Faculty Bibliography

Animal studies support the hypothesis that in slow-wave sleep, replay of waking neocortical activity under hippocampal guidance leads to memory consolidation. However, no intracranial electrophysiological evidence for replay exists in humans. We identified consistent sequences of population firing peaks across widespread cortical regions during complete waking periods. The occurrence of these "Motifs" were compared between sleeps preceding the waking period ("Sleep-Pre") when the Motifs were identified, and those following ("Sleep-Post"). In all subjects, the majority of waking Motifs (most of which were novel) had more matches in Sleep-Post than in Sleep-Pre. In rodents, hippocampal replay occurs during local sharp-wave ripples, and the associated neocortical replay tends to occur during local sleep spindles and down-to-up transitions. These waves may facilitate consolidation by sequencing cell-firing and encouraging plasticity. Similarly, we found that Motifs were coupled to neocortical spindles, down-to-up transitions, theta bursts, and hippocampal sharp-wave ripples. While Motifs occurring during cognitive task performance were more likely to have more matches in subsequent sleep, our studies provide no direct demonstration that the replay of Motifs contributes to consolidation. Nonetheless, these results confirm a core prediction of the dominant neurobiological theory of human memory consolidation.

Although responsive neurostimulation (RNS) is approved for treatment of resistant focal epilepsy in adults, little is known about response to treatment of specific cortical targets. We describe the experience of RNS targeting the insular lobe. We identified patients who had RNS implantation with at least one electrode within the insula between April 2014 and October 2015. We performed a retrospective review of preoperative clinical features, imaging, electrocardiogram (EEG), intraoperative electrocorticography (ECoG), and postoperative seizure outcome. Eight patients with at least 6 months of postimplant follow-up were identified. Ictal localization was inconclusive with MRI or scalp EEG findings. Intracranial EEG monitoring or intraoperative ECoG demonstrated clear ictal onsets and/or frequent interictal discharges in the insula. Four patients demonstrated overall 50-75% reduction in seizure frequency. Two patients did not show appreciable seizure improvement. One patient has experienced a 75% reduction of seizure frequency, and another is nearly seizure free postoperatively. There were no reported direct complications of insular RNS electrode placement or stimulation, though two patients had postoperative complications thought to be related to craniotomy (hydrocephalus and late infection). Our study suggests that insular RNS electrode placement in selected patients is relatively safe and that RNS treatment may benefit selected patients with insular epilepsy.

OBJECTIVES: We assessed the efficacy and risks of diagnostic bilateral intracranial EEG (bICEEG) in treatment-resistant epilepsy (TRE) patients with poorly lateralized epileptogenic zone (EZ) on non-invasive studies as reflected by progress to resection, Engel outcome and complication rate. METHODS: This is a retrospective chart review of 199 patients with TRE who had diagnostic bICEEG at New York University Medical Center between 1994 and 2013. Study endpoints were progress to resection, surgical outcome and perioperative complications. Univariate analysis was performed with ANOVA, t-test or Fischer's Exact test; multivariable analysis was performed using discriminant function analysis. RESULTS: bICEEG lateralized the EZ and the patient had resection in 60.3% of cases. The number of depth electrodes used was positively correlated with resection, and surgical complications during bICEEG negatively correlated. Vagal nerve stimulators were implanted in 58.2% of patients who did not undergo resection and 20.7% of those who did. Among the 87 patients who progressed to resection and had more than 1-year follow-up, 47.1% were seizure free compared with 12.7% of the 55 who did not. Male sex correlated with good postoperative seizure control. The most common complication was infection requiring debridement, occurring in 3.1% of admissions (9 of 290). CONCLUSION: At our center, 60% of patients undergoing bICEEG progress to resection and 57% of these had more than 90% reduction in seizures. We conclude that bICEEG allows the benefits of epilepsy surgery to be extended to patients with poorly lateralized and localized TRE.

The differential contribution of medial-temporal lobe regions to verbal declarative memory is debated within the neuroscience, neuropsychology, and cognitive psychology communities. We evaluate whether the extent of surgical resection within medial-temporal regions predicts longitudinal verbal learning and memory outcomes. This single-center retrospective observational study involved patients with refractory temporal lobe epilepsy undergoing unilateral anterior temporal lobe resection from 2007 to 2015. Thirty-two participants with Engel Classes 1 and 2 outcomes were included (14 left, 18 right) and followed for a mean of 2.3 years after surgery (+/-1.5 years). Participants had baseline and postsurgical neuropsychological testing and high-resolution T1-weighted MRI scans. Postsurgical lesions were manually traced and coregistered to presurgical scans to precisely quantify resection extent of medial-temporal regions. Verbal learning and memory change scores were regressed on hippocampal, entorhinal, and parahippocampal resection volume after accounting for baseline performance. Overall, there were no significant differences in learning and memory change between patients who received left and right anterior temporal lobe resection. After controlling for baseline performance, the extent of left parahippocampal resection accounted for 27% (p = .021) of the variance in verbal short delay free recall. The extent of left entorhinal resection accounted for 37% (p = .004) of the variance in verbal short delay free recall. Our findings highlight the critical role that the left parahippocampal and entorhinal regions play in recall for verbal material.

OBJECTIVE: Presently, there is no simple method at initial presentation for identifying a patient's likelihood of progressing to surgery and a favorable outcome. The Epilepsy Surgery Grading Scale (ESGS) is a three-tier empirically derived mathematical scale with five categories: magnetic resonance imaging (MRI), electroencephalography (EEG), concordance (between MRI and EEG), semiology, and IQ designed to stratify patients with drug-resistant focal epilepsy based on their likelihood of proceeding to resective epilepsy surgery and achieving seizure freedom. METHODS: In this cross-sectional study, we abstracted data from the charts of all patients admitted to the New York University Langone Medical Center (NYULMC) for presurgical evaluation or presented in surgical multidisciplinary conference (MDC) at the NYU Comprehensive Epilepsy Center (CEC) from 1/1/2007 to 7/31/2008 with focal epilepsy, who met minimal criteria for treatment resistance. We classified patients into ESGS Grade 1 (most favorable), Grade 2 (intermediate), and Grade 3 (least favorable candidates). Three cohorts were evaluated: all patients, patients presented in MDC, and patients who had resective surgery. The primary outcome measure was proceeding to surgery and seizure freedom. RESULTS: Four hundred seven patients met eligibility criteria; 200 (49.1%) were presented in MDC and 113 (27.8%) underwent surgery. A significant difference was observed between Grades 1 and 3, Grades 1 and 2, and Grades 2 and 3 for all presurgical patients, and those presented in MDC, with Grade 1 patients having the highest likelihood of both having surgery and becoming seizure-free. There was no difference between Grades 1 and 2 among patients who had resective surgery. SIGNIFICANCE: These results demonstrate that by systematically using basic information available during initial assessment, patients with drug-resistant epilepsy may be successfully stratified into clinically meaningful groups with varied prognosis. The ESGS may improve communication, facilitate decision making and early referral to a CEC, and allow patients and physicians to better manage expectations.

Objective: In this study, we tested the hypothesis that chances of subjective prediction of seizure freedom by experienced epileptologists at a Level IV epilepsy center are comparable to results actually achieved post-surgery. Background: In the era of evidence based medicine, the use of grading and scoring tools in guiding and prognosticating patient care has become a cornerstone of medical practice. However, care in the epilepsy world still remains more physician experience based, where outcome measures that predict the likelihood of post-surgical outcomes still remain underutilized. Design/Methods: We evaluated a cohort of 49 patients with treatment resistant epilepsy who were presented in multidisciplinary surgical conference (MDC) at our institution. At least two epileptologists with over 10 years of experience estimated chances of post-surgical seizure remission at the MDC. 33 of 49 patients (67%) discussed underwent intracranial EEG monitoring and resective epilepsy surgery. Seizure freedom was assessed at 1-year and 2-years post-surgery. Methods: To this end, we evaluated a cohort of 49 refractory epilepsy patients discussed at the multidisciplinary epilepsy conference (MDC) at our institution. Clinical history, imaging, EEG and neuro-psychology data was reviewed at the conference. At least two fellowship trained experts with more than 10 years of experience estimated chances of seizure remission post-surgery at the time of MDC. 33 of 49 patients (67%) discussed underwent surgery. Seizure freedom was assessed at 6-months, 1-year and 2-years post-surgery. Results: 23 of 33 patients who underwent surgery had Engel I outcomes at 2-year clinical follow-ups. Only 7 of 23 patients (30%) that achieved an Engel I outcome were estimated by expert physicians to have a 50% or more chance of seizure freedom post-surgery. Conclusions: Our results demonstrate that even experienced specialists in the field are conservative at predicting post-surgical seizure outcomes and highlight the need for development and utilization of better objective tools in the field

For patients with pharmacoresistant focal epilepsy in whom surgical resection of the epileptogenic focus fails or was not feasible in the first place, there were few therapeutic options. Increasingly, neurostimulation provides an alternative treatment strategy for these patients. Vagal nerve stimulation (VNS) is well established. Deep brain stimulation (DBS) and cortical responsive stimulation (CRS) are newer neurostimulation therapies with recently published long-term efficacy and safety data. In this literature review, we introduce these therapies to a non-specialist audience. Furthermore, we compare and contrast long-term (5-year) outcomes of newer neurostimulation techniques with the more established VNS. A search to identify all studies reporting long-term efficacy (>5 years) of VNS, CRS and DBS in patients with refractory focal/partial epilepsy was conducted using PubMed and Cochrane databases. The outcomes compared were responder rate, percentage seizure frequency reduction, seizure freedom, adverse events, neuropsychological outcome and quality of life. We identified 1 study for DBS, 1 study for CRS and 4 studies for VNS. All neurostimulation technologies showed long-term efficacy, with progressively better seizure control over time. Sustained improvement in quality of life measures was demonstrated in all modalities. Intracranial neurostimulation had a greater side effect profile compared with extracranial stimulation, though all forms of stimulation are safe. Methodological differences between the studies mean that direct comparisons are not straightforward. We have synthesised the findings of this review into a pragmatic decision tree, to guide the further management of the individual patient with pharmacoresistant focal-onset epilepsy.

PURPOSE: The aim of this study was to determine the relationship of fear to other auras and to gender and age using a large database. METHODS: The Epilepsy Phenome/Genome Project (EPGP) is a multicenter, multicontinental cross-sectional study in which ictal symptomatology and other data were ascertained in a standardized series of questionnaires then corroborated by epilepsy specialists. Auras were classified into subgroups of symptoms, with ictal fear, panic, or anxiety as a single category. RESULTS: Of 536 participants with focal epilepsy, 72 were coded as having ictal fear/panic/anxiety. Reviewing raw patient responses, 12 participants were deemed not to have fear, and 24 had inadequate data, leaving 36 (7%) of 512 with definite ictal fear. In univariate analyses, fear was significantly associated with auras historically considered temporal lobe in origin, including cephalic, olfactory, and visceral complaints; deja vu; and derealization. On both univariate and multivariate stepwise analyses, fear was associated with jamais vu and auras with cardiac symptoms, dyspnea, and chest tightening. Expressive aphasia was associated with fear on univariate analysis only, but the general category of aphasias was associated with fear only in the multivariate model. There was no age or gender relationship with fear when compared to the overall population with focal epilepsy that was studied under the EPGP. Patients with ictal fear were more likely to have a right hemisphere seizure focus. CONCLUSIONS: Ictal fear was strongly associated with other auras considered to originate from the limbic system. No relationship of fear with age or gender was observed.

Surface-based cortical thickness (CT) analyses are increasingly being used to investigate variations in brain morphology across the spectrum of brain health, from neurotypical to neuropathological. An outstanding question is whether individual differences in cortical morphology, such as regionally increased or decreased CT, are associated with domain-specific performance deficits in healthy adults. Since CT studies are correlational, they cannot establish causality between brain morphology and cognitive performance. A direct comparison with classic lesion methods is needed to determine whether the regional specificity of CT-cognition correlations is similar to that observed in patients with brain lesions. We address this question by comparing the neuroanatomical overlap of effects when 1) whole brain vertex-wise CT is tested as a correlate of performance variability on a commonly used neuropsychological test of executive function, Trailmaking Test Part B (TMT-B), in healthy adults and 2) voxel-based lesion-symptom mapping (VBLSM) is used to map lesion location to performance decrements on the same task in patients with frontal lobe lesions. We found that reduced performance on the TMT-B was associated with increased CT in bilateral prefrontal regions in healthy adults and that results spatially overlapped in the left dorsomedial prefrontal cortex with findings from the VBLSM analysis in patients with frontal brain lesions. Findings indicate that variations in the structural integrity of the left dorsomedial prefrontal lobe, ranging from individual CT differences in healthy adults to structural lesions in patients with neurological disorders, are associated with poor performance on the TMT-B. These converging results suggest that the left dorsomedial prefrontal region houses a critical region for the complex processing demands of TMT-B, which include visuomotor tracking, sequencing, and cognitive flexibility.

Objective: To characterize efficacy and risks of diagnostic bilateral intracranial electroencephalography (bICEEG) in treatment-resistant epilepsy (TRE) patients with poorly lateralized epileptogenic zone (EZ) on non-invasive studies. Background: Patients with TRE are candidates for epilepsy surgery if the EZ is localized and deemed resectable. For cases with discordant non-invasive studies, bICEEG may definitively lateralize the EZ to identify surgical candidates. Methods: We retrospectively reviewed all 208 bICEEG cases at New York University (NYU) between 1994 and 2013. Endpoints included: progress to resection, Engel outcome, and peri-operative complications. Results: Of 208 patients, 19 were lost to follow-up. For 60[percnt], bICEEG lateralized the EZ and they progressed to therapeutic resection or further regional ICEEG. Subdural and depth electrodes were routinely used together but only the number of depth electrodes positively correlated with progress to resection and depth electrode use was not greater in temporal lobe cases. Forty-eight percent who progressed to resection were seizure free at last follow-up (mean 5.4yrs) compared with 13[percnt] of patients who did not have resection (mean 5.6yrs). Pre-operative seizure frequency greater than 1/day was associated with worse post-operative seizure control. The most common complication was infection requiring surgical intervention; occurrence was 3.1[percnt]. Rates of superficial infection, DVT, pulmonary embolism, stroke, and hemorrhage were each below 1[percnt]. Conclusions: At NYU, 60[percnt] of patients with TRE who underwent bICEEG progressed to EZ resection and 48[percnt] of these cases were seizure free. The risks of bICEEG monitoring are similar to our unilateral invasive monitoring. We conclude that bICEEG extends the benefit of epilepsy surgery to poorly lateralized TRE patients. Future analysis will determine the relative predictive value of seizure semiology, vEEG monitoring, MRI, MEG, and PET to progress to resection and Engel outcome in this series; as well as determine how depth electrodes augment subdural monitoring