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      Responsive neurostimulation of the thalamus improves seizure control in idiopathic generalised epilepsy: initial case series

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          Abstract

          Objectives

          Up to 40% of patients with idiopathic generalised epilepsy (IGE) are drug resistant and potentially could benefit from intracranial neuromodulation of the seizure circuit. We present outcomes following 2 years of thalamic-responsive neurostimulation for IGE.

          Methods

          Four patients with pharmacoresistant epilepsy underwent RNS System implantation in the bilateral centromedian (CM) nucleus region. Electrophysiological data were extracted from the clinical patient data management system and analysed using a specialised platform (BRAINStim). Postoperative visualisation of electrode locations was performed using Lead-DBS. Seizure outcomes were reported using the Engel scale.

          Results

          Patients experienced a 75%–99% reduction in seizure frequency with decreased seizure duration and severity (Engel class IB, IC, IIA and IIIA), as well as significant improvements in quality of life. Outcomes were durable through at least 2 years of therapy. Detection accuracy for all patients overall decreased over successive programming epochs from a mean of 96.5% to 88.3%. Most electrodes used to deliver stimulation were located in the CM (7/10) followed by the posterior dorsal ventral lateral (2/2), posterior ventral posterior lateral (3/4) and posterior ventral ventral lateral (2/3). In all patients, stimulation varied from 0.2 to 2.0 mA and amplitude only increased over successive epochs. The raw percentage of intracranial electroencephalography recordings with stimulations delivered to electrographic seizures was 24.8%, 1.2%, 7.6% and 8.8%.

          Conclusion

          Closed-loop stimulation of the CM region may provide significant improvement in seizure control and quality of life for patients with drug-resistant IGE. Optimal detection and stimulation locations and parameters remain an active area of investigation for accelerating and fine-tuning clinical responses.

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          Most cited references42

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          Lead-DBS: a toolbox for deep brain stimulation electrode localizations and visualizations.

          To determine placement of electrodes after deep brain stimulation (DBS) surgery, a novel toolbox that facilitates both reconstruction of the lead electrode trajectory and the contact placement is introduced. Using the toolbox, electrode placement can be reconstructed and visualized based on the electrode-induced artifacts on post-operative magnetic resonance (MR) or computed tomography (CT) images. Correct electrode placement is essential for efficacious treatment with DBS. Post-operative knowledge about the placement of DBS electrode contacts and trajectories is a promising tool for clinical evaluation of DBS effects and adverse effects. It may help clinicians in identifying the best stimulation contacts based on anatomical target areas and may even shorten test stimulation protocols in the future. Fifty patients that underwent DBS surgery were analyzed in this study. After normalizing the post-operative MR/CT volumes into standard Montreal Neurological Institute (MNI)-stereotactic space, electrode leads (n=104) were detected by a novel algorithm that iteratively thresholds each axial slice and isolates the centroids of the electrode artifacts within the MR/CT-images (MR only n=32, CT only n=10, MR and CT n=8). Two patients received four, the others received two quadripolar DBS leads bilaterally, summing up to a total of 120 lead localizations. In a second reconstruction step, electrode contacts along the lead trajectories were reconstructed by using templates of electrode tips that had been manually created beforehand. Reconstructions that were made by the algorithm were finally compared to manual surveys of contact localizations. The algorithm was able to robustly accomplish lead reconstructions in an automated manner in 98% of electrodes and contact reconstructions in 69% of electrodes. Using additional subsequent manual refinement of the reconstructed contact positions, 118 of 120 electrode lead and contact reconstructions could be localized using the toolbox. Taken together, the toolbox presented here allows for a precise and fast reconstruction of DBS contacts by proposing a semi-automated procedure. Reconstruction results can be directly exported to two- and three-dimensional views that show the relationship between DBS contacts and anatomical target regions. The toolbox is made available to the public in form of an open-source MATLAB repository.
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            Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.

            We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.
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              National and State Estimates of the Numbers of Adults and Children with Active Epilepsy — United States, 2015

              Epilepsy, a brain disorder leading to recurring seizures, has garnered increased public health focus because persons with epilepsy experience pronounced and persistent health and socioeconomic disparities despite treatment advances, public awareness programs, and expanded rights for persons with disabilities ( 1 , 2 ). For almost all states, epilepsy prevalence estimates do not exist. CDC used national data sources including the 2015 National Health Interview Survey (NHIS) for adults (aged ≥18 years), the 2011–2012 National Survey of Children’s Health (NSCH), and the 2015 Current Population Survey data, describing 2014 income levels, to estimate prevalent cases of active epilepsy, overall and by state, to provide information for state public health planning. In 2015, 1.2% of the U.S. population (3.4 million persons: 3 million adults and 470,000 children) reported active epilepsy (self-reported doctor-diagnosed epilepsy and under treatment or with recent seizures within 12 months of interview) or current epilepsy (parent-reported doctor-diagnosed epilepsy and current epilepsy). Estimated numbers of persons with active epilepsy, after accounting for income and age differences by state, ranged from 5,900 in Wyoming to 427,700 in California. NHIS data from 2010–2015 indicate increases in the number of persons with active epilepsy, probably because of population growth. This study provides updated national and modeled state-specific numbers of active epilepsy cases. Public health practitioners, health care providers, policy makers, epilepsy researchers, and other epilepsy stakeholders, including family members and people with epilepsy, can use these findings to ensure that evidence-based programs meet the complex needs of adults and children with epilepsy and reduce the disparities resulting from it. Epilepsy has been assessed only intermittently in population surveys ( 1 , 2 ). Before 2010, the last U.S. national estimate of epilepsy prevalence was based on 1986–1990 data using one question assessing the occurrence of epilepsy or repeated seizures, convulsions, or blackouts in any household family members ( 3 ). Other recent estimates based on limited U.S. and international geographic regions, clinical samples, and decades-old data are not representative of the current U.S. population ( 2 , 4 ). Data from the 2010 and 2013 NHIS using a validated case definition indicate approximately 1% of the U.S. population had active epilepsy ( 5 ). A study using 2005 Behavioral Risk Factor Surveillance System data employing similar epilepsy case-ascertainment questions* provided state-level estimates of a history of epilepsy for 19 states (1.65%) and active epilepsy for 13 states (0.84%) ( 6 ). No substantial differences among states in the prevalence of a history of epilepsy or active epilepsy were detected ( 6 ). A third study, which extrapolated 2007–2011 administrative claims data from multiple states to the overall U.S. population found an epilepsy prevalence estimate of 0.84% ( 4 ). For almost all states, epilepsy prevalence estimates do not exist. Groups interested in reducing epilepsy prevalence need updated estimates of the numbers of persons living with epilepsy nationally and within their states. This study aims to provide updated national and modeled state-specific estimates of active epilepsy prevalence based on the latest data available to provide information for public health action to reduce epilepsy burden. To estimate the number of prevalent cases of active epilepsy among adults aged ≥18 years, CDC analyzed three questions on epilepsy from the 2015 Sample Adult component of NHIS, an annual, cross-sectional household survey of the civilian, noninstitutionalized U.S. population. Adults classified as having “active epilepsy” reported a history of doctor-diagnosed epilepsy and were taking medication to control it, had had one or more seizures in the past year, or both (Table 1) ( 5 , 6 ). Validation of survey questions for surveillance of active epilepsy yielded sensitivity and specificity exceeding 80% and 99%, respectively, with a positive predictive value of 74% similar to validation estimates seen in surveillance of other chronic disorders ( 5 ). Only 0.07% of adults in 2015 refused to answer or did not know if they had doctor-diagnosed active epilepsy. To estimate prevalent cases of active epilepsy among children aged 0–17 years, CDC analyzed data from the 2011–2012 NSCH, † a cross-sectional telephone survey of households with at least one resident child aged 0–17 years at interview. NSCH asks parents or guardians if a doctor or health care provider ever told them that their child had epilepsy or seizure disorder, and if so, if their child currently has epilepsy or seizure disorder (current epilepsy) (Table 1). Only 0.03% of parents or guardians refused to answer or did not know if a doctor had ever told them their child had epilepsy or a seizure disorder. Prevalence of current epilepsy among children based on NSCH data was estimated to be 6.3 per 1,000, similar to estimates from administrative data ( 7 , 8 ). TABLE 1 Epilepsy surveillance case ascertainment questions, by survey Survey Questions Possible responses National Health Interview Survey (2015) 1. Have you ever been told by a doctor or other health professional that you have a seizure disorder or epilepsy? 1) Yes, 2) No, 7) Refused, 8) Not ascertained, 9) Don’t know 2. Are you currently taking any medicine to control your seizure disorder or epilepsy? 1) Yes, 2) No, 7) Refused, 8) Not ascertained, 9) Don’t know 3. Today is . Think back to last year about the same time. About how many seizures of any type have you had in the past year? 0) None, 1) One, 2) Two or three, 3) Between four and ten, 4) More than 10, 7) Refused, 8) Not ascertained, 9) Don’t know National Survey of Children’s Health (2011–2012) 1. Has a doctor or health care provider ever told you that your child has epilepsy or a seizure disorder? 1) Yes, 2) No, 7) Refused, 8) Not ascertained, 9) Don’t know 2. Does your child currently have epilepsy or a seizure disorder? 1) Yes, 2) No, 7) Refused, 8) Not ascertained, 9) Don’t know Obtaining state-level estimates required using the best available data to confirm that epilepsy prevalence did not differ significantly across states ( 6 ). Epilepsy prevalence and state populations do differ by age and income distribution. NHIS and NSCH data was used to calculate the prevalence (proportion) of active epilepsy for three age groups (0–17 years, 18–64 years, and ≥65 years) stratified by three family income groups (0%–99%, 100%–199%, ≥200% of poverty thresholds). Data for 2014 was obtained for the three age groups and three family income groups among civilian and military noninstitutionalized populations for each state from the U.S. Census's Current Population Survey 2015 Annual Social and Economic Supplement. § Multiplying the age- and income-specific active epilepsy prevalence estimates by the population estimates for each of the three age and income groups yielded state-level estimates of active epilepsy, indirectly standardized for age and income. ¶ Adding these standardized estimates for both groups from each data set produced total estimated numbers of cases with active epilepsy. Combining the variance estimates of both adults and children with epilepsy from each survey and of these age- and income-specific population estimates as the variance of the product of these two random variables yielded 95% confidence intervals for these total estimates.** In 2015, 1.2% (95% confidence interval = 1.1–1.4) of the U.S. population was classified as having active epilepsy (3.4 million; 3 million adults and 470,000 children). Among adults, the estimated number of cases of active epilepsy ranged from 5,100 in Wyoming to 367,900 in California (Table 2). Among children, the estimated number of cases of current epilepsy ranged from 800 in Wyoming to 59,800 in California. The number of persons estimated to have active epilepsy was <14,000 in nine states and the District of Columbia, 14,000–32,799 in 11 states, 32,800–56,799 in nine states, 56,800–92,699 in 10 states, and ≥92,700 persons in 11 states. (Table 2). TABLE 2 Estimated numbers of active epilepsy cases, by state and age group — United States, 2015 Geographic area Age group (yrs) All ages <18* ≥18† No. (95% CI§) No. (95% CI) No. (95% CI) United States 3,439,600 (3,009,100–3,870,100) 471,900 (392,600–551,200) 2,967,700 (2,544,500–3,390,800) Alabama 54,100 (46,400–61,900) 7,500 (5,900–9,200) 46,600 (39,000–54,200) Alaska 7,200 (6,100–8,300) 1,100 (800–1,400) 6,100 (5,000–7,200) Arizona 77,000 (66,400–87,500) 11,200 (8,900–13,600) 65,700 (55,400–76,000) Arkansas 32,800 (28,000–37,600) 4,900 (3,700–6,100) 28,000 (23,300–32,600) California 427,700 (372,600–482,900) 59,800 (49,000–70,600) 367,900 (313,800–422,000) Colorado 56,800 (48,300–65,300) 7,800 (6,000–9,600) 49,000 (40,700–57,300) Connecticut 35,900 (30,400–41,400) 4,500 (3,400–5,700) 31,400 (26,000–36,800) Delaware 9,700 (8,200–11,100) 1,300 (900–1,600) 8,400 (7,000–9,900) District of Columbia 7,500 (6,300–8,800) 800 (600–1,100) 6,700 (5,500–7,900) Florida 223,900 (194,100–253,800) 27,300 (21,900–32,800) 196,600 (167,200–225,900) Georgia 110,200 (94,900–125,500) 16,700 (13,200–20,100) 93,500 (78,600–108,500) Hawaii 14,000 (11,900–16,100) 2,000 (1,500–2,400) 12,000 (10,000–14,100) Idaho 16,800 (14,200–19,300) 2,600 (2,000–3,200) 14,200 (11,700–16,600) Illinois 136,600 (117,900–155,400) 18,600 (14,900–22,400) 118,000 (99,700–136,400) Indiana 69,500 (59,600–79,400) 10,600 (8,300–13,000) 58,900 (49,200–68,500) Iowa 31,400 (26,800–36,100) 4,400 (3,400–5,400) 27,000 (22,500–31,600) Kansas 29,900 (25,500–34,300) 4,400 (3,400–5,400) 25,500 (21,200–29,900) Kentucky 49,500 (42,000–57,000) 6,800 (4,900–8,700) 42,700 (35,500–50,000) Louisiana 54,900 (46,600–63,200) 7,900 (6,200–9,700) 47,000 (38,900–55,100) Maine 14,100 (11,900–16,300) 1,700 (1,200–2,200) 12,400 (10,300–14,600) Maryland 59,900 (50,700–69,100) 7,900 (6,200–9,700) 52,000 (42,900–61,000) Massachusetts 71,600 (60,900–82,300) 8,400 (6,500–10,300) 63,200 (52,600–73,700) Michigan 108,900 (93,300–124,500) 13,600 (10,800–16,400) 95,300 (79,900–110,600) Minnesota 53,700 (45,700–61,700) 7,400 (5,900–9,000) 46,300 (38,400–54,100) Mississippi 35,700 (30,600–40,700) 5,100 (3,900–6,300) 30,600 (25,700–35,500) Missouri 61,200 (52,400–70,000) 8,300 (6,500–10,100) 52,900 (44,200–61,600) Montana 10,800 (9,100–12,600) 1,400 (1,000–1,800) 9,400 (7,700–11,100) Nebraska 19,600 (16,600–22,500) 2,800 (2,200–3,500) 16,700 (13,800–19,600) Nevada 31,600 (26,800–36,400) 4,400 (3,300–5,400) 27,200 (22,500–31,900) New Hampshire 13,100 (11,100–15,200) 1,500 (1,100–1,900) 11,600 (9,600–13,700) New Jersey 92,700 (79,100–106,200) 12,000 (9,500–14,500) 80,600 (67,300–93,900) New Mexico 23,200 (19,800–26,500) 3,400 (2,600–4,200) 19,800 (16,400–23,100) New York 215,200 (186,300–244,000) 26,600 (21,600–31,500) 188,600 (160,200–217,100) North Carolina 110,100 (94,700–125,500) 15,200 (11,800–18,500) 94,900 (79,900–110,000) North Dakota 7,300 (6,200–8,500) 1,000 (700–1,200) 6,400 (5,300–7,500) Ohio 126,400 (109,300–143,400) 16,900 (13,600–20,300) 109,400 (92,700–126,200) Oklahoma 41,100 (34,900–47,300) 6,400 (5,000–7,900) 34,700 (28,700–40,700) Oregon 42,900 (36,300–49,400) 5,400 (4,100–6,800) 37,400 (31,000–43,900) Pennsylvania 133,000 (114,600–151,400) 16,900 (13,500–20,200) 116,100 (98,000–134,200) Rhode Island 11,100 (9,300–12,900) 1,300 (900–1,700) 9,800 (8,100–11,500) South Carolina 53,400 (45,500–61,300) 7,100 (5,500–8,700) 46,300 (38,500–54,000) South Dakota 8,900 (7,400–10,400) 1,300 (900–1,600) 7,600 (6,200–9,100) Tennessee 73,900 (62,900–84,800) 10,000 (7,800–12,300) 63,800 (53,100–74,600) Texas 292,900 (255,400–330,300) 47,200 (38,500–56,000) 245,600 (209,200–282,000) Utah 29,300 (24,900–33,600) 5,300 (4,100–6,500) 24,000 (19,800–28,200) Vermont 6,300 (5,300–7,300) 700 (500–900) 5,600 (4,700–6,600) Virginia 84,800 (72,600–97,000) 11,000 (8,800–13,200) 73,800 (61,800–85,800) Washington 74,600 (64,000–85,200) 10,200 (8,100–12,300) 64,400 (54,000–74,800) West Virginia 21,500 (18,100–25,000) 2,500 (1,900–3,100) 19,000 (15,600–22,500) Wisconsin 59,600 (50,800–68,300) 7,900 (6,300–9,500) 51,700 (43,100–60,300) Wyoming 5,900 (5,000–6,800) 800 (600–1,000) 5,100 (4,200–6,000) Abbreviation: CI = confidence interval. * Active epilepsy cases in children are estimated from the current epilepsy prevalence in children (2011–2012 National Survey of Children's Health) and the population of children, accounting for the ratios of family income to poverty thresholds. † Active epilepsy cases in adults are estimated from the prevalence of active epilepsy (taking medication, having had a seizure in the past year, or both) in adults (2015 National Health Interview Survey) and the population of adults, accounting for the ratios of family income to poverty thresholds. The total population estimates come from the 2014 weighted person counts of the Current Population Survey, 2015 Annual Social and Economic Supplement of the civilian noninstitutionalized population living in houses and military population living in houses. § Confidence interval represents only sampling uncertainty from the sampling uncertainties in the prevalence estimates and in the state-specific and age-specific ratios of family income to poverty thresholds. Discussion This study provides updated national and estimated state-specific numbers of the active epilepsy cases. Affecting 3.4 million U.S. residents, epilepsy is not a rare condition. Epilepsy poses substantial individual and societal burdens that require heightened public health action ( 1 , 2 ). As a complex condition varying in severity and impact, it affects persons of all ages and racial and ethnic groups, especially those with the lowest incomes ( 2 , 5 , 9 ). Persons with epilepsy often have multiple co-occurring conditions (e.g., stroke, heart disease, depression, or developmental delay) that complicate their epilepsy management, impair life goals, and contribute to early mortality ( 1 , 2 ). Among five chronic conditions in children and adolescents selected because of their adverse impact on academic and health outcomes, epilepsy is the costliest and the second most common ( 8 ). Children with seizures are more likely to live in poverty, and their parents more frequently report food insecurity ( 9 ). Direct yearly health care costs per person with epilepsy ranged from $10,192 to $47,862 (2013 U.S. dollars) and were higher for persons with uncontrolled seizures ( 10 ). Medicaid recipients have a higher prevalence of epilepsy, especially among adults aged 20–64 years (3.4%) ( 4 ); this study adjusted for income to account for this confounder. The estimated 3 million U.S. adults with active epilepsy and 470,000 U.S. children with current epilepsy in 2015 exceed the estimated 2.3 million U.S. adults in 2010 ( 5 ) and the 450,000 U.S. children with current epilepsy in 2007 ( 7 ). The estimated increase in numbers of persons with epilepsy is not explained by age or income, because this study controlled for these known confounders. The increase is likely because of population growth over the past decade, or other unknown factors (e.g., an increased willingness to disclose one has epilepsy). The number of prevalent cases of active epilepsy by state generally mirrors the states’ population distributions. The 2015 NHIS epilepsy prevalence estimate (1.2%) in this study is roughly consistent with the BRFSS estimate from 13 states (0.84% [95% confidence interval = 0.74–0.96]) that used a slightly more conservative approach assessing a 3-month seizure recall period versus 12 months ( 6 ). The findings in this report are subject to at least four limitations. First, because these estimates depend on self-report, they might be subject to reporting bias. Second, these state estimates do not account for possible differences in seizure type, severity, or etiology. Third, underreporting associated with perceived repercussions in disclosing epilepsy (e.g., stigma or driver’s license restrictions) ( 2 ) and the exclusion of institutionalized adults from the NHIS and the Census might underestimate epilepsy prevalence. Fourth, the assumption of applying national estimates to states is based on findings from 13 geographically disparate states indicating no differences in epilepsy prevalence, after accounting for multiple comparisons and sample size limitations ( 6 ). Although adjusting for age and income might account for some of the variation in prevalence across all states in this study, without available direct surveillance data on epilepsy, these estimates of active epilepsy cases in states need empirical confirmation. Public health practitioners, health care providers, policy makers, epilepsy researchers, and other epilepsy stakeholders, including family members and people with epilepsy, can use these findings to ensure that evidence-based programs meet the complex needs of adults and children with epilepsy and reduce the disparities resulting from it. Summary What is already known about this topic? Epilepsy is a common neurologic disorder resulting in substantial health, social, and mortality disparities. What is added by this report? In 2015, approximately 3 million U.S. adults and 470,000 children had active epilepsy. For almost all states, epilepsy prevalence estimates do not exist. Estimated numbers of active epilepsy ranged from 5,900 persons with epilepsy in Wyoming to more than 427,000 in California. The number of persons with active epilepsy increased compared with earlier years, likely because of population growth. What are the implications for public health practice? This study provides updated national estimates and the first modeled estimates of active epilepsy cases for all States. Public health practitioners, health care providers, policy makers, epilepsy researchers, and other epilepsy stakeholders including family members and people with epilepsy, can use these findings to ensure that evidence-based programs meet the complex needs of adults and children with epilepsy and reduce the disparities resulting from it.
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                Author and article information

                Journal
                J Neurol Neurosurg Psychiatry
                J Neurol Neurosurg Psychiatry
                jnnp
                jnnp
                Journal of Neurology, Neurosurgery, and Psychiatry
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0022-3050
                1468-330X
                May 2022
                25 February 2022
                : 93
                : 5
                : 491-498
                Affiliations
                [1 ] departmentDepartment of Neurosurgery , Massachusetts General Hospital , Boston, Massachusetts, USA
                [2 ] departmentDepartment of Neurology , University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA
                [3 ] departmentDepartment of Neurology , Charite Universitatsmedizin Berlin , Berlin, Germany
                [4 ] departmentDepartment of Neurosurgery , Harvard Medical School , Boston, Massachusetts, USA
                Author notes
                [Correspondence to ] Dr R Mark Richardson, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; mark.richardson@ 123456mgh.harvard.edu
                Author information
                http://orcid.org/0000-0002-4309-5455
                http://orcid.org/0000-0003-2620-7387
                Article
                jnnp-2021-327512
                10.1136/jnnp-2021-327512
                9016239
                35217517
                5e3a3d65-d113-4562-ad48-73b017a054fe
                © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 06 July 2021
                : 01 February 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01NS110424
                Categories
                Epilepsy
                1506
                Original research
                Custom metadata
                unlocked

                Surgery
                epilepsy,surgery,electrical stimulation,neurosurgery
                Surgery
                epilepsy, surgery, electrical stimulation, neurosurgery

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