A. Simon Harvey

Defining the spectrum of international practice in pediatric epilepsy surgery patients

Purpose: The Pediatric Epilepsy Surgery Sub‐commission of the International League Against Epilepsy conducted a survey to determine the frequency of epilepsy procedures and etiologies.

EEG source localization in focal epilepsy: Where are we now?

Electroencephalographic source localization (ESL) by noninvasive means is an area of renewed interest in clinical epileptology. This has been driven by innovations in the computer‐assisted modeling of dipolar and distributed sources for the investigation of focal epilepsy; a process fueled by the ever‐increasing computational power available to researchers for the analysis of scalp EEG recordings. However, demonstration of the validity and clinical utility of these mathematically derived source modeling techniques has struggled to keep pace. This review evaluates the current clinical “fitness’ of ESL as applied to the focal epilepsies by examining some of the key studies performed in the field, with emphasis given to clinical work published in the last five years. In doing so, we discuss why ESL techniques have not made an impact on routine epilepsy practice, underlining some of the current problems and controversies in the field. We conclude by examining where ESL currently sits alongside magnetoencephalography and combined EEG‐functional magnetic resonance imaging in the investigation of focal epilepsy.

Accuracy of Bedside Electroencephalographic Monitoring in Comparison With Simultaneous Continuous Conventional Electroencephalography for Seizure Detection in Term Infants

OBJECTIVE. Our goals were to compare (1) single-channel amplitude-integrated electroencephalography alone, (2) 2-channel amplitude-integrated electroencephalography alone, and (3) amplitude-integrated electroencephalography plus 2-channel electroencephalography with simultaneous continuous conventional electroencephalography for seizure detection in term infants to check the accuracy of limited channels and compare the different modalities of bedside electroencephalography monitoring. METHODS. Infants referred to a tertiary center with clinical seizures underwent simultaneous continuous conventional electroencephalography and 2-channel (C3-P3 and C4-P4) bedside monitoring. Off-line analysis of the continuous conventional electroencephalographic results was performed independently by 2 neurologists. Two experienced neonatal readers reviewed results obtained with amplitude-integrated electroencephalography and 2-channel electroencephalography combined and single-channel and 2-channel amplitude-integrated electroencephalography. All readings were performed independently and then compared. RESULTS. Twenty-one term newborns were monitored. Seizures were detected in 7 patients who had up to 12 electrical seizures, with 1 infant in status epilepticus. Seizures were identified correctly in 6 of 7 patients with amplitude-integrated electroencephalography plus 2-channel electroencephalography. The missed infant had an isolated 12-second seizure. With amplitude-integrated electroencephalography plus 2-channel electroencephalography, 31 of 41 non–status epilepticus seizures were correctly identified (sensitivity, 76%; specificity, 78%; positive predictive value, 78%; negative predictive value, 78%), with a substantial level of interrater agreement. The seizures missed were predominantly slow sharp waves of occipital origin from a single patient (7 of 10 seizures). Nine false-positive results were obtained in 351 hours of recording (1 false-positive result per 39 hours). These were thought to be related to muscle, electrode, and patting artifacts. Use of amplitude-integrated electroencephalography alone (1 or 2 channel) provided low sensitivity (27%–56%) and low interobserver agreement. CONCLUSIONS. Limited-channel bedside electroencephalography combining amplitude-integrated electroencephalography with 2-channel electroencephalography, interpreted by experienced neonatal readers, detected the majority of electrical seizures in at-risk newborn infants.

Guidelines for imaging infants and children with recent-onset epilepsy

The International League Against Epilepsy (ILAE) Subcommittee for Pediatric Neuroimaging examined the usefulness of, and indications for, neuroimaging in the evaluation of children with newly diagnosed epilepsy. The retrospective and prospective published series with n ≥30 utilizing computed tomography (CT) and magnetic resonance imaging (MRI) (1.5 T) that evaluated children with new‐onset seizure(s) were reviewed. Nearly 50% of individual imaging studies in children with localization‐related new‐onset seizure(s) were reported to be abnormal; 15–20% of imaging studies provided useful information on etiology or and seizure focus, and 2–4% provided information that potentially altered immediate medical management. A significant imaging abnormality in the absence of a history of a localization‐related seizure, abnormal neurologic examination, or focal electroencephalography (EEG) is rare. Imaging studies in childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and benign childhood epilepsy with centrotemporal spikes (BECTS) do not identify significant structural abnormalities. Imaging provides important contributions to establishing etiology, providing prognostic information, and directing treatment in children with recently diagnosed epilepsy. Imaging is recommended when localization‐related epilepsy is known or suspected, when the epilepsy classification is in doubt, or when an epilepsy syndrome with remote symptomatic cause is suspected. When available, MRI is preferred to CT because of its superior resolution, versatility, and lack of radiation.

Hypothalamic Hamartoma and Seizures: A Treatable Epileptic Encephalopathy

Summary:  Hypothalamic hamartomas may be associated with gelastic seizures, focal seizures, and a generalized epileptic encephalopathy, with severe seizures and cognitive and behavior decline. Despite earlier views to the contrary, good evidence now exists that all these clinical features are caused, directly or indirectly, by the hamartoma. Resection of these lesions was long regarded as too hazardous and unlikely to benefit seizure control. It is now clear that hypothalamic hamartomas can be effectively treated with a variety of surgical approaches with sustained seizure control and often seizure freedom. Qualitative observations suggest that behavior and cognition also improve with treatment, but quantitative validation is required. The specific approach should be tailored according to the surgical anatomy of the lesion and the experience of the surgeon. Choices include a transcallosal approach (good for intraventricular lesions), a pterional approach (useful for interpeduncular lesions), a transventricular endoscopic approach, or destruction of the lesion with radiofrequency probes or gamma knife radiosurgery. The previously dismal outlook for children with severe seizures associated with this lesion has now dramatically changed. These insights may have implications for other epileptic encephalopathies of childhood.

Community‐Based Study of Mortality in Children with Epilepsy

Summary: Summary: We used the records of a statewide pediatric mortality surveillance system to determine mortality rates and causes of death in children with epilepsy. Of the 1,095 children aged 1–14 years who died in the state of Victoria during the study period 1985–1989,93 had a history of epilepsy. Six children (6%) had primary epilepsy, and 87 (94%) had secondary epilepsy. Death was (a) directly attributable to epilepsy in 20 (22%), including 11 with sudden unexplained death, (b) not directly attributable to epilepsy in 59 (63%), and (c) of undetermined cause in 14 (15%). No classifiable death occurred as a direct result of status epilepticus. The average annual mortality rates for children with epilepsy were (a) death from all causes, 30.6 in 10,000 [95% confidence interval (CI) 19.7, 47.51, and (b) death attributable to epilepsy, 6.6 in 10,000 (95% CI 3.7, 11.8). Relative to the all‐cause mortality rate in children without epilepsy, the all‐cause mortality rate ratios were (a) all children with epilepsy, 13.2 (95% CI 8.5, 20.7); (b) primary epilepsy, 1.1 (95% CI 0.5, 2.6); and (c) secondary epilepsy, 49.7 (95% CI 31.7, 77.9). The mortality rate ratios for secondary epilepsy relative to primary epilepsy were (a) death from all causes, 43.5 (95% CI 19.0, 99.5); and (b) death attributable to epilepsy, 9.0 (95% CI 3.3, 24.8). Epilepsy appeared on the death certificate of only 11 of 20 (55%) children whose deaths were attributable to epilepsy. We conclude that (a) there was an increased risk of death during childhood in children with epilepsy; (b) the risk of death was greatest for children with secondary epilepsy; (c) potentially preventable, epilepsy‐related deaths occurred in children with primary epilepsy; (d) sudden unexplained death accounted for at least 12% of deaths; and (e) death certification was deficient with respect to recording of epilepsy.

Febrile seizures and hippocampal sclerosis: Frequent and related findings in intractable temporal lobe epilepsy of childhood

The relationship between hippocampal sclerosis, febrile seizures, and complex partial seizures in temporal lobe epilepsy continues to be the subject of great debate in the literature. Hippocampal sclerosis is reported infrequently in young children with temporal lobe epilepsy, a factor that has supported the theory that hippocampal sclerosis develops in later life during the course of recurrent complex partial seizures. In a blinded review of magnetic resonance imaging in 53 children, aged 2-17 years (mean: 10 years) with temporal lobe epilepsy, hippocampal sclerosis was diagnosed in 30 children (57%), concordant with ictal electroencephalographic lateralization in 93% and pathologic diagnosis in all children who had undergone surgery and had hippocampal tissue available for histologic examination. Fourteen of the children (47%) with hippocampal sclerosis were younger than 10 years of age, the youngest being 2 years. Thirty-four children (64%) had histories of neurologic insults prior to the onset of complex partial seizures, including idiopathic febrile seizures in 22. Hippocampal sclerosis was associated with a history of a neurologic insult prior to the onset of complex partial seizures (P < .001) and was not associated with age at onset of temporal lobe epilepsy, age at magnetic resonance imaging, duration of epilepsy, or presence of secondarily generalized seizures. These findings suggest that hippocampal sclerosis is underdiagnosed in children and is the cause and not the consequence of temporal lobe epilepsy.

Vagus nerve stimulation for refractory epilepsy in children: More to VNS than seizure frequency reduction

Purpose:  Vagus nerve stimulation (VNS) is used increasingly as adjunctive therapy for refractory epilepsy. Studies of VNS in children report mainly seizure frequency reduction as a measure of efficacy and clinical details are often scanty. We report our experience with VNS in children with refractory epilepsy and emphasize the positive effects of VNS in terms of seizure severity.

Ictal 99mTc‐HMPAO Single Photon Emission Computed Tomography in Children with Temporal Lobe Epilepsy

Seventeen ictal 99mTc‐HMPAO single photon emission computed tomography (SPECT) studies were performed in 15 children with temporal lobe epilepsy (TLE) aged 7–14 years (mean 10.3 years). Ictal SPECT was informative in 16 of 17 (94%) studies in 14 of 15 (93%) children, showing unilateral temporal lobe hyperperfu sion. In all 16 informative ictal SPECT studies, lateral‐ization was concordant with ictal EEC, magnetic resonance imaging (MRI), and pathology. In 4 children, ictat SPECT provided additional localizing information that was not apparent from concurrent ictal EEC recording. Blinded interpretation of ictal SPECT studies by two independent investigators showed correct lateralization of the epileptic focus in every child. Results of visual analysis of ictal SPECT images were corroborated by quantitative analysis. Although interictal SPECT studies showed a degree of temporal lobe hypoperfusion in all children, in 9 of 15 hypoperfusion was either minimal, bilateral, contralateral, or associated with extratemporal hypoperfusion. In children with TLE, ictal SPECT provides reliable lateralizing information to corroborate or supplement that obtained from surface EEG and MRI.

SCN2A encephalopathy A major cause of epilepsy of infancy with migrating focal seizures

Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy. Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping. Results: Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1–4 in 8, week 2–6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one. Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile–onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control.