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Despite that mutations in mitochondrial DNA (mtDNA) have been associated with major epilepsy syndromes, the role of mtDNA instability and mitochondrial dysfunction in epileptogenesis has not been comprehensively examined. In the present study, we investigated the role of mtDNA copy number, oxidative damage, and mtDNA variants as independent or combined risk factors for the development of intractable childhood epilepsy. We analyzed mtDNA copy number and oxidative damage by quantitative polymerase chain reaction (PCR), and mtDNA variants by dot blot in brain tissue specimens collected from 21 pediatric intractable epilepsy patients and 11 non-epileptic patients. Bayesian network and mechanistic hierarchical structure Markov chain Monte Carlo (MCMC) modeling were used to analyze the relationship between these variables. The combined effects of oxidative mtDNA damages and mtDNA copy number produced more significant correlation with epilepsy than that of mtDNA copy number alone with epilepsy. Epilepsy patients showed significant correlations with mtDNA single nucleotide polymorphisms (SNPs) — A1555G, G3196A, T3197C, G9952A, A10006G, A10398G, cortical dysplasia status, oxidative mtDNA damage and relative mtDNA copy number. Comparison of 12 mechanistic structure models suggested that female children who have the wild type allele 10398A and variant allele 9952A, and high mtDNA copy number and oxidative stress have increased probability of developing intractable epilepsy. Estimation of nuclear genes controlling mitochondrial biogenesis, cortical dysplasia, and the effect of the environment using MCMC method showed that these latent variables had a very significant contribution in the development of intractable epilepsy. These data suggest that mitochondrial genetics play a significant role in the pathogenesis of epilepsy in children, and findings of this study may guide the prospects for targeting mitochondria for therapeutic treatment of childhood intractable epilepsy.

Summary Children with intractable epilepsy benefit from early surgical treatment when possible to reduce long-term morbidity. Issues for transition are variable according to type and timing of surgery, and the outcome. When surgery is successful, cognitive and behavioral improvements may not be apparent for several years. The value of continuing antiepileptic drug (AED) treatment after successful surgery remains unclear, and the adjustment to a life without seizures may be challenging.

Many patients who were once considered inoperable are candidates for a wide variety of surgical procedures. This trend is particularly striking at pediatric centers that serve patients with diverse forms of epilepsy that compromise development. Newer diagnostic techniques, including structural and functional imaging, EEG monitoring, and surgical technology, can provide a complete representation of the etiology and expression of the epileptic focus, including accurate cortical localization. This review focuses on several forms of epilepsy that, until recently, were not regarded to be surgically amenable. The adverse seizure and neurobehavioral prognosis in patients with these disorders provides the justification to search for innovative treatments. With more sophisticated tools for preoperative evaluation and an expanding knowledge base, it is likely that the number of surgical candidates will continue to increase in the future.

Malformations of cortical development (MCD) account for a high proportion of medically resistant partial seizures in children and figure prominently in pediatric surgical series. In contrast to the results of epilepsy surgery for postnatally acquired lesions, seizure freedom in patients with MCD is less certain owing to difficulties in defining the epileptic zone, and fully excising the epileptogenic cortex. The authors present evidence that, compared with postnatally acquired lesions such as those due to tumors or trauma, focal epileptogenesis associated with MCD is best conceptualized as a disorder of widespread and patchy disturbance of cortical networks. This developmental perspective implies that the epileptogenic region in MCD is rarely discrete even in patients with focal anatomic lesions, and may include remote cortical or subcortical areas. Preoperative investigative protocols based on this model have improved surgical results, but outcome remains far from optimal and further progress in understanding the complex developmentally based features of MCD is required.

Disorders of cortical development form a spectrum of lesions produced by insults to the developing neocortex. These conditions typically first manifest in childhood with epilepsy, developmental delay, and focal neurologic signs. Although the clinical and electrophysiologic findings are often nonspecific, high-resolution magnetic resonance imaging facilitates diagnosis during life, and assists in delineating specific clinical syndromes. While many patients are dysmorphic and severely affected by mental retardation and epilepsy, some have normal or near-normal cognitive function and no seizures. Molecular studies of dysplastic cortex are providing new insights into the basic mechanisms of brain function and development, while pathologic analysis of tissue removed at surgery is helping to define epileptic circuitry. Treatment of the epilepsy associated with cortical dysplasia is often frustrating, but surgical approaches based on accurately defining epileptogenic regions are proving increasingly successful. Genetic diagnosis is important for accurate counseling of families. (J Child Neurol 1999;14:759-771).

Partial seizures in early postnatal life may be catastrophic and associated with poor long-term outcome. Epilepsy surgery can alleviate partial seizures in older children and adults, but there is little experience with surgical therapy in infancy apart from hemispheric epilepsy syndromes.We analyzed the results of cortical resection to treat medically refractory partial epilepsy in 31 children (16 boys, 15 girls) aged3 years (mean, 18.3 months). Subjects were included only if seizure relief was the primary indication for surgery.Follow-up of at least 1 year (mean, 4.6 years) in 26 patients revealed that 16 were seizure-free, 4 had90% seizure reduction, and 6 had90% reduction. There was no significant difference in seizure outcome between hemispherectomy/multilobar resections and lobar resections or temporal versus extratemporal resection. Seizure outcome was independent of the amount of cortex removed in nonlesional patients. Only the presence of a discrete lesion on preoperative neuroimaging correlated with a favorable outcome. Family perceptions of accelerated development in seizure-free patients were not confirmed on developmental assessment.We conclude that cortical resection often benefits very young children with catastrophic partial seizures, but does not guarantee enhanced neurological development. The location and extent of the excised cortex may not be critical as long as the entire epileptogenic region and lesion are removed.

Object Refractory status epilepticus (RSE) is a life-threatening neurological emergency associated with high morbidity and mortality. Affected patients often require prolonged intensive care and can suffer multiple complications. Surgical intervention to control RSE is rarely used but can obviate the risks of prolonged seizures and intensive care treatment. Authors of the present study analyzed their experience with the surgical management of patients suffering from RSE. Methods The Epilepsy Surgery Database at Miami Children's Hospital was reviewed for patients who had undergone surgery for RSE. Clinical presentation, electrophysiological profile, radiological data, surgical details, and postoperative course were evaluated. Results Between 1990 and 2012, 15 patients underwent surgery for uncontrolled seizures despite high-dose medical suppressive therapy. The mean preoperative duration of status epilepticus was 8 weeks. Ictal SPECT and FDG-PET imaging in conjunction with intraoperative electrophysiological studies helped to outline the extent of resection. Surgical intervention controlled seizures in all patients and facilitated the transition out of intensive care. Adverse events related to a prolonged intensive care unit stay included sepsis and respiratory complications. Four patients had worsened neurological function, developing hemiparesis and dysphasia. There was no operative mortality. Conclusions Surgical intervention can successfully control refractory partial status epilepticus, prevent associated morbidity, and decrease intensive care unit stay. Ictal SPECT and PET are valuable in guiding resection.

Summary Purpose Variable predictors of postsurgical seizure outcome have been reported in children with tuberous sclerosis complex (TSC). We analyzed a large surgical series of pediatric TSC patients in order to identify prognostic factors crucial for selection of subjects for epilepsy surgery. Methods Thirty-three children with TSC who underwent excisional epilepsy surgery at Miami Children's Hospital were retrospectively reviewed. A total of 29 clinical, neuropsychological, electroencephalography (EEG), magnetic resonance imaging (MRI), and surgical variables were analyzed and related to seizure outcomes. Univariate Barnard's exact test, Wilcoxon's rank-sum test, and multivariate statistical Cox's model were used to examine the significance of associations between the variables and seizure outcome. Key Findings Eighteen patients (55%) have been seizure-free 2 years after (final) surgery; postoperative complications occurred in five subjects (15%). Complete removal of epileptogenic tissue detected by both MRI and intracranial EEG, regional scalp interictal EEG patterns, and agreement of interictal and ictal EEG localization were the most powerful predictors of seizure-free outcome. Other significant predictors included occurrence of regional scalp ictal EEG patterns, fewer brain regions affected by tubers, presence of preoperative hemiparesis, and one-stage surgery. Remaining factors such as age at seizure onset, incidence of infantile spasms or other seizure types, duration of epilepsy, seizure frequency, mental retardation, as well as types and extent of resections did not influence outcome. Significance Perioperative features rather than preoperative variables are the most important determinants of postsurgical seizure outcome in patients with TSC. Our findings may assist in the surgical management of these patients.

Although certain clinical, electroencephalographic (EEG), magnetic resonance imaging (MRI), and pathologic findings in adults with intractable temporal lobe epilepsy predict seizure outcome following temporal lobectomy, predictors of seizure outcome have not been studied systematically in pediatric temporal lobectomy series. We retrospectively analyzed preoperative clinical, EEG, and neuroimaging findings with reference to seizure outcome (seizure free or non-seizure free) in 33 children (mean age, 9.3 years) who underwent tailored temporal lobe resections for intractable temporal lobe epilepsy. Trends were apparent with (1) younger age at seizure onset, younger age at surgery, shorter duration of epilepsy, localized unilateral temporal lesions on MRI, and right-sided surgery more frequently associated with a seizure-free outcome, and (2) significant prior history, daily preoperative seizures, generalized motor seizures, mental retardation, and localized unilateral temporal epileptiform EEG activity more frequently associated with a non-seizure-free outcome. However, none of these findings, alone or in combination, correlated with postoperative seizure status at a statistically significant level. Submitting the four variables generally considered to be most predictive of favorable outcome (ie, normal intelligence, unilateral ictal and interictal EEG discharges, and focal temporal MRI lesion) to a multiple-cutoff procedure did not predict seizure freedom. Our data indicate that predictors of outcome of temporal lobectomy in adults may not apply in children, perhaps due to inherent neurobiologic differences in the etiology and expression of temporal lobe epilepsy, and should therefore not be used as sole determinants of surgical candidacy in children. (J Child Neurol 1996;11:445-450).

There has been important progress in the identification of antiepileptic compounds and their indications in children over the past 15 years: their number has doubled and specific pediatric trials are being performed to document their effect according to seizures and syndromes as well as their tolerability in pediatrics. The improved understanding of pharmacokinetics and drug–drug interactions has helped to optimize treatment. Specific issues specific of infants have also been studied although new antiepileptic drugs are still dramatically lacking for this age group. Before reaching a syndromic diagnosis, the choice of a first- line agent goes to compounds with the largest range of efficacy and least identified risks. Subsequent choices are mainly based on the epilepsy syndrome and seizure type in addition to good clinical practice to determine dose, adverse effect profile, risk of aggravating seizures and drug interactions, clinician's experience, cultural habits, and availability of drugs. If there are several options, preference is given to the compound that exhibits the best risk/benefit ratio, or the most rapid titration when seizure frequency is the major issue. For new antiepileptic compounds, price is often a limiting factor in countries with poor insurance coverage. Third generation anti-epileptic drugs are emerging which also seem to be promising.

Two children developed severe cognitive and behavioral deterioration suggestive of a degenerative disease while being treated with sodium valproate for idiopathic, localization-related epilepsy with centrotemporal spikes. Magnetic resonance imaging revealed marked central and generalized cortical and cerebellar atrophy. In both patients, clinical symptoms and signs cleared in a few weeks following valproate withdrawal. The magnetic resonance imaging appearance improved within 3 months in 1 of the patients and normalized in both after 6 and 12 months. No metabolic changes were associated with the clinical or imaging abnormalities. Although the mechanism of this rare idiosyncratic complication of valproate therapy is unknown, we advocate discontinuing valproate therapy in all epileptic patients with neuromental deterioration or brain atrophy of unknown etiology.

The practice of operating on children with chronic epilepsy is rapidly gaining acceptance as an important therapeutic modality. This review summarizes some of the recent advances in pediatric epilepsy surgery in relation to the natural history of chronic childhood seizures, surgical treatment, and outcome. Candidate selection has been greatly facilitated by new information bearing on the natural history of medically resistant seizures and the greater than expected incidence of early hippocampal sclerosis. Because the majority of children suffer from extratemporal epilepsy, ictal single photon emission computed tomography and subdural electroencephalogram recording are becoming increasingly important for both seizure and functional localization in the child, and have been shown to be well tolerated, even in very young patients. Furthermore, the outcome of both excisional and commissural procedures in early life with respect to seizure control is similar to that reported for adults, irrespective of age. More information about the long-term effects of epilepsy surgery in children is urgently needed, but the available data confirms surgical therapy as an effective intervention with low morbidity.

Summary Purpose To assess the predictive value of ictal single-photon emission computed tomography (SPECT) for outcome after excisional epilepsy surgery in a large population of children with focal cortical dysplasia (FCD). Methods One hundred seventy-three ictal SPECT studies in 106 children with histologically proven FCD were retrospectively analyzed. The extent and location of ictal hyperperfusion and completeness of surgical removal were assessed. Completeness of resection of epileptogenic regions defined by ictal SPECT, electroencephalography (EEG), and magnetic resonance imaging (MRI) were compared and correlated with postoperative seizure outcome. In addition, subcortical activation of the cerebellum, basal ganglia, and thalamus were analyzed. Key Findings The extent of hyperperfusion was focal or lobar in 58%, whereas multilobar activations occurred in only 32%; hemispheric or bilateral findings were rare. Favorable postsurgical seizure outcome was achieved in 67% patients with nonlocalized SPECT findings, 45% with nonresected ictal hyperperfusion, 36% with partially resected ictal hyperperfusion, and 86% when the zone of ictal hyperperfusion was completely resected (p = 0.000198). The favorable postsurgical outcome after complete removal of the SPECT hyperperfusion zone surpassed the 75% rate of seizure freedom in patients with removal of MRI/EEG-defined epileptogenic region. A similar predictive value of ictal SPECT for seizure outcome was found in nonoperated patients and subjects who were undergoing reoperation. Subcortical activation conferred no predictive value. Significance Ictal SPECT helps to define the epileptogenic zone in a high proportion of children with FCD undergoing surgical evaluation. Complete removal of both SPECT and MRI/EEG-defined regions is a strong predictor of surgical success and has important implications for surgical planning.

Epilepsy surgery has proven to be a valuable therapy in the management of pharmacoresistant seizures in childhood. The goal of surgery is to identify and safely remove epileptogenic tissue and render the child seizure free. This is accomplished through intensive multimodality preoperative investigations designed to accurately localize the epileptogenic region and anatomically characterize functionally critical cortical areas subserving language, movement, and vision. Seizure semiology must be characterized and correlated with the results of electroencephalograhy (EEG) investigations and anatomic and functional imaging. Most pediatric epilepsy surgery centers perform video-EEG and magnetic resonance imaging (MRI). Positron emission tomography and ictal single photon emission computed tomography are also obtained frequently. Postprocessing of the MRI utilizing techniques such as voxel-based three-dimensional analysis has shown exceptional promise for detecting subtle malformative lesions involving the cortex and subcortical white matter. All of these initial investigations can be performed noninvasively and reviewed by a multidisciplinary team. Patients with a poorly delineated epileptogenic zone or seizures that are thought to be arising in or near critical cortex often require chronic extraoperative implantation of subdural or depth electrodes. Newer investigative modalities and further refinement of existing techniques hold promise for improved candidate selection and cortical localization.

Summary: The relation between hyperventilation (HV)-induced high-amplitude rhythmical slowing (HIHARS) and altered responsiveness without generalized spike and wave activity has not been clearly defined. To test whether altered responsiveness is a nonspecific physiologic response rather than a symptom of generalized epilepsy, we assessed verbal recall ability and motor response testing in 12 healthy nonepileptic children (mean age 9.6 years). Both tasks were administered as a baseline before HV, during HV but before onset of EEG slowing, and during HIHARS. Verbal recall and motor responsiveness remained unchanged during baseline and HV before onset of slowing. During HIHARS, all children exhibited impaired verbal recall (p

In the course of evaluating children with posterior temporal lobe epilepsy with subdural electrodes, we observed that their seizures commonly arose from basal rather than convexity foci and that they followed a stereotyped clinical sequence. Seizures characteristically began with behavioral arrest that coincided with basal temporal seizure discharges and progressed to motor signs as the seizure activity spread to the ipsilateral cortical convexity. Behavioral automatisms were observed in approximately half the patients, but were never the first or most prominent ictal manifestation. Focal lesions were identified preoperatively in 7 patients. We performed tailored temporal lobe resections in 14 patients, 10 (71%) of whom were seizure free (N = 9) or had occasional auras (N = 1) at a mean follow-up of 2 years. These findings suggest that in childhood, posterior temporal seizures frequently arise from basal cortex and have a consistent and recognizable ictal and electrographic semiology. In medically refractory patients, tailored temporal resection is an effective therapy.

To define the contribution of the EEG evaluation in children with seizures and Sturge-Weber syndrome, we reviewed EEG data in 14 radiologically confirmed cases. Thirteen exhibited marked voltage attenuation that was localized to the region of the cerebral angiomatosis. Polymorphic slowing occurred ipsilateral to the lesion in six patients and was bilateral in six. By contrast, interictal spikes were evident in only two patients and did not always correlate with the angiomatosis. Seizures were captured in four patients and consistently revealed ictal discharges only at the periphery of the lesion. These findings indicate that abnormalities of EEG background rather than interictal spikes are consistently present early in the course of Sturge-Weber syndrome and correlate with the region of angiomatosis.

Dominant mesial temporal lobe resection for pharmacoresistant epilepsy is frequently associated with verbal memory impairment. More-extensive lesioning improves seizure outcome, but further compromises memory. A better understanding of ipsilateral neural structures and networks for verbal memory could improve selectivity of surgical ablation, thereby holding promise for seizure-freedom without memory impairment.

Prenatal and perinatal adverse events are reported to have a pathogenetic role in focal cortical dysplasia (FCD). However, no data are available regarding the prevalence and significance of this association. A cohort of children with significant prenatal and perinatal brain injury and histologically proven mild malformations of cortical development (mMCD) or FCD was analyzed.We retrospectively evaluated a surgical series of 200 patients with histologically confirmed mMCD/FCD. Combined historical and radiologic inclusion criteria were used to identify patients with prenatal and perinatal risk factors. Electroclinical, imaging, neuropsychological, surgical, histopathologic, and seizure outcome data were reviewed.Prenatal and perinatal insults including severe prematurity, asphyxia, bleeding, hydrocephalus, and stroke occurred in 12.5% of children with mMCD/FCD (n = 25). Their epilepsy was characterized by early seizure onset, high seizure frequency, and absence of seizure control. Patients with significant prenatal and perinatal risk factors had more abnormal neurologic findings, lower intelligence quotient (IQ) scores, and slower background EEG activity than mMCD/FCD subjects without prenatal or perinatal brain injury. MRI evidence of cortical malformations was identified in 74% of patients. Most patients underwent large multilobar resections or hemispherectomies; 54% were seizure-free 2 years after surgery. Histologically "milder" forms of cortical malformations (mMCD and FCD type I) were observed most commonly in our series.Surgically remediable low-grade cortical malformations may occur in children with significant prenatally and perinatally acquired encephalopathies and play an important role in the pathogenesis of their epilepsy. Presurgical detection of dysplastic cortex has important practical consequences for surgical planning.

This study investigated differences in propositional language organization in children with developmental and acquired brain lesions. We evaluated 30 right-handed subjects with intractable epilepsy due to either focal cortical dysplasia or hippocampal sclerosis with neuropsychological testing and functional MRI prior to epilepsy surgery. Atypical activations were seen in both prenatal and early postnatal lesions, but the contribution of specific histopathological substrate was minimal. Atypical organization of both temporal and frontal language areas also correlated inversely with receptive vocabulary scores. The data demonstrated a greater propensity toward atypical activation patterns for receptive than expressive networks, particularly when lesions were located in the dominant temporal lobe. Atypical language organization was not correlated with seizure-related factors such as age at onset or duration of epilepsy. The patterns of atypical language activation support prior studies implicating proximity of pathology to eloquent cortex in the dominant hemisphere as the primary determinant of functional reorganization.

According to the Epilepsy Foundation, about 45,000 children under the age of 15 develop epilepsy each year. One of the long-standing challenges in the field of pediatric epilepsy research is to differentiate between normal and epileptic brain areas. This problem is especially important for children with intractable epilepsy, because surgical intervention must be used to alleviate their epileptic symptoms. Optical spectroscopy may be used to assess the pathophysiological characteristics of the epileptic brain tissue intraoperatively in a non-destructive manner, which, in turn, allows surgeons to plan an epilepsy surgery. Herein, the study is focused on demonstrating the feasibility of using time-dependent, diffuse reflectance spectroscopy specifically to detect pathophysiological characteristics associated with epileptic brain tissue. In a pediatric patient undergoing epilepsy surgery, time-dependent, diffuse reflectance spectra were measured from the epileptic cortex and the surrounding tissue using a fiber-optic spectroscopy system. The system was designed to acquire diffuse reflectance spectra from 300 - 1100 nm at a maximum acquisition rate of 33 Hz. Spectral and temporal variations in the acquired spectral sequences were compared to the corresponding electrocorticographic results, and thosevariations unique to the epileptic cortex were identified using statistical methods. Furthermore, these spectral variations were related to the physiological and morphological characteristics of the brain tissue. The preliminary results obtained from this in vivo study demonstrate the feasibility of differentiating epileptic cortex tissue from normal tissue using time-dependent, diffuse reflectance data.

Children with medically resistant temporal lobe seizures that persist into adolescence often experience psychosocial deterioration and medical morbidity. It is therefore especially important to evaluate the contribution of surgical therapy in preadolescent children. We describe our experience with temporal lobectomy in 16 children less than 12 years (mean age 7 years) who had intractable seizures of temporal lobe origin. Structural lesions were identified on neuroimaging studies in 11 patients. In all patients, the standard anterior temporal lobectomy was tailored according to the extent of the lesion and epileptogenic field. At follow-up, 11 children were seizure-free, three were 90% improved, one was 50% improved, and one was unchanged. Neuropathological abnormalities were identified in virtually all children. Prenatally acquired abnormalities of neurogenesis were the most common, whereas mesial temporal sclerosis was found in only two children. We conclude that tailored temporal lobectomy in the first decade of life is highly beneficial in carefully selected children with medically refractory seizures.

Partial seizures, the most frequent type of epilepsy at all ages, remain a distinct yet relatively understudied disorder in early life. Their true incidence has not been defined, despite an extremely unfavorable long-term prognosis. They differ from partial seizures presenting later in life in several important aspects and are prone to misdiagnosis because of the difficulties inherent in recognizing subtle seizure manifestations and in assessing level of consciousness in very young patients. Most seizures are symptomatic of assorted prenatally acquired hemispheric insults; perinatal damage and tumors are less common. Video-electroencephalographic studies indicate that the majority of ictal events consist of behavioral arrest, stereotyped automatisms, and motor phenomena. Oroalimentary and gross motor automatisms are frequent, whereas highly organized gestural and behavioral sequences are extremely rare. Lateralized or asymmetric tonic, clonic, and occasional myoclonic motor manifestations characterize the majority of episodes. Pure behavioral arrest is much less common. These seizure patterns imply immaturity of systems responsible for inhibiting access to motor pathways and for organizing motor expression. Ictal and interictal epileptiform discharges are often focal or lateralized but lack age-specific features. Although as a rule partial seizures persist, some individuals display generalized or mixed seizure disorders in later life. ( J Child Neurol 1992;7:66-69).

There are no reports of an association between obsessive-compulsive disorder and cingulate epilepsy in childhood. We report the behavioral, cognitive, and EEG findings in a young girl with medically resistant seizures and severe obsessive-compulsive symptomatology. Her Scalp EEG and neuropsychological test scores suggested right frontal lobe dysfunction. The intractability of her seizures and progressive intellectual and psychosocial deterioration prompted evaluation for excisional surgery. Intracranial EEG recording demonstrated a focal seizure origin in the right anterior cingulate gyrus. Cingulotomy resulted in freedom from seizures and significant improvement in her obsessive-compulsive symptoms.

The pitfalls and difficulties in accurately localizing seizure foci are reviewed. Basic issues regarding modeling, volume conduction, inhomogeneities, and corticocortical propagation are discussed, and the limitations of scalp and intracranial recordings are outlined. The ambiguities in interpreting patterns and their significance are highlighted with a concluding commentary on pitfalls in defining the epileptogenic region.

The personality features, neuropsychological data, and ictal characteristics of 23 patients with nonepileptic seizures (NES) were compared to 25 patients with EEG-confirmed epileptic seizure (ES) disorders. A distinctive pattern of seizure, behavior, and personality features was evident in NES patients. NES was characterized by later disease onset and shorter disease duration. NES tends to last significantly longer than ES and rarely results in tongue-biting or self-injury. Patients who develop NES frequently have witnessed seizures prior to developing the disorder and have greater somatic concerns than patients with ES. Neuropsychological group data failed to differentiate NES from ES. However, the absence of group differences may reflect heterogeneity within the NES population. Although many NES patients performed well within normal limits on all neuropsychological measures, most were mildly to severely impaired. Qualitative analysis of neuropsychological data also revealed inconsistencies within the NES group. These findings suggest that a more global neurobehavioral profile may be useful in the diagnosis of NES. Future studies of NES must also recognize that important individual differences may be masked within group data.

The pre-operative assessment and surgical management of children and young adults with MRI-negative, frontal lobe epilepsy is often challenging owing to the semiologic expression being unusual or non-lateralizing. Localization based on functional tests may be non-convergent, further compounding the difficulty of surgical planning. We describe a patient with seizures presenting with early, subjective akinesia of the dominant hand that were at times triggered by repetitive motor tasks. Subdural EEG monitoring revealed seizure-origin in the ipsilateral dorsolateral frontal lobe. After resective surgery the patient has had a seizure free period of 9 months, and is free of deficits. This is the first report of frontal lobe seizure semiology consisting of ipsilateral ictal akinesia.

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.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.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 experienced90% reduction, 17 had50% reduction, and 25 were unchanged. At 5-year follow-up, 35 of 76 patients were seizure-free, 12 experienced90% reduction, 12 had50% reduction, and 17 were unchanged. At 10-year follow-up, 16 of 43 patients were seizure-free, 13 experienced90% reduction, 7 had50% reduction, and 7 were unchanged. Outcomes correlated with the presence of convergent focal interictal spikes (p0.005) on the scalp EEG and completeness of resection (p0.0005).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.

The defining role of language for communicating and forming social bonds has captured the imagination of scientists and scholars throughout the ages, and scientific inquiry into the neural correlates of language is now centuries old. Theories of linguistic structure and function occupy center stage in fields as diverse as neuroscience, embryology, anthropology and evolution. This should come as no surprise as the neural basis of linguistic function holds promise for understanding how the mind works and what makes us uniquely human.

Epileptogenic lesions and their margins are often difficult to define intraoperatively. We hypothesize that optical spectroscopy can detect unique pathophysiological features of epileptogenic lesions in children and hence differentiate them from normal brain. This hypothesis was tested by comparing the in vivo optical and fluorescence characteristics of epileptogenic brain lesions (non-neoplastic) with those of normal brain. Patients were recruited from those receiving epilepsy surgeries at Miami Children's Hospital. Using a portable spectroscopic system, optical characterization of brain was performed intraoperatively. Fluorescence spectra were measured at 337 nm excitation, and diffuse reflectance spectra were measured between 400 and 850 nm. To date, seven epilepsy patients have been enrolled in the study. A couple interesting trends have been observed in the recorded optical spectra. First, sites within the resection zone, as defined by the intracranial electroencephalogram data, often show higher diffuse reflectance signals than normal sites do. This is especially prominent around 500 nm and between 650 and 850 nm. Secondly, several investigated sites with abnormal electroencephalogram and/or pathology show a unique blue shift in their fluorescence spectra, which is not seen in other cases.

We describe the brain magnetic resonance imaging (MRI) findings in eight neonates with tuberous sclerosis complex to further delineate the spectrum of characteristic findings in these patients. In addition to the previously described characteristic brain MRI findings in neonates, which included cortical tuber, transmantle dysplasia, subependymal nodules, cerebral subependymal giant cell astrocytomas, white-matter anomalies, and hemimegalencephaly, we found one neonate with cerebellar subependymal giant cell astrocytomas and one patient who had a normal MRI and computed tomographic scan of the brain at 4 days of age but subsequently was found to have cortical tubers and subependymal nodules by MRI. ( J Child Neurol 2006;21:280—285; DOI 10.2310/7010.2006.00103).

Hallucinations are commonly believed to reflect temporal lobe dysfunction. This report presents the clinical, electroencephalographic, and neuroimaging findings in an 8-year-old male who experienced the acute onset of ictal auditory and visual hallucinations associated with epileptic activation of the right orbitofrontal region. Right frontal lobe surgery resulted in seizure freedom and disappearance of his psychotic symptoms. Histologic tissue examination revealed non-balloon cell Taylor type cortical dysplasia.

The authors compared interictal and ictal abnormalities from chronic intracranial recordings in children with Taylor-type cortical dysplasia (TTCD) and nondysplastic lesions. Interictal epileptiform discharges and ictal patterns were retrospectively analyzed in 13 children with TTCD and 12 children with nondysplastic lesions (tumor, 4; gliosis, 8). Features analyzed and compared between groups included the morphologic and temporal characteristics and field distribution of ictal and interictal patterns and rapidity of ictal propagation. The frequency of runs of interictal continuous epileptiform discharges (CEDs) or bursts of fast activity did not differ significantly between dysplastic and nondysplastic tissue. Fast frequencies characterized the majority of seizure onsets (49/67) in dysplastic patients and repetitive spikes were more frequent at seizure onset (31/56) in nondysplastic patients (P < 0.002). Field of ictal onset was limited to adjacent cortex and independent of histology. The interval between seizure onset and spread to adjacent or nonadjacent cortex was significantly shorter in dysplastic than nondysplastic patients. Interictal EEG patterns are not specific markers of dysplastic cortex but the morphology of ictal onset differs significantly with dysplastic cortex showing significantly more rapid propagation than nondysplastic cortex. These findings suggest that markers other than CEDs physiologically characterize dysplastic cortex and that children with TTCD exhibit more widespread excitability of neural pathways.

Two pathologic subtypes based on the presence or absence of balloon cells have been described in cortical dysplasia of Taylor (CDT).To determine whether the pathologic subtype has any distinct clinical or MRI features that are relevant to management.The histopathologic, clinical, and MRI features of 34 children with CDT who underwent epilepsy surgery at Miami Children's Hospital from 1990 to 2001 were investigated.Bizarre neuronal cytomegaly was the primary pathologic feature of 15 patients with the dysplasia-only subtype, and 19 cases showed additional characteristics including balloon cells and marked white matter abnormalities. Both groups presented with severe intractable epilepsy of very-early-onset, multiple daily seizures, cognitive disability, and focal neurologic deficits. The dysplasia-only subtype had higher rates of neonatal onset, hemiparesis, and severe mental retardation (p0.05). The MRI features of focal cortical thickening with associated cortical T2 signal change showed excellent sensitivity (94%) and reasonable specificity (73%) for the diagnosis of the balloon cell subtype. The overall surgical outcome was 59% seizure freedom at 2 years.Children with cortical dysplasia of Taylor type have in common a very-early-onset, severe epilepsy with neurologic co-morbidity. Patients with the non-balloon cell pathologic subtype have a more severe phenotype. A trend toward a better outcome in the balloon cell group suggests that preoperative identification of these subtypes may impact surgical planning.

Chinese star anise (Illicium verum Hook f.) is a well-known spice used in many cultures. Many populations use it as a treatment for infant colic. Japanese star anise (Illicium anisatum L), however, has been documented to have both neurologic and gastrointestinal toxicities. Recently, concern has been raised regarding the adulteration of Chinese star anise with Japanese star anise. We report 7 cases of adverse neurologic reactions in infants seen with the home administration of star anise tea. In addition, we have found evidence that Chinese star anise has been contaminated with Japanese star anise. More strict federal regulation of the import of star anise into the United States is warranted. Star anise tea should no longer be administered to infants because of its potential danger in this population.

Objective: To determine the current best practice for treatment of infantile spasms in children. Methods: Database searches of MEDLINE from 1966 and EMBASE from 1980 and searches of reference lists of retrieved articles were performed. Inclusion criteria were the documented presence of infantile spasms and hypsarrhythmia. Outcome measures included complete cessation of spasms, resolution of hypsarrhythmia, relapse rate, developmental outcome, and presence or absence of epilepsy or an epileptiform EEG. One hundred fifty-nine articles were selected for detailed review. Recommendations were based on a four-tiered classification scheme. Results: Adrenocorticotropic hormone (ACTH) is probably effective for the short-term treatment of infantile spasms, but there is insufficient evidence to recommend the optimum dosage and duration of treatment. There is insufficient evidence to determine whether oral corticosteroids are effective. Vigabatrin is possibly effective for the short-term treatment of infantile spasm and is possibly also effective for children with tuberous sclerosis. Concerns about retinal toxicity suggest that serial ophthalmologic screening is required in patients on vigabatrin; however, the data are insufficient to make recommendations regarding the frequency or type of screening. There is insufficient evidence to recommend any other treatment of infantile spasms. There is insufficient evidence to conclude that successful treatment of infantile spasms improves the long-term prognosis. Conclusions: ACTH is probably an effective agent in the short-term treatment of infantile spasms. Vigabatrin is possibly effective.

The aim of this study was to adapt the Australian Quality of Life in Childhood Epilepsy Questionnaire (QOLCE) and determine its psychometric properties in a North American population. Participants were North American families with children diagnosed with epilepsy. Parents were asked to complete the American QOLCE (USQOLCE) and the Child Health Questionnaire (CHQ). Seventy-one families completed the USQOLCE. The internal consistency reliability of the subscales was good. USQOLCE subscales correlated highly with theoretically similar subscales contained in the CHQ. Theoretically dissimilar subscales on the two instruments did not correlate as well. USQOLCE correlated significantly with a parental rating of seizure severity and an independent measure of degree of postoperative seizure control. This study demonstrated that the USQOLCE is suitable for a North American population with evidence of its reliability and validity including its sensitivity to seizure burden.

Accumulating data suggest that the antiepilepsy drug lamotrigine, which has been available for adult use for more than a decade, also confers broad-spectrum, well-tolerated control of epilepsy in children. The current study—the open-label continuation phase of several short-term clinical trials—was conducted to assess the long-term tolerability and efficacy of lamotrigine as open-label adjunctive therapy or monotherapy in pediatric patients for a variety of seizure types and syndromes including partial seizures, absence seizures, and Lennox-Gastaut syndrome. Clinic visits occurred every 24 weeks throughout the treatment period. A total of 252 patients under 16 years of age were enrolled in the study. The numbers of patients exposed to at least 48 weeks, 96 weeks, and 144 weeks of treatment with lamotrigine were 185 (73.4%), 119 (47.2%), and 60 (23.8%), respectively, for an average duration of exposure of 96.7 weeks. The most common adverse events considered by the investigator to be drug related were dizziness (9.1%), somnolence (7.9%), nausea (6.3%), vomiting (5.2%), and headache (5.2%). The most common serious adverse events (regardless of suspected cause) included pneumonia (3.0%) and infection (1.9%). Investigators judged that the overall clinical status of three-fourths of the patients had improved at treatment weeks 48 and 96 relative to prelamotrigine clinical status. Lamotrigine administered as monotherapy or adjunctive therapy for an average of 2 years (96.7 weeks) was well tolerated and effective in pediatric patients with partial or generalized epilepsy. These results complement and extend the large body of data demonstrating the tolerability and efficacy of lamotrigine with short- and long-term use in adults. (J Child Neurol 2002;17:278-285).