Global and intertuberal epileptic networks in tuberous sclerosis based on stereoelectroencephalographic (sEEG) findings: a quantitative EEG analysis in pediatric subjects and surgical implications.

OBJECTIVE: Recent evidence favors a network concept in tuberous sclerosis (TSC) with seizure generation and propagation related to changes in global and regional connectivity between multiple, anatomically distant tubers. Direct exploration of network dynamics in TSC has been made possible through intracranial sampling with stereoelectroencephalography (sEEG). The objective of this study is to define epileptic networks in TSC using quantitative analysis of sEEG recordings. We also discuss the impact of the definition of these epileptic networks on surgical decision-making. METHODS: Intracranial sEEG recordings were obtained from four pediatric patients who presented with medically refractory epilepsy secondary to TSC and subjected to quantitative signal analysis methods. Cortical connectivity was quantified by calculating pairwise coherence between all contacts and constructing an association matrix. The global coherence, defined as the ratio of the largest eigenvalue to the sum of all the eigenvalues, was calculated for each frequency band (delta, theta, alpha, beta, gamma). Spatial distribution of the connectivity was identified by plotting the leading principal component (product of the largest eigenvalue and its corresponding eigenvector). RESULTS: Four pediatric subjects with TSC underwent invasive intracranial monitoring with sEEG, comprising 31 depth electrodes and 250 contacts, for localization of the epileptogenic focus and guidance of subsequent surgical intervention. Quantitative connectivity analysis revealed a change in global coherence during the ictal period in the beta/low gamma (14-30 Hz) and high gamma (31-80 Hz) bands. Our results corroborate findings from existing literature, which implicate higher frequencies as a driver of synchrony and desynchrony. CONCLUSIONS: Coordinated high-frequency activity in the beta/low gamma and high gamma bands among spatially distant sEEG define the ictal period in TSC. This time-dependent change in global coherence demonstrates evidence for intra-tuberal and inter-tuberal connectivity in TSC. This observation has surgical implications. It suggests that targeting multiple tubers has a higher chance of seizure control as there is a higher chance of disrupting the epileptic network. The use of laser interstitial thermal therapy (LITT) allowed us to target multiple disparately located tubers in a minimally invasive manner with good seizure control outcomes.

Factors associated with treatment delays in pediatric refractory convulsive status epilepticus.

OBJECTIVE: To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). METHODS: This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. RESULTS: We studied 219 patients (53% males) with a median (25th-75th percentiles [p25-p75]) age of 3.9 (1.2-9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p25-p75) time from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107-539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. CONCLUSION: Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment.

fMRI language dominance and FDG-PET hypometabolism.

BACKGROUND: Atypical language dominance is common in patients with temporal lobe epilepsy. We examined the association of left temporal hypometabolism with laterality of fMRI activation in a language task in a cross-sectional study. METHODS: Thirty patients with temporal lobe epilepsy (mean age 32.4 ± 11.0 years [range 18-55]; epilepsy onset 15.3 ± 11.3 years [range 0.8-40]; 22 left focus, 8 right focus) had (18)fluoro-deoxyglucose (FDG)-PET using noninvasive cardiac input function. After MRI-based partial volume correction, regional glucose metabolism (CMRglc) was measured and asymmetry index, AI = 2(l - R)/(L + R), calculated. fMRI language dominance was assessed with an auditory definition decision paradigm at 3 T. fMRI data were analyzed in SPM2 using regions of interest from Wake Forest PickAtlas (Wernicke area [WA], inferior frontal gyrus [IFG], middle frontal gyrus [MFG]) and bootstrap laterality index, LI = (l - R/L + R). RESULTS: Nineteen patients had ipsilateral temporal hypometabolism; 3 of 4 patients with atypical language had abnormal FDG-PET. Increasing left midtemporal hypometabolism correlated with decreased MFG LI (r = -0.41, p < 0.05) and showed trends with WA LI (r = -0.37, p = 0.055) and IFG LI (r = -0.31, p = 0.099); these relationships became more significant after controlling for age at onset. Increasing hypometabolism was associated with fewer activated voxels in WA ipsilateral to the focus and more activated voxels contralaterally, but overall, activation amount in left WA was similar to subjects without left temporal hypometabolism (t = -1.39, p > 0.10). CONCLUSIONS: We did not find evidence of impaired blood oxygenation level-dependent response in hypometabolic cortex. Regional hypometabolism appears to be a marker for the temporal lobe dysfunction that leads to displacement of language function.

New-onset afebrile seizures in infants: role of neuroimaging.

OBJECTIVE: To investigate the presenting characteristics of new-onset afebrile seizures in infants (age 1-24 months) and the yield of neuroimaging. METHODS: Prospective data were obtained from a standardized evaluation and management plan mandated by a critical care pathway. A total of 317 infants presented with new-onset afebrile seizures between 2001 and 2007. EEG was performed on 90.3%, head CT was obtained on 94%, and MRI was obtained on 57.4%. RESULTS: We found half of the infants had partial features to their seizures, yet evidence for primary generalized seizures was rare. The majority had more than 1 seizure upon presentation. Seizures in this age group tended to be brief, with 44% lasting less than 1 minute. EEG abnormalities were found in half. One-third of CTs were abnormal, with 9% of all CTs requiring acute medical management. Over half of MRIs were abnormal, with cerebral dysgenesis being the most common abnormality (p < 0.05). One-third of normal CTs had a subsequent abnormal MRI-only 1 resulted in altered medical management. CONCLUSIONS: Infantile seizures are usually brief, but commonly recurrent, and strong consideration should be made for inpatient observation. Acute imaging with CT can alter management in a small but important number of infants. Due to the superior yield, strong consideration for MRI should be given for all infants, as primary generalized seizures are rare, and there is a high rate of cerebral dysgenesis.

Prospective study of new-onset seizures presenting as status epilepticus in childhood.

OBJECTIVE: To characterize children with new-onset seizures presenting as status epilepticus at a tertiary care children's hospital. METHODS: Prospectively collected data were reviewed from a database derived from a mandated critical care pathway. A total of 1,382 patients presented with new-onset seizures between 2001 and 2007. RESULTS: A total of 144 patients presented in status epilepticus. The average age was 3.4 years. The majority of seizures (72%) lasted between 21 and 60 minutes. The majority of patients had no significant past medical history; one-fourth had a family history of epilepsy. Five (4%) patients with EEGs had electrographic seizures during the study, captured only with prolonged monitoring. The most common etiology was febrile convulsion, followed by cryptogenic. The most common acute symptomatic cause was CNS infection; the most common remote symptomatic cause was cerebral dysgenesis. Combined CT and MRI provided a diagnosis in 30%. CT was helpful in identifying acute vascular lesions and acute edema, whereas MRI was superior in identifying subtle abnormalities and remote symptomatic etiologies such as dysplasia and mesial temporal sclerosis. CONCLUSIONS: Children who present in status epilepticus that is not a prolonged febrile convulsion should undergo neuroimaging in the initial evaluation. For any child who presents in status epilepticus and has not yet returned to baseline, the possibility of nonconvulsive status epilepticus should be considered. Although CT is often more widely accepted, especially in the urgent setting, strong consideration for MRI should be given when available, due to the superior yield.

Interhemispheric and intrahemispheric language reorganization in complex partial epilepsy.

OBJECTIVE: To investigate interhemispheric and intrahemispheric reorganization in patients with localization-related epilepsy. METHOD: We studied 50 patients with a left hemispheric focus and 20 normal right-handed controls with a 3T echoplanar imaging blood oxygen level dependent functional MRI auditory-based word definition decision task. Data were analyzed using SPM 2. Using region of interest for Broca and Wernicke areas and an asymmetry index (AI), patients were categorized as left language (LL; AI > or = 0.20) or atypical language (AL; AI <0.20) for region. The point maxima activation for normal controls (p <0.05 corrected FDR) was identified in Broca and midtemporal regions and then used as a point of reference for individual point maxima identified at p < 0.001, uncorrected. RESULTS: Patient groups showed increased frequency of having activation in right homologues. Activation in AL groups occurred in homologous right regions; distances for point maxima activation in homologous regions were the same as point maxima distances in normal control activation in left regions. Distances for LL patient in left regions showed a trend for differences for midtemporal gyrus (6 mm posterior, 3 mm superior) but variability around mean difference distance was significant. There was no effect of age at epilepsy onset, duration, or pathology on activation maxima. CONCLUSIONS: Right hemisphere language regions in patients with left hemispheric focus are homologues of left hemisphere Broca and broadly defined Wernicke areas. We found little evidence for intrahemispheric reorganization in patients with left hemisphere epilepsy who remain left language dominant by these methods.

Limitations to plasticity of language network reorganization in localization related epilepsy.

Neural networks for processing language often are reorganized in patients with epilepsy. However, the extent and location of within and between hemisphere re-organization are not established. We studied 45 patients, all with a left hemisphere seizure focus (mean age 22.8, seizure onset 13.3), and 19 normal controls (mean age 24.8) with an fMRI word definition language paradigm to assess the location of language processing regions. Individual patient SPM maps were compared to the normal group in a voxel-wise comparison; a voxel was considered to be significant if its z-value exceeded mid R:2mid R:. Subsequently, we used principal component analysis with hierarchical clustering of variance patterns from individual difference maps to identify four patient sub-groups. One did not differ from normal controls; one had increased left temporal activation on the margin of regions activated in controls; two others had recruitment in right inferior frontal gyrus, middle frontal gyrus and temporal cortex. Right hemisphere activation in these two groups occurred in homologues of left hemisphere regions that sustained task activation. Our study used novel data driven methods to find evidence for constraints on inter-hemispheric reorganization of language in recruitment of right homologues, and, in a subpopulation of patients, evidence for intra-hemispheric reorganization of language limited to the margins of typical left temporal regional activation. These methods may be applied to investigate both normal and pathological variance in other developmental disorders and cognitive domains.

Altered language processing in autosomal dominant partial epilepsy with auditory features.

BACKGROUND: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is an idiopathic focal epilepsy syndrome with auditory symptoms or receptive aphasia as major ictal manifestations, frequently associated with mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene. Although affected subjects do not have structural abnormalities detected on routine MRI, a lateral temporal malformation was identified through high resolution MRI in one family. We attempted to replicate this finding and to assess auditory and language processing in ADPEAF using fMRI and magnetoencephalography (MEG). METHODS: We studied 17 subjects (10 affected mutation carriers, 3 unaffected carriers, 4 noncarriers) in 7 ADPEAF families, each of which had a different LGI1 mutation. Subjects underwent high-resolution structural MRI, fMRI with an auditory description decision task (ADDT) and a tone discrimination task, and MEG. A control group comprising 26 volunteers was also included. RESULTS: We found no evidence of structural abnormalities in any of the 17 subjects. On fMRI with ADDT, subjects with epilepsy had significantly less activation than controls. On MEG with auditory stimuli, peak 2 auditory evoked field latency was significantly delayed in affected individuals compared to controls. CONCLUSIONS: These findings do not support the previous report of a lateral temporal malformation in autosomal dominant partial epilepsy with auditory features (ADPEAF). However, our fMRI and magnetoencephalography data suggest that individuals with ADPEAF have functional impairment in language processing.

1H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency.

OBJECTIVE: To evaluate brain metabolism in subjects with partial ornithine transcarbamylase deficiency (OTCD) utilizing (1)H MRS. METHODS: Single-voxel (1)H MRS was performed on 25 medically-stable adults with partial OTCD, and 22 similarly aged controls. Metabolite concentrations from frontal and parietal white matter (FWM, PWM), frontal gray matter (FGM), posterior cingulate gray matter (PCGM), and thalamus (tha) were compared with controls and IQ, plasma ammonia, glutamine, and disease severity. RESULTS: Cases ranged from 19 to 59 years; average 34 years; controls ranged from 18 to 59 years; average 33 years. IQ scores were lower in cases (full scale 111 vs. 126; performance IQ 106 vs. 117). Decreased myoinositol (mI) in FWM (p=0.005), PWM (p<0.001), PCGM (p=0.003), and tha (p=0.004), identified subjects with OTCD, including asymptomatic heterozygotes. Glutamine (gln) was increased in FWM (p<0.001), PWM (p<0.001), FGM (p=0.002), and PCGM (p=0.001). Disease severity was inversely correlated with [mI] in PWM (r=-0.403; p=0.046) and directly correlated with [gln] in PCGM (r=0.548; p=0.005). N-Acetylaspartate (NAA) was elevated in PWM (p=0.002); choline was decreased in FWM (p=0.001) and tha (p=0.002). There was an inverse relationship between [mI] and [gln] in cases only. Total buffering capacity (measured by [mI/mI+gln] ratio, a measure of total osmolar capacity) was inversely correlated with disease severity in FWM (r=-0.479; p=0.018), PWM (r=-0.458; p=0.021), PCGM (r=-0.567; p=0.003), and tha (r=-0.345; p=0.037). CONCLUSION: Brain metabolism is impaired in partial OTCD. Depletion of mI and total buffering capacity are inversely correlated with disease severity, and serve as biomarkers.

Atypical language in lesional and nonlesional complex partial epilepsy.

OBJECTIVE: We investigated the relationship between partial epilepsy, MRI findings, and atypical language representation. METHODS: A total of 102 patients (4 to 55 years) with left hemisphere epileptogenic zones were evaluated using three fMRI language tasks obtained at 1.5 or 3T with EPI BOLD techniques: verbal fluency, reading comprehension, and auditory comprehension. fMRI maps were visually interpreted at a standard threshold and rated as left or atypical language. RESULTS: Atypical language dominance occurred in 30 patients (29%) and varied with MRI type (p < 0.01). Atypical language representation occurred in 36% (13/36) with normal MRI, 21% (6/29) with mesial temporal sclerosis, 14% (4/28) with focal cortical lesions (dysplasia, tumor, vascular malformation), and all (6/6) with a history of stroke. Multivariate logistic regression analysis found handedness, seizure onset, and MRI type accounted for much of the variance in language activation patterns (chi(2) = 24.09, p < 0.01). Atypical language was more prevalent in patients with early seizure onset (43.2%, p < 0.05) and atypical handedness (60%, p < 0.01). None of the three clinical factors were correlated with each other (p > 0.40). Patients with atypical language had lower verbal abilities (F = 6.96, p = 0.01) and a trend toward lower nonverbal abilities (F = 3.58, p = 0.06). There were no differences in rates of atypical language across time, age groups, or MRI scanner. CONCLUSION: Early seizure onset and atypical handedness, as well as the location and nature of pathologic substrate, are important factors in language reorganization.

Prognosis of children with partial epilepsy: MRI and serial 18FDG-PET.

OBJECTIVE: To study the evolution of cerebral glucose metabolism after partial seizure onset in children, and its relation to clinical variables. METHODS: Thirty-eight children had 3.4 +/-.8 (18)FDG-PET scans over 3.0 +/- 1.3 years starting within a year after their third unprovoked partial seizure. (18)FDG-PET was analyzed with a region of interest template to measure normalized metabolism in 12 paired anatomic areas. Scans with absolute asymmetry index, |AI|, greater than 0.13 in at least one cortical region other than the cerebellum were considered abnormal. Standard clinical T1- and T2-weighted MRI (1.5 T) scans were obtained. RESULTS: Patients with initial normal PET (n = 28) were significantly more likely to remain in good seizure control than those with abnormal initial PET. Patients with initially normal PET scans that became abnormal had longer epilepsy duration before the first PET scan, but not greater seizure frequency, than those with PET always normal. There was no evidence for progression of hypometabolism. Patients with shorter time since last seizure and higher seizure frequency were more likely to have abnormal PET scans. Six of the seven patients whose PET scans were always abnormal had poor seizure control. Febrile seizure history did not affect PET findings. MRI was strongly predictive of initial PET results (chi(2) = 13.1; p < 0.02) but did not predict fluctuation hypometabolism. A model combining MRI and initial PET was strongly predictive of clinical course. CONCLUSIONS: Initial imaging studies can help predict clinical course for children who have had at least three partial seizures. Serial FDG-PET is affected by seizure frequency and time since last seizure.

Language lateralization and the role of the fusiform gyrus in semantic processing in young children.

We used blood oxygen-dependent (BOLD) fMRI technique at 1.5 T to examine brain regions associated with language comprehension in normally developing children, age 5 to 10 years. Twenty-three children participated in the study using an auditory semantic decision task which varied in task difficulty. Analysis of individual participants' data showed patterns of activation largely consistent with previous neuroimaging findings in adult language processing. Group data analysis also showed a strong left-lateralized pattern of activation that closely resembles those typically observed in adults. In addition, significant activation in the left fusiform gyrus was observed and was associated with task accuracy. This finding suggests that auditory semantic processing in young children may recruit cortical regions associated with word reading in adults prior to the initiation of a semantic category decision, a process which is consistent with patterns of early word recognition process and language development.

Seizure focus affects regional language networks assessed by fMRI.

OBJECTIVE: To investigate the degree of language dominance in patients with left and right hemisphere seizure foci compared to normal volunteers using a fMRI reading comprehension task. METHODS: Fifty patients with complex partial epilepsy, aged 8 to 56 years and 33 normal volunteers, aged 7 to 34 had fMRI (1.5 T) and neuropsychological testing. Participants silently named an object described by a sentence compared to a visual control. Data were analyzed with region of interest (ROI) analysis based on t maps for inferior frontal gyrus (IFG), midfrontal gyrus (MFG), and Wernicke area (WA). Regional asymmetry indices (AIs) were calculated [(L - R)/(L + R)]; AI > 0.20 was deemed left dominant and AI < 0.20 as atypical language. RESULTS: Left hemisphere focus patients had a higher likelihood of atypical language than right hemisphere focus patients (21% vs 0%, chi2 < 0.002). Left hemisphere focus patients, excluding those with atypical language, had lower regional AI in IFG, MFG, and WA than controls. Right hemisphere focus patients were all left language dominant and had a lower AI than controls in WA and MFG, but not for IFG. AI in MFG and WA were similar between left hemisphere focus/left language patients and right hemisphere focus patients. Patients activated more voxels than healthy volunteers. Lower AIs were attributable to greater activation in right homologous regions. Less activation in the right-side WA correlated with better verbal memory performance in right focus/left hemisphere-dominant patients, whereas less strongly lateralized activation in IFG correlated better with Verbal IQ in left focus/left hemisphere-dominant patients. CONCLUSIONS: Patients had lower asymmetry indices than healthy controls, reflecting increased recruitment of homologous right hemisphere areas for language processing. Greater right hemisphere activation may reflect greater cognitive effort in patient populations, the effect of epilepsy, or its treatment. Regional activation patterns reflect adaptive efforts at recruiting more widespread language processing networks that are differentially affected based on hemisphere of seizure focus.

fMRI language task panel improves determination of language dominance.

BACKGROUND: fMRI language tasks reliably identify language areas in presurgical epilepsy patients, but activation using single paradigms may disagree with the intracarotid amobarbital test (IAT). OBJECTIVE: To determine whether a panel of fMRI tasks targeting different aspects of language processing increases accuracy in determining hemisphere language dominance. METHODS: Twenty-six patients age 12 to 56 years, predominantly with temporal lobe epilepsy, were studied using whole-brain 1.5 T fMRI (echo planar imaging, blood oxygenation level-dependent) with three task categories using a block design: verbal fluency, reading comprehension, and auditory comprehension. fMRI t maps were visually rated at three thresholds. All patients had assessment of language lateralization by IAT. RESULTS: fMRI showed left dominance in 21 patients, right dominance in 2, and bilateral activation in 2; raters disagreed over a left vs right bilateral rating in 1 patient. There was full agreement between IAT and fMRI in 21 of 25 patients (IAT failed in 1). In three instances of partial disparity with IAT, the fMRI panel showed consistent findings across raters. Agreement between raters was excellent (partial disagreement in only one patient); the panel of tasks was superior to any single task for interrater agreement (Cramer V 0.93 [range 0.91 to 1.0] vs 0.72 [range 0.60 to 0.86]). CONCLUSIONS: A panel of fMRI language paradigms may be more accurate for evaluating partial epilepsy patients than a single task. A panel of tasks reduces the likelihood of nondiagnostic findings, improves interrater reliability, and helps confirm language laterality.

Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections.

BACKGROUND: Human herpesvirus-6 (HHV-6), a ubiquitous beta-herpesvirus, is the causative agent of roseola infantum and has been associated with a number of neurologic disorders including seizures, encephalitis/meningitis, and multiple sclerosis. Although the role of HHV-6 in human CNS disease remains to be fully defined, a number of studies have suggested that the CNS can be a site for persistent HHV-6 infection. OBJECTIVE: To characterize the extent and distribution of HHV-6 in human glial cells from surgical brain resections of patients with mesial temporal lobe epilepsy (MTLE). METHOD: Brain samples from eight patients with MTLE and seven patients with neocortical epilepsy (NE) undergoing surgical resection were quantitatively analyzed for the presence of HHV-6 DNA using a virus-specific real-time PCR assay. HHV-6 expression was also characterized by western blot analysis and in situ immunohistochemistry (IHC). In addition, HHV-6-reactive cells were analyzed for expression of glial fibrillary acidic protein (GFAP) by double immunofluorescence. RESULTS: DNA obtained from four of eight patients with MTLE had significantly elevated levels of HHV-6 as quantified by real-time PCR. HHV-6 was not amplified in any of the seven patients with NE undergoing surgery. The highest levels of HHV-6 were demonstrated in hippocampal sections (up to 23,079 copies/10(6) cells) and subtyped as HHV-6B. Expression of HHV-6 was confirmed by western blot analysis and IHC. HHV-6 was co-localized to GFAP-positive cells that morphologically appeared to be astrocytes. CONCLUSIONS: HHV-6B is present in brain specimens from a subset of patients with MTLE and localized to astrocytes in the absence of inflammation. The amplification of HHV-6 from hippocampal and temporal lobe astrocytes of MTLE warrants further investigation into the possible role of HHV-6 in the development of MTLE.

Auditory comprehension of language in young children: neural networks identified with fMRI.

OBJECTIVE: The organization of neuronal systems that process language in young children is poorly understood. The authors used fMRI to identify brain regions underlying auditory comprehension in healthy young children. METHODS: Fifteen right-handed children (mean age 6.8 years) underwent fMRI at 1.5-T using blood oxygen level dependent echoplanar imaging. They listened to stories with a reverse speech control condition. Group data were analyzed with statistical parametric mapping. Individual subject data were analyzed with a region of interest approach based on t-maps. An asymmetry index (AI = [(L-R)/(L+R)]) was calculated for each region. RESULTS: Group analysis showed significant activation in the left middle temporal gyrus (Brodmann area [BA] 21) and left superior temporal gyrus (BA 22) along the superior temporal sulcus extending back to the angular gyrus (BA 39). Individual maps showed lateralized activation in temporal regions (AI > 0.49 +/- 0.39). There was minimal activation in the frontal lobe. There were no significant correlations between age and regional AI. CONCLUSION: Networks for auditory language processing are regionally localized and lateralized by age 5. These data may provide a means to interpret language fMRI studies performed in preparation for brain surgery, and may be employed to investigate the effect of chronic disease states, such as epilepsy, on language organization during critical periods for plasticity.

Practice parameter: treatment of the child with a first unprovoked seizure: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence regarding risks and benefits. This parameter reviews published literature relevant to the decision to begin treatment after a child or adolescent experiences a first unprovoked seizure and presents evidence-based practice recommendations. Reasons why treatment may be considered are discussed. Evidence is reviewed concerning risk of recurrence as well as effect of treatment on prevention of recurrence and development of chronic epilepsy. Studies of side effects of anticonvulsants commonly used to treat seizures in children are also reviewed. Relevant articles are classified according to the Quality Standards Subcommittee classification scheme. Treatment after a first unprovoked seizure appears to decrease the risk of a second seizure, but there are few data from studies involving only children. There appears to be no benefit of treatment with regard to the prognosis for long-term seizure remission. Antiepileptic drugs (AED) carry risks of side effects that are particularly important in children. The decision as to whether or not to treat children and adolescents who have experienced a first unprovoked seizure must be based on a risk-benefit assessment that weighs the risk of having another seizure against the risk of chronic AED therapy. The decision should be individualized and take into account both medical issues and patient and family preference.

fMRI identifies regional specialization of neural networks for reading in young children.

BACKGROUND: fMRI allows mapping of neural networks underlying cognitive networks during development, but few studies have systematically examined children 7 and younger, in whom language networks may be more diffusely organized than in adults. OBJECTIVE: To identify neural networks during early reading consolidation in young children. METHODS: The authors studied 16 normal, right-handed, native English-speaking children with a mean age of 7.2 years (range 5.8 to 7.9) with fMRI reading paradigms adjusted for reading level. Data were acquired with the echoplanar imaging BOLD technique at 1.5 T. Group data were analyzed with statistical parametric mapping (SPM-99); individual data sets were analyzed with a region of interest approach from individual study t maps (t = 4). The number of activated pixels in brain regions was determined and an asymmetry index (AI) ([L-R]/[L+R]) calculated for each region. RESULTS: In group analysis the authors found prominent activation in left inferior temporal occipital junction and left fusiform gyrus (Brodmann area [BA] 37), middle temporal gyrus (BA 21, 22), middle frontal gyrus (BA 44, 45), and the supplementary motor area. Activation was strongly lateralized in middle frontal gyrus and Wernicke areas (AI 0.54, 0.62). Fourteen subjects had left-sided language lateralization, one was bilateral, and one had poor activation. CONCLUSIONS: The neural networks that process reading are strongly lateralized and regionally specific by age 6 to 7 years. Neural networks in early readers are similar to those in adults.

Language dominance in partial epilepsy patients identified with an fMRI reading task.

BACKGROUND: fMRI language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment to quantitative region of interest (ROI) analysis. OBJECTIVE: To identify temporal language areas in patients with partial epilepsy using a reading paradigm with clinical and ROI interpretation. METHODS: Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared to a visual control. Data were analyzed with ROI analysis from t-maps. Regional asymmetry indices (AI) were calculated ([L-R]/[L+R]) and language dominance defined as >0.20. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had intracarotid amobarbital test (IAT). RESULTS: The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients, three had partial agreement, none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 (Cramer V; p < 0.0001); agreement between visual and ROI reading with IAT was 0.71 to 0.77 (Cramer V; p < 0.0001). Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and 8 with ROI analysis. CONCLUSIONS: An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis.

Low incidence of abnormal (18)FDG-PET in children with new-onset partial epilepsy: a prospective study.

OBJECTIVE: Patients with refractory partial epilepsy often exhibit regional hypometabolism. It is unknown whether the metabolic abnormalities are present at seizure onset or develop over time. METHODS: The authors studied 40 children within 1 year of their third unprovoked partial seizure with EEG, MRI, and [(18)F]-fluorodeoxyglucose ((18)FDG)-PET (mean age at seizure onset = 5.8 years, range 0.9 to 11.9 years; mean epilepsy duration = 1.1 years, range 0.3 to 2.3 years; mean number of seizures = 30, range 3 to 200). The authors excluded children with abnormal structural MRI, except four with mesial temporal sclerosis and two with subtle hippocampal dysgenesis. (18)FDG-PET was analyzed with a region of interest template. An absolute asymmetry index, [AI], greater than 0.15 was considered abnormal. RESULTS: Thirty-three children had a presumptive temporal lobe focus, five frontotemporal, and two frontal. Mean AI for all regions was not different from 10 normal young adults, even when children less likely to have a temporal focus were excluded. Eight of 40 children (20%) had focal hypometabolism, all restricted to the temporal lobe, especially inferior mesial and inferior lateral regions. Abnormalities were ipsilateral to the presumed temporal lobe ictal focus. CONCLUSIONS: Abnormalities of glucose utilization may be less common and profound in children with new-onset partial seizures than in adults with chronic partial epilepsy. Although these patients' prognosis is uncertain, resolution of epilepsy after three documented seizures is uncommon. If the subjects develop a higher incidence of hypometabolism in the future with planned follow-up studies, metabolic dysfunction may be related to persistent epilepsy rather than present at seizure onset.