Does Early Recognition of Treatment Failure and Changing Anti-Epilepsy Medication Regimen Improve Short-Term Seizure Remission Rates In Childhood Absence Epilepsy?

PURPOSE: To study the role of early serial EEGs in improving seizure freedom rates after initiation of ethosuximide or valproic acid for childhood absence epilepsy. METHODS: Retrospective data analysis study of AED naive patients with childhood absence epilepsy undergoing treatment at the community-based epilepsy clinic. Due to small sample size Fisher's exact test was used to determine two-tailed p value at less than 0.05 statistical significance.. RESULTS: At 2-month study period 71.4% patients in the ethosuximide and 87.5% in the valproic acid group achieved seizure freedom, with EEG normalization in 21.4% and 50% respectively. At 6-month study period, in patients continuing ethosuximide, seizure freedom and EEG normalization rates were 89.5% and 52.6% respectively; while in patients continuing valproic acid, results were 100% and 78.6% respectively. Both at 2-month and 6-month study periods, a trend towards higher seizure freedom was noted in patients with typical versus non-typical epileptiform discharges at baseline with the valproic acid group showing a superior response. CONCLUSION: Although no statistically significant difference in response rates was noted, 1) a shift towards higher seizure freedom with valproic acid; 2) improved response after switching to valproic acid at 2 months, if warranted; and 3) superior response rate in patients with typical EEG epileptiform discharges at baseline were observed. A larger study is needed to define the role of early serial EEGs to delineate higher drug failure probability; and to determine the importance of non-typical EEG characteristics at baseline in relation to the choice of AED and long-term outcome Keywords: childhood absence epilepsy, ethosuximide, valproic acid, non-typical epileptiform discharges.

Effectiveness at 24 Months of Single-Source Generic Carbamazepine, Lamotrigine, or Levetiracetam in Newly Diagnosed Focal Epilepsy.

BACKGROUND: Kaiser Permanente advocates using single-source generics for brand-name drugs. We compared the effectiveness of 3 different-generation generic antiepileptic drugs (AEDs) in patients with focal epilepsies. OBJECTIVE: To compare the effectiveness of the 3 most commonly used AEDs (carbamazepine [CBZ], lamotrigine [LTG], and levetiracetam [LEV]) after 24-month monotherapy. METHODS: This is a retrospective data analysis of 646 consecutive AED-naive patients aged 1-88 years treated with CBZ, LTG, or LEV between 2006 and 2012 with dosing adjustments permitted during the first 6 months. Chi-squared test with p < 0.05 was used to calculate seizure-freedom and tolerability rates. RESULTS: At the end of the 24-month study period, 65.69% patients in the CBZ group continued to remain seizure free, 25.98% were drug failures, and 8.33% dropped out due to adverse events, with the corresponding numbers being 66.49%, 23.94%, and 9.57% in the LTG group and 72.44%, 12.99%, and 14.57% in the LEV group. Rash was the most common adverse event for CBZ (3.43%) and LTG (6.38%), and mood changes were the most commen adverse event for LEV (7.87%). Among the 3 groups (n = 646), AED tolerance rates and AED retention rates showed no significant difference (p = 0.08 and p = 0.23, respectively). Seizure-freedom rate difference among the 3 groups (n = 574) was significant (p = 0.003), and seizure-freedom rate for LEV was superior to CBZ (p = 0.001) and to LTG (p = 0.006). CONCLUSION: At the end of the 24-month study period, in a head-to-head comparison of single-source bioequivalent generic formulations, superior seizure-freedom rate and comparable tolerability and retention rates for LEV were observed when compared with CBZ and LTG.

Identification of risk for severe psychiatric comorbidity in pediatric epilepsy.

OBJECTIVE: This study identified items on the Child Behavior Checklist (CBCL) that predict those children and adolescents with epilepsy at highest risk for multiple psychiatric diagnoses. METHODS: Three hundred twenty-eight children, ages 5-18 years, and their parents participated in separate structured psychiatric interviews about the children, which yielded Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) diagnoses. Parents completed the CBCL. The sample was divided into a younger (≤12 years, n = 214) group and an older (>12-18 years, n = 114) group. This study identified a reduced set of parent-reported CBCL items associated with Multiple Diagnoses versus Single Diagnosis versus No Diagnosis using chi-square tests and stepwise logistic regression. We then performed a generalized logistic regression with Multiple Diagnoses versus Single Diagnosis versus No Diagnosis as the dependent variable and the reduced CBCL set of items as predictors. We calculated the area under the ROC (receiver operating characteristic) curve (AUC) as a measure of diagnostic accuracy for pairwise comparisons. RESULTS: For the younger group, seven items (clingy, cruelty/bullying, perfectionist, nervous, poor school work, inattentive, and sulks) had high diagnostic accuracy (AUC = 0.88), and for the older group, three items (disobedient at school, loner, and lies/cheats) had high accuracy (AUC = 0.91) when comparing children with multiple psychiatric diagnoses to children with no diagnosis. For both age groups, there was less diagnostic accuracy in identifying children with a single versus no diagnosis (AUC = 0.75 [young]; 0.70 [older]). SIGNIFICANCE: These findings suggest that responses to these two subsets of parent-reported CBCL items should alert clinicians to children and adolescents with epilepsy at risk for multiple psychiatric diagnoses and in need of a psychiatric referral.

Neuromodulation Therapy with Vagus Nerve Stimulation for Intractable Epilepsy: A 2-Year Efficacy Analysis Study in Patients under 12 Years of Age.

To study the efficacy of vagus nerve stimulation (VNS) therapy as an adjunctive treatment for intractable epilepsy in patients under 12 years of age, we analyzed 2-year postimplant data of 35 consecutive patients. Of the 35 patients, 18 (51.4%) at 6 months, 18 (51.4%) at 12 months, and 21 (60.1%) at 24 months showed ≥50% reduction in seizure frequency (responders). Although incremental seizure freedom was noted, no patient remained seizure-free throughout the 3 study periods. Partial response (≥50% seizure reduction in 2 or less study periods) was seen in 8 (22.9%) patients. Twelve patients (34.3%) were nonresponders. Out of 29 patients with primary generalized epilepsy, 20 (68.9%) and, out of 6 patients with focal epilepsy, 3 (50%) had ≥50% seizure control in at least one study period. No major complications or side effects requiring discontinuation of VNS therapy were encountered. We conclude that (1) patients with intractable primary generalized epilepsy respond better to VNS therapy, (2) cumulative effect of neuromodulation with improving responder rate to seizure freedom with continuation of VNS therapy is noted, and (3) VNS therapy is safe and is well tolerated in children receiving implant under 12 years of age.

Neurobehavioral comorbidities of pediatric epilepsies are linked to thalamic structural abnormalities.

PURPOSE: Neurobehavioral comorbidities are common in pediatric epilepsy with enduring adverse effects on functioning, but their neuroanatomic underpinning is unclear. Striatal and thalamic abnormalities have been associated with childhood-onset epilepsies, suggesting that epilepsy-related changes in the subcortical circuit might be associated with the comorbidities of children with epilepsy. We aimed to compare subcortical volumes and their relationship with age in children with complex partial seizures (CPS), childhood absence epilepsy (CAE), and healthy controls (HC). We examined the shared versus unique structural-functional relationships of these volumes with behavior problems, intelligence, language, peer interaction, and epilepsy variables in these two epilepsy syndromes. METHODS: We investigated volumetric differences of caudate, putamen, pallidum, and thalamus in children with CPS (N = 21), CAE (N = 20), and HC (N = 27). Study subjects underwent structural magnetic resonance imaging (MRI), intelligence, and language testing. Parent-completed Child Behavior Checklists provided behavior problem and peer interaction scores. We examined the association of age, intelligence quotient (IQ), language, behavioral problems, and epilepsy variables with subcortical volumes that were significantly different between the children with epilepsy and HC. KEY FINDINGS: Both children with CPS and CAE exhibited significantly smaller left thalamic volume compared to HC. In terms of developmental trajectory, greater thalamic volume was significantly correlated with increasing age in children with CPS and CAE but not in HC. With regard to the comorbidities, reduced left thalamic volumes were related to more social problems in children with CPS and CAE. Smaller left thalamic volumes in children with CPS were also associated with poor attention, lower IQ and language scores, and impaired peer interaction. SIGNIFICANCE: Our study is the first to directly compare and detect shared thalamic structural abnormalities in children with CPS and CAE. These findings highlight the vulnerability of the thalamus and provide important new insights on its possible role in the neurobehavioral comorbidities of childhood-onset epilepsy.

Screening for suicidal ideation in children with epilepsy.

Given the FDA's warning regarding the potential connection between suicidal behavior and antiepileptic drugs, this study examined methods by which to detect suicidal ideation in children with epilepsy. It compared the sensitivity, specificity, and area under the curve for identifying children with suicidal behavior using the Child Behavior Checklist (CBCL) and a structured psychiatric interview. Parent-completed CBCLs provided behavioral problem scores on 177 children with epilepsy, aged 5-16years. Psychiatric diagnoses were made based on separate child and parent structured psychiatric interviews about the child. The children answered questions on suicidal behaviors during the interview. A clinically elevated score in the CBCL Total Problems scale and having more than one psychiatric diagnosis, irrespective of the type of diagnosis, were significant predictors and correctly classified children with suicidal ideation in 79% of the cases based on the CBCL and 80% of the cases with more than one psychiatric diagnosis. These findings indicate that elevated CBCL Total Problems scores, a commonly used instrument, can screen and identify risk for suicidal behavior in children with epilepsy. Additionally, irrespective of diagnosis, if a child with epilepsy has more than one psychiatric diagnosis, further assessment of suicidal behavior is warranted. Importantly, the results underscore the utility of having parents complete a questionnaire in the waiting room in order to identify children with epilepsy at risk for suicidal behavior.

Neurocognitive profiles in children with epilepsy.

PURPOSE: The presence of specific neurocognitive deficits may help explain why school achievement and psychosocial functioning are often worse in children with epilepsy than would be predicted by their global intellectual functioning. This study compared children with two forms of epilepsy: localization-related epilepsy with complex partial seizures (CPS) and childhood absence epilepsy (CAE), to determine whether they display distinct neurocognitive profiles. METHODS: Fifty-one children with CPS, 31 children with CAE, and 51 controls underwent neuropsychological testing assessing verbal memory, visual memory, and executive functioning. Groups were compared in these cognitive domains. Within-group analyses were also conducted to examine seizure-related factors that may be related to neuropsychological test performance. KEY FINDINGS: When compared to controls, children with CPS showed a mild generalized cognitive deficit, whereas children with CAE did not. When we controlled for intelligent quotient (IQ), both epilepsy groups showed poorer performance relative to controls in the domain of verbal memory. When the epilepsy groups were compared to one another, the CPS group performed significantly poorer than the CAE group on a test of generalized cognitive functioning. However, in the specific domains of executive functioning, verbal memory, and visual memory the epilepsy groups did not differ when compared to one another. SIGNIFICANCE: Neurocognitive deficits present in the context of grossly intact global intellectual functioning highlight the importance of neuropsychological screening in both children with CPS and children with CAE.

Evaluation of maturation and function of visual pathways in neonates: role of flash visual-evoked potentials revisited.

The purpose of our study was to establish the guidelines for interpreting neonatal flash visual-evoked potentials (FVEPs) by examining the correlation between maturation of the waveforms and conceptual age (CA). We retrospectively analyzed 220 consecutive neonatal FVEPs performed on premature and full-term infants. The CA of the participants ranged from 28 to 52 weeks. The FVEPs were categorized into 6 groups according to CA: 28 to 31+ weeks, 32 to 35+ weeks, 36 to 39+ weeks, 40 to 43+ weeks, 44 to 47+ weeks, and 48 to 52 weeks. The data were analyzed in each group and compared among these 6 groups. The waveforms changed from 28 weeks to 52 weeks of CA. In the CA age range 28 to 31+ weeks N3 was well visualized, followed by P3. The morphology of P2 including both latency and amplitude became prominent starting from CA age range 32 to 35+ weeks. The triphasic waveform with clear negative-positive-negative components (N2-P2-N3) presented after 32 weeks. Mean P2 latencies decreased steadily with increasing age. Mean amplitudes of all waveforms (P2-N3 and N3-P3) varied except that of N2-P2 which increased steadily with CA. We conclude that FVEPs can be useful in the evaluation of maturation and function of the visual pathway in neonates. The FVEP is abnormal when the waveforms N3 and P3 are nondetectable in neonates at 28 weeks of CA or older; and when the waveform P2 is non-detectable, or has low amplitude or prolonged latency, in neonates at 36 weeks of CA or older.

1H MRSI and social communication deficits in pediatric complex partial seizures.

PURPOSE: To investigate relationships between regional brain metabolites, social communication deficits, and seizure frequency in children and adolescents with cryptogenic epilepsy with complex partial seizures (CPS). METHODS: In 12 children and adolescents with CPS and 23 age- and gender-matched healthy controls, we acquired proton magnetic resonance spectroscopic imaging (MRSI) at 1.5 T and 30 ms echo-time from bilateral inferior frontal and superior temporal gyri, regions associated with social communication deficits. Videotaped speech samples of all the subjects were coded for social communication deficits and parents provided information on seizure frequency. KEY FINDINGS: Four MRSI findings emerged in right inferior frontal gyrus. N-acetyl-aspartate (NAA) plus N-acetyl-aspartyl-glutamate (NAAG)--together called "tNAA"--was 11.4% lower in patients with CPS than in controls. Choline-compounds (Cho) were 15.4% lower in CPS than in controls. Within CPS, higher tNAA was associated with more frequent seizures and abnormal social communication. SIGNIFICANCE: Localization of findings to right inferior frontal cortex supports the involvement of this area in social communication deficits and may be related to atypical lateralization of expressive language in pediatric epilepsy. Lower levels of tNAA and Cho may indicate local neuronal or glial damage or underpopulation due to excitotoxicity or other causes. The sensitivity of tNAA to seizure frequency suggests effects of ongoing CPS on neuronal and glial function in this brain region.

Intelligence and cortical thickness in children with complex partial seizures.

Prior studies on healthy children have demonstrated regional variations and a complex and dynamic relationship between intelligence and cerebral tissue. Yet, there is little information regarding the neuroanatomical correlates of general intelligence in children with epilepsy compared to healthy controls. In vivo imaging techniques, combined with methods for advanced image processing and analysis, offer the potential to examine quantitative mapping of brain development and its abnormalities in childhood epilepsy. A surface-based, computational high resolution 3-D magnetic resonance image analytic technique was used to compare the relationship of cortical thickness with age and intelligence quotient (IQ) in 65 children and adolescents with complex partial seizures (CPS) and 58 healthy controls, aged 6-18 years. Children were grouped according to health status (epilepsy; controls) and IQ level (average and above; below average) and compared on age-related patterns of cortical thickness. Our cross-sectional findings suggest that disruption in normal age-related cortical thickness expression is associated with intelligence in pediatric CPS patients both with average and below average IQ scores.

Cognition, academic achievement, language, and psychopathology in pediatric chronic epilepsy: Short-term outcomes.

Children with epilepsy and control children were followed over a 2-year interval. Comorbidities of epilepsy, often defined as problems related to IQ, academic achievement, language, and psychopathology, were evaluated prospectively. It was hypothesized that over time (1) the presence of comorbidities would predict worse outcomes, and (2) epilepsy variables would negatively impact comorbidities. The study included 39 children with complex partial seizures (CPS), 25 children with childhood absence epilepsy (CAE), and 27 healthy children, aged 7.6-16.1years. The findings were notable for stability over the interval in all three groups. Additionally, baseline seizure variables and change over the interval appear to play a role in IQ and math achievement scores of children with epilepsy with average IQ and in the reading achievement scores of those with below-average IQ. However, seizure variables at baseline and follow-up were not predictors of DSM-IV diagnoses, depression, anxiety, or behavioral problems.

Suicidality and brain volumes in pediatric epilepsy.

This study examined the relationship between suicidal ideation and frontotemporal volumes, particularly orbital frontal gyrus volume, in 51 subjects with epilepsy with a mean age of 9.8 (2.1) years. Structured psychiatric interviews of the children and parents provided information on suicidal behavior and DSM-IV diagnoses. Tissue of 1.5-T MRI scans was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. The 11 subjects with epilepsy with suicidal ideation had significantly smaller right orbital frontal gyrus white matter volumes and larger left temporal lobe gray matter volumes than the 40 children without suicidal thoughts. Given the role of the orbital frontal gyrus in both emotional regulation and epilepsy, these findings highlight the biological underpinnings of suicidal ideation in pediatric epilepsy.

Language and brain volumes in children with epilepsy.

In this study the relationship between language skill and frontotemporal volumes was compared in 69 medically treated subjects with epilepsy and 34 healthy children, aged 6.1-16.6 years. Also, whether patients with linguistic deficits had abnormal volumes and atypical associations between volumes and language skills in these brain regions was determined. The children underwent language testing and MRI scans at 1.5 T. Brain tissue was segmented and frontotemporal volumes were computed. Higher mean language scores were significantly associated with larger inferior frontal gyrus, temporal lobe, and posterior superior temporal gyrus gray matter volumes in the epilepsy group and in the children with epilepsy with average language scores. Increased total brain and dorsolateral prefrontal gray and white matter volumes, however, were associated with higher language scores in the healthy controls. Within the epilepsy group, linguistic deficits were related to smaller anterior superior temporal gyrus gray matter volumes and there was a negative association between language scores and dorsolateral prefrontal gray matter volumes. These findings demonstrate abnormal development of language-related brain regions, and imply differential reorganization of brain regions subserving language in children with epilepsy with normal linguistic skills and in those with impaired language.

Amygdala volumes in childhood absence epilepsy.

Abnormal amygdala volumes in pediatric mood-anxiety disorders and attention deficit hyperactivity disorder (ADHD), as well as high rates of these diagnoses in childhood absence epilepsy (CAE), prompted this study of amygdala volume in CAE. Twenty-six children with CAE and 23 normal children, aged 6.6-15.8 years, underwent MRI at 1.5 T. The tissue imaged with MRI was segmented, and amygdala volumes were obtained by manual tracings. There were no significant amygdala volume differences between the CAE and normal groups. Within the CAE group, however, the children with ADHD had significantly smaller amygdala volumes than the subjects with CAE with no psychopathology and those with mood/anxiety diagnoses. There was also a significant relationship between higher seizure frequency and greater amygdala asymmetry in the epilepsy group. Given ongoing development of the amygdala during late childhood and adolescence, despite the lack of significant group differences in amygdala volumes, the association of amygdala volume abnormalities with ADHD and seizure frequency implies a possible impact of the disorder on amygdala development and CAE-associated comorbidities, such as ADHD.

Language in pediatric epilepsy.

PURPOSE: This study examined the severity and range of linguistic impairments in young, intermediate, and adolescent youth with epilepsy and how these deficits were associated with illness effects, nonverbal intelligence, psychopathology, and reading. METHODS: Tests of language, intelligence, achievement, and structured psychiatric interviews were administered to 182 epilepsy youth, aged 6.3-8.1, 9.1-11.7, and 13.0-15.2 years, as well as to 102 age- and gender-matched normal children. Parents provided demographic, seizure-related, and behavioral information on their children. RESULTS: Significantly more epilepsy subjects had language scores 1 standard deviation (SD) below average than the age-matched control groups did. The intermediate and adolescent epilepsy groups also had significantly lower mean language scores compared to their matched controls. The older compared to the younger epilepsy groups had more language impairment and a wider range of linguistic deficits. Longer duration of illness, childhood absence epilepsy, psychiatric diagnosis, and socioeconomic status were associated with linguistic deficits in the young group. Prolonged seizures, lower Performance IQ, and minority status predicted low language scores in the intermediate epilepsy group. In the adolescent group, language impairment was associated with poor seizure control, decreased Performance IQ, and lower socioeconomic status. Linguistic and reading deficits were significantly related in each epilepsy group. CONCLUSIONS: The age-related increase in linguistic impairment, different profiles of predictors in each age group, and the relationship of linguistic deficits with poor reading skills have important clinical, developmental, theoretical, and academic implications.

Frontal and temporal volumes in Childhood Absence Epilepsy.

PURPOSE: This study compared frontotemporal brain volumes in children with childhood absence epilepsy (CAE) to age- and gender-matched children without epilepsy. It also examined the association of these volumes with seizure, demographic, perinatal, intelligence quotient (IQ), and psychopathology variables. METHODS: Twenty-six children with CAE, aged 7.5-11.8 years, and 37 children without epilepsy underwent brain magnetic resonance imaging (MRI) scans at 1.5 Tesla. Tissue was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. All children had IQ testing and structured psychiatric interviews. Parents provided seizure, perinatal, and behavioral information on each child. RESULTS: The CAE group had significantly smaller gray matter volumes of the left orbital frontal gyrus as well as both left and right temporal lobes compared to the age- and gender-matched children without epilepsy. In the CAE group these volumes were related to age, gender, ethnicity, and pregnancy complications but not to seizure, IQ, and psychopathology variables. In the group of children without epilepsy, however, the volumes were related to IQ. CONCLUSION: These findings suggest that CAE impacts brain development in regions implicated in behavior, cognition, and language. In addition to supporting the cortical focus theory of CAE, these findings also imply that CAE is not a benign disorder.

Thought disorder and frontotemporal volumes in pediatric epilepsy.

The aim of this study was to determine if volumes of frontotemporal regions associated with language were related to thought disorder in 42 children, aged 5-16 years, with cryptogenic epilepsy, all of whom had complex partial seizures (CPS). The children with CPS and 41 age- and gender-matched healthy children underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, and temporal lobe volumes were computed. Thought disorder measures, IQ, and seizure information were collected for each patient. The subjects with CPS had more thought disorder, smaller total gray matter and orbital frontal gray matter volumes, as well as larger temporal lobe white matter volumes than the control group. In the CPS group, thought disorder was significantly related to smaller orbital frontal and inferior frontal gray matter volumes, increased Heschl's gyrus gray matter volumes, and smaller superior temporal gyrus white matter volumes. However, significantly larger orbital frontal gyrus, superior temporal gyrus, and temporal lobe gray matter volumes and decreased Heschl's gyrus white matter volumes were associated with thought disorder in the control group. These findings suggest that thought disorder might represent a developmental disability involving frontotemporal regions associated with language in pediatric CPS.

Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities.

PURPOSE: Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absence epilepsy (CAE) suggests long-term unmet mental health, social, and vocational needs. This cross-sectional study examined behavioral/emotional, cognitive, and linguistic comorbidities as well as their correlates in children with CAE. METHODS: Sixty-nine CAE children aged 9.6 (SD = 2.49) years and 103 age- and gender-matched normal children had semistructured psychiatric interviews, as well as cognitive and linguistic testing. Parents provided demographic, seizure-related, and behavioral information on their children through a semi-structured psychiatric interview and the child behavior checklist (CBCL). RESULTS: Compared to the normal group, 25% of the CAE children had subtle cognitive deficits, 43% linguistic difficulties, 61% a psychiatric diagnosis, particularly attention deficit hyperactivity disorder (ADHD) and anxiety disorders, and 30% clinically relevant CBCL broad band scores. The most frequent CBCL narrow band factor scores in the clinical/borderline range were attention and somatic complaints, followed by social and thought problems. Duration of illness, seizure frequency, and antiepileptic drug (AED) treatment were related to the severity of the cognitive, linguistic, and psychiatric comorbidities. Only 23% of the CAE subjects had intervention for these problems. CONCLUSIONS: The high rate of impaired behavior, emotions, cognition, and language and low intervention rate should alert clinicians to the need for early identification and treatment of children with CAE, particularly those with longer duration of illness, uncontrolled seizures, and AED treatment.

Amygdala volume and psychopathology in childhood complex partial seizures.

OBJECTIVE: The purpose of this study was to compare amygdala volume in children with cryptogenic epilepsy who have complex partial seizures (CPS) with that of age- and gender-matched normal children. The relationship of amygdala volume to seizure variables and presence of psychopathology was also examined in these patients. METHODS: Twenty-eight children with cryptogenic epilepsy, all of whom had CPS, and gender-matched normal children, all aged 6-16 years, underwent magnetic resonance imaging (MRI) at 1.5T. Tissue was segmented, and total brain volume and amygdala volumes obtained from manual tracings were computed. RESULTS: There were no significant differences in amygdala volume between the CPS and normal groups. Within the CPS group, the children with an affective/anxiety disorder had significantly larger left amygdala volumes, as well as greater amygdala asymmetry, compared with those with no psychopathology. Exploring the association between seizure variables and amygdala volume yielded no significant predictors. CONCLUSIONS: In pediatric CPS, left amygdala involvement may reflect effects of the neuropathology underlying comorbid affective or anxiety disorders on amygdala development rather than effects of ongoing seizures.

Frontal and temporal volumes in children with epilepsy.

This study examined if children with cryptogenic epilepsy and complex partial seizures (CPS) have smaller total brain, frontal, and temporal lobe volumes than normal children and how this is related to seizure, cognitive, psychiatric, and demographic variables. Forty-four children with CPS and 38 normal children, aged 5-16 years, underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, frontal parcellation, and temporal lobe volumes were computed. Other than significantly larger temporal lobe white matter volumes in the CPS group, there were no significant differences in brain volumes between the CPS and normal groups. Earlier onset, longer duration of illness, younger chronological age, and presence of a psychiatric diagnosis were significantly related to smaller frontotemporal volumes in subjects with CPS. Although these findings suggest that CPS might affect development of the temporal and frontal regions, we are unable to rule out the possibility that smaller frontotemporal volumes might predispose children to CPS. These findings highlight the need to control for seizure, cognitive, psychiatric, and demographic variables in studies of frontotemporal volumes in pediatric CPS.