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Objective Intelligence quotient (IQ) outcomes after pediatric epilepsy surgery show significant individual variation. Clinical factors such as seizure cessation or antiepileptic medication discontinuation have been implicated, but do not fully account for the heterogeneity seen. Less is known about the impact of neurobiological factors, such as brain development and resection location. This study examines clinical and neuroimaging factors associated with cognitive outcome after epilepsy surgery in childhood. Methods Fifty-two children (28 boys, 24 girls) were evaluated for epilepsy surgery and reassessed on average 7.7 years later. In the intervening time, 13 were treated pharmacologically and 39 underwent focal surgery (17 temporal, 16 extratemporal, six multilobar; mean age at surgery = 14.0 years). Pre- and postsurgical assessments included IQ tests and T1-weighted brain images. Predictors of IQ change were investigated, including voxel-based analyses of resection location, and gray and white matter volume change. Results Overall modest IQ improvement was seen in children treated surgically, but not in those treated pharmacologically only. Applying a ≥10-point change threshold, 39% of the surgically treated children improved, whereas 10% declined. Clinical factors associated with IQ increases were lower preoperative IQ and longer follow-up duration, whereas seizure and antiepileptic medication cessation were not predictive. Among neuroimaging factors, we observed that left anterior temporal resections impacted negatively on verbal reasoning, linked to full-scale IQ decline. In contrast, gray matter volume change in ipsi- and contralesional hemispheres was positively correlated with IQ change. Voxel-based morphometry identified the gray matter volume change in the contralesional dorsolateral frontal cortex as most strongly associated with IQ improvement. Significance We show that a variety of factors are likely to contribute to patterns of postsurgical change in IQ. Neuroimaging results indicate that left anterior temporal resections constrain development of verbal cognition, whereas simultaneously cortical growth after surgical treatment can support improvements in IQ.

SummaryObjective For patients with medically intractable focal epilepsy, the benefit of epilepsy surgery must be weighed against the risk of cognitive decline. Clinical factors such as age and presurgical cognitive level partially predict cognitive outcome; yet, little is known about the role of cross-hemispheric white matter pathways in supporting postsurgical recovery of cognitive function. The purpose of this study is to determine whether the presurgical corpus callosum (CC) midsagittal area is associated with pre- to postsurgical change following epilepsy surgery. Methods In this observational study, we retrospectively identified 24 adult patients from an epilepsy resection series who completed preoperative high-resolution T1-weighted magnetic resonance imaging (MRI) scans, as well as pre- and postsurgical neuropsychological testing. The total area and seven subregional areas of the CC were measured on the midsagittal MRI slice using an automated method. Standardized indices of auditory-verbal working memory and delayed memory were used to probe cognitive change from pre- to postsurgery. CC total and subregional areas were regressed on memory-change scores, after controlling for overall brain volume, age, presurgical memory scores, and duration of epilepsy. Results Patients had significantly reduced CC area relative to healthy controls. We found a positive relationship between CC area and change in working memory, but not delayed memory; specifically, the larger the CC, the greater the postsurgical improvement in working memory (β = 0.523; p = 0.009). Effects were strongest in posterior CC subregions. There was no relationship between CC area and presurgical memory scores. Significance Findings indicate that larger CC area, measured presurgically, is related to improvement in working memory abilities following epilepsy surgery. This suggests that transcallosal pathways may play an important, yet little understood, role in postsurgical recovery of cognitive functions.

Summary Objective Birth weight is an important indicator of prenatal environment, and subtle variations of birth weight within the normal range have been associated with differential risk for cognitive and behavioral problems. Therefore, we aimed to determine if there are differences in birth weight between full-term children with uncomplicated new/recent-onset epilepsies and typically developing healthy controls. We further examined the relationships between birth weight and childhood/adolescent cognition, behavior, and academic achievement. Methods One hundred eight children with new-onset/recent-onset epilepsy and 70 healthy controls underwent neuropsychological assessment. All participants were born full-term (>37 weeks) without birth complications. Parents were interviewed regarding their child's gestation, birth, and neurodevelopmental history. Results Birth weight of children with epilepsy was significantly lower than healthy controls (p = 0.023). Whereas birth weight (covaried with age, sex, handedness, and mother's education) was significantly associated with cognition in controls in multiple domains (intelligence, language, aspects of academic achievement), this relationship was absent in children with epilepsy. Birth weight was not associated with clinical epilepsy variables (age of onset, epilepsy syndrome) and was not predictive of a variety of other academic or psychiatric comorbidities of epilepsy. Significance Although the origin of lower birth weight in children with epilepsy is unknown, these findings raise the possibility that abnormal prenatal environment may affect childhood-onset epilepsy. Furthermore, the positive relationship between birth weight and cognition evident in healthy controls was disrupted in children with epilepsy. However, birth weight was not related to academic and psychiatric comorbidities of childhood epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

The Boston Naming Test (BNT) is often used in the evaluation of surgical epilepsy patients to assess left temporal lobe function. In 2005, Busch et al. demonstrated the diagnostic utility of the BNT in predicting ultimate side of surgery in patients with temporal lobe epilepsy. BNT raw score significantly predicted ultimate side of surgery, moderated by Full Scale IQ (FSIQ), age at seizure onset, and duration of epilepsy. The final regression equation correctly predicted side of surgery in 69.5% of the sample. The current study demonstrated excellent cross-validation of this equation in an independent sample of 104 patients who eventually underwent temporal lobectomies, correctly predicting side of surgery in 67.3% of patients. The combination of the two samples resulted in a new, more-stable regression equation that correctly predicted side of surgery in 68.8% of the combined sample. These results further support the clinical utility of the BNT in predicting side of surgery.

Summary: Purpose: The effect of unilateral temporal lobectomy on seizure frequency is well recognized, but little is known about the neuropsychological changes that occur after surgical treatment. We assessed neuropsychological status in 26 patients with an average age of 35 years before and after unilateral temporal lobectomy for medically intractable TLE. Methods: Neuropsychological examination to assess cognitive function, memory, attention, visuospatial analysis, language, and emotional functions was performed preoperatively and at 1 month and 1 year after the surgery. Results: At both 1 month and 1 year after the surgery, the patients had improved scores, compared with the preoperative scores, on the Wechsler Adult Intelligence Scale–Revised (WAIS-R: verbal IQ, performance IQ, and full-scale IQ), Wechsler Memory Scale–Revised (WMS-R: verbal, general, and delayed paired associates memory), and Raven Colored Progressive Matrices. In the Minnesota Multiphasic Personality Inventory (MMPI), significant decreases were observed at 1 year after the surgery in the scores for infrequency, hypochondriasis, psychasthenia, and schizophrenia. Patients in whom the seizures had been relieved postoperatively also had improved scores on the WAIS-R, WMS-R, and Raven Colored Progressive Matrices. Conclusions: These data suggest that neuropsychological improvement postoperatively is influenced by the reduction in the frequency of seizures after surgery.

Summary Purpose: To determine the frequency and determinants of subnormal global cognitive function in a representative, community-based sample of children prospectively identified at the time of initial diagnosis of epilepsy. Methods: In children enrolled with newly diagnosed epilepsy and followed a median of 10.5 years, level of cognitive function (within normal, borderline, mild, moderate to severe mental retardation (MR), neurologically devastated, and impaired but not further classified (NFC)) was determined based upon neurologists' and school records, repeated parental interviews, and, in over half the participants, standardized neuropsychological testing. For multivariable analyses, subnormal cognitive function was designated as consistent with a full scale IQ < 80. Results: Global cognitive function was considered within normal, N = 451 (73.6%), borderline, N = 31 (5.1%), mild MR, N = 21 (3.4%), more severe MR, N = 45 (7.3%), devastated, N = 29 (4.7%), and impaired-NFC, N = 36 (5.9%). Age at onset

Summary: Health-related quality of life (HRQOL) is an important outcome measure in clinical research. Given the psychosocial and behavioral difficulties associated with pediatric epilepsy, evaluating HRQOL in this patient population is of particular importance. Though HRQOL has been examined in pediatric patients receiving focal resection or pharmacological (antiepileptic drug; AED) treatment, it has not been assessed in patients receiving hemispherectomy (HE) for intractable epilepsy. The current study evaluated HRQOL in a sample of pediatric HE cases (N = 26) using previously validated questionnaires relative to surgical (N = 30) and nonsurgical (N = 84) comparison groups. Compared with focal resection and nonsurgical patients, parents of children who received HE reported similar levels of HRQOL. In surgical cases, worse HRQOL was correlated with residual seizure frequency. In both surgical and nonsurgical cases, female gender, higher AED load, and lower functional independence predicted worse HRQOL. Interestingly, HE status (i.e., having undergone HE) predicted fewer epilepsy-related limitations. Consistent with previous findings, AED load, in addition to lower functional abilities, appear particularly detrimental to life quality in pediatric epilepsy. HE, however, is not associated with increased risk for poor HRQOL. When considered in light of the multiple, significant risk factors for poor outcome associated with HE, children who undergo the procedure fare surprisingly well.

Summary: Purpose: Benign myoclonic epilepsy in infants (BMEI) is a rare epileptic syndrome characterized only by generalized myoclonic seizures (MSs) in normal children during the first 2 years. Our aim was to assess the electroclinical features and the follow-up of this syndrome. Methods: BMEI was confirmed by electroencephalogram (EEG) in four neuropediatric units in France between 1981 and 2002. Clinical and electroencephalographic findings at diagnosis and during the follow-up were collected. The Vineland scale or Wechsler scale or both were used to perform neuropsychological evaluations. Results: We report 34 patients with BMEI characterized by MSs occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes-and-waves, or spikes-and-waves. The interictal EEG was usually normal. A family history of febrile seizures (FSs) or epilepsy was noted in six patients. A history of FSs was noted in 11 patients. Eleven patients had reflex MSs. Monotherapy with valproic acid was effective in 23 of 30 treated patients. The onset of epilepsy was known in all patients. Four patients had seizures after the initial symptoms. Juvenile myoclonic epilepsy developed in two patients, and cryptogenic partial epilepsy in another. Neuropsychological outcome was evaluated in 20 patients (10 with Wechsler scales and 17 with the Vineland scale). Cognitive functions were normal in 17 patients, whereas developmental delay was observed in three others. Conclusions: BMEI is clinically characterized by myoclonic seizures involving the upper part of the body, occurring many times a day. The ictal EEG showed a generalized discharge of polyspikes, polyspikes-and-waves, or spikes-and-waves. The interictal EEG was usually normal. Reflex MSs were frequently observed, suggesting that two distinctive syndromes are not necessary. BMEI may be followed by juvenile myoclonic epilepsy. Despite a generally favorable neuropsychological outcome, mental retardation can be observed more frequently than in the general population.

Summary: Purpose: Growing evidence suggests that temporal lobe epilepsy (TLE) is a network disease. In this view, the seizure focus may produce measurable deficits in specific cortical functions. Methods: A tactile grating orientation (GrOr) discrimination task associated with parietal lobe function was administered at the index fingertip to 15 subjects with medically intractable TLE and to 19 neurologically normal controls. TLE subjects were tested bilaterally at baseline while taking their usual antiepileptic drugs (AEDs), and off AEDs during inpatient video-EEG monitoring (n = 9). Three subjects also were tested after temporal lobectomy. t Tests were used to compare baseline performance between TLE subjects and controls, and between hands ipsilateral and contralateral to side of seizure onset, with Bonferroni correction for multiple comparisons. TLE subjects' baseline thresholds were compared with those obtained off AEDs by using a repeated measures analysis of variance. Results: TLE subjects were severely impaired bilaterally on the GrOr task, with mean discrimination thresholds nearly twice those of controls (p ≤ 0.001 for each hand). No significant difference was found in baseline performance between hands (p = 0.37), or between baseline and off-AED testing (p = 0.42). The three subjects tested after temporal lobectomy demonstrated improved performance compared with baseline, but statistics were not performed because of the small subject number. Conclusions: Patients with medically intractable TLE have impaired tactile GrOr discrimination bilaterally that is not due to nonspecific effects of AEDs. This impaired perceptual ability may be reversible with surgical removal of the seizure focus.

Summary: Purpose: Mesiotemporal lobe epilepsy (MTLE) can be treated with different surgical approaches. In tailored resections, neocortex is removed beyond “standard” margins when spikes are present in the electrocorticogram. We hypothesized that these larger resections are justified because spiking neocortex is dysfunctional. This would imply that in patients with spikes (a) postoperative cognitive performance is not affected, and (b) preoperative performance is worse than without spikes. Methods: We studied 80 operated-on MTLE patients with pathologically confirmed nonlesional hippocampal sclerosis. All patients were left-sided language dominant and underwent cognitive tests 6 months pre- and postoperatively. A repeated measures analysis of variance (ANOVA) was performed, looking for within- and between-subjects interactions with presence of intraoperative neocortical spikes. Results: Intraoperatively, neocortical spikes were present in 61% of patients. Improved postoperative cognitive outcome was seen only in left-sided patients with spikes. Their performance IQ (PIQ) increased by 8.1 points (95% confidence interval, 3.8–12.3; p = 0.02), and visual naming latency by 12.8 s (95% CI, 2.1–23.5; p = 0.07). Conversely, in left-sided patients without spikes, naming latency declined by 7.5 s (95% CI, −2.3–17.2; p = 0.07). Preoperative scores were comparable except for a 15.3-point (95% CI, 0.1–30.5; p = 0.02) lower VIQ in left-sided patients without spikes. Conclusions: Tailoring does not harm cognitive performance and is, in left-sided MTLE, associated with postoperative improvement. Left-sided MTLE without neocortical spikes has lower verbal scores, which tend to decline after standard resection and may represent a special pathophysiologic entity.

Summary: Purpose: Memory disorders are prominent among patients with intractable epilepsy. It has, however, been frequently observed that subjective memory complaints of these patients did not match their performance on objective memory tests. This discrepancy may reflect emotional, cognitive, or selfawareness deficits among these individuals. The aim of the current study was to explore the interference of cerebral dysfunction on accuracy of self-appraisal for memory. Methods: The degree of concordance between self-perception of memory function, as measured by a visual analogue scale, and actual performance on memory tests was computed in 35 patients who were candidates for epilepsy surgery and demographically matched normal control subjects. The difference between the self-estimated memory ability and performance on memory tests and its relation to the laterality of an epileptogenic lesion, cognitive factors, and affective status was then examined. Results: The results show that the discrepancy between the self-estimated memory ability and performance on memory tests in patients with right hemisphere epileptogenic lesions was significantly larger in magnitude compared with that in patients with left hemisphere lesions and demographically matched control subjects (p = 0.001). Furthermore, whereas patients with left hemisphere lesions and normal controls had about an equal number of positive and negative discrepancy scores, all patients with right hemisphere lesions had positive discrepancy scores, suggesting a tendency for overestimation of memory abilities. Conclusions: These results suggest that right hemisphere lesions may introduce a systematic bias in self-awareness for memory. This bias may color patients’ perceptions of self and others, affecting their perceptions of the quality of life, and necessitating an adjustment of the treatment goals and procedures. Key Words: Self-awareness—Memory—Lateralization—Epilepsy surgery.

Summary: Purpose: This study addressed whether cognitive impairment in children with epilepsy is caused by disease-related stable factors, such as the type of epilepsy, or by acute effects of paroxysmal epileptic activity such as epileptic EEG discharges. We studied a nonselected group with short nonconvulsive seizures, as these seizures may elude detection and may therefore persist over a longer period. In this group, the diagnostic issue is to differentiate between the combined effects of several epilepsy-related factors on cognition. Methods: All children were assessed with 32-channel EEG, synchronized with a computerized cognitive test system and a video-monitoring system. Recording time was 2 h. The primary inclusion criteria were unclear seizures and fluctuations in cognitive performance and/or frequent epileptic EEG discharges in a recent EEG. Results: One hundred fifty-two patients met the inclusion criteria; 31 patients appeared not to have a diagnosis of epilepsy and were used as a nonepilepsy control group. Our results show that type of epilepsy has an impact on stable cognitive functions, such as educational achievement. Paroxysmal epileptic activity (acute effects of seizures and epileptic EEG discharges) affects primarily transient mechanistic cognitive processes (alertness, mental speed). Conclusions: These results suggest that the effects of paroxysmal epileptic activity on transient cognitive mechanisms may accumulate over time and consequently affect the more stable aspects of cognitive function such as educational achievement. The clinical relevance is that early detection of the cognitive impact of seizure-related activity and subsequent treatment may prevent its detrimental impact on cognitive and educational development. Key Words: Epilepsy and cognitive function—Subclinical epileptiform discharges—Transient cognitive impairment—EEG and cognitive impairment—Short nonconvulsive seizures.

Summary: Purpose: Reliable change indices (RCIs) and standardized regression-based (SRB) change scores norms were established for the recently revised Wechsler Adult Intelligence Scale–III (WAIS-III) and Wechsler Memory Scale–III (WMS-III) in patients with complex partial seizures. Establishment of such standardized change scores can be useful in determining the effects of epilepsy surgery on cognitive functioning independent of test–retest artifacts including practice effects. Methods: Forty-two nonoperated-on adult patients with complex partial seizures (primarily of temporal lobe onset) were administered the WMS-III and WAIS-III on two occasions (mean 7-month interval). All patients were receiving stable antiepileptic drug (AED) treatment at both testings. RCI and SRB change scores were calculated. Confidence interval cutoff scores (90% and 80%) and standardized regression equations were calculated for each of the WAIS-III and WMS-III Primary Indices and individual subtests. Age, gender, education, test–retest interval, preoperative test performance, seizure onset, and seizure duration were predictor variables for the SRB equations. Results: Test–retest reliabilities for the WAIS-III and WMS-III Primary Indices were within acceptable ranges, although considerable individual subtest variability was found. Preoperative performance was the single largest contributor to each of the predictive regression equations. Age, gender, education, seizure onset, and seizure duration contributed modest variance to several of the regression equations. Conclusions: We calculated both RCI and SRB change score indices for the recently revised Wechsler instruments. These formulas help control for test–retest methodologic artifacts and provide a standardized method with which to examine both individual and group level cognitive change after epilepsy surgery.

Summary: Purpose: Despite the benign prognoses of idiopathic partial epilepsies, particularly regarding the response of seizures to treatment, some evidence now exists that patients with such disorders may have subtle neuropsychological deficits. This study was designed to investigate several modalities of neuropsychological functioning in a group of 21 patients, ranging from 6 to 14 years of age, with idiopathic occipital lobe epilepsy (IOLE). The case patients were compared with 21 healthy controls matched for age, sex, and socioeconomic status. Methods: A battery of age-appropriate neuropsychological tests was administered individually to all the participants. Tests were chosen on the basis of age-appropriate norms, their ability to represent a wide variety of functional domains, and their appropriateness in a cross-cultural setting. The tests were selected to measure functioning in six domains: intellectual functioning, attention, memory, academic achievement, visual-motor functioning, and executive functioning; some were further subdivided by their verbal-versus-visual modality of functioning. Results: The results revealed no significant difference in basic neurophysiological functions between the patient and control groups, although the case patients' performance scores were lower in attention (p

Summary: Purpose: To characterize patterns of base rate change on measures of verbal and visual memory after anterior temporal lobectomy (ATL) using a newly developed regression-based outcome methodology that accounts for effects of practice and regression towards the mean, and to comment on the predictive utility of baseline memory measures on postoperative memory outcome. Methods: Memory change was operationalized using regression-based change norms in a group of left (n = 53) and right (n = 48) ATL patients. All patients were administered tests of episodic verbal (prose recall, list learning) and visual (figure reproduction) memory, and semantic memory before and after ATL. Results: ATL patients displayed a wide range of memory outcome across verbal and visual memory domains. Significant performance declines were noted for 25-50% of left ATL patients on verbal semantic and episodic memory tasks, while one-third of right ATL patients displayed significant declines in immediate and delayed episodic prose recall. Significant performance improvement was noted in an additional one-third of right ATL patients on delayed prose recall. Base rate change was similar between the two ATL groups across immediate and delayed visual memory. Approximately one-fourth of all patients displayed clinically meaningful losses on the visual memory task following surgery. Robust relationships between preoperative memory measures and nonstandardized change scores were attenuated or reversed using standardized memory outcome techniques. Conclusions: Our results demonstrated substantial group variability in memory outcome for ATL patients. These results extend previous research by incorporating known effects of practice and regression to the mean when addressing meaningful neuropscyhological change following epilepsy surgery. Our findings also suggest that future neuropsychological outcome studies should take steps towards controlling for regression-tothe-mean before drawing predictive conclusions. Key Words: Epilepsy-Memory-Temporal Iobectomy-Postoperative outcome-Neuropsychology .

Summary: Purpose: The Wechsler Memory Scale-Revised (WMS-R) is used routinely for presurgical assessment of memory for patients considering elective resection of the temporal lobe and/or hippocampus for the relief of intractable temporal lobe epilepsy (TLE). We investigated the validity of the WMS-R in a population of people with TLE. Methods: The sample consisted of 138 patients with a diagnosis of TLE in which the epileptogenic focus was clearly and exclusively lateralized to either the right or left hemisphere. They underwent a complete neuropsychological examination as a routine part of their investigation for epilepsy surgery. Psychometric scores included in this study were: Wechsler Adult Intelligence Scale-Revised (WAIS-R) I.Q. scores, National Adult Reading Test Revised (NART-R) predicted-I.Q. scores, and WMS-R Memory Index and subtest scores. Results: Multiple univariate analyses were performed. The group with left temporal focus had significantly lower Verbal Memory Index, Logical memory (both immediate and delayed), and Digit Span scores. Visual/Verbal discrepancy scores incorrectly identified most patients with right temporal focus. Analyses of a total group of people with epilepsy (i.e., mixed temporal, frontal, occipital and unknown foci) as compared with the normative sample indicated that the patient group scored significantly lower across all memory index scores and most memory subtests. Conclusions: Our results confirm that the WMS-R is capable of lateralizing to left hemispheric impairment but is more problematic in the assessment of right hemispheric impairment. The Visual/Verbal Memory Index discrepancy has questionable validity. People with epilepsy performed less well on the WMS-R than did the normative sample. The need for reliable and valid nonverbal tests of memory is therefore warranted.

Summary Purpose Thalamic hemorrhage has been associated with neonatal cerebral sinovenous thrombosis (CSVT), especially when the straight sinus is involved, and often presents with neonatal seizures. Early thalamic injury has previously been shown to predispose to epilepsy and electrical status epilepticus in slow wave sleep (ESES). The objective of this study was to assess the prevalence of sleep-induced epileptic electroencephalography (EEG) abnormalities and postneonatal epilepsy after neonatal thalamic hemorrhage associated with CSVT, in the absence of more widespread cerebral damage. Methods Between 2003 and 2008 15 neonates were diagnosed with a thalamic hemorrhage due to suspected or proven CSVT. Neurodevelopment and the history of seizures were assessed at follow-up in the outpatient clinic in all 14 survivors (age 2–9 years). Whole-night or sleep-deprived EEG recordings were obtained to assess the prevalence of interictal epileptiform activity (EA) and calculate a sleep-induced spike and wave index (SWI). Key Findings Three children were diagnosed with classic ESES (SWI >85%). Two children had ESES spectrum disorder (SWI between 50% and 85%), and in two children significant sleep-induced epileptiform activity (SIEA) was noted (SWI between 25% and 50%). Two other children were diagnosed with focal epilepsy, in the absence of sleep-induced epileptiform EEG abnormalities. Five children (age 2–7 years) had normal EEG recordings at follow-up. Deficits in neurodevelopment were seen significantly more often in children with ESES, ESES spectrum, or SIEA. Significance Neonates with thalamic hemorrhage associated with straight sinus thrombosis, without evidence of more widespread cerebral damage, are at high risk of developing ESES (spectrum) disorder (35%), SIEA (14%), or focal epilepsy (14%). Electrographic abnormalities may already be present prior to recognition of cognitive deficits. Early diagnosis may guide parents and caregivers, and subsequent treatment may improve neurodevelopmental outcome. Routine annual sleep EEG recordings in children with neonatal thalamic injury following CSVT may improve recognition of ESES.

Summary We examined the relationship of age of onset of epilepsy, chronological age at time of operation, and adequacy of preoperative memory performance to pre- to postoperative verbal memory decline. Patients who underwent left (n = 50) or right (n = 51) anterior temporal lobectomy (ATL) were administered tests of verbal episodic (list learning, paragraph recall) and semantic memory (visual naming, vocabulary), both preoperatively and 6 months postoperatively. As a group, left ATL patients showed the classic selective decrease on measures of episodic but not semantic memory. However, examination of episodic memory outcome showed considerable individual variability. Stepwise regression analyses indicated that both later age at onset and older chronologic age were significant and selective predictors of episodic memory decrease for left ATL patients. Adequacy of preoperative memory performance was a nonspecific predictor, associated with decrease in postoperative memory performance for both left and right ATL patients and for multiple types of memory indices. The clinical and theoretical implications are discussed.

The Wechsler Intelligence Scale for Children - Fourth Edition is the most widely used intelligence quotient (IQ) test in use today. However, despite numerous studies on IQ in childhood epilepsy, data exist almost exclusively from prior editions of the test, and no studies to date provide information on the sensitivity of specific WISC-IV scores (full-scale IQ [FSIQ], index, and subtest scores) to epilepsy-related cognitive impairments. The goal of this study was to determine the relative sensitivity of WISC-IV index and subscale scores in detecting cognitive problems in a group of clinically referred children with epilepsy compared to matched controls, and to define the relationship among WISC-IV scales, demographic factors, and epilepsy-related variables.WISC-IV data for children with epilepsy and high seizure burden were obtained from the Alberta Children's Hospital (ACH) and the New York University Comprehensive Epilepsy Center (NYU), two tertiary care medical centers for pediatric epilepsy. All children were clinically referred and received a standard assessment including WISC-IV. Matched controls were obtained from the WISC-IV Canadian and American standardization samples.WISC-IV scores from 212 children were included: 106 children with epilepsy (46 girls, 60 boys; mean age 11.0 years, standard deviation [SD] 3.1; parental education 14.5 years, SD 2.8), and 106 controls matched for age, gender, ethnicity, and parental education. Of the children with epilepsy, 44 had a clearly lateralized focus on electroencephalography (EEG) involving either the right or left hemisphere (26 left, 18 right). FSIQ for the epilepsy group was significantly lower than for controls, and 36.8% of children had IQs compatible with intellectual disability (FSIQ70), versus1% of controls. In children with epilepsy, Working Memory and Processing Speed Index scores were lower than those for Verbal Comprehension and Perceptual Reasoning (p0.01). At the subtest level, scores for children with epilepsy were highest on visual and verbal subtests measuring reasoning skills such as Matrix Reasoning, and lowest on Coding (mean 5.93, SD 3.6). In terms of percentage of children on each subtest with low scores (i.e., scores below 2 SDs from the expected normative mean of 10), the Coding subtest identified the most children (28.3%) with low scores, and the Similarities subtest identified the fewest (16%). Later age at onset and shorter epilepsy duration were both correlated with higher WISC-IV FSIQ and index scores (r correlation coefficient values ranging from 0.36 to 0.44, p0.0001), and number of current and previous antiepileptic drug trials were both inversely correlated with FSIQ and index scores (r -0.27 to -0.47, all p-values0.01). Neither the FSIQ nor the index scores were significantly related to seizure frequency. A similar pattern was found for subtest scores. No differences in FSIQ, index scores, or subtest scores were found between children with left- and right-hemisphere seizure foci, or between those with positive or negative magnetic resonance imaging (MRI) findings.The WISC-IV is sensitive to epilepsy-related cognitive problems in clinically referred children with high seizure burden, particularly problems relating to expressive verbal, working memory, and processing speed difficulties. Compared to healthy children, these children have a very high rate of cognitive difficulties as assessed by the WISC-IV. The usefulness of the WISC-IV in detecting cognitive deficits in children with milder forms of epilepsy remains to be determined.

Cognitive testing was repeated at intervals ranging from 1 to 8 years in 47 adult patients with temporal lobe epilepsy (TLE). Each patient underwent standardized batteries, including the Wechsler Adult Intelligence Scale, Revised (WAIS-R), and Wechsler Memory Scale (WMS). Both surgically treated and nonsurgical patients were examined. The nonsurgical group underwent serial testing for clinical indications, usually for complaints of memory dysfunction. Longitudinal testing could not verify any mean deterioration of intellect or memory in this group; variance over time was similar to test-retest norms in healthy controls. WAIS-R scores before and after resection in the surgical group were similar to our serial WAIS-R data in nonsurgical patients. When we divided surgical patients according to side of epileptogenesis, we noted the expected differences in verbal and visual memory. Right-sided surgery patients improved significantly in Full-Scale IQ (FSIQ) and tended to improve in logical memory on postoperative testing. Patients undergoing left resections had no retest improvement and tended to show decrease in several measures of verbal memory. Our findings should stimulate continued investigation into the natural history of lateralized memory and intellectual function in epilepsy, particularly to clarify long-term cognitive outcome in nonsurgical patients.

The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high-resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long-term outcomes of consecutive true MRI-negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes.In this study we present all adult MRI-negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high-resolution MRI were included in this study.Among the 38 patients who finally underwent surgery, at the latest follow-up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure-free (Engel class IA). Twenty-one (55%) of 38 patients had poor outcomes (Engel class III-IV). Outcomes did not change compared to 12-month follow-up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR-negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044).Our results suggest that epilepsy surgery outcomes in MRI-negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long-term also remain stable. Modern imaging techniques could further improve the postsurgical seizure-free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.

To determine the long-term cognitive and educational outcomes in children prospectively identified at the time of a first unprovoked seizure.A cohort of children with a first unprovoked seizure was enrolled and followed for a mean of 15 years. Cognitive function and educational outcomes were determined 10 or more years after the first seizure via standardized neuropsychological tests, school records, and structured interviews. Children with symptomatic etiology were excluded from the analysis. When available, siblings of study subjects were recruited as normal controls. Primary educational outcome was defined as enrollment into special education services or grade repetition.Twenty-eight percent of (43 of 153) of children with a single seizure and 40% (42 of 105) of children with epilepsy received special education service or repeated a grade (p = 0.05). There was a statistically significant trend in which the children with more seizures tended to require special education or repeat a grade more often (28% in single seizure group vs. 34% in 2-9 seizure group vs. 64% in ≥10 seizure group; p = 0.004). Of 163 subjects who completed neuropsychological testing, children with single seizures tended to score higher than children with epilepsy on Wide Range Achievement Test-3 (WRAT) reading (p = 0.08), Test of Non-Verbal Intelligence-II (TONI-II) (p = 0.02), and Wechsler Intelligence Scale for Children (WISC)/Wechsler Adult Intelligence Scale (WAIS) (p = 0.07). There was no statistically significant difference between children with a single seizure and sibling controls.The results suggest that children with a single seizure represent a group that is distinctly different from children with epilepsy and are more similar to sibling controls. In contrast, even children with very mild epilepsy have significantly worse educational outcomes.

To assess cognitive and epilepsy outcomes in tuberous sclerosis complex (TSC) patients with a history of infantile spasms (IS), in relation to spasm history, electroencephalography (EEG) characteristics, genetic mutation, and treatment history.The authors conducted a retrospective review of 45 children and adults with TSC and a history of IS. EEG reports from the time of spasms were evaluated for all patients, and EEG tracings were accessible and evaluated for 20 patients.Clinical outcome was unfavorable for the majority of patients. However, 33% had experienced at least one year of seizure freedom at follow-up, and 24% of those tested had IQs above 70. Hypsarrhythmia severity scores varied widely, with some EEGs severely hypsarrhythmic and others essentially normal. Lower IQ was significantly associated with higher hypsarrhythmia severity scores on EEG report, the presence of background disorganization on EEG report, the absence of normal sleep patterns on EEG, and a lower degree of treatment success on vigabatrin. A relationship between poor cognitive outcome and poor epilepsy outcome was confirmed. The correlation between poor epilepsy outcome and a greater degree of background disorganization on EEG approached significance, as did the association between subsequent intractable epilepsy and an older age at IS cessation. A greater than expected ratio of TSC2 to TSC1 patients was observed across this IS population.Early detection and successful treatment portend a more favorable outcome in TSC patients with IS. Although EEG findings in these patients vary, specific characteristics may serve as clinically useful prognostic markers.

Cognitive impairment is regarded as the link between epileptic conditions and the inability to learn in school. The neuropsychological approach to learning disabilities in epilepsy, therefore, first concentrates on analyzing the differential effects of epileptic factors on cognitive function. The impact of seizure activity, localization of epileptogenic foci, and antiepileptic treatment on cognitive functioning can be evaluated based upon the results of continuous assessment with a computerized neuropsychological test system. Second, learning disabilities may be evaluated on observations made during classroom performance. Three issues seem to predominate in learning studies among disabled children with epilepsy: test-retest variability, deterioration, and the supposed specificity of the learning disabilities.

Summary Purpose: Our aim was to develop a screening test to predict Dravet syndrome before the first birthday based on the clinical characteristics of infants and the SCN1A mutation analysis. Methods: Ninety-six patients who experienced febrile seizures before the age of one were enrolled. The patients were divided into two groups—the Dravet syndrome group (n = 46) and the non-Dravet syndrome group (n = 50). We compared the clinical characteristics before one year of age of the two groups. We analyzed all coding exons of the SCN1A gene by the direct sequencing method. Scores from 0 to 3 were assigned to each risk factor based on the odds ratio and p-value. Results: An age of onset of febrile seizure ≤ 7 months, a total number of seizures ≥ 5, and prolonged seizures lasting more than 10 min. were regarded as significant risk factors for Dravet syndrome. Other factors highly predictive of this syndrome were hemiconvulsions, partial seizures, myoclonic seizures, and hot water–induced seizures. A total clinical score of six or above was the cutoff value indicating a high risk of Dravet syndrome. SCN1A missense and truncated mutations were detected significantly more often in the Dravet syndrome group than in the non-Dravet syndrome group. Discussion: This simple screening test was designed to be used by general pediatricians. It could help to predict Dravet syndrome before one year of age. If the sum of the clinical risk score is ≥ 6, then the performance of an SCN1A mutation analysis is recommended.

To clarify the differences between postictal mania (PIM) and postictal psychosis (PIP).Five patients with PIM were compared to 17 patients with PIP, with respect to clinical, epileptological, electrophysiological, and neuroimaging features. PIM was distinguished from PIP by the symptoms observed in the postictal period based on the ICD-10 criteria.Postictal manic episodes lasted for a longer period than postictal psychotic episodes. Patients with PIM had more recurrent postictal episodes than patients with PIP. The age at onset of epilepsy in patients with PIM was older than that in patients with PIP. PIM was associated with frontal lobe and temporal lobe epilepsies, whereas PIP was associated with temporal lobe epilepsy. The estimated epileptogenic zone was on the language dominant side in PIM, whereas there was no predominant hemispheric laterality in PIP. Electroencephalography (EEG) performed during the early period of postictal manic and psychotic episodes showed decreased frequency of interictal epileptiform discharges in both PIM and PIP. Single-photon emission computed tomography (SPECT) during postictal manic and psychotic episodes showed increased perfusion in the temporal and/or frontal lobes in both PIM and PIP. Three patients with PIM showed increased perfusion during postictal episodes on bilateral or the language nondominant side, which were contralateral to the estimated epileptogenic zone, whereas three patients with PIP showed increased perfusion on the areas, which were ipsilateral to the estimated epileptogenic zone.PIM has a distinct position among the mental disorders observed in the postictal period.

Summary: Purpose: To study the neuropsychological status of an epileptic patient presenting with epileptic activity triggered by eye closure in a 14-year follow-up period. Methods: The patient was studied at 12 and 26 years of age; during this period he underwent periodical clinical evaluations and EEG investigations; brain magnetic resonance imaging (MRI) was performed at 12 years of age. A neuropsychological assessment was carried out both at 12 years of age (T0) and at 26 years of age. At T0 and T1, neuropsychological tests (digits and words span, graphoestesia, reactions time to auditory stimuli, sentences repetition, words repetition, digital gnosis, backward counting [i.e.,100–0]) were performed during video-EEG monitoring either with eyes closed or with eyes open, to evaluate possible transitory effects related to ongoing epileptic activity. Moreover, at T0 the patient underwent Wechsler Intelligence Scale for Children-Revised, and at T1 to Wechsler Adult Intelligence Scale-Revised. Results: EEG recordings showed continuous epileptic activity triggered by eye closure, disappearing only with eyes opening, both at T0 and T1 (in this latter case, anteriorly predominant). The results of neuropsychological assessment during eyes closed as compared to performances with eyes open did not show significant differences, at T0 as well as at T1. Wechsler Intelligence scales showed a deterioration of performances at T1 with respect to T0; in addition, at T1, attention and short-term memory abnormalities, impairment in facial recognition and block design, and defective results in Continuous Performance Test and Wisconsin Card Sorting Test were observed. Conclusions: Lack of differences between the results of neuropsychological tests performed with eyes closed as compared to the eyes open condition suggests that in our patient epileptic activity did not cause transitory cognitive abnormalities. Deterioration of Wechsler Intelligence Scales in the follow-up period might be interpreted as the result of a disruption of cognitive processes possibly related to the persistence of a continuous epileptic activity during eye closure over the years. We speculate whether a dysfunction in posterior cortical areas involved in visual processing might be related to the impairment in face recognition and block design tests as well to eye closure sensitivity.

Summary: Purpose: Decline in verbal memory as a surgical complication remains an unresolved problem in mesial temporal lobe epilepsy. Some areas in the temporal lobe associated with the language function, often including the basal temporal language area, have been removed or transected by conventional surgical procedures. The authors defined the basal temporal language area and removed only the epileptogenic zone with a subtemporal approach. Methods: The basal temporal language area was evaluated by using long-term subdural electrodes in five patients with language-dominant–side mesial temporal lobe epilepsy. While preserving this area, the hippocampus and the parahippocampal gyrus were removed by using a combined subtemporal, transventricular, transchoroidal fissure approach. Verbal memory performance was assessed with the Wechsler Memory Scale–Revised (WMS-R) before and after the operation. Results: The basal temporal language area, defined as a part of the inferior temporal gyrus, the fusiform gyrus, and the parahippocampal gyrus, was spared by entering the temporal horn via collateral sulcus. Verbal memory was significantly improved by 3 months and 1 year after the operation. Conclusions: In language-dominant–side mesial temporal lobe epilepsy, preserving the basal temporal language area would have potential to improve verbal memory outcomes after removal of the epileptogenic zone.

Summary: Purpose: Status epilepticus (SE) appears to cause cognitive dysfunction as well as other serious neurologic sequelae. To confirm whether SE produces a subsequent intellectual decline, we evaluated intellectual function prospectively in adult epilepsy patients with and without SE. Methods: Of 1,685 patients with epilepsy who underwent comprehensive neuropsychological testing in two national hospitals in Japan, 15 patients experienced an episode of SE afterward and underwent the second neuropsychological examination after the SE episode. Forty clinically matched patients with epilepsy, but without an episode of SE since their initial neuropsychological examination, were also reevaluated. We compared IQs and subscores from the Wechsler Adult Intelligence Scale–Revised between the two groups by repeated measures analysis of variance. In the patients who experienced an SE episode, SE-related variables (i.e., age at the SE episode and type and duration of SE) and epilepsy-related variables such as epilepsy type, lateralization of EEG abnormalities, the presence of mesial temporal sclerosis, and previous history of SE, were evaluated in relation to intellectual outcome. Results: Patients with SE, in comparison to those without SE, failed to show any significant post-SE intellectual decline. Furthermore, neither the SE-related variables nor the clinical characteristics were correlated with intellectual outcome. Conclusions: Our findings suggest that SE does not lead to a significant intellectual decline in adult patients receiving treatment for epilepsy.

Summary: Purpose: This study examined affective disorders, anxiety disorders, and suicidality in children with epilepsy and their association with seizure-related, cognitive, linguistic, family history, social competence, and demographic variables. Methods: A structured psychiatric interview, mood self-report scales, as well as cognitive and language testing were administered to 100 children with complex partial seizures (CPSs), 71 children with childhood absence epilepsy (CAE), and 93 normal children, aged 5 to 16 years. Parents provided behavioral information on each child through a structured psychiatric interview and behavior checklist. Results: Significantly more patients had affective and anxiety disorder diagnoses (33%) as well as suicidal ideation (20%) than did the normal group, but none had made a suicide attempt. Anxiety disorder was the most frequent diagnosis among the patients with a diagnosis of affective or anxiety disorders, and combined affective/anxiety and disruptive disorder diagnoses, in those with suicidal ideation. Only 33% received some form of mental health service. Age, verbal IQ, school problems, and seizure type were related to the presence of a diagnosis of affective or anxiety disorder, and duration of illness, to suicidal ideation. Conclusions: These findings together with the high rate of unmet mental health underscore the importance of early detection and treatment of anxiety disorders and suicidal ideation children with CPSs and CAE. Ke yW ords: Depression—Anxiety—Suicide—Complex partial seizure disorder— Absence epilepsy—Child.

Wada memory asymmetries were examined in children from four comprehensive epilepsy surgery centers who subsequently underwent epilepsy surgery to determine whether Wada memory performance could predict degree of seizure relief in children.One hundred fifty-six children (between ages 5 and 16 years) with intractable epilepsy underwent Wada testing before resective epilepsy surgery (93 within the left hemisphere, and 63 within the right hemisphere). Memory stimuli were presented soon after intracarotid amobarbital injection, and recognition memory for the items was assessed after return to neurologic baseline. Eighty-eight children underwent unilateral temporal lobe resection, and 68 had extratemporal lobe resections. One hundred four (67%) children were seizure free (Engel class I), and 52 (33%) were not seizure free (Engel classes II-IV) at follow-up (mean follow-up interval, 2.3 years).Seizure-free children recalled 19.3% more Wada memory items after ipsilateral injection than did non-seizure-free children (p = 0.008). If analysis was restricted to youngsters with temporal lobectomies (TLs), seizure-free children recalled 27.7% more items after ipsilateral injection than did non-seizure-free TL children (p = 0.004). With regard to individual patient prediction, 75% of children who had memory score asymmetries consistent with the seizure focus were seizure free. In contrast, only 56% of children whose memory score asymmetries were inconsistent with the seizure focus were seizure free (p = 0.01).Results suggest that Wada memory performance asymmetries are related to the degree of seizure relief after epilepsy surgery in children and adolescents.

Summary: Purpose: We investigated the relationship between preoperative quantitative magnetic resonance imaging (MRI) T2 relaxometry and volumetry of the hippocampi and pre- and postoperative verbal memory in temporal lobectomy patients who had nonlesional temporal lobe epilepsy. Methods: Pre- and postoperative memory data based on the Logical Memory (LM) subtest of the Wechsler Memory Scale–Revised (WMS–R) and the 30-min delayed recall trial of the Rey Auditory Verbal Learning Test (AVLT) were obtained from 26 left and 15 right temporal lobectomy patients. Coronal MRI T2 maps were generated for these 41 temporal lobectomy patients as well as 61 control patients. Hippocampal T2 relaxation times and hippocampal volumes, converted to z scores using control group data, were correlated with neuropsychological performance in the patients. Results: In left temporal lobe–onset patients, high T2 in the left hippocampal body predicted higher LM performance after surgery. Asymmetrically high T2 in the left hippocampal body (i.e., the right-minus-left difference), compared with the right hippocampal body, also predicted higher LM performance after surgery. In right temporal lobe–onset patients, high T2 in the left hippocampal body predicted relatively lower AVLT performance after surgery. Multiple regression analysis in left temporal–onset patients revealed that high T2 in the left hippocampal body together with higher preoperative LM performance predict higher postoperative LM performance. Conclusions: Our findings suggest that elevated (i.e., abnormal) hippocampal T2 signal is associated with memory ability (or hippocampal functional capacity) independent of MRI-determined hippocampal atrophy. Therefore, our findings support the use of quantitative T2 relaxometry as an independent predictor of verbal memory outcome in both left and right TLE patients who are candidates for temporal lobectomy.

Summary: Purpose: The intracarotid amobarbital test (IAT) has been shown to predict verbal memory changes after anterior temporal lobectomy (ATL). Seeking to extend these findings, we examined two questions: (a) What is the relationship between material-specific aspects of IAT memory and material-specific memory changes after ATL? and (b) Which IAT memory score(s) optimally predict memory changes after surgery, the memory score after injection ipsilateral to the seizure focus, the memory score after injection contralateral to the seizure focus, or the IAT asymmetry score, comprising the ipsilateral minus contralateral injection scores? Methods: Seventy left hemisphere language-dominant patients undergoing ATL for treatment of medically refractory seizures were administered a verbal and visuospatial recognition memory test before surgery and 3 weeks after surgery. IAT memory recognition scores for words and designs were used to predict verbal and visuospatial memory changes after surgery. Results: After surgery, left ATL patients declined in verbal memory, whereas right ATL patients declined in visuospatial memory. IAT total recognition memory scores (collapsed across all types of materials) and IAT word memory scores were associated with postoperative verbal memory decline. This relationship was significant for the IAT ipsilateral injection memory scores and the IAT hemispheric asymmetry scores. IAT memory performances were not related to visuospatial memory changes. Conclusions: Results indicate IAT memory measures to be related to postoperative verbal, but not visuospatial, memory change. A specific relationship was found between postoperative verbal memory change and IAT verbal memory after injection ipsilateral to the seizure focus, when relying primarily on the contralateral hemisphere. This finding is consistent with the functional reserve model of memory change in ATL.

Summary: Purpose: To examine the lateralization utility of preoperative verbal retention in patients with and without bilateral hippocampal atrophy. Methods: The sample consisted of 74 patients with EEG-defined unilateral temporal lobe epilepsy (TLE) who had also undergone volumetric magnetic resonance imaging (MRI). Verbal retention was operationalized by the Logical Memory percentage retention subtest (LM%) of the Wechsler Memory Scale. Patients were divided into groups with (a) bilaterally normal hippocampal volumes, (b) unilateral atrophy, or (c) bilateral atrophy. Two different thresholds (empirically derived vs. normative) were used to lateralize on the basis of LM%. LM% lateralization was then examined by group using χ2, sensitivity, positive predictive values, and odds ratios. Analyses were also conducted separately in the subset of patients who were seizure free after surgery. Results: Mean LM% performance was significantly lower in patients with left versus right TLE in the subset with bilateral hippocampal atrophy (p = 0.018), but not in patients with a normal MRI (p = 0.918) or unilateral atrophy (p = 0.087). The odds of a correct lateralization by LM% increased from 1.67 in patients with normal MRI to 36.11 in patients with bilateral hippocampal atrophy. The power of a right and left lateralization prediction by LM% was 100% and 75%, respectively, in patients with bilateral hippocampal atrophy. Similar results were obtained when analysis was restricted to patients who were seizure free after surgery. Conclusions: Preoperative verbal retention as measured by LM% may provide meaningful lateralization information in patients who are difficult to lateralize via MRI.

Summary Purpose: To examine how cognitive, personality, and seizure outcome variables influence the subjective cognitive functioning of patients with refractory temporal lobe seizures after epilepsy surgery. Methods: Thirty-three consecutive patients with drug-resistant partial epilepsy who underwent surgical treatment at a tertiary referral university epilepsy center were tested before surgery and 1 year after surgery. Objective cognitive and subjective cognitive functioning tests were used, and personality was assessed. Seizure control was operationalized as a dichoto-mous variable. Results: A significant inverse relationship was found between neuroticism and subjective cognitive functioning. None of the other pre- and postoperative cognitive and surgery outcome variables were significant predictors of subjective cognitive functioning, even after controlling for the effect of neuroticism. Conclusions: Subjective and objective memory functioning are independent in patients with epilepsy after surgical treatment. Subjective memory functioning appears to be related not to seizure relief but to neuroticism. These data suggest that psychological factors such as personality traits predisposing to emotional distress should be taken into consideration in the clinical management and counseling of patients undergoing epilepsy surgery.

Summary: Purpose: To evaluate attentional difficulties in children with complex partial seizures, we reviewed the records of 12 children with complex partial seizures with attention deficient hyperactivity disorder (CPS/ADHD); 21 children with CPS without ADHD (CPS); 22 children with ADHD; and 15 control children. Methods: Each child completed a computerized performance test (CPT), which evaluated sustained attention, inhibition of response, response time, and consistency of response. The ADHD groups also completed the CPT after a dose of methylphenidate. Results: The results found poorest performance on the CPT by the CPS/ADHD group. Particular difficulty in attention was found for children with epilepsy regardless of the ADHD diagnosis. When methylphenidate was administered to the ADHD groups, both groups improved in performance on the CPT. Conclusions: Epilepsy may predispose children to attention problems that can significantly interfere with learning. Similar improvement for children with CPS/ADHD was found with methylphenidate compared with baseline as for children with ADHD but without CPS.

Summary: Purpose: Decreased memory function represents the area of greatest neuropsychological morbidity after anterior temporal lobectomy (ATL), particularly for left ATL candidates. We wished to identify easily derived demographic and neuropsychological predictors of risk of pre-to postoperative memory decline using only information available preoperatively. Methods: We assessed decline in memory as measured by the California Verbal Learning Test (CVLT) by deriving multiple regression equations using the following measures as independent variables: age at onset, chronological age at time of surgery, sex, Full Scale IQ (FSIQ), level of education, and preoperative memory scores. In all, 203 patients (93 males, 110 females), undergoing ATL (107 left, 96 right) with preoperative and 6-month postoperative testing, were examined. Results: The combination of age, FSIQ, sex, side of surgery and preoperative score was highly predictive (p-values

Summary: Purpose: To describe an 11-year-old girl with symptomatic localization-related epilepsy and normal intelligence who developed reversible mental deterioration and pseudoatrophic brain changes while receiving valproate (VPA). Methods: Assessment of mental function using Wechsler Intelligence Scale for Children-III (WISC) and Raven's Progressive Matrices (PM), EEG recordings while awake and asleep, and brain magnetic resonance imaging (MRI), were performed at the beginning of VPA therapy, after 2 years and 8 months of treatment and following VPA discontinuation. Results: After 2 years and 6 months on VPA (≤26 mg/kg/day) the girl insidiously developed mental deterioration (loss of 18 IQ points and drop in age-adjusted PM score from the 95th to the 50th percentile) associated with MRI-documented pseudoatrophy of the brain. Onset of severe cognitive impairment coincided with serum VPA concentrations near 100 μg/ml. There were no other manifestations of drug toxicity or hyperammonemia. Background EEG activity was normal. Reduction of VPA dosage and subsequent discontinuation 4 months later resulted in disappearance of clinical symptoms with a 20-point improvement at IQ testing and recovery of previous PM score. Repeat MRI showed disappearance of pseudoatrophic changes. Conclusions: The striking cognitive improvement and reversal of pseudoatrophic brain changes following VPA discontinuation strongly suggest a drug-induced condition. Based on this and previous reports, the syndrome of VPA-associated mental deterioration and pseudoatrophy of the brain appears to encompass different but possibly related clinical entities, which include parkinsonism with cognitive deterioration, mental deterioration with signs of VPA-toxicity, and isolated mental deterioration, as seen in our patient. A drug-induced effect should be considered whenever cognitive deterioration and imaging findings of brain atrophy occur in VPA-treated patients.

Neuropsychology has played a prominent role throughout the modern era of epilepsy surgery. Neuropsychology, including the Wada test, has been of benefit in documenting dysfunction associated with a lateralized temporal lobe seizure onset. In addition, neuropsychological results have some predicative power regarding seizure outcome following anterior temporal lobectomy. The current status of neuropsychology in patient evaluation and outcome prediction will be presented. Differences between the Wada test, an inactivation procedure, and functional magnetic resonance imaging, which is an activation procedure, will be discussed. This paper will also present preliminary information about the Wechsler Adult Intelligence Scale-III, the recent revision of the most commonly used test of intellectual function, and its effects on neuropsychological performance results.

Summary: Purpose: We assessed test-retest neuropsychological performance in patients with complex partial seizures to derive reliable change indices (RCIs) and regression-based norms for change, indices that may be helpful in assessing cognitive outcome after anterior temporal lobectomy. Methods: Forty patients with complex partial seizures (CPS) who did not undergo epilepsy surgery were administered a comprehensive neuropsychological battery on two. occasions. Their test-retest data were used to compute both RCIs and regression-based norms for change for each neuropsychological index. RCIs corrected for practice effects provide a confidence interval (CI) indicating the degree of performance change required to exceed the variability attributable to sources of error (e.g., practice, test-retest reliability). Regression-based norms for change also correct for several sources of measurement measurement error and examine observed versus expected test-retest changes on a common metric, thereby facilitating determination of the degree and relative magnitude of change across cognitive domains. Results: Mean changes in test-retest performance were generally modest, but were evident across several test measures. Our data indicate a considerable degree of individual variability in test-retest Performance. Conclusions: RCIs and regression-based norms are complementary indexes and can be particularly useful in examining the test-retest performance of individual patients who undergo epilepsy surgery as well as in the more general investigation of cognitive outcome after epilepsy surgery.

Summary: We investigated pre- and postoperative verbal memory in temporal lobectomy patients who had volumetrically symmetric hippocampi. Pre- and postoperative verbal memory data based on the Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R) were obtained from 15 left and 18 right temporal lobectomy patients. The difference between hippocampal volumes (R/L) was between -0.1 and 0.3 cm3, which is indeterminate for lateralizing hippocampal atrophy. Patients were divided into four groups based on side of operation and combined hippocampal volume expressed as a function of total intracranial volume (R + L volume/total intracranial volume). Patients with a combined hippocampal volume that was smaller than any combined hippocampal value of a normal control group were defined as bilaterally atrophic. Left temporal lobectomy patients demonstrated the expected decrease in verbal memory postoperatively regardless of whether the volumetrically symmetric hippocampi were nonatrophic or atrophic. Left temporal lobectomy patients with bilaterally atrophic hippocampi, however, had the poorest verbal memory before and after operation. Right temporal lobectomy patients tended to have improved verbal memory after operation whether or not the volumetrically symmetric hippocampi were atrophic. We conclude that side of operation is a more potent predictor of verbal memory outcome than is hippocampal atrophy when hippocampi are bilaterally symmetric and that left temporal lobectomy patients with bilateral atrophy may be at risk for greater functional deficits after operation.

Summary: We examined the ability of preoperative memory performance to distinguish between patients who had been diagnosed as having left (LTLE, n = 31), right (RTLE, n = 37), and extra-(ETLE, n = 17) temporal lobe focal epilepsy. All patients eventually underwent surgical resections. Analyses indicated that the ETLE group performed better than the RTLE group on nonverbal memory measures and better than the LTLE group on verbal memory measures. Discriminant function analyses indicated that use of a combination of measures that assess different aspects of memory were of significant value in distinguishing between patients with focal TLE and ETLE. This approach, as compared the use of single measures, improved classification rates of all three groups. The best single predictor of group membership, an index of verbal learning, yielded a 47% overall correct classification rate, with sensitivities ranging from 25 to 59%, and performed at worse than chance levels in classifying RTLE patients. A multivariate approach, which included an index of verbal and nonverbal learning, incidental nonverbal memory, and consolidation of organized and rote verbal material, yielded a 65% correct classification rate, with sensitivities ranging from 57 to 75%. This compares favorably with other noninvasive techniques for lateralizing epileptogenic lesions.

Using a randomized parallel group study design, we compared the cognit ive effects of carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) in children with epilepsy. Seventy-three children with newly diagnosed epilepsy were tested with the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt test, and auditory event-related potentials (P 300) before and 6 and 12 months after antiepileptic drug (AED) treatment. There were no significant differences in WISC-R IQs and Bender-Gestalt scores for children in any group at any of the three sessions. P 300 latencies were increased in the children receiving PB but not in children receiving CBZ and VPA. P 300 amplitudes were significantly reduced in treated children in all three groups, but amplitudes were not significantly different among the three groups. These findings suggest that PB may affect cognitive function of epileptic children and that the P 300 may be a sensitive additional procedure that can be used to assess the cognitive effect of AEDs.

We wished to (a) determine the ability of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to discriminate between patients with epilepsy of left or right temporal lobe (LTLE, RTLE) origin and (b) examine the ability of Kaufman's (1990) WAIS-R short forms to estimate actual Full-Scale IQ (FSIQ). We administered the WAIS-R to 215 nonretarded, left hemisphere dominant patients with invasively verified epilepsy of unilateral TL origin without lesions demonstrated by magnetic resonance imaging (MRI) (excluding mesial temporal sclerosis, MTS). LTLE (n = 106) and RTLE (n = 109) groups were compared on the WAIS-R subtests and summary IQ scores. Verbal-Performance IQ (VIQ-PIQ) discrepancies of various magnitudes, and Verbal Comprehension (VC) and Perceptual Organization (PO) scores derived by factor analysis. The LTLE group scored significantly lower on the Vocabulary subtest, and none of the other indexes reliably distinguished LTLE from RTLE patients. The Kaufman 2, 3, and 4 subtest short forms were significant predictors of FSIQ, with the 4 subtest short form having the highest correlation and lowest error of estimate.

To determine the IQ profile of children with epilepsy and the influence of various epilepsy-related variables on IQ scores, we studied 50 children with idiopathic generalized epilepsy of1-year duration, 25 of their siblings, and 30 healthy controls. IQ assessments were made with Malin's Indian modification of the Wechsler Intelligence Scale for Children. The mean +/- SD IQ scores of children with epilepsy (85.6 +/- 12) and their siblings (93.2 +/- 11) were significantly lower than those of the controls (101.6 +/- 9). The IQ scores of the children with epilepsy were also significantly lower than those of their siblings (p0.05). The IQ scores showed a significant correlation with socioeconomic status (SES) score (r = 0.33), a history of status epilepticus (r = -0.38), duration of seizure disorder (r = -0.31), and total number of seizures (r = -0.31). On multiple regression analysis, status epilepticus emerged as the most significant variable, accounting for 14% variance, followed by SES score (9% variance), duration of seizure disorder (6% variance), and sex of the child (5% variance). Genetic or environmental factors that probably lead to cognitive deficit in children with epilepsy and their siblings require further study.

The major problems in the study of the cognitive effects of antiepileptic drugs (AEDs) are explored. These problems include subject selection factors, statistical difficulties, matters pertaining to choice of cognitive tests, and the impacts of seizures on performance. A tendency is noted for these contaminating factors to result in attributing to AEDs adverse changes that might more accurately be related to other causes. Although all of these active central nervous system medications likely have some adverse cognitive effects, at least at high levels, the magnitude of these effects may have been exaggerated in the past. This is confirmed by more recent and better-controlled investigations.

Common methodological problems in the assessment of interictal cognitive deficits in epilepsy include limitations in neuropsychological tests selected and subject sampling problems. Neuropsychological functioning is related to a series of seizure history variables with an emphasis on those seizure factors showing the closest relationships. However, even these relationships are limited in scope, and it has been noted that no study has used multivariate procedures to demonstrate maximal relationships with measures of mental abilities. This technique was applied to data on 487 cases, and slightly stronger relationships were produced. However, this still did not account for the vast majority of the variance in cognitive tests. Conclusions concerning neuropsychological functioning in epilepsy require careful attention to sampling problems and other factors, and seizure history variables have only limited relationships with cognitive functioning, even when they are combined in an optimal fashion.