were no apparent differences on either Rey Auditory-Verbal Learning Test or Boston Naming Test. There was no apparent relationship between performance and side of stimulation (language dominant or non-dominant). There were no complications. Preliminary evidence in this small sample of patients with drug-resistant epilepsy suggests that theta burst stimulation of the fornix may be associated with improvement in visual-spatial memory.

Depressive symptoms in parents of adolescents with myelomeningocele: the association of clinical, adolescent neuropsychological functioning, and family protective factors.

PURPOSE: The purpose of this study is to determine if neuropsychological functioning and family protective factors are related to depressive symptoms in parents of adolescents with myelomeningocele (MMC). METHODS: Fifty adolescents (28 females, 22 males; predominately Caucasian; ages 12-21 years, M=15.7, SD=2.4) and their parents from a large Midwestern MMC Program participated in a cross-sectional descriptive mixed-methods study. Participants completed measures of adolescent clinical status (WeeFIM®, Demographic and Clinical Information Form), neuropsychological (NP) functioning, family protective factors and parents' depressive symptoms. RESULTS: Parents' depressive symptoms correlated significantly with NP functioning in the domains of Mental Processing Speed, Psychomotor Speed, Executive Functioning, Fine Motor Skills, and Language, and with each self-reported family protective factor. Multiple regression analysis revealed independent main effects for the NP variable, Executive Functioning and the Family Protective Factors Composite (p< 0.05); there was no interaction (p> 0.10). CONCLUSION: Clinicians are especially encouraged to include assessment of parental depressive symptoms if the adolescent has executive functioning impairments or if the parents have few family protective factors.

Language and social functioning in children and adolescents with epilepsy.

Individuals with epilepsy have difficulties with social function that are not adequately accounted for by seizure severity or frequency. This study examined the relationship between language ability and social functioning in 193 children with epilepsy over a period of 36months following their first recognized seizure. The findings show that children with persistent seizures have poorer language function, even at the onset of their seizures, than do their healthy siblings, children with no recurrent seizures, and children with recurrent but not persistent seizures. They continue to demonstrate poorer language function 36months later. This poor language function is associated with declining social competence. Intervention aimed at improving social competence should include consideration of potential language deficits that accompany epilepsy and social difficulty.

Adaptive functioning in children with epilepsy and learning problems.

In the study we describe adaptive functioning in children with epilepsy whose primary caregivers identified them as having learning problems. This was a cross-sectional study of 50 children with epilepsy and learning problems. Caregivers supplied information regarding the child's adaptive functioning and behavior problems. Children rated their self-concept and completed a battery of neuropsychological tests. Mean estimated IQ (PPVT-III) in the participant children was 72.8 (SD = 18.3). On average, children scored 2 standard deviations below the norm on the Vineland Adaptive Behavior Scale-II and this was true even for children with epilepsy who had estimated IQ in the normal range. In conclusion, children with epilepsy and learning problems had relatively low adaptive functioning scores and substantial neuropsychological and mental health problems. In epilepsy, adaptive behavior screening can be very informative and guide further evaluation and intervention, even in those children whose IQ is in the normal range.

Self-esteem and symptoms of depression in children with seizures: relationships with neuropsychological functioning and family variables over time.

PURPOSE: To test over time the relationships of neuropsychological functioning to mental health in children following a first recognized seizure and, of primary importance, to determine if the strength of these relationships differs based on risk and protective factors. METHODS: In a larger prospective study, 135 children with a first seizure (ages 8-14 years) and 73 healthy sibling controls completed neuropsychological testing at baseline and 36 months. Structured telephone interviews were used to obtain data from children on mental health and family environment; major caregiving parents provided data on demographic and family variables. Data analyses included correlation coefficients and linear regression models. RESULTS: Children with seizures showed an overall trend for improvement in mental health. More children with seizures than siblings had declines in processing speed. Declines in neuropsychological functioning were correlated with worse mental health. With regard to risk and protective factors, higher parent education protected against decline in self-esteem related to decline in processing speed. Better family functioning and greater parental support protected against decline in self-esteem related to decrease in verbal memory and learning. Older child age protected against increase in depressive symptoms related to decline in processing speed. DISCUSSION: Seizure onset had a negative impact on mental health in children with declines in cognitive functioning except for older children and those with more family resources. Children should be assessed for declines in processing speed and, if found, those subgroups of children with less educated or more anxious parents and those in less supportive families should be targeted for interventions.

Magnetic resonance imaging findings in children with a first recognized seizure.

This study characterized structural abnormalities associated with onset of seizures in children, using magnetic resonance imaging and a standardized classification system in a large prospective cohort. Two hundred eighty-one children aged 6-14 years completed magnetic resonance imaging within 6 months of their first recognized seizure. Most examinations were performed with a standardized, dedicated seizure protocol; all were scored using a standard scoring system. At least one magnetic resonance imaging abnormality was identified in 87 of 281 (31%) children with a first recognized seizure. Two or more abnormalities were identified in 34 (12%). The commonest abnormalities were ventricular enlargement (51%), leukomalacia/gliosis (23%), gray-matter lesions such as heterotopias and cortical dysplasia (12%), volume loss (12%), other white-matter lesions (9%), and encephalomalacia (6%). Abnormalities defined as significant, or potentially related to seizures, occurred in 40 (14%). Temporal lobe and hippocampal abnormalities were detected at a higher frequency than in previous studies (13/87). Magnetic resonance imaging and a standardized, reliable, valid scoring system demonstrated a higher rate of abnormal findings than previously reported, including findings formerly considered incidental. Practice parameters may need revision, to expand the definition of significant abnormalities and support wider use of magnetic resonance imaging in children with newly diagnosed seizures.

The relationship of neuropsychological functioning to adaptation outcome in adolescents with spina bifida.

Adolescents with spina bifida (SB) vary in their ability to adapt to the disease, and it is likely that numerous risk and protective factors affect adaptation outcomes. The primary aim was to test neuropsychological impairment, exemplified herein by executive dysfunction, as a risk factor in the Ecological Model of Adaptation for Adolescents with SB. Specific hypotheses were that: (1) executive functioning predicts the adaptation outcome of functional independence in adolescents with SB; (2) executive functioning mediates the impact of neurological severity on functional independence; and (3) family and adolescent protective factors are related to functional independence and moderate the relationship between executive functioning and functional independence. Forty-three adolescents aged 12-21 years completed neuropsychological measures and an interview that assessed risk, adolescent and family protective factors, and functional independence. Age, level of lesion, executive functioning, and the protective factor adolescent activities were significantly correlated with the functional independence outcome. In hierarchical regression analysis, the model accounted for 61% of the variance in functional independence outcomes. Executive functioning mediated the impact of neurological severity on functional independence.

The relationship between sleep problems and neuropsychological functioning in children with first recognized seizures.

Epilepsy is associated with sleep disturbance, but little is known about how early this relationship develops and how it affects neuropsychological functioning. This study documented the frequency and types of sleep problems and examined how sleep problems are associated with seizures and neuropsychological functioning in 332 children following their first recognized seizure (ages 6-14) and in 225 sibling controls. Formal neuropsychological batteries were administered to all subjects. Sleep was measured using the Sleep Behavior Questionnaire and the Child Behavior Checklist. Sleep problems were more frequent in the seizure sample relative to siblings and previously published norms; bedtime difficulties, daytime somnolence, and parasomnias were the most frequently occurring sleep problems. In the seizure group, sleep problems were related to seizure parameters and to neuropsychological functioning. Seizure patients with significant sleep problems had worse neuropsychological functioning on all measures. Findings demonstrate the significant impact of sleep disturbance on children with newly recognized seizures.

Academic underachievement among children with epilepsy: proportion exceeding psychometric criteria for learning disability and associated risk factors.

This study assessed rates of learning disabilities (LD) by several psychometric definitions in children with epilepsy and identified risk factors. Participants (N = 173, ages 8-15 years) completed IQ screening, academic achievement testing, and structured interviews. Children with significant head injury, chronic physical conditions, or mental retardation were excluded. Using an IQ-achievement discrepancy definition, 48% exceeded the cutoff for LD in at least one academic area; using low-achievement definitions, 41% to 62% exceeded cutoffs in at least one academic area. Younger children with generalized nonabsence seizures were at increased risk for math LD using the IQ-achievement discrepancy definition; age of seizure onset and attention-deficit/hyperactivity disorder (ADHD) were risk factors for reading and math LD using low-achievement definitions. Writing was the most common domain affected, but neither ADHD nor seizure variables reliably identified children at risk for writing LD. Although children with earlier seizure onset, generalized nonabsence seizures, and comorbid ADHD appear to be at increased risk for some types of LD by some definitions, these findings largely suggest that all children with epilepsy should be considered vulnerable to LD. A diagnosis of epilepsy (even with controlled seizures and less severe seizure types) should provide sufficient cause to screen school-age children for LD and comorbid ADHD.

The association of MRI findings and neuropsychological functioning after the first recognized seizure.

PURPOSE: To explore relationships between MRI abnormalities of the brain and neuropsychological functioning in children who were evaluated following their first recognized seizure. METHODS: Subjects were children aged 6 to 14 years with a first recognized seizure within the past 3 months who participated in a larger prospective study of child adaptation. The 249 children with neuropsychological testing and neuroimaging were studied. Children underwent neuropsychological examination an average of 2.8 months and MRI examination an average of 1.3 months after the first recognized seizure. On factor analysis four factors were found for neuropsychological function: LANG = Language, PS = Processing Speed, EC = Executive/ Construction, VMEM = Verbal Memory and Learning. For analysis, structural abnormalities found on MRI were classified as significant (yes/no) based on whether they were presumed to be related to the seizure condition. RESULTS: On MRI, 34 (14%) had structural abnormalities that were judged to be significant in that they were possibly related to their seizures. Children with significant abnormalities had significantly lower estimated IQ scores and significantly lower language, processing speed, executive/constructional ability, and verbal memory and learning factor scores than did children without significant abnormalities. CONCLUSIONS: Children who have structural brain abnormalities at onset have slightly lower cognitive functioning overall, and all neuropsychological domains seemed to be affected relatively equally. This pattern was apparent even when we restricted the analysis to children with intellectual functioning in the broadly normal range.

Teachers' ratings of the academic performance of children with epilepsy.

The present study examined how knowledge of a child's seizure condition is related to teachers' assessment of the child's academic ability. Children with epilepsy were divided into two groups based on teachers' awareness of the children's seizure condition (Label). The children's achievement was assessed using the Woodcock Johnson Tests of Achievement-Revised (WJ-R), and the teacher's ratings were obtained from the Child Behavior Checklist Teacher Report Form (TRF) (Source). A 2 (Source) x 2 (Label) mixed-design analysis of covariance (controlling for IQ and how well the teacher knew the child) revealed a significant interaction, F(1,121)=4.22, P=0.04. For the WJ-R there was no effect of Label on Achievement, but on the TRF lower scores were observed for children who were labeled. These results support the hypothesis that some teachers might underestimate the academic abilities of children with epilepsy.

Development and validation of the Subjective Awareness of Neuropsychological Deficits Questionnaire for Children (SAND-C).

Although lowered awareness of abilities has been associated with poorer outcome in adults with neurological compromise, a dearth of research exists examining whether lowered awareness exists in younger populations. Using findings from recent literature and expert opinion, a 47-item Subjective Awareness of Neuropsychological Deficits Questionnaire for Children (SAND-C) was created to assess awareness of cognitive functioning in 6 domains (attention, psychomotor, visual-spatial, language, memory, and executive functioning). Confirmatory factor analysis (CFA) of the SAND-C was conducted on a sample consisting of 365 healthy children and 48 children with epilepsy. The SAND-C was found to have strong reliability. Factor analysis confirmed the a priori 6 factor model, but the 6-factor model was only marginally better than a more parsimonious 1-factor solution. Post-hoc exploratory factor analyses indicate that the SAND-C may measure more constructs for adolescents than for younger children. The difference between younger and older children may reflect developmental changes in metacognitive awareness and abstraction about their own abilities.

Practice effects and the use of alternate forms in serial neuropsychological testing.

Accurate understanding of practice characteristics, performance stability, and error on neuropsychological tests is essential to both valid clinical assessment and maximization of signal detection for clinical trials of cognitive enhancing drugs. We examined practice effects in 28 healthy adults. As part of a larger study using donepezil and simulating a Phase I trial, participants were randomized into: placebo, no-treatment and donepezil. Donepezil results are presented elsewhere. Neuropsychological tests were administered in a fixed order for 6 weeks, with alternate forms available for most tests. Despite alternate forms, ANOVAs revealed significant improvements for the pooled control group (placebo and no-treatment) on all tests except Letter Number Sequencing and Trails B. Learning occurred principally in the first three to four sessions. PASAT and Stroop interference showed the greatest learning. Thus, serial assessment with alternate forms may attenuate retest effects on some tests, but continued learning occurs on novel tests or those in which an advantageous test-taking strategy can be identified. Alternate forms and baseline practice sessions may help control early, rapid improvements in clinical trials.

Neuropsychological correlates of electroencephalograms in children with epilepsy.

INTRODUCTION: This study examined the degree to which neurophysiological activity on routine clinical EEG is associated with neuropsychological deficiencies in children with epilepsy. METHODS: Ninety-five children with epilepsy (58 chronic, 37 recent-onset; mean age = 10.41 years, S.D. = 2.87 years; mean age at onset = 5.86 years, S.D. = 3.46 years) completed a neuropsychological battery. Neurophysiological data were collected from the most recent EEG. RESULTS: In the recent-onset sample, no neuropsychological scores were related to any EEG variable. In the chronic sample, however, presence of slow-wave activity was related to memory impairment (p < 0.01). Post-hoc analyses on other neuropsychological measures showed localization of epileptiform activity (EA) might be related to verbal learning. DISCUSSION: Children with slow-wave activity on EEG might be at increased risk for developing neuropsychological deficits. When these abnormalities are observed on a child's EEG, closer monitoring of cognitive and academic functioning seems warranted. Differences between these findings and past research suggest that conclusions drawn from adult surgical studies cannot be generalized to pediatric patients, especially recent-onset samples, without qualification. Differences between the recent-onset and chronic samples in this cross-sectional study raise the possibility that neurophysiological abnormalities have a cumulative effect on cognitive development.

Test-retest reliability of the Extended Complex Figure Test--Motor Independent administration (ECFT-MI).

The Extended Complex Figure Test (ECFT; Fastenau, 1996b, 2003a), adds recognition and matching trials to the Rey-Osterrieth Complex Figure Test (ROCFT). An alternate administration of the ECFT, the ECFT-Motor Independent version (ECFT-MI; Fastenau, 2003a) measures visuospatial memory without the motoric demands of the ROCFT. ECFT-MI test-retest reliabilities were examined in 55 healthy adults tested two times separated by one week. The Recognition Trial showed strong reliability for the Total Score (r = .80, p < .0001). Reliabilities for Recognition Detail Scale and Subscales (r = .62-.74, p < .0001) and for the Global Scale (r = .51, p < or = .005) were attenuated by fewer items per subscale but were comparable to other memory tests. Matching Trial reliability coefficients were attenuated by extreme ceiling effects and restriction of range, but scores were very consistent between the two administrations. This study supports the temporal stability of the ECFT-MI.