Ann Hyslop Segeren

All Publications

• Proposed anti-seizure medication combinations with rufinamide in the treatment of Lennox-Gastaut syndrome: Narrative review and expert opinion SEIZURE-EUROPEAN JOURNAL OF EPILEPSY Sankar, R., Chez, M., Pina-Garza, J., Dixon-Salazar, T., Flamini, J., Hyslop, A., Mcgoldrick, P., Millichap, J. J., Resnick, T., Rho, J. M., Wolf, S. 2023; 110: 42-57

  Abstract

  Lennox-Gastaut syndrome (LGS) is a severe, chronic, complex form of early childhood-onset epilepsy characterized by multiple seizure types, generalized slow (≤2.5 Hz) spike-and-wave activity and other electroencephalography abnormalities, and cognitive impairment. A key treatment goal is early seizure control, and several anti-seizure medications (ASMs) are available. Due to the low success rate in achieving seizure control with monotherapy and an absence of efficacy data supporting any particular combination of ASMs for treating LGS, a rational approach to selection of appropriate polytherapy should be applied to maximize benefit to patients. Such "rational polytherapy" involves consideration of factors including safety (including boxed warnings), potential drug-drug interactions, and complementary mechanisms of action. Based on the authors' clinical experience, rufinamide offers a well-considered first adjunctive therapy for LGS, particularly in combination with clobazam and other newer agents for LGS, and may be particularly useful for reducing the frequency of tonic-atonic seizures associated with LGS.

  View details for DOI 10.1016/j.seizure.2023.05.018

  View details for Web of Science ID 001058079800001

  View details for PubMedID 37321047

• Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. Journal of neurosurgery Tierney, T. S., Alavian, K. N., Altman, N., Bhatia, S., Duchowny, M., Hyslop, A., Jayakar, P., Resnick, T., Wang, S., Miller, I., Ragheb, J. 2022: 1-8

  Abstract

  Magnetic resonance-guided focused ultrasound (MRgFUS) is an incisionless procedure capable of thermoablation through the focus of multiple acoustic beams. Although MRgFUS is currently approved for the treatment of tremor in adults, its safety and feasibility profile for intracranial lesions in the pediatric and young adult population remains unknown.The long-term outcomes of a prospective single-center, single-arm trial of MRgFUS at Nicklaus Children's Hospital in Miami, Florida, are presented. Patients 15-22 years of age with centrally located lesions were recruited, clinically consistent with WHO grade I tumors that require surgical intervention. This cohort consisted of 4 patients with hypothalamic hamartoma (HH), and 1 patient with tuberous sclerosis complex harboring a subependymal giant cell astrocytoma (SEGA).In each case, high-intensity FUS was used to target the intracranial lesion. Real-time MRI was used to monitor the thermoablations. Primary outcomes of interest were tolerability, feasibility, and safety of FUS. The radiographic ablation volume on intra- and postoperative MRI was also assessed. All 5 patients tolerated the procedure without any complications. Successful thermoablation was achieved in 4 of the 5 cases; the calcified SEGA was undertreated due to intratumor calcification, which prevented attainment of the target ablation temperature. The HHs underwent target tissue thermoablations that led to MR signal changes at the treatment site. For the patients harboring HHs, FUS thermoablations occurred without procedure-related complications and led to improvement in seizure control or hypothalamic hyperphagia. All 5 patients were discharged home on postoperative day 1 or 2, without any readmissions. There were no cases of hemorrhage, electrolyte derangement, endocrinopathy, or new neurological deficit in this cohort.This experience demonstrates that FUS thermoablation of centrally located brain lesions in adolescents and young adults can be performed safely and that it provides therapeutic benefit for associated symptoms.

  View details for DOI 10.3171/2021.10.JNS21416

  View details for PubMedID 35171812

• Stereo-electroencephalography (SEEG) in pediatric epilepsy: Utility in children with and without prior epilepsy surgery failure. Epilepsy research Hyslop, A., Wang, S., Bryant, J. P., Bhatia, S., Sandoval-Garcia, C., Karkare, K., Ragheb, J. 2021; 177: 106765

  Abstract

  When noninvasive modalities fail to adequately localize the seizure onset zone (SOZ) in children with medically refractory epilepsy, invasive interrogation with stereo-electroencephalography (SEEG) or subdural electrodes may be required. Our center utilizes SEEG for invasive monitoring in a carefully selected population of children, many of whom have seizures despite a prior surgical resection. We describe the cohort of patients who underwent SEEG in the first 5 years of its employment in our institution, almost half of which had a history of a failed epilepsy surgery.We retrospectively reviewed the records of the first 44 consecutive children who underwent SEEG at Nicklaus Children's Hospital (Miami, Florida), a large, level 4 epilepsy referral center. Patient demographic, clinical, radiographic, and electrophysiological information was collected prospectively. Student's t-test was used for sampling of means and analysis of variance (ANOVA) for evaluation of variance beyond 2 means; chi-square test of independence was used to assess the relationship between categorical variables.There were 44 patients in this cohort, of whom 17 (38.6 %) were male. The mean age of seizure onset was 6.2 years. Twenty-one patients (47.7 %) had previously failed an epilepsy surgery. Patients with a history of prior epilepsy surgery failure were older at SEEG implantation (17.6 vs. 13.7 years; p = 0.043), were more likely to have SEEG for identification of resection margins (9 vs. 4; p = 0.034), and had fewer electrodes placed (5.9 vs. 7.5; p = 0.016). No difference was seen in complication rates between groups with only 3/297 electrodes placed associated with complications, all of which were minor. Post-SEEG, 29 (65.9 %) patients underwent focal resection, 7 patients had VNS insertion, 3 underwent RNS placement, and 5 had no further intervention. The majority of patients that underwent resection in both groups experienced an improvement in seizures (Engel class I-III), reported by 13/15 (86.7 %) in those naive to surgery and 10/14 (71.4 %) in those with prior surgical failure. Seizure-freedom was much lower in those with prior epilepsy surgery, seen in only 4/14 (28.6 %) versus 8/15 (53.3 %).Our data supports current literature on SEEG as a safe and effective method of electrophysiological evaluation in children naive to surgery and adds that it is a safe technique in children with a history of failed epilepsy surgery. There was no difference in complication rates, which were <1 % in both groups. A favorable outcome was seen in the majority of patients in both groups; the seizure freedom rate, however, was much lower in those with prior epilepsy surgery.

  View details for DOI 10.1016/j.eplepsyres.2021.106765

  View details for PubMedID 34537417

• Neuromodulation for Intractable Childhood Epilepsy. Seminars in pediatric neurology Hyslop, A., Tatachar, P. 2021; 39: 100918

  Abstract

  In the past few years significant advances made in the field of neuromodulation have led to practical therapeutic strategies for children with medically refractory epilepsy. Here, we briefly discuss the various options that are currently available including vagus nerve stimulation, responsive neurostimulation, deep brain stimulation, chronic subthreshold cortical stimulation, as well as repetitive transcranial magnetic and transcranial direct current stimulation. The current indications, proposed mechanisms, method of administration, efficacy, adverse effects, and mention of clinical trials currently in enrollment or development are discussed.

  View details for DOI 10.1016/j.spen.2021.100918

  View details for PubMedID 34620463

• Time to onset of cannabidiol treatment effects in Dravet syndrome: Analysis from two randomized controlled trials. Epilepsia Madan Cohen, J., Checketts, D., Dunayevich, E., Gunning, B., Hyslop, A., Madhavan, D., Villanueva, V., Zolnowska, M., Zuberi, S. M. 2021; 62 (9): 2218-2227

  Abstract

  We conducted a post hoc analysis of two randomized controlled trials, GWPCARE1 (NCT02091375) and GWPCARE2 (NCT02224703), to estimate the time to onset of cannabidiol (CBD) treatment effects (seizure reduction and adverse events [AEs]) in patients with Dravet syndrome (DS).Patients received either plant-derived highly purified CBD (Epidiolex in the United States; 100 mg/ml oral solution) 10 mg/kg/day (CBD10; GWPCARE2) or 20 mg/kg/day (CBD20; GWPCARE1&2), or matching placebo for 14 weeks. Treatment started at 2.5 mg/kg/day, reached 10 mg/kg/day on Day 7, and went up to 20 mg/kg/day on Day 11 during the 14-day titration period. Percentage change from baseline in convulsive seizure frequency was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were also evaluated.Overall, 124 patients received placebo and 194 received CBD (CBD10, n = 64; CBD20, n = 130). Mean age was 9.5 years (range = 2.2-18.9). Patients had discontinued a median of four antiepileptic drugs (range = 0-26) and were currently taking a median of three (range = 1-5). Differences in convulsive seizure reduction between placebo and CBD emerged during titration and became nominally significant by Day 12 for CBD20 (p = .02) and Day 13 for CBD10 (p = .03). Additionally, differences in the 50% responder rate between placebo and CBD became apparent during titration. Onset of the first reported AE occurred during the titration period in 48.4% of placebo patients and 54.1% of CBD patients. The three most common AEs of somnolence, decreased appetite, and diarrhea resolved within 4 weeks of onset in the majority of CBD-treated patients (56.3%-72.9%).The therapeutic effect of CBD in DS may start within 2 weeks of treatment in some patients. Although AEs lasted longer for CBD than placebo, most resolved within the 14-week study period.

  View details for DOI 10.1111/epi.16974

  View details for PubMedID 34265088

  View details for PubMedCentralID PMC8456817

• Early vagus nerve stimulator implantation as a main predictor of positive outcome in pediatric patients with epileptic encephalopathy. Epileptic disorders : international epilepsy journal with videotape Russo, A., Hyslop, A., Gentile, V., Boni, A., Miller, I., Chiarello, D., Pellino, G., Zenesini, C., Martinoni, M., Lima, M., Ragheb, J., Cordelli, D. M., Pini, A., Jayakar, P., Duchowny, M. 2021; 23 (4): 563-571

  Abstract

  We describe a multicenter experience with VNS implantation in pediatric patients with epileptic encephalopathy. Our goal was to assess VNS efficacy and identify potential predictors of favorable outcome. This was a retrospective study. Inclusion criteria were: ≤18 years at the time of VNS implantation and at least one year of follow-up. All patients were non-candidates for excisional procedures. Favorable clinical outcome and effective VNS therapy were defined as seizure reduction >50%. Outcome data were reviewed at one, two, three and five years after VNS implantation. Fisher's exact test, Kaplan-Meier and multiple logistic regression analysis were employed. Twenty-seven patients met inclusion criteria. Responder rate (seizure frequency reduction ≥ 50%) at one-year follow-up was 25.9%, and 15.3% at last follow-up visit. The only variable significantly predicting favorable outcome was time to VNS implantation, with the best outcome achieved when VNS implantation was performed within five years of seizure onset (overall response rate of 83.3% at one year of follow-up and 100% at five years). In total, 63% of patients evidenced improved QOL at last follow-up visit. Only one patient exited the study due to an adverse event at two years from implantation. Early VNS implantation within five years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients with epileptic encephalopathy. Improved QOL and a very low incidence of adverse events were observed.

  View details for DOI 10.1684/epd.2021.1299

  View details for PubMedID 34184987

• Early Implantation as a Main Predictor of Response to Vagus Nerve Stimulation in Childhood-Onset Refractory Epilepsy. Journal of child neurology Russo, A., Hyslop, A., Gentile, V., Chiarello, D., Messana, T., Miller, I., Zucchelli, M., Lima, M., Ragheb, J., Pini, A., Cordelli, D. M., Resnick, T., Jayakar, P., Duchowny, M. 2021; 36 (5): 365-370

  Abstract

  We describe a multicenter experience with vagus nerve stimulator implantation in pediatric patients with drug-resistant epilepsy. Our goal was to assess vagus nerve stimulation efficacy and identify potential predictors of favorable outcome.This is a retrospective study. Inclusion criteria: ≤18 years at time of vagus nerve stimulator implantation, at least 1 year of follow-up. All patients were previously found to be unsuitable for an excisional procedure. Favorable clinical outcome and effective vagus nerve stimulation therapy were defined as seizure reduction >50%. Outcome data were reviewed at 1, 2, 3, and 5 years after vagus nerve stimulator implantation. Fisher exact test and multiple logistic regression analysis were employed.Eighty-nine patients met inclusion criteria. Responder rate (seizure frequency reduction >50%) at 1-year follow-up was 25.8% (4.5% seizure-free). At last follow-up, 31.5% had a favorable outcome and 5.2% were seizure free. The only factor significantly predicting favorable outcome was time to vagus nerve stimulator implantation, with the best outcome achieved when vagus nerve stimulator implantation was performed within 3 years of seizure onset. Implantation between 3 and 5 years after epilepsy onset correlated with better long-term seizure freedom (13.3% at T5). Overall, 65.2% of patients evidenced improved quality of life at last follow-up. However, 12.4% had adverse events, but most were mild and disappeared after 3-4 months.Early vagus nerve stimulator implantation within 5 years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients. Improved quality of life and a low incidence of significant adverse events were observed.

  View details for DOI 10.1177/0883073820974855

  View details for PubMedID 33236677

• Electrical stimulation mapping in children. Seizure Hyslop, A., Duchowny, M. 2020; 77: 59-63

  Abstract

  Electrical stimulation mapping is a longstanding practice that aids in identification and delineation of eloquent cortex. Initially used to expand our understanding of the typical human cortex, it now plays a significant role in mapping cortical function in individuals with atypical structural and functional tissue organization undergoing epilepsy surgery. This review discusses the unique challenges that arise in the functional testing of the immature cortex of a child and the parameters of stimulation that optimize accurate results in conventional open implantation and in stereo-electroencephalography. The prerequisite baseline evaluation and preparation recommended to increase the yield from pediatric stimulation mapping sessions is described, as are ideal approaches to the mapping of the sensory, motor, language, and visual cortices.

  View details for DOI 10.1016/j.seizure.2019.07.023

  View details for PubMedID 31445890

• Presurgical hyperconnectivity of the ablation volume is associated with seizure-freedom after magnetic resonance-guided laser interstitial thermal therapy. Seizure Ibrahim, G. M., Weil, A. G., Sedighim, S., Schoen, N. B., Mikhail, M., Sharma, P., Guillen, M. R., Morgan, B. R., Wong, S., Cajigas, I., Jermakowicz, W. J., Sandoval-Garcia, C., Lewis, E. C., Fallah, A., Altman, N., Medina, S., Pacheco-Jacome, E., Jayakar, P., Hyslop, A., Miller, I., Ragheb, J., Bhatia, S., Bernal, B. 2018; 61: 89-93

  Abstract

  Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) is an emerging minimally-invasive alternative to resective surgery for medically-intractable epilepsy. The precise lesioning effect produced by MRgLITT supplies opportunities to glean insights into epileptogenic regions and their interactions with functional brain networks. In this exploratory analysis, we sought to characterize associations between MRgLITT ablation zones and large-scale brain networks that portended seizure outcome using resting-state fMRI.Presurgical fMRI and intraoperatively volumetric structural imaging were obtained, from which the ablation volume was segmented. The network properties of the ablation volume within the brain's large-scale brain networks were characterized using graph theory and compared between children who were and were not rendered seizure-free.Of the seventeen included children, five achieved seizure freedom following MRgLITT. Greater functional connectivity of the ablation volume to canonical resting-state networks was associated with seizure-freedom (p < 0.05, FDR-corrected). The ablated volume in children who subsequently became seizure-free following MRgLITT had significantly greater strength, and eigenvector centrality within the large-scale brain network.These findings provide novel insights into the interaction between epileptogenic cortex and large-scale brain networks. The association between ablation volume and resting-state networks may supply novel avenues for presurgical planning and patient stratification.

  View details for DOI 10.1016/j.seizure.2018.08.006

  View details for PubMedID 30118930

• Neuroimmune disorders of the central nervous system in children in the molecular era. Nature reviews. Neurology Wells, E., Hacohen, Y., Waldman, A., Tillema, J. M., Soldatos, A., Ances, B., Benseler, S., Bielekova, B., Dale, R. C., Dalmau, J., Gaillard, W., Gorman, M., Greenberg, B., Hyslop, A., Pardo, C. A., Tasker, R. C., Yeh, E. A., Bar-Or, A., Pittock, S., Vanderver, A., Banwell, B. 2018; 14 (7): 433-445

  Abstract

  Immune-mediated disorders of the CNS in children are a complex group of demyelinating, inflammatory, parainfectious and postinfectious disorders with heterogeneous pathobiological mechanisms and clinical manifestations, often associated with fundamental derangement in immune regulation. In this Review, we aim to provide an update on our knowledge of neuroimmune disorders and highlight areas of research that are priorities for improving clinical management. We outline the clinical features of neuroimmune disorders, the current approaches to their treatment and new approaches in development. We then consider the pathological features, including biomarkers, pathological mechanisms and genetics, and discuss the value of immune assays in clinical investigation and basic research. On the basis of current knowledge and techniques, we propose four research priorities: rigorous and consistent collection of core clinical data, cooperative investigation of treatments, development of biological assays and genetic studies. These priorities should help us to achieve the shared goal of precision medicine for neuroimmune disorders. However, multicentre research and the creation of clinical consortia for these rare disorders will be necessary, and we hope that this Review serves as a call to action that is timely given current exciting advances in neuroimmune therapeutics.

  View details for DOI 10.1038/s41582-018-0024-9

  View details for PubMedID 29925924

• Presurgical thalamocortical connectivity is associated with response to vagus nerve stimulation in children with intractable epilepsy. NeuroImage. Clinical Ibrahim, G. M., Sharma, P., Hyslop, A., Guillen, M. R., Morgan, B. R., Wong, S., Abel, T. J., Elkaim, L., Cajigas, I., Shah, A. H., Fallah, A., Weil, A. G., Altman, N., Bernal, B., Medina, S., Widjaja, E., Jayakar, P., Ragheb, J., Bhatia, S. 2017; 16: 634-642

  Abstract

  Although chronic vagus nerve stimulation (VNS) is an established treatment for medically-intractable childhood epilepsy, there is considerable heterogeneity in seizure response and little data are available to pre-operatively identify patients who may benefit from treatment. Since the therapeutic effect of VNS may be mediated by afferent projections to the thalamus, we tested the hypothesis that intrinsic thalamocortical connectivity is associated with seizure response following chronic VNS in children with epilepsy. Twenty-one children (ages 5-21 years) with medically-intractable epilepsy underwent resting-state fMRI prior to implantation of VNS. Ten received sedation, while 11 did not. Whole brain connectivity to thalamic regions of interest was performed. Multivariate generalized linear models were used to correlate resting-state data with seizure outcomes, while adjusting for age and sedation status. A supervised support vector machine (SVM) algorithm was used to classify response to chronic VNS on the basis of intrinsic connectivity. Of the 21 subjects, 11 (52%) had 50% or greater improvement in seizure control after VNS. Enhanced connectivity of the thalami to the anterior cingulate cortex (ACC) and left insula was associated with greater VNS efficacy. Within our test cohort, SVM correctly classified response to chronic VNS with 86% accuracy. In an external cohort of 8 children, the predictive model correctly classified the seizure response with 88% accuracy. We find that enhanced intrinsic connectivity within thalamocortical circuitry is associated with seizure response following VNS. These results encourage the study of intrinsic connectivity to inform neural network-based, personalized treatment decisions for children with intractable epilepsy.

  View details for DOI 10.1016/j.nicl.2017.09.015

  View details for PubMedID 28971013

  View details for PubMedCentralID PMC5619991

• The diagnostic utility of 3D-ESI rotating and moving dipole methodology in the pre-surgical evaluation of MRI-negative childhood epilepsy due to focal cortical dysplasia. Epilepsia Russo, A., Lallas, M., Jayakar, P., Miller, I., Hyslop, A., Dunoyer, C., Resnick, T., Duchowny, M. 2016; 57 (9): 1450-7

  Abstract

  This study investigates whether a combined rotating dipole (RD) and moving dipole (MD) solution enhances three-dimensional electroencephalography (EEG) source imaging (3D-ESI) localization in magnetic resonance imaging (MRI)-negative pediatric patients with focal cortical dysplasia (FCD).We retrospectively selected 14 MRI-negative patients with FCD from a cohort of 60 pediatric patients previously used to evaluate the diagnostic utility of 3D-ESI in epilepsy surgery. Patients were younger than 18 years at time of surgery and had at least 1 year of outcome data. RD and MD models were constructed for each interictal spike or sharp wave, and it was determined whether each inverse algorithm localized within the surgical resection cavity (SRC). We also compared the 3D-ESI findings and surgical outcome with positron emission tomography (PET) and ictal single photon emission computed tomography (iSPECT).RD analyses revealed a high concordance with the SRC (78.6%), particularly for temporal lobe resection (100.0%), and showed superior localization compared to PET and iSPECT, with the highest correlation in FCD type I and temporal lobe resection. Furthermore, the RD method was superior to iSPECT in FCD type II cases and to PET in extratemporal resections. RD and MD results were comparable, but in 18.2% of patients with FCD type I with localizing RDs, the MD solution was only partially within the SRC; in all of these patients 3D-ESI also correlated with superior surgical outcome compared to PET and iSPECT, especially when RD and MD solutions were analyzed together.3D-ESI in MRI-negative cases showed superior localization compared to iSPECT or PET, especially in FCD type I and temporal lobe epilepsy, and correlated with superior surgical outcome compared to iSPECT and PET at 1 year and 2 years postoperatively, especially when RD and MD solutions were analyzed together. These findings suggest that 3D-ESI based on a combined RD-MD solution improves surgical accuracy in MRI-negative patients with FCD.

  View details for DOI 10.1111/epi.13454

  View details for PubMedID 27387565

• Sensitivity of quantitative EEG for seizure identification in the intensive care unit NEUROLOGY Haider, H. A., Esteller, R., Hahn, C. D., Westover, M., Halford, J. J., Lee, J. W., Shafi, M. M., Gaspard, N., Herman, S. T., Gerard, E. E., Hirsch, L. J., Ehrenberg, J. A., LaRoche, S. M., Critical Care EEG Monitoring Res 2016; 87 (9): 935-944

  Abstract

  To evaluate the sensitivity of quantitative EEG (QEEG) for electrographic seizure identification in the intensive care unit (ICU).Six-hour EEG epochs chosen from 15 patients underwent transformation into QEEG displays. Each epoch was reviewed in 3 formats: raw EEG, QEEG + raw, and QEEG-only. Epochs were also analyzed by a proprietary seizure detection algorithm. Nine neurophysiologists reviewed raw EEGs to identify seizures to serve as the gold standard. Nine other neurophysiologists with experience in QEEG evaluated the epochs in QEEG formats, with and without concomitant raw EEG. Sensitivity and false-positive rates (FPRs) for seizure identification were calculated and median review time assessed.Mean sensitivity for seizure identification ranged from 51% to 67% for QEEG-only and 63%-68% for QEEG + raw. FPRs averaged 1/h for QEEG-only and 0.5/h for QEEG + raw. Mean sensitivity of seizure probability software was 26.2%-26.7%, with FPR of 0.07/h. Epochs with the highest sensitivities contained frequent, intermittent seizures. Lower sensitivities were seen with slow-frequency, low-amplitude seizures and epochs with rhythmic or periodic patterns. Median review times were shorter for QEEG (6 minutes) and QEEG + raw analysis (14.5 minutes) vs raw EEG (19 minutes; p = 0.00003).A panel of QEEG trends can be used by experts to shorten EEG review time for seizure identification with reasonable sensitivity and low FPRs. The prevalence of false detections confirms that raw EEG review must be used in conjunction with QEEG. Studies are needed to identify optimal QEEG trend configurations and the utility of QEEG as a screening tool for non-EEG personnel.This study provides Class II evidence that QEEG + raw interpreted by experts identifies seizures in patients in the ICU with a sensitivity of 63%-68% and FPR of 0.5 seizures per hour.

  View details for DOI 10.1212/WNL.0000000000003034

  View details for Web of Science ID 000383980600020

  View details for PubMedID 27466474

  View details for PubMedCentralID PMC5035158

• PET hypermetabolism in medically resistant childhood epilepsy: Incidence, associations, and surgical outcome. Epilepsia Bansal, L., Miller, I., Hyslop, A., Bhatia, S., Duchowny, M., Jayakar, P. 2016; 57 (3): 436-44

  Abstract

  We observed several children with medically resistant epilepsy demonstrating focal positron emission tomography (PET) hypermetabolism, a finding rarely reported and of questionable significance. We therefore retrospectively reviewed the incidence of hypermetabolic PET, and its relationship to electroencephalography (EEG) and magnetic resonance imaging (MRI) findings, and to the outcome of epilepsy surgery.We retrospectively reviewed 498 PET brain studies in patients with medically resistant childhood epilepsy for evidence of hypermetabolism. In patients with PET hypermetabolism, we correlated metabolic abnormality with the scalp EEG and MRI findings. In a subset of patients who underwent surgical resection, we further correlated the PET findings with histopathologic and surgical outcomes.Focal PET hypermetabolism was identified in 33 (6.6%) of 498 studies. The region of hypermetabolism correlated with a spike count of ≥10 per minute in 26 of 32 concomitant scalp EEG studies and 18 of 21 lesions evident on MRI. In 17 patients who underwent surgical resection, PET hypermetabolism further correlated with regions revealing almost continuous epileptiform discharges on the intracranial EEG and with histopathologically malformative tissue. At a minimum follow-up of 1 year postsurgery (median 33 months), 7 (50%) of 14 patients had Engel's class I outcome, 4 patients had class II, and 2 had class III outcome, whereas one patient was unchanged. At last follow-up, seizure freedom was noted in five of seven patients with focal PET hypermetabolism alone versus three of eight patients with PET hypometabolism.Focal PET hypermetabolism is associated with high spike frequency on scalp EEG and can occur in the absence of ictal events during the peri-injection period. Correlation with intracranial EEG usually corroborates the highly epileptogenic pathophysiologic state. Cortical malformations constitute the most common pathologic substrate, and resection of the hypermetabolic PET region may facilitate favorable outcomes. These observations indicate that focal PET hypermetabolism is an important marker of the epileptogenic zone and may represent its epicenter.

  View details for DOI 10.1111/epi.13311

  View details for PubMedID 26778272

• The diagnostic utility of 3D electroencephalography source imaging in pediatric epilepsy surgery. Epilepsia Russo, A., Jayakar, P., Lallas, M., Miller, I., Hyslop, A., Korman, B., Dunoyer, C., Resnick, T., Duchowny, M. 2016; 57 (1): 24-31

  Abstract

  The aim of this study was to investigate the utility of three-dimensional electroencephalography source imaging (3D-ESI) with low-resolution electroencephalographic data in the pediatric noninvasive presurgical evaluation, and to compare the findings with positron emission tomography (PET) and ictal single-photon emission computed tomography (iSPECT).We retrospectively selected 60 patients from a database of 594 patients who underwent excisional surgery for drug-resistant epilepsy. Patients were <18 years at time of surgery, had at least one presurgical volumetric brain magnetic resonance imaging (MRI), and at least 1 year of outcome data. 3D-ESI was performed with NeuroScan software CURRY V.7.0. For each patient the surgical resection was planned utilizing 3D-ESI as an adjunctive tool to supplement MRI and electrocorticographic data. Our analyses addressed three critical variables: pathology (focal cortical dysplasia vs. other pathologies), imaging (MRI negative vs. positive cases), and surgery (temporal resection vs. extratemporal and multilobar resections). We also compared the localizing utility and surgical outcome of 3D-ESI findings with PET, iSPECT, and the colocalized surgical resection. Statistical analyses were performed using the Statistical Package for the Social Sciences, Version 20.Mean age at surgery was 11.18 years (range 1-18 years). 3D-ESI showed a strong correlation with the surgical resection cavity (65.0%), particularly within the temporal lobe. 3D-ESI demonstrated better localization in MRI-negative cases (78.6%), which was not statistically significant. 3D-ESI also correlated with a superior surgical outcome profile compared to PET and iSPECT.Our findings demonstrate that 3D-ESI data obtained with low-resolution electroencephalography achieves reasonably accurate noninvasive localization of epileptic spikes in pediatric focal epilepsy, especially in temporal lobe and MRI-negative cases, and is comparable to iSPECT and PET. Given its lesser expense and lack of radiation exposure, 3D-ESI is a useful and efficient tool for evaluating surgical candidacy in pediatric epilepsy surgery centers, particularly if PET and iSPECT are unavailable.

  View details for DOI 10.1111/epi.13228

  View details for PubMedID 26696504

• Minimally resective epilepsy surgery in MRI-negative children. Epileptic disorders : international epilepsy journal with videotape Hyslop, A., Miller, I., Bhatia, S., Resnick, T., Duchowny, M., Jayakar, P. 2015; 17 (3): 263-74

  Abstract

  Performing epilepsy surgery on children with non-lesional brain MRI often results in large lobar or multilobar resections. The aim of this study was to determine if smaller resections result in a comparable rate of seizure freedom.We reviewed 25 children who had undergone focal corticectomies restricted to one aspect of a single lobe or the insula at our institution within a 5.5-year period. Data collected in the comprehensive non-invasive pre-surgical evaluation (including scalp video-EEG, volumetric MRI, functional MRI, EEG source localization, and SPECT and PET), as well as from invasive recordings performed in each patient, was reviewed. Data from each functional modality was identified as convergent or divergent with the epileptogenic zone using image coregistration. Specific biomarkers (from extra-operative and invasive testing) previously indicated to be indicative of focal epileptogenicity were used to further tailor each resection to an epileptogenic epicentre. Tissue pathology and postoperative outcomes were obtained from all 25 patients.Two years postoperatively, 15/25 (60%) children were seizure-free, three (12%) experienced >90% reduction in seizure frequency, two (8%) had a 50-90% reduction in seizure frequency, and the remaining five (20%) had no change in seizure burden. There was no significant difference in outcome based on numerous pre- and postoperative factors including location of resection, the number of preoperative functional tests providing convergent data, and tissue pathology.In MRI-negative children with focal epilepsy, an epileptogenic epicentre within a larger epileptogenic zone can be identified when specific biomarkers are recognized on non-invasive and invasive testing. When such children undergo resection of a small, well-defined epileptogenic epicentre, favourable outcomes can be achieved.

  View details for DOI 10.1684/epd.2015.0766

  View details for PubMedID 26293180

• Electroencephalographic monitoring in the pediatric intensive care unit. Current neurology and neuroscience reports Abend, N. S., Chapman, K. E., Gallentine, W. B., Goldstein, J., Hyslop, A. E., Loddenkemper, T., Nash, K. B., Riviello, J. J., Hahn, C. D. 2013; 13 (3): 330

  Abstract

  Continuous electroencephalographic (CEEG) monitoring is used with increasing frequency in critically ill children to provide insight into brain function and to identify electrographic seizures. CEEG monitoring use often impacts clinical management, most often by identifying electrographic seizures and status epilepticus. Most electrographic seizures have no clinical correlate, and thus would not be identified without CEEG monitoring. There are increasing data showing that electrographic seizures and electrographic status epilepticus are associated with worse outcome. Seizure identification efficiency may be improved by further development of quantitative electroencephalography trends. This review describes the clinical impact of CEEG data, the epidemiology of electrographic seizures and status epilepticus, the impact of electrographic seizures on outcome, the utility of quantitative electroencephalographic trends for seizure identification, and practical considerations regarding CEEG monitoring.

  View details for DOI 10.1007/s11910-012-0330-3

  View details for PubMedID 23335026

  View details for PubMedCentralID PMC3569710

• Clinical Reasoning: An unexpected diagnosis in a 4-month-old infant with lethargy and H1N1 influenza NEUROLOGY Hyslop, A. E., Droker, B. S., Jansen, L. A. 2011; 76 (18): E88-E92

  View details for DOI 10.1212/WNL.0b013e3182190cf2

  View details for Web of Science ID 000290150800002

  View details for PubMedID 21536632

  View details for PubMedCentralID PMC4094169

• Quantification of colorectal cancer micrometastases in lymph nodes by nested and real-time reverse transcriptase-PCR analysis for carcinoembryonic antigen CLINICAL CANCER RESEARCH Ho, S. B., Hyslop, A., Albrecht, R., Jacobson, A., Spencer, M., Rothenberger, D. A., Niehans, G. A., D'Cunha, J., Kratzke, R. A. 2004; 10 (17): 5777-5784

  Abstract

  Reverse-transcriptase PCR (RT-PCR) assays for carcinoembryonic antigen (CEA) have been described to identify lymph node micrometastases. These assays are not quantitative and can be confounded by false-positive results. The purpose of this study was to determine whether quantification of CEA in lymph nodes could more readily identify clinically relevant groups.Specimens included 400 lymph nodes from 64 patients undergoing colon resections. Specimens were tested by immunohistochemistry and by RT-PCR using nested primers for CEA. Specimens from 59 patients that were positive by nested RT-PCR were further quantified by detection of CEA mRNA fluorescence increase at a threshold PCR cycle.CEA was detected by nested RT-PCR analysis in 4 of 34 (12%) nodes of nonneoplastic disease, 2 of 13 (15%) nodes from T(1)N(0) patients, 32 of 81 (40%) nodes of T(2)N(0) patients, 49 of 109 (45%) nodes from T(3)N0 patients, and 92 of 163 (56%) nodes from T(1-4)N(1-2) patients. The overall presence of any RT-PCR-detectable CEA in nodes did not differentiate patient groups. Immunohistochemistry was positive in nodes from 7% of T(3)N(0) patients and 100% of T(1-3)N(1-2) patients. CEA quantification revealed that 0 of 7 patients with nonneoplastic disease and 2 of 17 (12%) patients with stage I T(1-2)N(0) cancers had one or more lymph nodes with >/=1.0 x 10(2) CEA transcripts per sample. In contrast, 4 of 13 (31%) patients with stage II T(3)N(0) cancer and 10 of 22 (45%) stage III patients with known metastases had lymph nodes with >/=1.0 x 10(2) CEA transcripts.These data suggest that quantification of CEA levels in lymph nodes may more accurately identify patients at risk for cancer recurrence than does routine nested RT-PCR or immunohistochemistry.

  View details for DOI 10.1158/1078-0432.CCR-03-0507

  View details for Web of Science ID 000223724700021

  View details for PubMedID 15355906