Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

Risk analysis of hemorrhage in stereo-electroencephalography procedures.

OBJECTIVE: To examine the true incidence of hemorrhage related to stereo-electroencephalography (SEEG) procedures. To analyze risk factors associated with the presence of different types of hemorrhage in SEEG procedures. METHODS: This was a retrospective, single-center observational study examining every SEEG implantation performed at our center from 2009 to 2017. This consisted of 549 consecutive SEEG implantations using a variety of stereotactic and imaging techniques. A hemorrhage grading system was applied by a blinded neuroradiologist to every postimplant and postexplant computed tomography (CT) scan. Hemorrhages were classified as asymptomatic or symptomatic based on neurologic deficit seen on examination. Statistical analysis included multivariate regression using relevant preoperative variables to predict the presence of hemorrhage. RESULTS: One hundred five implantations (19.1%) had any type of hemorrhage seen on postimplant CT. Of these, 93 (16.9%) were asymptomatic and 12 (2.2%) were symptomatic, with 3 implantations (0.6%) resulting in either a permanent deficit (2, 0.4%) or death (1, 0.2%). Male sex, increased number of electrodes, and increasing age were associated with increased risk of postimplant hemorrhage on multivariate analysis. Increasing score in the grading system was related to a statistically significant increase in the likelihood of a symptomatic hemorrhage. SIGNIFICANCE: Detailed examination of every postimplant CT reveals that the total hemorrhage rate appears higher than previously reported. Most of these hemorrhages are small and asymptomatic. Our grading system may be useful to risk stratify these hemorrhages and awaits prospective validation.

Hemispherectomy in adults and adolescents: Seizure and functional outcomes in 47 patients.

OBJECTIVE: To examine longitudinal seizure and functional outcomes after hemispherectomy in adults and adolescents. METHODS: We reviewed 47 consecutive patients older than 16 years who underwent hemispherectomy between 1996 and 2016 at our center. Clinical, electroencephalographic (EEG), imaging, neuropsychological, surgical, and functional status data were analyzed. RESULTS: Thirty-six patients were 18 years or older at surgery; 11 were aged between 16 and 18 years. Brain injury leading to hemispheric epilepsy occurred before 10 years of age in 41 (87%) patients. At a mean follow-up of 5.3 postoperative years (median = 2.9 years), 36 (77%) had Engel class I outcome. Longitudinal outcome analysis showed 84% seizure freedom (Engel IA) at 6 months, 76% at 2 years, and 76% at 5 years and beyond, with stable longitudinal outcomes up to 12 years from surgery. Multivariate analysis demonstrated that acute postoperative seizures and contralateral interictal spikes at 6-month follow-up EEG were associated with seizure recurrence. Patients who could walk unaided preoperatively and had no cerebral peduncle atrophy on brain magnetic resonance imaging were more likely to experience worsening of motor function postoperatively. Otherwise, postoperative ambulatory status and hand function were unchanged. Of the 19 patients who completed neuropsychological testing, 17 demonstrated stable or improved postoperative outcomes. SIGNIFICANCE: Hemispherectomy in adults is a safe and effective procedure, with seizure freedom rates and functional outcome similar to those observed in children.

Placement of subdural grids in pediatric patients: technique and results.

PURPOSE: The purpose of this study is to describe common indications and technique for the application of chronic invasive electrodes in the pediatric patient suffering from medically intractable epilepsy. METHODS: This chapter was prepared based on a retrospective review of the literature and personal experience based from a large tertiary epilepsy center. CONCLUSIONS: Invasive subdural recordings are a safe and efficacious tool to identify the epileptogenic zone and its relationship to functional cortex in highly selected patients with medically refractory epilepsy. The ability to localize the EZ approaches 90 to 100 %, but seizure-free outcome is more complex depending greatly on the experience of the surgical team and the extent of resection.

Imag(in)ing seizure propagation: MEG-guided interpretation of epileptic activity from a deep source.

Identification and accurate localization of seizure foci is vital in patients with medically-intractable focal epilepsy, who may be candidates for potentially curative resective epilepsy surgery. We present a patient with difficult-to-control seizures associated with an occult focal cortical dysplasia residing within the deeper left parietal operculum and underlying posterior insula, which was not detected by conventional MRI analysis. Propagated activities from this deeper generator produced misleading EEG patterns both on surface and subdural electrode recordings suggesting initial activation of the perirolandic and mesial frontal regions. However, careful spatio-temporal analysis of stereotyped interictal activities recorded during MEG, using sequential dipole modeling, revealed a consistent pattern of epileptic propagation originating from the deeper source and propagating within few milliseconds to the dorsal convexity. In this instance, careful dissection of noninvasive investigations (interictal MEG along with ictal SPECT findings) allowed clinicians to dismiss the inaccurate and misleading findings of the traditional "gold-standard" intracranial EEG. In fact, this multimodal noninvasive approach uncovered a subtle dysplastic lesion, resection of which rendered the patient seizure-free. This case highlights the potential benefits of dynamic analysis of interictal MEG in the appropriate clinical context. Pathways of interictal spike propagation may help elucidate essential neural networks underlying focal epilepsy.

Seizure outcomes following multilobar epilepsy surgery.

PURPOSE: Outcomes following unilobar surgeries for refractory epilepsy have been well described. However, little is known about long-term seizure outcomes following multilobar resections. The aim of the current study was to identify long-term seizure control and predictors of seizure recurrence in this patient population. METHODS: Records of patients who underwent multilobar epilepsy surgery at the Cleveland Clinic between 1994 and 2010 were retrospectively reviewed. A postoperative follow-up of at least 6 months was required. Patients were classified as seizure free if they achieved an Engel class I at last follow-up. Long-term chances of seizure freedom were illustrated using a survival analysis, and predictors of recurrence were identified using Cox proportional hazard modeling. KEY FINDINGS: Sixty-three patients with medically intractable epilepsy underwent multilobar surgical resections during the study period (mean follow-up of 4.6 years). Predominant resection types included extended occipital (temporoparietooccipital, parietooccipital, temporooccipital: 57%), frontotemporal (21%), and temporoparietal (17%). Mean age at surgery was 21.4 years and mean age at seizure onset was 10.1 years. Fifty-six percent of the patients underwent extraoperative invasive electroencephalography (EEG) evaluations. At 6 postoperative months, 71% (95% confidence interval (CI) 65-77) were seizure-free (SF), 64% (CI 58-70) were SF at 1 year, 52% (CI 46-59) were SF at 5 years, and 41% (CI 32-50) remained SF at 10 years. Forty-one patients had at least one breakthrough seizure after surgery (median timing of recurrence 6.1 months), with an Engel class 1 achieved again by last follow-up in 12 of these 41 cases. Nine patients required a reoperation. Patients who underwent extended occipital/posterior quadrant resections had more favorable outcomes as compared to the other groups. With multivariate analysis, the type of resection (p = 0.03), preoperative auras (p = 0.03), an incomplete resection (0.03), and the presence of postoperative spikes (p = 0.0003) correlated with seizure recurrence. The risk of seizure recurrence for an incomplete resection was 2.3 (CI 1.53-3.36), preoperative aura 2.3 (CI 1.34-3.87), and postoperative spikes on surface EEG 2.5 (CI 1.29-4.71). SIGNIFICANCE: A favorable outcome can be achieved in 41% of patients undergoing multilobar resections for epilepsy surgery at 10 years of follow-up. Close to one-third of patients who have breakthrough seizures after surgery are able to regain seizure freedom by last follow-up. Predictors of recurrence include resection type (frontotemporal and parietotemporal resections did worse), presence of preoperative aura, an incomplete surgical resection, and the presence of postoperative interictal discharges on EEG.

The Clinical Utility of Surgical Histopathology in Predicting Seizure Outcomes in Patients with Rasmussen Encephalitis Undergoing Hemispherectomy.

OBJECTIVE: The objectives of this study were to determine the relationship between the severity of pathology and seizure outcomes in patients who underwent hemispherectomy for Rasmussen encephalitis (RE) and to investigate which clinical factors correlated with severity of pathology. METHODS: In this retrospective cohort study, we collected and reviewed pathology and clinical variables. We ascertained seizure outcomes using Engel's classification, and Pardo stages were used to grade pathology. RESULTS: We included 29 unique patients who underwent 34 hemispherectomy procedures for analysis. There was no statistically significant correlation between Pardo stage and seizure outcome (P = 1). Increasing duration of epilepsy (ß = 0.011, P = 0.02) and duration of hemiparesis (ß = 0.024, P = 0.01) were significantly associated with a more severe Pardo stage. In contrast, the presence of epilepsia partialis continua had a negative relationship with Pardo stage (ß = -0.49, P = 0.04). Twenty-six (89.75%) patients were Engel class I at the last follow-up, including all 5 patients who underwent redo hemispherectomy in our cohort. CONCLUSIONS: Consistent with the progressive nature of RE, more severe pathology was associated with a longer duration of epilepsy and longer duration of hemiparesis, while the presence of epilepsia partialis continua was associated with less severe pathology. Results from this series suggest the degree of cortical involvement with RE as assessed on surgical histopathology does not correlate with seizure outcome after hemispherectomy, which appears to be more dependent on surgical technique/complete disconnection.

Seizure Outcomes and Reoperation in Surgical Rasmussen Encephalitis Patients.

BACKGROUND: Rasmussen encephalitis (RE) is a rare inflammatory disease affecting one hemisphere, causing progressive neurological deficits and intractable seizures. OBJECTIVE: To report long-term seizure outcomes, reoperations, and functional outcomes in patients with RE who underwent hemispherectomy at our institution. METHODS: Retrospective review was performed for all patients with RE who had surgery between 1998 and 2020. We collected seizure history, postoperative outcomes, and functional data. Imaging was independently reviewed in a blinded fashion by 2 neurosurgeons and a neuroradiologist. RESULTS: We analyzed 30 patients with RE who underwent 35 hemispherectomies (5 reoperations). Using Kaplan-Meier analysis, seizure-freedom rate was 81.5%, 63.6%, and 55.6% at 1, 5, and 10 years after surgery, respectively. Patients with shorter duration of hemiparesis preoperatively were less likely to be seizure-free at follow-up (P = .011) and more likely to undergo reoperation (P = .004). Shorter duration of epilepsy (P = .026) and preoperative bilateral MRI abnormalities (P = .011) were associated with increased risk of reoperation. Complete disconnection of diseased hemisphere on postoperative MRI after the first operation improved seizure-freedom (P = .021) and resulted in fewer reoperations (P = .034), and reoperation resulted in seizure freedom in every case. CONCLUSION: Obtaining complete disconnection is critical for favorable seizure outcomes from hemispherectomy, and neurosurgeons should have a low threshold to reoperate in patients with RE with recurrent seizures. Rapid progression of motor deficits and bilateral MRI abnormalities may indicate a subpopulation of patients with RE with increased risk of needing reoperation. Overall, we believe that hemispherectomy is a curative surgery for the majority of patients with RE, with excellent long-term seizure outcome.

ResectVol: A tool to automatically segment and characterize lacunas in brain images.

OBJECTIVE: To assess and validate the performance of a new tool developed for segmenting and characterizing lacunas in postoperative MR images of epilepsy patients. METHODS: A MATLAB-based pipeline was implemented using SPM12 to produce the 3D mask of the surgical lacuna and estimate its volume. To validate its performance, we compared the manual and automatic lacuna segmentations obtained from 51 MRI scans of epilepsy patients who underwent temporal lobe resections. RESULTS: The code is consolidated as a tool named ResectVol, which can be run via a graphical user interface or command line. The automatic and manual segmentation comparison resulted in a median Dice similarity coefficient of 0.77 (interquartile range: 0.71-0.81). SIGNIFICANCE: Epilepsy surgery is the treatment of choice for pharmacoresistant focal epilepsies, and despite the extensive literature on the subject, we still cannot predict surgical outcomes accurately. As the volume and location of the resected tissue are fundamentally relevant to this prediction, researchers commonly perform a manual segmentation of the lacuna, which presents human bias and does not provide detailed information about the structures removed. In this study, we introduce ResectVol, a user-friendly, fully automatic tool to accomplish these tasks. This capability enables more advanced analytical techniques applied to surgical outcomes prediction, such as machine-learning algorithms, by facilitating coregistration of the resected area and preoperative findings with other imaging modalities such as PET, SPECT, and functional MRI ResectVol is freely available at https://www.lniunicamp.com/resectvol.

Surgical candidates in children with epileptic spasms can be selected without invasive monitoring: A report of 70 cases.

OBJECTIVE: Prior surgical series in children with drug-resistant epileptic spasms have reported use of intracranial EEG monitoring in up to two-third of patients. We report outcome after epilepsy surgery for drug-resistant epileptic spasms in a cohort of children without the use of intracranial EEG monitoring in any of the patients. METHODS: Medical records of all consecutive children aged 5 years or under who had epilepsy surgery for epileptic spasms at Cleveland Clinic between 2000 and 2018 were reviewed. Post-operative seizure outcome and predictors of prognosis of seizure outcome were analyzed. RESULTS: Seventy children with active epileptic spasms underwent surgical resections during the study period. Mean age at seizure onset was 6.8 (+9.31) months and median age at surgery was 18.5 months. An epileptogenic lesion was identified on brain MRI in all patients; 17 (24%) had bilateral abnormalities. Etiologies included malformations of cortical development (58%), perinatal infarct/encephalomalacia (39%), and tumor (3%). None of the patients had intracranial EEG. Surgical procedures included hemispherectomy (44%), lobectomy/ lesionectomy (33%), and multilobar resections (23%). Twelve children needed repeat surgery; six (50%) became seizure free after the second surgery. At six months follow-up, 73% (51/70) were seizure-free since surgery. At a mean follow-up of 4.7 years, 60% (42/70) had Engel 1 outcome. In those with seizure recurrence, 17 (60%) reported improvement. Shorter epilepsy duration (p = 0.05) and lobar or sub-lobar epileptogenic lesions (p = 0.02) predicted favorable seizure outcome at 6 months after surgery. For long term outcome, patients with bilateral abnormalities on MRI (p = 0.001), and multilobar extent on MRI (p = 0.02) were at higher risk for recurrence. SIGNIFICANCE: Children with drug-resistant epileptic spasms secondary to an epileptogenic lesion detected on MRI could be selected for epilepsy surgery without undergoing intracranial EEG monitoring. A surgical selection paradigm without intracranial monitoring may allow early surgery without the risks of invasive monitoring.

Contralateral MRI abnormalities in candidates for hemispherectomy for refractory epilepsy.

PURPOSE: To assess the impact of contralateral magnetic resonance imaging (MRI) findings on seizure outcome after hemispherectomy for refractory epilepsy. METHODS: We retrospectively reviewed 110 children, 0.4-18 (median 5.9) years of age, who underwent hemispherectomy for severe refractory epilepsy at Cleveland Clinic Children's Hospital. In children with contralateral (as well as ipsilateral) MRI findings appreciated preoperatively, the decision to proceed to surgery was based on other features concordant with the side with the most severe MRI abnormality, including ipsilateral epileptiform discharges, lateralizing seizure semiology, and side of hemiparesis. RESULTS: We retrospectively observed contralateral MRI abnormalities (predominantly small hemisphere, white matter loss or abnormal signal, or sulcation abnormalities) in 81 patients (74%), including 31 of 43 (72%) with malformations of cortical development (MCD), 31 of 42 (73%) with perinatal injury from infarction or hypoxia, and 15 of 25 (60%) with Rasmussen's encephalitis, Sturge-Weber syndrome, or posttraumatic encephalomalacia. Among 84 children (76%) with lesions that were congenital or acquired pre- or perinatally, 67 (83%) had contralateral MRI abnormalities (p = 0.02). Contralateral findings were subjectively judged to be mild or moderate in 70 (86%). At follow-up 12-84 (median 24) months after surgery, 79% of patients with contralateral MRI abnormalities were seizure-free compared to 83% of patients without contralateral MRI findings, with no differences based on etiology group or type or severity of contralateral MRI abnormality. DISCUSSION: MRI abnormalities, usually mild to moderate in severity, were seen in the contralateral hemisphere in the majority of children who underwent hemispherectomy for refractory epilepsy due to various etiologies, especially those that were congenital or early acquired. The contralateral MRI findings, always much less prominent than those in the ipsilateral hemisphere, did not correlate with seizure outcome and may not contraindicate hemispherectomy in otherwise favorable candidates.

Occipital epilepsy: spatial categorization and surgical management.

OBJECT: Occipital resections for epilepsy are rare. Reasons for this are the relative infrequency of occipital epilepsy, difficulty in localizing epilepsy originating in the occipital lobe, imprecisely defined seizure outcome in patients treated with focal occipital resections in the MR imaging era, and concerns about producing visual deficits. The impact of lesion location on vision and seizure biology, the management decision-making process, and the outcomes following resection need elaboration. METHODS: The authors studied 21 consecutive patients who underwent focal occipital resections for epilepsy at Cleveland Clinic Epilepsy Center over a 13-year period during which MR imaging was used. Demographics, imaging, and data relating to the epilepsy and its surgical management were collected. The collateral sulcus, the border between the medial surface and the lateral convexity, and the inferior temporal sulcus were used to subdivide the occipital lobe into medial, lateral, and basal zones. Lesions that did not involve most or all of the occipital lobe (sublobar) were spatially categorized into these zones. Visual function, semiology, and scalp electroencephalography were evaluated in relation to these spatial categories. Preresection and postresection visual function and seizure frequency were evaluated and compared. Lastly, an exhaustive review and discussion of the published literature on occipital resections for epilepsy was carried out. RESULTS: Five lesions were lobar and 16 were sublobar. Patients with medial or lobar lesions had a much greater likelihood of preoperative visual field defects. Those with basal or lateral lesions had a greater likelihood of having a visual aura preceding some or all of their seizures and a trend (not significant) toward having a concordant lateralized onset by scalp electroencephalography. Invasive recordings were used in 8 cases. All patients had lesions (malformations of cortical development, tumors, or gliosis) that were completely resected, as evaluated on postoperative MR imaging. At last follow-up, 17 patients (81%) were seizure free or had only occasional auras (Wieser Class 1 or 2). The remaining 4 patients (19%) had a worthwhile improvement in seizure control (Class 3 or 4). Of the patients for whom both pre- and postoperative visual testing data were available, 50% suffered no new visual deficits, and 17% each developed a new quadrantanopia or a hemianopia. CONCLUSIONS: Lesional occipital lobe epilepsy can be successfully managed with resection to obtain excellent seizure-free rates. Individually tailored resections (in lateral occipital lesions, for example) may help preserve intact vision in a subset of cases (38% in this series). Invasive recordings may further guide surgical decision-making as delineated by an algorithm generated by the authors. The authors' results suggest that the spatial location of the lesion correlates both with the semiology of the seizure and with the presence of visual deficit.

Neuronal nitric oxide synthase expression in resected epileptic dysplastic neocortex.

OBJECT: Nitric oxide has been associated with epileptogenesis. Previous studies have shown increased expression of N-methyl-d-aspartate (NMDA) subunit NR2B receptors in epileptic dysplastic human neocortex. The expression of neuronal nitric oxide synthase (nNOS), and its relation to this subunit NR2B in epileptic dysplastic tissue has never been addressed. METHODS: Ten patients with medically intractable epilepsy caused by focal cortical dysplasia (CD), and 2 patients with mesial temporal sclerosis (control group) underwent pre- and/or intraoperative invasive monitoring evaluations. Cortical samples from epileptogenic and nonepileptogenic areas were collected from each patient intraoperatively. Samples were processed for cresyl violet staining, immunocytochemical tests with nNOS, NeuN, and NR2B, and immunofluorescence analyses to evaluate colocalized immunoreactivity between nNOS and NR2B. RESULTS: All samples obtained in the patients with epilepsy revealed CD in various degrees. In the nonepileptic sample group, cresyl violet staining revealed normal cortical architecture in 9 samples, but a mild degree of CD in 3. The density and intensity of nNOS-stained neurons was remarkably increased in the epileptic tissue compared with nonepileptic samples (p < 0.05). Two types of nNOS-stained neurons were identified: Type I, expressing strong nNOS immunoreactivity in larger neurons; and Type II, expressing weak nNOS immunoreactivity in slightly smaller neurons. Different from Type I neurons, Type II nNOS-stained neurons revealed immunoreactivity colocalized with NR2B antibody. CONCLUSIONS: The overexpression of nNOS in the epileptic samples and the immunoreactivity colocalization between nNOS and NR2B may suggest a possible role of nNOS and NO in the pathophysiological mechanisms related to in situ epileptogenicity.

Robot-Assisted Responsive Neurostimulator System Placement in Medically Intractable Epilepsy: Instrumentation and Technique.

BACKGROUND: The management of medically refractory epilepsy patients who are not surgical candidates has remained challenging. Closed loop-or responsive-neurostimulation (RNS) is now an established therapy for the treatment of epilepsy with specific indications. The RNS® system (NeuroPace Inc, Mountainview, California) has recently been shown to be effective in reducing the seizure frequency of partial onset seizures. The electrode design consists of either intracerebral depth electrodes or subdural strip electrodes, and stereotaxis is typically used to guide placement into the EZ. Details on the operative techniques used to place these electrodes have been lacking. OBJECTIVE: To address the advantage of using a robotic-assisted technique to place depth electrodes for RNS® system placement compared to the typical frame-based or frameless stereotactic systems. METHODS: We retrospectively reviewed our single center, technical operative experience with RNS® system placement using robotic assistance from 2014 to 2016 via chart review. RESULTS: Twelve patients underwent RNS® system placement using robotic assistance. Mean operative time was 121 min for a median of 2 depth electrodes with mean deviation from intended target of ∼3 mm in x, y, and z planes. Two patients developed wound infections, 1 of whom was reimplanted. Seizures were reduced by ∼40% at 2 yr, similar to the results seen in the open label portion of the pivotal RNS trial. CONCLUSION: Robotic-assisted stereotaxis can be used to provide a stable and accurate stereotactic platform for insertion of intracerebral RNS electrodes, representing a safe, efficient and accurate procedure.

Robot-assisted stereoelectroencephalography in children.

OBJECTIVEThe goal in the study was to describe the clinical outcomes associated with robot-assisted stereoelectroencephalography (SEEG) in children.METHODSThe authors performed a retrospective, single-center study in consecutive children with medically refractory epilepsy who were undergoing robot-assisted SEEG. Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom. Both univariate and multivariate methods were used to analyze the preoperative and operative factors associated with seizure freedom.RESULTSFifty-seven children underwent a total of 64 robot-assisted procedures. The patients' mean age was 12 years, an average of 6.4 antiepileptic drugs (AEDs) per patient had failed prior to implantation, and in 56% of the patients the disease was considered nonlesional. On average, children had 12.4 electrodes placed per implantation, with an implantation time of 9.6 minutes per electrode and a 10-day postoperative stay. SEEG analysis yielded a definable epileptogenic zone in 51 (89%) patients; 42 (74%) patients underwent surgery, half of whom were seizure free at last follow-up, 19.6 months from resection. In a multivariate generalized linear model, resective surgery, older age, and shorter SEEG-related hospital length of stay were associated with seizure freedom. In a Cox proportional hazards model including only the children who underwent resective surgery, older age was the only significant factor associated with seizure freedom. Complications related to bleeding were the major contributors to morbidity. One patient (1.5%) had a symptomatic hemorrhage resulting in a permanent neurological deficit.CONCLUSIONSThe authors report one of the largest pediatric-specific SEEG series demonstrating that the modern surgical management of medically refractory epilepsy in children can lead to seizure freedom in many patients, while also highlighting the challenges posed by this difficult patient population.

Neurogenesis in the postnatal human epileptic brain.

OBJECT: The normal adult human telencephalon does not reveal evidence of spontaneous neuronal migration and differentiation despite the robust germinal capacity of the subventricular zone (SVZ) astrocyte ribbon that contains neural stem cells. This might be because it is averse to accepting new neurons into an established neuronal network, probably representing an evolutionary acquisition to prevent the formation of anomalous neuronal circuits. Some forms of epilepsy, such as malformations of cortical development, are thought to be due to abnormal corticogenesis during the embryonic and early postnatal periods. The role of postnatal architectural reorganization and possibly postnatal neurogenesis in some forms of epilepsy in humans remains unknown. In this study the authors used resected specimens of epileptic brain to determine whether neurogenesis could occur in the diseased tissue. METHODS: The authors studied freshly resected brain tissue obtained in 47 patients who underwent neurosurgical procedures and four autopsies. Forty-four samples were harvested in patients who underwent resection for the treatment of pharmacoresistant epilepsy. RESULTS: Using organotypic brain slice preparations cultured with 5-bromodeoxyuridine (a marker for cell proliferation), immunohistochemistry, and cell trackers, the authors demonstrate the presence of spontaneous cell proliferation, migration, and neuronal differentiation in the adult human telencephalon that starts in the SVZ and progresses to the adjacent white matter and neocortex in human neocortical pathological structures associated with epilepsy. No cell migration or neuronal differentiation was found in the control group. CONCLUSIONS: The presence of spontaneous neurogenesis associated with some forms of human neocortical epilepsy may represent an erroneous and maladaptive mechanism for neuronal circuitry repair, or it may be an intrinsic part of the pathogenic process.

Pediatric epilepsy surgery in focal lesions and generalized electroencephalogram abnormalities.

Generalized abnormalities on scalp electroencephalograms (EEG) are not uncommon in children with partial epilepsy in whom a dominant focus of interictal and ictal abnormalities concordant to the brain lesion usually clarifies surgical candidacy. Children with exclusively generalized or multiregional EEG abnormalities and mental retardation are usually not considered surgical candidates, even when brain lesions are seen on imaging. Of 176 pediatric epilepsy surgeries at our center, we describe 10 children with exclusively generalized and multiregional interictal and ictal EEG abnormalities who had resection of a focal lesion seen on brain MRI. Surgical decisions were strengthened by clinical data. Surgery was offered as a last resort because of catastrophic epilepsy and treatment failures. At 26 months' mean postoperative follow-up, eight had no seizures, and two had infrequent seizures. Six months after surgery, generalized electroencephalographic abnormalities had resolved in all. We conclude that generalized and multiregional EEG abnormalities in the absence of dominant focus may not preclude epilepsy surgery in children with a congenital or acquired lesion seen on MRI. Generalized EEG abnormalities are likely secondary phenomena that resolve after surgery. Maladaptive neural plasticity and secondary epileptogenesis are potential mechanisms that mask an epileptogenic lesion with generalized EEG abnormalities.

Oligoastrocytoma presenting with intractable epilepsy.

OBJECTIVE: Oligoastrocytomas (OA) are mixed gliomas with distinct oligodendroglial and astrocytic neoplastic components. Very little about OA has been reported in the intractable epilepsy population. METHODS: We undertook a retrospective review of 923 patients who underwent resective surgery for intractable epilepsy between 1996 and 2004. RESULTS: 6/923 (0.7%) patients were diagnosed with OA. Five patients were female, one was male. Median age at diagnosis was 25 years (range 19-44 years). Tumors arose from the left side in all patients and from the temporal lobe in five patients. Three patients had complex partial seizures. Median length of refractory epilepsy prior to surgery was 10.5 years (range 1-28 years), and the median number of antiepileptic drugs used was 2 (range 1-10). Preoperative WADA testing for language and memory localization was done for three patients; preoperative stereotactical localization was done for three patients. Surgical pathology revealed low-grade OA (WHO II) in five patients, and anaplastic OA in one. There were no surgical complications, clinical or radiographic tumor recurrence at a mean follow up period of 3.2 years (range 2-8). Excellent seizure freedom was achieved in 5/6 patients. CONCLUSION: As a result of our small sample size, general conclusions may be imprecise, but this review suggests that OA behave similar to other tumors related to intractable epilepsy: they usually have a preoperative seizure course of many years, an excellent rate of seizure-freedom following surgery, and are in general, low-grade tumors with an indolent course for which serial imaging is sufficient follow-up.

Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy.

PURPOSE: To retrospectively review our experience with VNS in pediatric patients with pharmacoresistant epilepsy and examine the seizure-frequency outcome and rates of discontinuation in two age groups: adolescent and pre-adolescent children. RESULTS: Complete pre- and post-VNS data were available for 46/49 patients. Median age at implantation was 12.1 (range 2.3-17.9) and median duration of epilepsy 8.0 (1.9-16.9) years. Twenty-one patients (45.6%) were under 12 years at the time of surgery. Median follow-up was 2 years; follow-up exceeded 4 years in 9/46 patients. As compared to baseline, median seizure-frequency reduction in the setting of declining numbers was 56% at 3 months, 50% at 6, 63% at 12, 83% at 24 and 74% at 36 months. When a last observation carried forward analysis was employed median seizure-frequency reduction in the range of 60% was observed at 1, 2 and 3 years post-VNS. Twenty patients (43.5%) had >75% seizure-frequency reduction. No response (increase or <50% reduction) was observed in 19/46 (41.3%). Five patients (10.1%) were seizure-free for more than 6 months by their last follow-up. There was no difference in the number of AEDs used before and after VNS. The long-term discontinuation rate was 21.7% and reflected a lack of clinical response or infection. CONCLUSIONS: In this series VNS was well-tolerated and effective as add-on therapy for refractory seizures in children of all ages. Response was even more favorable in the younger group (<12 years at implantation). Infection and lack of efficacy were the most common reasons for discontinuation of long-term VNS therapy in this group.