Faculty Bibliography

PURPOSE/OBJECTIVE:The objective of the study was to compare the psychiatric and behavioral side effect (PBSE) profiles of both older and newer antiepileptic drugs (AEDs) in children and adolescent patients with epilepsy. METHOD/METHODS:We used logistic regression analysis to test the correlation between 83 non-AED/patient related potential predictor variables and the rate of PBSE. We then compared for each AED the rate of PBSEs and the rate of PBSEs that led to intolerability (IPBSE) while controlling for non-AED predictors of PBSEs. RESULTS:922 patients (≤18 years old) were included in our study. PBSEs and IPBSEs occurred in 13.8% and 11.2% of patients, respectively. Overall, a history of psychiatric condition, absence seizures, intractable epilepsy, and frontal lobe epilepsy were significantly associated with increased PBSE rates. Levetiracetam (LEV) had the greatest PBSE rate (16.2%). This was significantly higher compared to other AEDs. LEV was also significantly associated with a high rate of IPBSEs (13.4%) and dose-decrease rates due to IPBSE (6.7%). Zonisamide (ZNS) was associated with significantly higher cessation rate due to IPBSE (9.1%) compared to other AEDs. CONCLUSION/CONCLUSIONS:Patients with a history of psychiatric condition, absence seizures, intractable epilepsy, or frontal lobe epilepsy are more likely to develop PBSE. PBSEs appear to occur more frequently in adolescent and children patients taking LEV compared to other AEDs. LEV-attributed PBSEs are more likely to be associated with intolerability and subsequent decrease in dose. The rate of ZNS-attributed IPBSEs is more likely to be associated with complete cessation of AED.

INTRODUCTION/BACKGROUND:It is difficult to provide standardized formal education in EEG because of time limitations and the availability of expert teachers. Video-based miniature lectures are a useful way to standardize the foundational principles of EEG and support learning during EEG/epilepsy rotations. METHODS:A curriculum of 10 EEG teaching videos was developed based on concepts outlined in the Accreditation Council for Graduate Medical Education Neurology Milestones. The videos were short (6-17 minutes) and made available to residents rotating through an EEG/epilepsy rotation in two neurology residency programs. Residents were instructed to review the videos and then apply their newly learned skills during EEG reading sessions. A survey about the process was completed at the end of the year. RESULTS:Twenty-one residents participated in the curriculum, and 15 (71%) responded to the survey. Two-thirds of respondents (10/15) said that they watched all of the videos, and 87% (13/15) watched at least half of the videos. All of the respondents used the videos as introductions to EEG concepts, and approximately half of respondents returned to the videos as a refresher after the rotation was over. Nearly all respondents either agreed or strongly agreed that the curriculum was a useful component of the rotation and helped them to understand difficult concepts. All strongly agreed that they would recommend the curriculum to other residents. DISCUSSION/CONCLUSIONS:A video-based approach to EEG teaching could complement existing curricula and ensure that learners have access to foundational miniature lectures when and where they need them.

There are extensive studies evaluating mesial temporal sclerosis (MTS) in adults and limited studies in children, with adolescents being included within both patient populations. Our aim was to evaluate predictors of surgical outcome solely in adolescent patients with MRI- and pathology -proven MTS. The Yale Epilepsy Surgery Database was reviewed from 1987 to 2012 for adolescent patients with confirmed MTS on MRI and pathology who underwent temporal lobectomy and had greater than two-year postsurgical follow-up. Clinical and electrographic data were reviewed. Eighteen patients were identified. Eleven patients (61%) were seizure-free. All seven patients (39%) who were not seizure-free free were found to have lateralized ictal onset within one hemisphere involving two or more lobes on scalp EEG (p<0.001). Of the 7 patients who were not seizure-free, 4 had a history of status epilepticus (compared to 1/11 seizure-free patients; p=0.047), and 4 had lateralized hypometabolism involving two or more lobes within a hemisphere seen on PET (compared to 0/8 seizure-free patients; p=0.002). A novel finding in our study was that lateralized (rather than localized) ictal onset on scalp EEG, lateralized hypometabolism on PET, and history of status epilepticus were risk factors for not attaining seizure freedom in adolescents with MTS who underwent temporal lobectomy.

OBJECTIVE:Aberrant glutamate and γ-aminobutyric acid (GABA) neurotransmission contribute to seizure generation and the epileptic state. However, whether levels of these neurochemicals are abnormal in epileptic patients is unknown. Here, we report on interictal levels of glutamate, glutamine, and GABA in epilepsy patients at seizure onset and nonepileptic sites, cortical lesions, and from patients with poorly localized neocortical epilepsies. METHODS:Subjects (n = 79) were medically refractory epilepsy patients undergoing intracranial electroencephalogram evaluation. Microdialysis probes (n = 125) coupled to depth electrodes were implanted within suspected seizure onset sites and microdialysis samples were obtained during interictal periods. Glutamate, glutamine, and GABA were measured using high-performance liquid chromatography. Probe locations were subsequently classified by consensus of expert epileptologists. RESULTS:Glutamate levels were elevated in epileptogenic (p = 0.03; n = 7), nonlocalized (p < 0.001), and lesional cortical sites (p < 0.001) when compared to nonepileptogenic cortex. Glutamate was also elevated in epileptogenic (p < 0.001) compared to nonepileptogenic hippocampus. There were no statistical differences in GABA or glutamine, although GABA levels showed high variability across patients and groups. INTERPRETATION:Our findings indicate that chronically elevated extracellular glutamate is a common pathological feature among epilepsies with different etiology. Contrary to our predictions, GABA and glutamine levels were not decreased in any of the measured areas. Whereas variability in GABA levels may in part be attributed to the use of GABAergic antiepileptic drugs, the stability in glutamine across patient groups indicate that extracellular glutamine levels are under tighter metabolic regulation than previously thought. Ann Neurol 2016;80:35-45.

The aim of our study was to evaluate the role of auras in preventing motor vehicle accidents (MVAs) among patients with medically refractory epilepsy. The Multicenter Study of Epilepsy Surgery database was used to perform a case-control study by identifying patients who had seizures while driving that led to MVAs (cases) and those who had seizures while driving without MVAs (controls). We compared presence of reliable auras and other aura-related features between the two groups. Two hundred fifteen of 553 patients reported having seizure(s) while driving; 74 were identified as "controls" and 141 as "cases." The two groups had similar demographic and clinical features. The presence of reliable auras was not different between the two groups (67% in cases vs. 65% in controls; odds ratio [OR] 0.89, 95% confidence interval [CI] 0.49-1.61, p = 0.76). In addition, the groups did not differ in the proportion of patients who reported longer (>1 min) auras (OR 0.7, 95% CI 0.28-1.76, p = 0.47), or who thought that their auras were of sufficient duration to be protective (OR 1.19, 95% CI 0.62-2.00, p = 0.77). Our study questions the long-held belief of a protective role of reliable auras against MVAs in people with epilepsy.

OBJECTIVE:The purpose of this study was to investigate functional connectivity (FC) changes in epileptogenic networks in intractable partial epilepsy obtained from resting-state fMRI by using intrinsic connectivity contrast (ICC), a voxel-based network measure of degree that reflects the number of connections to each voxel. METHODS:We measured differences between intrahemispheric- and interhemispheric-ICC (ICCintra-inter) that could reveal localized connectivity abnormalities in epileptogenic zones while more global network changes would be eliminated when subtracting these values. The ICCintra-inter map was compared with the seizure onset zone (SOZ) based on intracranial EEG (icEEG) recordings in 29 patients with at least 1 year of postsurgical follow-up. Two independent reviewers blindly interpreted the icEEG and fMRI data, and the concordance rates were compared for various clinical factors. RESULTS:Concordance between the icEEG SOZ and ICCintra-inter map was observed in 72.4% (21/29) of the patients, which was higher in patients with good surgical outcome, especially in those patients with temporal lobe epilepsy (TLE) or lateral temporal seizure localization. Concordance was also better in the extratemporal lobe epilepsy than the TLE group. In 85.7% (18/21) of the cases, the ICCintra-inter values were negative in the SOZ, indicating decreased FC within the epileptic hemisphere relative to between hemispheres. CONCLUSIONS:Assessing alterations in FC using fMRI-ICC map can help localize the SOZ, which has potential as a noninvasive presurgical diagnostic tool to improve surgical outcome. In addition, the method reveals that, in focal epilepsy, both intrahemispheric- and interhemispheric-FC may be altered, in the presence of both regional as well as global network abnormalities.

PURPOSE/OBJECTIVE:To evaluate the clinical significance, characteristics and prognostic value of subclinical seizures of temporal and extra-temporal origin. METHODS:Our epilepsy database from 2003 to 2011 was reviewed to identify patients with subclinical seizures during intracranial EEG recording who underwent surgical resection. Two groups were formed: Group 1 where both the clinical and subclinical seizures had the same seizure onset region, and Group 2 where some or all of the clinical and subclinical seizures originated from different regions. RESULTS:A total of 27 patients were identified with 791 seizures, of which 310 were subclinical. In Group 1 (n=14), 64% had good surgical outcome, and 36% had poor surgical outcome. In Group 2 (n=12), 83% had poor outcome while 17% had good outcome. One patient had only subclinical seizures. Eleven patients had subclinical seizures that propagated to a region beyond their onset zone. Of those 11 patients, 6 patients had subclinical seizures propagate to a different anatomical region than their clinical seizures. These six patients had poor surgical outcome. DISCUSSION/CONCLUSIONS:Our study, like others, found that subclinical seizures are clinically significant and including their onset region in the volume of surgical resection correlates with good surgical outcome for both temporal and extra-temporal lobe epilepsy (Fisher's exact test p=0.017). Propagation of subclinical seizures to a different region than clinical seizures can affect surgical outcome (Fisher's exact test p=0.06). Subclinical seizures may represent a distinct epileptic network.