Douglas F. Rose

Multimodality imaging in the surgical treatment of children with nonlesional epilepsy

Objectives: To evaluate the diagnostic value of individual noninvasive presurgical modalities and to study their role in surgical management of nonlesional pediatric epilepsy patients. Methods: We retrospectively studied 14 children (3–18 years) with nonlesional intractable focal epilepsy. Clinical characteristics, surgical outcome, localizing features on 3 presurgical diagnostic tests (subtraction peri-ictal SPECT coregistered to MRI [SISCOM], statistical parametric mapping [SPM] analysis of [18F] FDG-PET, magnetoencephalography [MEG]), and intracranial EEG (iEEG) were reviewed. The localization of each individual test was determined for lobar location by visual inspection. Concordance of localization between each test and iEEG was scored as follows: 2 = lobar concordance; 1 = hemispheric concordance; 0 = discordance or nonlocalization. Total concordance score in each patient was measured by the summation of concordance scores for all 3 tests. Results: Seven (50%) of 14 patients were seizure-free for at least 12 months after surgery. One (7%) had only rare seizures and 6 (43%) had persistent seizures. MEG (79%, 11/14) and SISCOM (79%, 11/14) showed greater lobar concordance with iEEG than SPM-PET (13%, 3/14) (p < 0.05). SPM-PET provided hemispheric lateralization (71%, 10/14) more often than lobar localization. Total concordance score tended to be greater for seizure-free patients (4.7) than for non–seizure-free patients (3.9). Conclusions: Our data suggest that MEG and SISCOM are better tools for lobar localization than SPM analysis of FDG-PET in children with nonlesional epilepsy. A multimodality approach may improve surgical outcome as well as selection of surgical candidates in patients without MRI abnormalities.

Adverse events related to extraoperative invasive EEG monitoring with subdural grid electrodes: A systematic review and meta-analysis

Implantation of subdural grids and invasive electroencephalography (EEG) monitoring is important to define the ictal‐onset zone and eloquent cortex in selected patients with medically refractory epilepsy. The objective of this systematic review is to summarize data about adverse events related to this procedure.

Attention, learning, and arousal of experimentally sleep-restricted adolescents in a simulated classroom.

PURPOSE To experimentally test whether chronic sleep restriction, which is common among adolescents, is causally related to poor learning, inattentive behaviors, and diminished arousal in a classroom-like situation. METHODS Sixteen healthy adolescents underwent a sleep manipulation that included, in counterbalanced order, five consecutive nights of sleep deprivation (6½ hours in bed) versus five nights of healthy sleep duration (10 hours in bed). At the end of each condition, participants viewed educational films and took related quizzes in a simulated classroom. Eight participants also underwent video and electroencephalography monitoring to assess levels of inattentive behaviors and arousal, respectively. RESULTS As compared with the healthy sleep condition, sleep-deprived participants had lower quiz scores (p = .05), more inattentive behaviors (p < .05), and lower arousal (p = .08). CONCLUSIONS These pilot data complement previous correlational reports by showing that chronic sleep restriction during adolescence can cause inattention, diminished learning, and lowered arousal in a simulated classroom.

Resection of ictal high-frequency oscillations leads to favorable surgical outcome in pediatric epilepsy

Purpose:  Intracranial electroencephalography (EEG) is performed as part of an epilepsy surgery evaluation when noninvasive tests are incongruent or the putative seizure‐onset zone is near eloquent cortex. Determining the seizure‐onset zone using intracranial EEG has been conventionally based on identification of specific ictal patterns with visual inspection. High‐frequency oscillations (HFOs, >80 Hz) have been recognized recently as highly correlated with the epileptogenic zone. However, HFOs can be difficult to detect because of their low amplitude. Therefore, the prevalence of ictal HFOs and their role in localization of epileptogenic zone on intracranial EEG are unknown.

Nonconvulsive Status Epilepticus: The Encephalopathic Pediatric Patient

OBJECTIVE: A high prevalence of nonconvulsive status epilepticus (NCSE) has been reported in critically ill adults and neonates. Recent prospective pediatric studies focus on critically ill children and show wide variability in the frequency of NCSE. This study examines prevalence of pediatric NCSE regardless of inpatient setting and retrospectively identifies risk factors indicating a need for urgent continuous EEG. METHODS: Medical records from patients aged 3 months to 21 years were identified either by (1) searching a clinical EEG database (n = 18) or (2) consecutive inpatient EEG referrals for NCSE over an 8-month period (n = 57). RESULTS: Seventy-five children, mean age of 7.8 years, were studied. NCSE was identified in 26 patients (35%) and in 8 of 57 (14%) patients referred for possible NCSE. More than half of the patients referred were outside of the ICU. A witnessed clinical seizure was observed in 24 of 26 (92%) patients with NCSE. Acute cortical neuroimaging abnormalities were significantly more frequent in patients with NCSE. The presence of clinical seizures and acute neuroimaging abnormality was associated with an 82% probability of NCSE. All but 1 patient with NCSE had electrographic or electroclinical seizures within the first hour of monitoring. CONCLUSIONS: A high prevalence of NCSE was observed, comparable to adult studies, but within a wider range of inpatient settings. Children with acute encephalopathy should undergo continuous EEG. This evaluation is more urgent if certain clinical risk factors are present. Optimal duration of monitoring and the effect of NCSE on prognosis should be studied.

Frequency and spatial characteristics of high-frequency neuromagnetic signals in childhood epilepsy

PURPOSE Invasive intracranial recordings have suggested that high-frequency oscillation is involved in epileptogenesis and is highly localized to epileptogenic zones. The aim of the present study is to characterize the frequency and spatial patterns of high-frequency brain signals in childhood epilepsy using a non-invasive technology. METHODS Thirty children with clinically diagnosed epilepsy were studied using a whole head magnetoencephalography (MEG) system. MEG data were digitized at 4,000 Hz. The frequency and spatial characteristics of high-frequency neuromagnetic signals were analyzed using continuous wavelet transform and beamformer. Three-dimensional magnetic resonance imaging (MRI) was obtained for each patient to localize magnetic sources. RESULTS Twenty-six patients showed high-frequency (100-1,000 Hz) components (26/30, 86%). Nineteen patients showed more than one high-frequency component (19/30, 63%). The frequency range of high-frequency components varied across patients. The highest frequency band was identified around 910 Hz. The loci of high-frequency epileptic activities were concordant with the lesions identified by magnetic resonance imaging for 21 patients (21/30, 70%). The MEG source localizations of high-frequency components were found to be concordant with intracranial recordings for nine of the eleven patients who underwent epilepsy surgery (9/11, 82%). CONCLUSION The results have demonstrated that childhood epilepsy was associated with high-frequency epileptic activity in a wide frequency range. The concordance of MEG source localization, MRI and intracranial recordings suggests that measurement of high-frequency neuromagnetic signals might provide a novel approach for clinical management of childhood epilepsy.

Focal corticothalamic sources during generalized absence seizures: A MEG study

Magnetoencephalography (MEG) was used to determine cortical and subcortical contributions to the formation of spike and wave discharges in twelve newly diagnosed, drug naïve children during forty-four generalized absence seizures. Previous studies have implicated various cortical areas and thalamic nuclei in the generation of absence seizures, but the relative timing of their activity remains unclear. Beamformer analysis using synthetic aperture magnetometry (SAM) was used to confirm the presence of independent thalamic activity, and standardized Low Resolution Brain Electromagnetic Topography (sLORETA) was used to compute statistical maps indicating source locations during absence seizures. Sources detected in the 50ms prior to the start of the seizure were more likely to be localized to the frontal cortex or thalamus. At the time of the first spike on EEG, focal source localization was seen in the lateral frontal cortex with decreased thalamic localization. Following the spike, localization became more widespread throughout the cortex. Comparison of the earliest spike and wave discharge (SWD) (Ictal Onset) and a SWD occurring 3s into the seizure (mid-Ictal) revealed significant differences during the slow wave portion of the SWDs. This study of MEG recordings in childhood absence seizures provides additional evidence that there are focal brain areas responsible for these seizures which appear bilaterally symmetric and generalized with a conventional 10-20 placement scalp EEG.

Complex Partial Seizures: Cerebral Structure and Cerebral Function

Summary: We studied the relationships between cerebral structure and function in 10 patients with complex partial seizures who had major cerebral lesions, including porencephalic cysts, tuberose sclerosis, agenesis of the corpus callosum, and cerebral hemiatrophy. Evaluation included computed tomography (CT) and magnetic resonance imaging (MRI) scanning, EEG, and positron emission tomography (PET) using [18F]‐2‐deoxyglucose. Surface EEG usually showed widespread, bilateral epileptiform discharges even if pathology was clearly restricted to one hemisphere. In several cases, interictal PET hypometabolism was more widespread than structural changes seen on CT and MRI, extending to involve the ipsilateral temporal lobe in patients with extratemporal lesions. This study shows that patterns of metabolic and electrophysiologic dysfunction may not be predicted by structural lesions in patients with partial seizure disorders.

Ictal MEG onset source localization compared to intracranial EEG and outcome: improved epilepsy presurgical evaluation in pediatrics.

PURPOSE Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy as MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ. METHODS We identified 20 pediatric patients with one habitual seizure during MEG recordings between October 2007 and April 2011. MEG was recorded with sampling rates of 600Hz and 4000Hz for 10 and 2min respectively. Continuous head localization (CHL) was applied. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome. KEY FINDINGS Eight patients met all inclusion criteria. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG. SIGNIFICANCE Although the capture of seizures during MEG recording is challenging, the source localization for ictal MEG onset proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy.

Modeling the Developmental Patterns of Auditory Evoked Magnetic Fields in Children

Background As magnetoencephalography (MEG) is of increasing utility in the assessment of deficits and development delays in brain disorders in pediatrics, it becomes imperative to fully understand the functional development of the brain in children. Methodology The present study was designed to characterize the developmental patterns of auditory evoked magnetic responses with respect to age and gender. Sixty children and twenty adults were studied with a 275-channel MEG system. Conclusions Three main responses were identified at approximately 46 ms (M50), 71 ms (M70) and 106 ms (M100) in latency for children. The latencies of M70 and M100 shortened with age in both hemispheres; the latency of M50 shortened with age only in the right hemisphere. Analysis of developmental lateralization patterns in children showed that the latency of the right hemispheric evoked responses shortened faster than the corresponding left hemispheric responses. The latency of M70 in the right hemisphere highly correlated to the age of the child. The amplitudes of the M70 responses increased with age and reached their peaks in children 12–14 years of age, after which they decreased with age. The source estimates for the M50 and M70 responses indicated that they were generated in different subareas in the Heschls gyrus in children, while not localizable in adults. Furthermore, gender also affected developmental patterns. The latency of M70 in the right hemisphere was proposed to be an index of auditory development in children, the modeling equation is 85.72-1.240xAge (yrs). Our results demonstrate that there is a clear developmental pattern in the auditory cortex and underscore the importance of M50 and M70 in the developing brain.