Carter Snead

Prospective Preliminary Analysis of the Development of Autism and Epilepsy in Children With Infantile Spasms

The objective of this study was to compare the efficacy of corticotropin (ACTH) versus vigabatrin in treating infantile spasms and to determine which medication has a more favorable long-term outcome in terms of cognitive function, evolution of epilepsy, and incidence of autism. Patients with infantile spasms were included in the study if they were 3 to 16 months old, had hypsarrhythmia, and had no previous treatment with vigabatrin or corticosteroids. Patient evaluation included electroencephalographic and psychometric measures before and after treatment. Patients were stratified based on etiology (idiopathic or symptomatic) and sex and then randomized between the ACTH and vigabatrin treatment groups. Each of the treatment groups received either ACTH or vigabatrin for 2 weeks. At the end of 2 weeks of treatment, patients were considered responders if spasms and hypsarrhythmia resolved. Nonresponders were crossed over and treated with the alternate drug. Nine patients were included in the study. Three patients received ACTH, one of whom was a responder. Six patients received vigabatrin, three of whom were responders. The five nonresponders received both therapies. All patients had some degree of developmental plateau or regression before the initiation of treatment. Four patients with idiopathic infantile spasms showed improved cognitive function following treatment. The remaining five patients remained significantly delayed. Five patients with symptomatic infantile spasms had epilepsy following treatment; three of them were in the autistic spectrum. The small number of infants in this pilot study is insufficient to determine which of the two drugs is more effective. However, the following trends were identified: vigabatrin may be more effective for patients with symptomatic infantile spasms; patients with idiopathic infantile spasms tend to have a better cognitive outcome; and patients with symptomatic infantile spasms tend to develop both epilepsy and autism. (J Child Neurol 2003; 18: 165—170).

A randomized controlled trial of flunarizine as add-on therapy and effect on cognitive outcome in children with infantile spasms.

Purpose:  Cognitive impairment is observed commonly in children with a history of infantile spasms (IS). The goal of this study was to prospectively examine the effect on cognitive outcome of a neuroprotective agent used as adjunctive therapy during treatment of the spasms.

Source localization of interictal spike-locked neuromagnetic oscillations in pediatric neocortical epilepsy

OBJECTIVE To evaluate the utility of an event-related beamforming (ERB) algorithm in source localization of interictal discharges. METHODS We analyzed interictal magnetoencephalography data in 35 children with intractable neocortical epilepsy. We used a spatiotemporal beamforming method to estimate the spatial distribution of source power in individual interictal spikes. We compared ERB results to source localization using the equivalent current dipole model and to the seizure onset zones on intracranial EEG. RESULTS Focal beamformer localization was observed in 66% of patients and multifocal in the remaining 34%. ERB localized within 2 cm of the equivalent current dipole cluster centroid in 77% of the patients. ERB localization was concordant with the seizure onset zone on intracranial EEG at the gyral level in 69% of patients. Focal ERB localization area was included in the resection margin in 22/23 patients. However, focal ERB localization was not statistically associated with better surgical outcome. CONCLUSIONS ERB can be used for source localization of interictal spikes and can be predictive of the ictal onset zone in a subset of patients with neocortical epilepsy. SIGNIFICANCE These results support the utility of beamformer source localization as a fast semi-automated method for source localization of interictal spikes and planning the surgical strategy.

Diagnostic evaluation and surgical management of pediatric insular epilepsy utilizing magnetoencephalography and invasive EEG monitoring

INTRODUCTION The diagnosis and surgical management of pediatric patients with insular epilepsy is challenging due to variable and indistinct seizure semiology arising within the insular cortex. In addition, surgical approaches are associated with potential morbidity given the regional neurosurgical and vascular anatomy. Our institutional experience in evaluation and surgical management of insular epilepsy patients is presented. Diagnostic evaluation, surgical treatment and seizures outcomes are highlighted. METHODS The institutional database for all pediatric surgical epilepsy patients was reviewed over a period of 15 years (2000-2015). Study subjects were defined as patients who had undergone surgical resection of the epileptogenic zone involving the insular cortex. Diagnostic imaging, electrophysiological studies and surgical records were assessed. RESULTS Six (n = 6) patients with insular epilepsy were identified with a mean follow up of 2.8 years (range: 0.8-6.8 years). Mean age at surgical resection was 9.5 ± 2.5 years (range: 2.5-16 years). Majority of patients (n = 4/6, 67%) underwent more than 1 surgical procedure. Magnetoencephalography (MEG) identified insular cortex involvement presurgically in all cases. MEG cluster localization was useful in guiding invasive EEG monitoring in 5 patients and was concordant with identification of epileptogenic zone through intracranial monitoring in all 5 patients. Surgical resection of the epileptogenic zone, as delineated through MEG spike sources and invasive EEG monitoring, was associated with favorable seizure outcome in 4 of 6 patients (67%; Engel Class I). Cortical dysgenesis was identified on histopathology in 4 cases. CONCLUSION Diagnostic evaluation through invasive and noninvasive electrophysiological studies is critical to identify pediatric patients with insular epilepsy. Our findings suggest that MEG may help with identifying the epileptogenic zone within the insular cortex, which could be confirmed with invasive intracranial monitoring.

Total intravenous anesthesia affecting spike sources of magnetoencephalography in pediatric epilepsy patients: Focal seizures vs. non-focal seizures

PURPOSE Magnetoencephalography (MEG) provides source localization of interictal spikes. This study evaluated the inhibitory effects of propofol on MEG spike sources (MEGSSs) among different types of seizures in patients who underwent two separate MEG studies with and without total intravenous anesthesia (TIVA) using propofol. METHODS We studied 19 children (1-14 years; mean, 6.2 years) who had MEG with and without TIVA. TIVA was administered using propofol (0.03-0.06 mg/kg/min) to record MEG with simultaneous EEG. We analyzed number of spikes of MEG and MEGSSs comparing MEG studies done with and without TIVA. RESULTS Seizures were divided into nine focal seizure (FS) with/without secondary generalization, five epileptic spasm (ES), and five generalized seizure (GS). TIVA significantly decreased the number of MEG spikes/min (from 4.5 to 2.0) in five FS without secondary generalization (p<0.05). The number of MEG spikes/min was significantly lower (1.9) in FS than that in non-FS (ES+GS, 6.1) (p<0.01). MEGSSs without TIVA were clustered in 15 patients (6FS; 4ES; 5GS), scattered in four (3FS; 1ES). MEG under TIVA showed clusters in 10 patients (1FS; 4ES; 5GS), scatters in three (2FS; 1ES) and no MEGSS in six patients with FS. Under TIVA, nine (90%) of ten patients with non-FS showed MEGSSs clusters compared to one (11%) of nine patients with FS (p<0.01). CONCLUSIONS Reduction of MEGSSs occurred in patients with FS under TIVA. Diffuse/generalized spikes in non-FS are not affected by TIVA. Propofol may decrease focal spikes in the epileptic cortex in FS. Cortical hyperexcitability in non-FS group would be stronger or more extensive than that in the FS group of patients.

Systematic review and network meta-analysis of resective surgery for mesial temporal lobe epilepsy

Objective To evaluate the effectiveness of anterior temporal lobectomy (ATL) versus selective amygdalohippocampectomy (SAH) on seizure-free outcome in patients with temporal lobe epilepsy, using both direct and indirect evidence from the literature. Methods MEDLINE, Embase and Cochrane databases were searched for original research articles and systematic reviews comparing ATL versus SAH, and ATL or SAH versus medical management (MM). The outcome was seizure freedom at 12 months of follow-up or longer. Direct pairwise meta-analyses were conducted, followed by a random-effect Bayesian network meta-analysis (NMA) combining direct and indirect evidence. Results Twenty-eight articles were included (18 compared ATL vs SAH, 1 compared ATL vs SAH vs MM, 8 compared ATL vs MM, and 1 compared SAH vs MM). Direct pairwise meta-analyses showed no significant differences in seizure-free outcome of ATL versus SAH (OR 1.14, 95% CI 0.93 to 1.39; p=0.201), but the odds of seizure-free outcome were higher for ATL versus MM (OR 29.16, 95% CI 10.44 to 81.50; p<0.00001), and SAH versus MM (OR 28.42, 95% CI 10.17 to 79.39; p<0.00001). NMA also showed that the odds of seizure-free outcome were no different in ATL versus SAH (OR 1.15, 95% credible interval (CrI) 0.84–1.15), but higher for ATL versus MM (OR 27.22, 95% CrI 15.38–27.22), and SAH versus MM (OR 23.57, 95% CrI 12.67–23.57). There were no significant differences between direct and indirect comparisons (all p>0.05). Conclusion Direct evidence, indirect evidence and NMA did not identify a difference in seizure-free outcome of ATL versus SAH.

“Saved by the Bell”: Near SUDEP during intracranial EEG monitoring

SUDEP is the sudden unexpected death of a person with epilepsy, when no structural or toxicological cause of death can be found. The majority of witnessed cases are reported to be preceded by a convulsive seizure and postictal hypoventilation. Here, we report an 8‐year‐old girl with drug‐resistant focal seizures secondary to a focal cortical dysplasia type IIb. While undergoing invasive intracranial monitoring with subdural and depth electrodes, she had a clinical apnea event recorded on video, followed by bradycardia, which required resuscitation. Her intracranial electroencephalogram (EEG) during the event showed diffuse slowing and attenuation of cortical activity, with bradycardia that responded to positive pressure ventilation with oxygen. This near SUDEP event was not preceded by either an electroclinical or electrographic seizure. This is the first report of a witnessed, near‐SUDEP event during intracranial monitoring. It emphasizes the fact that near‐SUDEP can occur without a preceding seizure.

T22. Intra-operative motor mapping using subdural grid electrodes in children undergoing invasive EEG monitoring

Introduction Extra-operative motor mapping (EOMM) in the pediatric population can be challenging, especially in young and/or developmentally delayed children, due to lack of cooperation, and higher motor stimulation thresholds. This study examined the feasibility and safety of intra-operative motor mapping (IOMM) using subdural grid electrodes in children undergoing epilepsy surgery evaluation. Methods Twenty consecutive children under18 years of age with drug refractory epilepsy who underwent invasive EEG monitoring using subdural grid placement and intra-operative motor mapping at our institution between December 2015 and June 2017 were enrolled. Stimulation was delivered to the subdural grid electrode using a train of five pulses, with an interstimulus interval of 1.1 ms and a pulse duration of 50 microseconds. Stimulation intensity was commenced at 25 Volts (V) and increased gradually until acceptable motor evoked potential (MEP) waveforms were generated. MEPs were recorded from the contralateral six muscle groups (orbicularis oris, deltoid, extensor digitorum communis, first dorsal interossei, tibialis anterior and abductor halluces). Extra-operative motor mapping (previously published procedure) was also done 3 days after the subdural grid placement. Results IOMM using sub-dural grid electrodes was completed in 20 patients, and simultaneous EOMM was done in 17 patients. The mean age at the time of mapping was 11.7 years (SD 4.2). 13/20 patients had malformations of cortical development. MEP responses were more commonly obtained in the deltoid (19/20), extensor digitorum communis (20/20) and first dorsal inerossei (19/20). The mean threshold varied from 44.5 V to 55.8 V for the six muscle groups. With increasing age, there was a decline in the motor thresholds with a possible exponential relationship. No seizures or anaesthesia related complications were noted. EOMM could not be completed in 4/17 children (3-clinical seizures, 1-limited patient cooperation). The mapping was incomplete in the majority of cases with 1 being the median number of areas mapped (IQR, 1–2). Seizures were seen in 6/17 (35.3%) and after-discharges in 7/17 (41.2%) children. Nine patients demonstrated 100% concordance between the common mapped areas, 4 patients showed 50% concordance and 3 patients showed no concordance between IOMM and EOMM. The median duration of follow up was 10.2 months (IQR, 3.6 to 14.4 months). ILAE seizure outcome 1 was seen in 15 patients (75%) at the last follow up. Post-operative neurological deficits were seen in 11 patients: contralateral motor deficits (6; 2 were transient), contralateral sensory deficits (2), homonymous hemianopia (1) and seizures (3). Conclusion IOMM was found to be feasible and safe procedure in children with drug refractory epilepsy undergoing invasive EEG monitoring using the subdural grid.

Microscopic and macroscopic infarct complicating pediatric epilepsy surgery

There is some suggestion that microscopic infarct could be associated with invasive monitoring, but it is unclear if the microscopic infarct is also visible on imaging and associated with neurologic deficits. The aims of this study were to assess the rates of microscopic and macroscopic infarct and other major complications of pediatric epilepsy surgery, and to determine if these complications were higher following invasive monitoring.