Disentanglement of Resting State Brain Networks for Localizing Epileptogenic Zone in Focal Epilepsy.

The objective of this study is to extract pathological brain networks from interictal period of E/MEG recordings to localize epileptic foci for presurgical evaluation. We proposed here a resting state E/MEG analysis framework, to disentangle brain functional networks represented by neural oscillations. By using an Embedded Hidden Markov Model, we constructed a state space for resting state recordings consisting of brain states with different spatiotemporal patterns. Functional connectivity analysis along with graph theory was applied on the extracted brain states to quantify the network features of the extracted brain states, based on which the source location of pathological states is determined. The method is evaluated by computer simulations and our simulation results revealed the proposed framework can extract brain states with high accuracy regarding both spatial and temporal profiles. We further evaluated the framework as compared with intracranial EEG defined seizure onset zone in 10 patients with drug-resistant focal epilepsy who underwent MEG recordings and were seizure free after surgical resection. The real patient data analysis showed very good localization results using the extracted pathological brain states in 6/10 patients, with localization error of about 15 mm as compared to the seizure onset zone. We show that the pathological brain networks can be disentangled from the resting-state electromagnetic recording and could be identified based on the connectivity features. The framework can serve as a useful tool in extracting brain functional networks from noninvasive resting state electromagnetic recordings, and promises to offer an alternative to aid presurgical evaluation guiding intracranial EEG electrodes implantation.

Epilepsy monitoring unit practices and safety among NAEC epilepsy centers: A census survey.

OBJECTIVE: An epilepsy monitoring unit (EMU) is a specialized unit designed for capturing and characterizing seizures and other paroxysmal events with continuous video electroencephalography (vEEG). Nearly 260 epilepsy centers in the United States are accredited by the National Association of Epilepsy Centers (NAEC) based on adherence to specific clinical standards to improve epilepsy care, safety, and quality. This study examines EMU staffing, safety practices, and reported outcomes. METHOD: We analyzed NAEC annual report data and results from a supplemental survey specific to EMU practices reported in 2019 from 341 pediatric or adult center directors. Data on staffing, resources, safety practices and complications were collated with epilepsy center characteristics. We summarized using frequency (percentage) for categorical variables and median (inter-quartile range) for continuous variables. We used chi-square or Fisher's exact tests to compare staff responsibilities. RESULTS: The supplemental survey response rate was 100%. Spell classification (39%) and phase 1 testing (28%) were the most common goals of the 91,069 reported admissions. The goal ratio of EEG technologist to beds of 1:4 was the most common during the day (68%) and off-hours (43%). Compared to residents and fellows, advanced practice providers served more roles in the EMU at level 3 or pediatric-only centers. Status epilepticus (SE) was the most common reported complication (1.6% of admissions), while cardiac arrest occurred in 0.1% of admissions. SIGNIFICANCE: EMU staffing and safety practices vary across US epilepsy centers. Reported complications in EMUs are rare but could be further reduced, such as with more effective treatment or prevention of SE. These findings have potential implications for improving EMU safety and quality care.

Deep learning based source imaging provides strong sublobar localization of epileptogenic zone from MEG interictal spikes.

Electromagnetic source imaging (ESI) offers unique capability of imaging brain dynamics for studying brain functions and aiding the clinical management of brain disorders. Challenges exist in ESI due to the ill-posedness of the inverse problem and thus the need of modeling the underlying brain dynamics for regularizations. Advances in generative models provide opportunities for more accurate and realistic source modeling that could offer an alternative approach to ESI for modeling the underlying brain dynamics beyond equivalent physical source models. However, it is not straightforward to explicitly formulate the knowledge arising from these generative models within the conventional ESI framework. Here we investigate a novel source imaging framework based on mesoscale neuronal modeling and deep learning (DL) that can learn the sensor-source mapping relationship directly from MEG data for ESI. Two DL-based ESI models were trained based on data generated by neural mass models and either generic or personalized head models. The robustness of the two DL models was evaluated by systematic computer simulations and clinical validation in a cohort of 29 drug-resistant focal epilepsy patients who underwent intracranial EEG (iEEG) evaluation or surgical resection. Results estimated from pre-operative MEG interictal spikes were quantified using the overlap with resection regions and the distance to the seizure-onset zone (SOZ) defined by iEEG recordings. The DL-based ESI provided robust results when no personalized head geometry is considered, reaching a spatial dispersion of 21.90 ± 19.03 mm, sublobar concordance of 83 %, and sublobar sensitivity and specificity of 66 and 97 % respectively. When using personalized head geometry derived from individual patients' MRI in the training data, personalized DL-based ESI model can further improve the performance and reached a spatial dispersion of 8.19 ± 8.14 mm, sublobar concordance of 93 %, and sublobar sensitivity and specificity of 77 and 99 % respectively. When compared to the SOZ, the localization error of the personalized approach is 15.78 ± 5.54 mm, outperforming the conventional benchmarks. This work demonstrates that combining generative models and deep learning enables an accurate and robust imaging of epileptogenic zone from MEG recordings with strong sublobar precision, suggesting its added value to enhancing MEG source localization and imaging, and to epilepsy source localization and other clinical applications.

Role of optically pumped magnetometers in presurgical epilepsy evaluation: Commentary of the American Clinical Magnetoencephalography Society.

One of the major challenges of modern epileptology is the underutilization of epilepsy surgery for treatment of patients with focal, medication resistant epilepsy (MRE). Aggravating this distressing failure to deliver optimum care to these patients is the underuse of proven localizing tools, such as magnetoencephalography (MEG), a clinically validated, non-invasive, neurophysiological method used to directly measure and localize brain activity. A sizable mass of published evidence indicates that MEG can improve identification of surgical candidates and guide pre-surgical planning, increasing the yield of SEEG and improving operative outcomes. However, despite at least 10 common, evidence supported, clinical scenarios in MRE patients where MEG can offer non-redundant information and improve the pre-surgical evaluation, it is regularly used by only a minority of USA epilepsy centers. The current state of the art in MEG sensors employs SQUIDs, which require cooling with liquid helium to achieve superconductivity. This sensor technology has undergone significant generational improvement since whole head MEG scanners were introduced around in 1990s, but still has limitations. Further advances in sensor technology which may make ME G more easily accessible and affordable have been eagerly awaited, and development of new techniques should be encouraged. Of late, optically pumped magnetometers (OPMs) have received considerable attention, even prompting some potential acquisitions of new MEG systems to be put on hold, based on a hope that OPMs will usher in a new generation of MEG equipment and procedures. The development of any new clinical test used to guide intracranial EEG monitoring and/or surgical planning must address several specific issues. The goal of this commentary is to recognize the current state of OPM technology and to suggest a framework for it to advance in the clinical realm where it can eventually be deemed clinically valuable to physicians and patients. The American Clinical MEG Society (ACMEGS) strongly supports more advanced and less expensive technology and looks forward to continuing work with researchers to develop new sensors and clinical devices which will improve the experience and outcome for patients, and perhaps extend the role of MEG. However, currently, there are no OPM devices ready for practical clinical use. Based on the engineering obstacles and the clinical tradeoffs to be resolved, the assessment of experts suggests that there will most likely be another decade relying solely on "frozen SQUIDs" in the clinical MEG field.

Epilepsy center characteristics and geographic region influence presurgical testing in the United States.

OBJECTIVE: Persons with drug-resistant epilepsy may benefit from epilepsy surgery and should undergo presurgical testing to determine potential candidacy and appropriate intervention. Institutional expertise can influence use and availability of evaluations and epilepsy surgery candidacy. This census survey study aims to examine the influence of geographic region and other center characteristics on presurgical testing for medically intractable epilepsy. METHODS: We analyzed annual report and supplemental survey data reported in 2020 from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Test utilization data were compiled with annual center volumes, available resources, and US Census regional data. We used Wilcoxon rank-sum, Kruskal-Wallis, and chi-squared tests for univariate analysis of procedure utilization. Multivariable modeling was also performed to assign odds ratios (ORs) of significant variables. RESULTS: The response rate was 100% with individual element missingness < 11% across 342 observations undergoing univariate analysis. A total of 278 complete observations were included in the multivariable models, and significant regional differences were present. For instance, compared to centers in the South, those in the Midwest used neuropsychological testing (OR = 2.87, 95% confidence interval [CI] = 1.2-6.86; p = .018) and fluorodeoxyglucose-positron emission tomography (OR = 2.74, 95% CI = = 1.14-6.61; p = .025) more commonly. For centers in the Northeast (OR = .46, 95% CI = .23-.93; p = .031) and West (OR = .41, 95% CI = .19-.87; p = .022), odds of performing single-photon emission computerized tomography were lower by nearly 50% compared to those in the South. Center accreditation level, demographics, volume, and resources were also associated with varying individual testing rates. SIGNIFICANCE: Presurgical testing for drug-resistant epilepsy is influenced by US geographic region and other center characteristics. These findings have potential implications for comparing outcomes between US epilepsy centers and may inject disparities in access to surgical treatment.

Associations between testing and treatment pathways in lesional temporal or extratemporal epilepsy: A census survey of NAEC center directors.

OBJECTIVE: The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug-resistant epilepsy (DRE) is not uniform. Many non-invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)-positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice. METHODS: We analyzed annual report data and a supplemental epilepsy practice survey reported in 2020 from 206 adult and 136 pediatric epilepsy center directors in the United States. Non-invasive and invasive testing and surgical treatment strategies were compiled for the two scenarios. We used chi-square tests to compare testing utilization between the two scenarios. Multivariable logistic regression modeling was performed to assess associations between variables. RESULTS: The supplemental survey response rate was 100% with 342 responses included in the analyses. Differing testing and treatment approaches were noted between the temporal and extratemporal scenarios such as chronic invasive monitoring selected in 60% of the temporal scenario versus 93% of the extratemporal scenario. Open resection was the most common treatment choice; however, overall treatment choices varied significantly (p < .001). Associations between non-invasive testing, invasive testing, and treatment choices were present in both scenarios. For example, in the temporal scenario stereo-electroencephalography (SEEG) was more commonly associated with fluorodeoxyglucose-positron emission tomography (FDG-PET) (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.06-3.29; p = .033), magnetoencephalography (MEG) (OR 2.90; 95% CI 1.60-5.28; p = <.001), high density (HD) EEG (OR 2.80; 95% CI 1.27-6.24; p = .011), functional MRI (fMRI) (OR 2.17; 95% CI 1.19-4.10; p = .014), and Wada (OR 2.16; 95% CI 1.28-3.66; p = .004). In the extratemporal scenario, choosing SEEG was associated with increased odds of neuromodulation over open resection (OR 3.13; 95% CI 1.24-7.89; p = .016). SIGNIFICANCE: In clinical vignettes of temporal and extratemporal lesional DRE, epilepsy center directors displayed varying patterns of non-invasive testing, invasive testing, and treatment choices. Differences in practice underscore the need for comparative trials for the surgical management of DRE.

ASCEND: A randomized controlled trial of titration strategies for vagus nerve stimulation in drug-resistant epilepsy.

Vagus Nerve Stimulation (VNS) therapy is widely understood to provide clinically meaningful improvements in seizure control to patients with drug-resistant epilepsy, and has been a staple in the clinical armamentaria available to epileptologists for over 25 years. Despite the long history of evidence-based reviews by neurology professional societies, there is still evidence of a practice gap in VNS titration and dosing that aims to maximize clinical benefit. Recent retrospective analyses have strongly argued for a more consistent application of a population-wide target dose of VNS, and further argued the importance of quickly achieving this target dose to hasten the onset of clinical benefits; however, these analyses failed to provide evidence for practical implementation. Herein, we describe a randomized controlled trial assessing the impact of titrating VNS according to three different protocols to achieve the target dose of 1.5 mA at 500µsec, for a 20-Hz signal frequency. The study was registered as NCT02385526 on March 11, 2015. Sixty-two patients were randomized into treatment groups that followed different titration protocols. One protocol (Group A) was designed to align with currently accepted professional guidance for VNS titration and the manufacturer's labeling for VNS in epilepsy (Heck et al., 2002), while the other two protocols were derived from VNS applications in other therapeutic areas. Group A participants were most likely to achieve the target dose parameters in 12 weeks or less (81.8%), with a median time-until-achievement of the target dose of 8.1 weeks, while less than 60% of patients in other groups were able to achieve the same endpoint. Participants in all groups experienced low levels of transient tolerability concerns and adverse events, suggesting titration to the target dose in 12 weeks or less following the Group A protocol is generally acceptable to most patients. These findings indicate that patients receiving VNS for epilepsy can achieve the manufacturer-recommended dose range in 12 weeks or less. A wider implementation of the approach will likely improve the clinical impact of VNS on seizure control and prevent undertreatment.

A new paradigm for investigating real-world social behavior and its neural underpinnings.

Eye tracking and other behavioral measurements collected from patient-participants in their hospital rooms afford a unique opportunity to study natural behavior for basic and clinical translational research. We describe an immersive social and behavioral paradigm implemented in patients undergoing evaluation for surgical treatment of epilepsy, with electrodes implanted in the brain to determine the source of their seizures. Our studies entail collecting eye tracking with other behavioral and psychophysiological measurements from patient-participants during unscripted behavior, including social interactions with clinical staff, friends, and family in the hospital room. This approach affords a unique opportunity to study the neurobiology of natural social behavior, though it requires carefully addressing distinct logistical, technical, and ethical challenges. Collecting neurophysiological data synchronized to behavioral and psychophysiological measures helps us to study the relationship between behavior and physiology. Combining across these rich data sources while participants eat, read, converse with friends and family, etc., enables clinical-translational research aimed at understanding the participants' disorders and clinician-patient interactions, as well as basic research into natural, real-world behavior. We discuss data acquisition, quality control, annotation, and analysis pipelines that are required for our studies. We also discuss the clinical, logistical, and ethical and privacy considerations critical to working in the hospital setting.

Surgical outcomes between temporal, extratemporal epilepsies and hypothalamic hamartoma: systematic review and meta-analysis of MRI-guided laser interstitial thermal therapy for drug-resistant epilepsy.

BACKGROUND: Approximately 1/3 of patients with epilepsy have drug-resistant epilepsy (DRE) and require surgical interventions. This meta-analysis aimed to review the effectiveness of MRI-guided laser interstitial thermal therapy (MRgLITT) in DRE. METHODS: The Population, Intervention, Comparator and Outcome approach and Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. PubMed, MEDLINE and EMBASE databases were systematically searched for English language publications from 2012 to Nov 2020. Data on the prevalence outcome using the Engel Epilepsy Surgery Outcome Scale (Class I-IV), and postoperative complications were analysed with 95% CIs. RESULTS: Twenty-eight studies that included a total of 559 patients with DRE were identified. The overall prevalence of Engel class I outcome was 56% (95% CI 0.52% to 0.60%). Hypothalamic hamartomas (HH) patients had the highest seizure freedom rate of 67% (95% CI 0.57% to 0.76%) and outcome was overall comparable between mesial temporal lobe epilepsy (mTLE) (56%, 95% CI 0.50% to 0.61%) and extratemporal epilepsy (50% 95% CI 0.40% to 0.59%). The mTLE cases with mesial temporal sclerosis had better outcome vs non-lesional cases of mTLE. The prevalence of postoperative adverse events was 19% (95% CI 0.14% to 0.25%) and the most common adverse event was visual field deficits. The reoperation rate was 9% (95% CI 0.05% to 0.14%), which included repeat ablation and open resection. CONCLUSION: MRgLITT is an effective and safe intervention for DRE with different disease aetiologies. The seizure freedom outcome is overall comparable in between extratemporal and temporal lobe epilepsy; and highest with HH. TRAIL REGISTRATION NUMBER: The study protocol was registered with the National Institute for Health Research (CRD42019126365), which serves as a prospective register of systematic reviews. It is an international database of prospectively registered systematic reviews with a focus on health-related outcomes. Details about the protocol can be found at https://wwwcrdyorkacuk/PROSPERO/.

Cardiac-induced cerebral pulsatility, brain structure, and cognition in middle and older-aged adults.

Changes of cardiac-induced regional pulsatility can be associated with specific regions of brain volumetric changes, and these are related with cognitive alterations. Thus, mapping of cardiac pulsatility over the entire brain can be helpful to assess these relationships. A total of 108 subjects (age: 66.5 ± 8.4 years, 68 females, 52 healthy controls, 11 subjective cognitive decline, 17 impaired without complaints, 19 MCI and 9 AD) participated. The pulsatility map was obtained directly from resting-state functional MRI time-series data at 3T. Regional brain volumes were segmented from anatomical MRI. Multidomain neuropsychological battery was performed to test memory, language, attention and visuospatial construction. The Montreal Cognitive Assessment (MoCA) was also administered. The sparse partial least square (SPLS) method, which is desirable for better interpreting high-dimensional variables, was applied for the relationship between the entire brain voxels of pulsatility and 45 segmented brain volumes. A multiple holdout SPLS framework was used to optimize sparsity for assessing the pulsatility-volume relationship model and to test the reliability by fitting the models to 9 different splits of the data. We found statistically significant associations between subsets of pulsatility voxels and subsets of segmented brain volumes by rejecting the omnibus null hypothesis (any of 9 splits has p < 0.0056 (=0.05/9) with the Bonferroni correction). The pulsatility was positively associated with the lateral ventricle, choroid plexus, inferior lateral ventricle, and 3rd ventricle and negatively associated with hippocampus, ventral DC, and thalamus volumes for the first pulsatility-volume relationship. The pulsatility had an additional negative relationship with the amygdala and brain stem volumes for the second pulsatility-volume relationship. The spatial distribution of correlated pulsatility was observed in major feeding arteries to the brain regions, ventricles, and sagittal sinus. The indirect mediating pathways through the volumetric changes were statistically significant between the pulsatility and multiple cognitive measures (p < 0.01). Thus, the cerebral pulsatility, along with volumetric measurements, could be a potential marker for better understanding of pathophysiology and monitoring disease progression in age-related neurodegenerative disorders.

Use of Innovative SPECT Techniques in the Presurgical Evaluation of Patients with Nonlesional Extratemporal Drug-Resistant Epilepsy.

Up to 30% of patients with epilepsy may not respond to antiepileptic drugs. Patients with drug-resistant epilepsy (DRE) should undergo evaluation for seizure onset zone (SOZ) localization to consider surgical treatment. Cases of drug-resistant nonlesional extratemporal lobe epilepsy (ETLE) pose the biggest challenge in localizing the SOZ and require multiple noninvasive diagnostic investigations before planning the intracranial monitoring (ICM) or direct resection. Ictal Single Photon Emission Computed Tomography (i-SPECT) is a unique functional diagnostic tool that assesses the SOZ using the localized hyperperfusion that occurs early in the seizure. Subtraction ictal SPECT coregistered to MRI (SISCOM), statistical ictal SPECT coregistered to MRI (STATISCOM), and PET interictal subtracted ictal SPECT coregistered with MRI (PISCOM) are innovative SPECT methods for the determination of the SOZ. This article comprehensively reviews SPECT and sheds light on its vital role in the presurgical evaluation of the nonlesional extratemporal DRE.

High resolution automated labeling of the hippocampus and amygdala using a 3D convolutional neural network trained on whole brain 700 µm isotropic 7T MP2RAGE MRI.

Image labeling using convolutional neural networks (CNNs) are a template-free alternative to traditional morphometric techniques. We trained a 3D deep CNN to label the hippocampus and amygdala on whole brain 700 µm isotropic 3D MP2RAGE MRI acquired at 7T. Manual labels of the hippocampus and amygdala were used to (i) train the predictive model and (ii) evaluate performance of the model when applied to new scans. Healthy controls and individuals with epilepsy were included in our analyses. Twenty-one healthy controls and sixteen individuals with epilepsy were included in the study. We utilized the recently developed DeepMedic software to train a CNN to label the hippocampus and amygdala based on manual labels. Performance was evaluated by measuring the dice similarity coefficient (DSC) between CNN-based and manual labels. A leave-one-out cross validation scheme was used. CNN-based and manual volume estimates were compared for the left and right hippocampus and amygdala in healthy controls and epilepsy cases. The CNN-based technique successfully labeled the hippocampus and amygdala in all cases. Mean DSC = 0.88 ± 0.03 for the hippocampus and 0.8 ± 0.06 for the amygdala. CNN-based labeling was independent of epilepsy diagnosis in our sample (p = .91). CNN-based volume estimates were highly correlated with manual volume estimates in epilepsy cases and controls. CNNs can label the hippocampus and amygdala on native sub-mm resolution MP2RAGE 7T MRI. Our findings suggest deep learning techniques can advance development of morphometric analysis techniques for high field strength, high spatial resolution brain MRI.

MR spectroscopic imaging at 3 T and outcomes in surgical epilepsy.

For the spectroscopic assessment of brain disorders that require large-volume coverage, the requirements of RF performance and field homogeneity are high. For epilepsy, this is also challenging given the inter-patient variation in location, severity and subtlety of anatomical identification and its tendency to involve the temporal region. We apply a targeted method to examine the utility of large-volume MR spectroscopic imaging (MRSI) in surgical epilepsy patients, implementing a two-step acquisition, comprised of a 3D acquisition to cover the fronto-parietal regions, and a contiguous parallel two-slice Hadamard-encoded acquisition to cover the temporal-occipital region, both with TR /TE = 2000/40 ms and matched acquisition times. With restricted (static, first/second-order) B0 shimming in their respective regions, the Cramér-Rao lower bounds for creatine from the temporal lobe two-slice Hadamard and frontal-parietal 3D acquisition are 8.1 ± 2.2% and 6.3 ± 1.9% respectively. The datasets are combined to provide a total 60 mm axial coverage over the frontal, parietal and superior temporal to middle temporal-occipital regions. We applied these acquisitions at a nominal 400 mm3 voxel resolution in n = 27 pre-surgical epilepsy patients and n = 20 controls. In controls, 86.6 ± 3.2% voxels with at least 50% tissue (white + gray matter, excluding CSF) survived spectral quality inclusion criteria. Since all patients were clinically followed for at least 1 year after surgery, seizure frequency outcome was available for all. The MRSI measurements of the total fractional metabolic dysfunction (characterized by the Cr/NAA metric) in FreeSurfer MRI gray matter segmented regions, in the patients compared with the controls, exhibited a significant Spearman correlation with post-surgical outcome. This finding suggests that a larger burden of metabolic dysfunction is seen in patients with poorer post-surgical seizure control.

Outcomes in three cases after brivaracetam treatment during pregnancy.

BACKGROUND: Use of certain antiseizure drugs (ASDs) during pregnancy increases the risk of major congenital malformations, while less is known about newer ASDs. Based on the safety of levetiracetam, brivaracetam may be similarly safe in pregnancy; however, no cases have been published to date. AIMS OF THE STUDY: We retrospectively identified three women with epilepsy treated with brivaracetam during pregnancy and described the maternal and neonatal outcomes. METHODS: We reviewed the patients' medical records as well as the linked medical records of their infants to identify complications during pregnancy and delivery, neonatal complications, and evidence of major/minor congenital malformations. RESULTS: Our series included one woman with idiopathic generalized epilepsy and two women with focal epilepsy (brivaracetam doses ranging from 50 to 200 mg daily). One patient with focal epilepsy experienced breakthrough seizures, and lamotrigine was added to brivaracetam. The other women had no neurologic complications during pregnancy. All three women had full-term deliveries without significant complications. Three healthy infants were born with Apgar scores of 9 and 9 and no major congenital malformations. Three minor congenital malformations were observed in two infants. CONCLUSIONS: While the absence of major congenital malformations in these cases is encouraging, further data are needed to determine the safety of brivaracetam in pregnancy.

Direct and indirect costs associated with stereotactic radiosurgery or open surgery for medial temporal lobe epilepsy: Results from the ROSE trial.

OBJECTIVE: To determine whether a less-invasive approach to surgery for medically refractory temporal lobe epilepsy is associated with lower health care costs and costs of lost productivity over time, compared to open surgery. METHODS: We compared direct medical costs and indirect productivity costs associated with treatment with stereotactic radiosurgery (SRS) or anterior temporal lobectomy (ATL) in the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial. Health care use was abstracted from hospital bills, the study database, and diaries in which participants recorded health care use and time lost from work while seeking care. Costs of use were calculated using a Medicare costing approach used in a prior study of the costs of ATL. The power of many analyses was limited by the sample size and data skewing. RESULTS: Combined treatment and follow-up costs (in thousands of US dollars) did not differ between SRS (n = 20, mean = $76.6, 95% confidence interval [CI] = 50.7-115.6) and ATL (n = 18, mean = $79.0, 95% CI = 60.09-103.8). Indirect costs also did not differ. More ATL than SRS participants were free of consciousness-impairing seizures in each year of follow-up (all P < 0.05). Costs declined following ATL (P = 0.005). Costs tended to increase over the first 18 months following SRS (P = 0.17) and declined thereafter (P = 0.06). This mostly reflected hospitalizations for SRS-related adverse events in the second year of follow-up. SIGNIFICANCE: Lower initial costs of SRS for medial temporal lobe epilepsy were largely offset by hospitalization costs related to adverse events later in the course of follow-up. Future studies of less-invasive alternatives to ATL will need to assess adverse events and major costs systematically and prospectively to understand the economic implications of adopting these technologies.

Indications and methodology for video-electroencephalographic studies in the epilepsy monitoring unit.

Although the epilepsy and neurology communities have position papers on a number of topics pertaining to epilepsy diagnosis and management, no current paper exists for the rationale and appropriate indications for epilepsy monitoring unit (EMU) evaluation. General neurologists, hospital administrators, and insurers also have yet to fully understand the role this type of testing has in the diagnosis and management of individuals with paroxysmal neurologic symptoms. This review outlines the indications for long-term video-electroencephalography (VEEG) for typical elective admissions to a specialized inpatient setting. The common techniques used in EMUs to obtain diagnostic information are reviewed. The added benefit of safety measures and clinical testing above that available for routine or long-term ambulatory electroencephalography is also discussed. The indications for admission to the EMU include differential diagnosis of paroxysmal spells, characterization of seizure types, presurgical epilepsy evaluations, seizure quantification, monitoring medication adjustment in a safe setting, and differentiation between seizures and side effects. We conclude that the appropriate use of this specialized testing can lead to an early and correct diagnosis in a variety of clinical circumstances. The EMU evaluation is considered the gold standard test for the definitive diagnosis of epilepsy and seizure-like spells.

Radiosurgery versus open surgery for mesial temporal lobe epilepsy: The randomized, controlled ROSE trial.

OBJECTIVE: To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE). METHODS: This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up. RESULTS: A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English-speaking, dominant-hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients. SIGNIFICANCE: These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.

Diagnostic accuracy of paroxysmal spells: Clinical history versus observation.

Our goal was to evaluate how accurate neurologists are at differentiating between different paroxysmal events based on clinical history versus observation of the spell in question. Forty-seven neurologists reviewed 12 clinical histories and videos of recorded events of patients admitted in the Epilepsy Monitoring Unit (EMU). They were asked to diagnose events as epileptic seizures, non-epileptic behavioral spells (NEBS), or other physiologic events as well as rate their confidence in their diagnosis. The median diagnostic accuracy for all paroxysmal events was 67% for clinical history and 75% for observation (p=.001). This was largely due to the difference in accuracy within the subgroup of patients with NEBS (67% history vs. 83% observation, p<.001). There were trends for higher diagnostic accuracy and increased inter-rater agreement with higher levels of training. Physicians with higher levels of training were more confident with diagnosis based on observation. In summary, reviewing videos of paroxysmal spells may improve diagnostic accuracy and enhance the evaluation of patients. Neurologists at all levels of training should encourage the recording and review of videos of recurrent spells to aid in medical decision-making especially when there is high concern that the spells in question are NEBS.

Empirical validation of directed functional connectivity.

Mapping directions of influence in the human brain connectome represents the next phase in understanding its functional architecture. However, a host of methodological uncertainties have impeded the application of directed connectivity methods, which have primarily been validated via "ground truth" connectivity patterns embedded in simulated functional MRI (fMRI) and magneto-/electro-encephalography (MEG/EEG) datasets. Such simulations rely on many generative assumptions, and we hence utilized a different strategy involving empirical data in which a ground truth directed connectivity pattern could be anticipated with confidence. Specifically, we exploited the established "sensory reactivation" effect in episodic memory, in which retrieval of sensory information reactivates regions involved in perceiving that sensory modality. Subjects performed a paired associate task in separate fMRI and MEG sessions, in which a ground truth reversal in directed connectivity between auditory and visual sensory regions was instantiated across task conditions. This directed connectivity reversal was successfully recovered across different algorithms, including Granger causality and Bayes network (IMAGES) approaches, and across fMRI ("raw" and deconvolved) and source-modeled MEG. These results extend simulation studies of directed connectivity, and offer practical guidelines for the use of such methods in clarifying causal mechanisms of neural processing.

Short-term neurocognitive outcomes following anterior temporal lobectomy.

Changes in cognitive function are a well established risk of anterior temporal lobectomy (ATL). Deficits in verbal memory are a common postoperative finding, though a small proportion of patients may improve. Postoperative evaluation typically occurs after six to 12months. Patients may benefit from earlier evaluation to identify potential needs; however, the results of a formal neuropsychological assessment at an early postoperative stage are not described in the literature. We compared pre- and postoperative cognitive function for 28 right ATL and 23 left ATL patients using repeated measures ANOVA. Changes in cognitive function were compared to ILAE seizure outcome. The mean time to postoperative neuropsychological testing was 11.1weeks (SD=6.7weeks). There was a side×surgery interaction for the verbal tasks: immediate memory recall (F(1,33)=20.68, p<0.001), short delay recall (F(1,29)=4.99, p=0.03), long delay recall (F(1,33)=10.36, p=0.003), recognition (F(1,33)=5.69, p=0.02), and naming (F(1,37)=15.86, p<0.001). This indicated that the left ATL group had a significant decrement in verbal memory following surgery, while the right ATL group experienced a small but significant improvement. For the right ATL group, there was a positive correlation between ILAE outcome and improvement in immediate recall (r=-0.62, p=0.02) and long delay recall (r=-0.57, p=0.03). There was no similar finding for the left ATL group. This study demonstrates that short-interval follow-up is effective in elucidating postoperative cognitive changes. Right ATL was associated with improvement in verbal memory, while left ATL resulted in a decrement in performance. Improvement in the right ATL group was related to improved seizure outcome. Short-interval follow-up may lend itself to the identification of patients who could benefit from early intervention.