Quantitative MRI in Outpatient Childhood Epilepsy

Summary: Purpose: In adult studies, MRI volumetrics is a proven technique in presurgical assessment of epilepsy. Hippocampal volume loss is maximal in the syndrome of mesial temporal lobe epilepsy. We aimed (a) to validate this methodology in a pediatric outpatient epilepsy population (b) to determine the relationship of hippocampal asymmetry (HA) to epileptic syndromes and risk factors. Methods: Two neurologists classified the epileptic syndrome in 79 pediatric outpatients, according to the International Classification of Epilepsies and Epileptic Syndromes (ILAE). Hippocampal volumetrics were performed in all patients. HA was defined according to adult control values. Results: Inter-rater variability on measurement of HA was very small (Correlation of test retest of 0.97 on 17 children <3 years old). The rate of HA was 44/79 (57%). In 21 patients, (27%) potentially epileptogenic lesions (other than HA) were identified (cerebral dysgenesis n = 11). HA was present in 9/15 (60%) of temporal lobe epilepsy and in 15/28 (54%) extratemporal onset epilepsy and 5/11 (46%) of generalized symptomatic epilepsy. Analysis confined to <13 years also showed HA was not specific for epileptic syndrome. There was no significant association of febrile convulsions (13%) with HA or temporal lobe epilepsy. Conclusions: There is a high incidence of HA in childhood epilepsy. HA was not confined to clinically defined temporal lobe epilepsy. The poor correlation of epileptic syndrome to quantitative MRI findings may be due to the inadequacies of epilepsy classification in the younger child, with the clinical semiology providing misleading localizing information. Normative childhood data for hippocampal volumes and symmetry is needed.     

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.     

Routine EEG and Temporal Lobe Epilepsy: Relation to Long-Term EEG Monitoring, Quantitative MRI, and Operative Outcome

Summary: Purpose: To investigate the relation among routine EEG, long-term EEG monitoring (LTM), quantitative magnetic resonance imaging (MRI), and surgical outcome in temporal lobe epilepsy (TLE).
Methods: We evaluated 159 patients with intractable TLE who underwent an anterior temporal lobectomy between 1988 and 1993. The epileptogenic temporal lobe was determined by ictal LTM. A single awake-sleep outpatient EEG with standard activating procedures was performed before LTM. EEGs were analyzed by a blinded investigator.
Results: MRI scans showed unilateral medial temporal atrophy (109 patients) or symmetrical hippocampal volumes (50 patients). The surgically excised epileptogenic brain tissue revealed mesial temporal sclerosis, gliosis, or no histopathologic alteration. Routine EEG revealed temporal lobe epileptiform discharges in 123 patients. Routine EEG findings correlated with the temporal lobe of seizure origin (p < 0.0001) and the results of MRI volumetric studies (p < 0.0001). Interictal epileptiform discharges were seen only during LTM in 24 patients. Routine EEG was disconcordant with interictal LTM in another 20 patients. MRI-identifed unilateral medial temporal lobe atrophy was a strong predictor of operative success (p < 0.0001). There was no significant relation between the routine EEG findings and operative outcome (p > 0.20).
Conclusions: Results of this study modified our approach in patients with TLE. Interictal epileptiform discharges localized to one temporal lobe on serial routine EEGs or during LTM may be adequate to identify the epileptogenic zone in patients with MRI-identified unilateral medial temporal lobe atrophy.     

Quality of Life in Children with Epilepsy

Summary: To study quality of life in school children with epilepsy, we surveyed families of 443 elementary and junior high school children with epilepsy, as well as their school teachers. Approximately 80% responded. Seizures were controlled in 70% of the children. Of the children with epilepsy, 27% received education for disturbed children. Main family concerns were the future of their child, seizures, and school performance. Main concerns of the children were medication and seizures. The majority of both families and teachers agreed that children should participate in all physical education and school events based on individual considerations. Many teachers expressed the opinion that correct information about epilepsy and close communication between teachers and physicians are necessary. To establish comprehensive medical care that satisfies the needs of children with epilepsy and their families, further training of medical specialists in epilepsy, establishment of more hospitals specializing in epilepsy, and enhancement of the network among relevant organizations are needed. For children with intractable epilepsy, special considerations include associated handicaps and antiepileptic drug side effects.     

Quantitative Approaches to Functional MRI: Applications in Epilepsy

Summary:  The application of functional magnetic resonance imaging (fMRI) to elucidation of seizures and epilepsy has been built primarily upon a framework derived from cortical responses to periodic sensory (and cognitive) stimuli. This analytical approach relies upon assumptions that may be less applicable to the problem of seizure origination. Because of the heterogeneous and complex nature of seizures, a number of quantitative methodologies have been derived to understand fMRI changes that are associated with epileptiform neural activity. Separated broadly, these can be divided into those making some set of assumptions about the form of the MRI signal response to neural activation (the general linear model), and those that are data driven. It is likely that a combination of methodologies, where data driven methods are "informed" by knowledge of the underlying neurobiological process will provide the greatest insight into the underlying neurobiological basis of seizure origination.     

Bilateral Hippocampal Volume Loss in Patients with a History of Encephalitis or Meningitis

Volumetric analysis of high-quality magnetic resonance imaging (MRI) scans identifies asymmetric hippocampal atrophy in most patients with temporal lobe epilepsy. However, bilateral hippocampal atrophy can be missed by unnormalized volume measures. We considered two patient groups with temporal lobe epilepsy, one with a history of febrile convulsions (FC, n = 14) and one with a history of encephalitis or meningitis (E/M, n = 12), to compare the prevalence of bilateral volume loss between the groups. A volume normalization process defines a normal range of hippocampal volumes in control subjects (n = 32). Normalized volumes indicated that 11 of 14 subjects with a history of FC had unilateral hippocampal atrophy and 9 of 12 subjects with a history of E/M had bilateral hippocampal atrophy as compared with the controls. Visual assessments of unilateral hippocampal atrophy (n = 17) correlated well with measured unilateral volume loss (n = 14), but visual assessment of bilateral hippocampal atrophy (n = 3) correlated poorly with measured bilateral volume loss (n = 12). Mean age at seizure onset was lower in the FC group (7 years) than in the E/M group (13 years), but other clinical features were similar between the two groups. Hippocampal volume normalization is necessary to detect bilateral volume loss, which is common in patients with a history of encephalitis or meningitis.     

Epilepsy surgery outcomes in temporal lobe epilepsy with a normal MRI

Purpose:   To determine the long-term efficacy of anterior temporal lobectomy for medically refractory temporal lobe epilepsy in patients with nonlesional magnetic resonance imaging (MRI).
Methods:   We identified a retrospective cohort of 44 patients with a nonlesional modern "seizure protocol" MRI who underwent anterior temporal lobectomy for treatment of medically refractory partial epilepsy. Postoperative seizure freedom was determined by Kaplan-Meyer survival analysis. Noninvasive preoperative diagnostic factors potentially associated with excellent surgical outcome were examined by univariate analysis in the 40 patients with follow-up of >1 year.
Results:   Engel class I outcomes (free of disabling seizures) were observed in 60% (24 of 40) patients. Preoperative factors associated with Engel class I outcome were: (1) absence of contralateral or extratemporal interictal epileptiform discharges, (2) subtraction ictal single photon emission computed tomography (SPECT) Coregistered to MRI (SISCOM) abnormality localized to the resection site, and (3) subtle nonspecific MRI findings in the mesial temporal lobe concordant to the resection.
Discussion:   In carefully selected patients with temporal lobe epilepsy and a nonlesional MRI, anterior temporal lobectomy can often render patients free of disabling seizures. This favorable rate of surgical success is likely due to the detection of concordant abnormalities that indicate unilateral temporal lobe epilepsy in patients with nonlesional MRI.     

Children with Epilepsy: The Effect of Seizures, Syndromes, and Etiological Factors on Cognitive Functioning

Summary: Overall, children with epilepsy have poorer concentration and mental processing and are less alert than age-matched controls. The relationship between cognitive functioning and epilepsy is complex, however, with widely differing degrees of intellectual impairment–ranging from minimal to severe and progressive–related to diverse types of epileptic seizures, syndromes, and etiological factors. Prolonged and frequently repeated seizures are typically associated with more severe effects on cognitive functioning, particularly if epilepsy is symptomatic, i.e., secondary to a demonstrable brain lesion. A combination of such factors may contribute to the mental deterioration seen in many children suffering from severe epilepsy.     

Epilepsy surgery in children with tuberous sclerosis complex: presurgical evaluation and outcome

PURPOSE: Children with tuberous sclerosis complex (TSC) benefit from excisional surgery if seizures can be localized to a single tuber. We evaluated the role of noninvasive studies to localize the epileptogenic tuber/region (ET/R) and the outcome of focal resection. METHODS: We identified 21 children with TSC, ages 3 months to 15 years (mean 4.8 years). All had video-(electroencephalogram) EEG and magnetic resonance imaging (MRI) scans, and 18 also had ictal single photon emission-computed tomography (SPECT) studies. An ET/R was localized in 17 patients. Thirteen patients underwent resection guided by intraoperative electrocorticography (n = 7) or subdural monitoring (n = 6). RESULTS: Interictal EEG revealed a principal spike focus (PSF) that corresponded to the ET/R in 14 children. In seven, PSFs occurred in rhythmic runs. PSFs were not observed remote from the ET/R. Focal polymorphic slowing and attenuation occurred in the region of the PSF in 11 patients. Sixteen patients demonstrated an ictal focus corresponding to the ET/R. Ictal SPECT revealed focal hyperperfusion correlating with the ET/R in 10 patients. Although the MRIs in all children revealed multiple tubers, the ET/R corresponded to a large discrete tuber in 8 patients and a calcified tuber in 13 patients. Patchy calcified tubers were also seen elsewhere in six patients. At a mean follow-up of 26 months, 9 of the 13 children who underwent surgery were seizure-free, one had greater than 75% reduction in seizures, two were unchanged, and one was lost to follow-up. New seizures developed in one child from a contralateral tuber. CONCLUSIONS: Surgical resection of an ET/R alleviates seizures in most children with TSC and intractable epilepsy. The scalp EEG and MRI help define the ET/R and improve case selection when ictal SPECT is nonlocalizing.     

Prevalence, Classification, and Severity of Epilepsy and Epileptic Syndromes in Children

Summary: Purpose: To determine the point prevalence of active childhood epilepsy in a defined area and evaluate the usefulness of ILAE classification of seizures, and epilepsies/syndromes with special interest in severe epilepsies. Methods: By using the latest ILAE International Classification of Epileptic Seizures (ICES, 1981) and Epilepsies and Epileptic Syndromes (ICE, 1989), we determined the age- and sex-specific prevalence rates of epilepsy, type of seizures, epilepsies, and recognizable epileptic syndromes, as well as the proportion of severe cases in each seizure/epilepsy/syndrome category in all children 0–15 years of age from a geographically defined area in Finland. All medical records, neurophysiological recordings and available clinical data were reviewed retrospectively. Results: Point prevalence of active epilepsy on December 12, 1992 was 3.94 per 1,000. According to ICESDCE, we were able to classify 96% of seizures and 90% of epilepsies and syndromes. Generalized seizure and epilepsy/syndrome types were more prevalent in children 0–6 years of age and partial/ localization-related in children 6–15 years of age. Epilepsy was intractable in 17% of all cases and correlated significantly with symptomatic etiology and early onset of epilepsy, as well as with additional neuroimpairments. Conclusions: A considerable number of cases fell into the nonspecific categories of ICE, which limits the value of present epilepsy/syndrome classification in terms of prognosis, prediction, and indication for special investigations in individual cases. A number of intractable cases was relatively low, indicating good prognosis in many childhood epilepsies, especially when additional neuroimpairments are absent.     

Epilepsy in pervasive developmental disorder without brain MRI abnormalities

Background: Epilepsy has been reported in patients with pervasive developmental disorder (PDD), with an incidence ranging from 5% to 40%; however most of the studies included patients with brain magnetic resonance imaging (MRI) abnormalities (e.g., tuberous sclerosis) and patients with epilepsy whose seizure onset was in the first year of life. Methods: We retrospectively examined 67 patients (45 males, 22 females) with PDD and epilepsy, who did not have brain MRI abnormalities. Patients who had seizures in the first year of life were excluded. We divided the patients into two groups: group A included 34 patients with an IQ < 50, and group B included 33 patients with an IQ ? 50. Results: The median age of epilepsy onset was higher in group A than group B (8.8 vs. 5.2 years, P < 0.01). Only one patient (3%) in group A and nine patients (27%) in group B were classified with generalized epilepsy (P < 0.05). At the last observation, 16 patients (47%) in group A and 25 patients (76%) in group B were seizure-free for ?1 year (not statistically significant). Conclusion: The relationship between PDD and epilepsy may be different between patients with lower (group A) and higher (group B) IQs in patients who do not have brain MRI abnormalities.     

Electrocorticography and Temporal Lobe Epilepsy: Relationship to Quantitative MRI and Operative Outcome

Summary: We investigated the relationship between electrocorticography (ECoG), quantitative magnetic resonance imaging (MRI), and surgical outcome in 165 patients with intractable nonlesional temporal lobe epilepsy (NLTLE). A standard mesial temporal resection was performed in all patients. Patients with an operative follow-up <1 year were excluded from the study. The extent of the lateral temporal neocortex resection (LCR) was guided by ECoG and the side of surgery. The extent of the LCR was not predictive of seizure outcome in patients with or without hippocampal formation atrophy (p > 0.5). Patients undergoing a right anterior temporal lobectomy had a larger LCR (p < 0.000l), but the side of surgery was not of predictive value in determining seizure outcome (p > 0.1). The topography of the acute intracranial spikes did not correlate with operative outcome (p > 0.5) and was independent of hippocampal volumetric studies (p > 0.5). The postexcision ECoG was also shown not to be of prognostic importance (p > 0.5). Our results indicates that the extent of the lateral temporal cortical resection and the ECoG findings are not important determinants of surgical outcome in patients with NLTLE.     

Childhood Epilepsy and Asthma: Comparison of Quality of Life

Summary: We report results from the first data collection on an ongoing longitudinal study aimed at describing thenatural history of adaptation to childhood epilepsy andasthma in children and their families. We studied 136 children with epilepsy and 134 children with asthma aged 8–12 years. Data were collected from the children, theirmothers, and their school teachers through interviews, school records, and questionnaires. The two sampleswere compared on four domains of quality of life: physical, psychological, social, and school. Data were analyzed by a 2 × 2 between-subjects multivariate analysis ofcovariance with type of illness (epilepsy or asthma) as theindependent variable and length of time since onset ofillness as a covariate. A significant main effect was notedfor illness [multivariate F (15, 236) = 11.36, p < 0.001].Our major finding was that children with epilepsy had arelatively more compromised quality of life in the psychological, social, and school domains. In contrast, children with asthma had a more compromised quality of lifein the physical domain. Our findings suggest that attention simply to seizure control in the clinical setting willnot address the full range of quality-of-life problems ofchildren with epilepsy.     

Hippocampus and amygdala volumes in a random community-based sample of 60–64 year olds and their relationship to cognition

Reduced volumes of the hippocampus (HC) and amygdala (AG) are potential biomarkers for Alzheimer's disease (AD) and other neuropsychiatric disorders. Published studies on HC and AG volumes suffer from methodological limitations, and a valid and reliable normative database does not exist. This study aimed to establish a database of HC and AG volumes from a large community sample of participants 60–64 years old and relate them to cognition. A total of 452 randomly selected participants (from 622 approached) were retained in the study (238 males, 214 females), and all received brain MRI scans, as well as cognitive and physical assessments. HC and AG volumes were estimated from manual tracings on T1-weighted images, and intracranial volume (ICV) was obtained from an automated program. In both sexes, right hippocampi were larger than left, while left amygdalae were larger than right. The only correlation to remain significant after normalization was left HC volume and percent retention of a word list in females. This study provides a HC and AG volumetrics database and describes its relationship with cognitive performance in a representative sample using a standard methodology that will be a reference for future studies. It will therefore have clinical applicability in early AD and other disorders.     

Epilepsy surgery in patients with normal or nonfocal MRI scans: integrative strategies offer long-term seizure relief

PURPOSE: Excisional surgery achieves seizure freedom in a large proportion of children with intractable lesional epilepsy, but the outcome for children without a focal lesion on MRI is less clear. We report the outcome of a cohort predominantly of children with nonlesional intractable partial epilepsy undergoing resective surgery. METHODS: We studied 102 patients with nonlesional intractable partial epilepsy who underwent excisional surgery. The epileptogenic region was identified by integrating clinical exam and video-EEG data complemented by ictal SPECT (n = 40), PET (n = 10), extraoperative subdural monitoring (n = 80), and electrocorticography (n = 22). All patients had follow-up greater than 2 years, 76 patients had 5-year follow-up, and 43 patients had 10-year follow-up. RESULTS: A total of 66 resections were unilobar; 36 were multilobar. One patient died of causes unrelated to seizures or surgery. At 2-year follow-up, 44 of 101 patients were seizure-free, 15 experienced >90% reduction, 17 had >50% reduction, and 25 were unchanged. At 5-year follow-up, 35 of 76 patients were seizure-free, 12 experienced >90% reduction, 12 had >50% reduction, and 17 were unchanged. At 10-year follow-up, 16 of 43 patients were seizure-free, 13 experienced >90% reduction, 7 had >50% reduction, and 7 were unchanged. Outcomes correlated with the presence of convergent focal interictal spikes (p < 0.005) on the scalp EEG and completeness of resection (p < 0.0005). CONCLUSIONS: Our findings demonstrate that excisional surgery is successful in the majority of children with nonlesional partial epilepsy. A multimodal integrative approach can minimize the size of resection and alleviate the need for invasive EEG monitoring. Focal interictal spikes and completeness of resection predict good outcome. The benefits of surgery are long-lasting.     

Epilepsy in Children with Mental Retardation: A Cohort Study

The cumulative risk of seizures and epilepsy was investigated in a prospectively identified cohort of 221 children with mental retardation (MR) born between 1951 and 1955 in Aberdeen, Scotland. By age 22 years, 33 (15%) had epilepsy. An additional 16 (7%) had had at least one seizure, but did not meet the criteria for epilepsy. The cumulative risk of epilepsy was 9, 11, 13, and 15% at 5, 10, 15, and 22 years, respectively. In children with MR and no associated disabilities, the cumulative risk of epilepsy was only 2.6, 3.2, 3.9, and 5.2% at 5, 10, 15, and 22 years. In children with MR and cerebral palsy (CP), the cumulative risk was 28, 31, and 38% at 5, 10, and 22 years. Children with a postnatal injury associated with MR had a cumulative risk of epilepsy of 53, 66, and 66% at 5, 10, and 15 years after the injury. By age 22 years, 39% had achieved 5-year seizure-free remission, including 56% of children with MR without associated disability, 47% of children with MR and CP, and 11% of children with a postnatal injury. We conclude that, in the absence of associated disability or postnatal injury, the risk of epilepsy in the retarded population is low. Epilepsy in this population also will frequently enter remission in later life.