Presurgical Evaluation For Intractable Epilepsy Research Articles

18F]DPA-714 PET Imaging in the Presurgical Evaluation of Patients With Drug-Resistant Focal Epilepsy.

Translocator protein 18 kDa (TSPO) PET imaging is used to monitor glial activation. Recent studies have proposed TSPO PET as a marker of the epileptogenic zone (EZ) in drug-resistant focal epilepsy (DRFE). This study aims to assess the contributions of TSPO imaging using [18F]DPA-714 PET and [18F]FDG PET for localizing the EZ during presurgical assessment of DRFE, when phase 1 presurgical assessment does not provide enough information. We compared [18F]FDG and [18F]DPA-714 PET images of 23 patients who had undergone a phase 1 presurgical assessment, using qualitative visual analysis and quantitative analysis, at both the voxel and the regional levels. PET abnormalities (increase in binding for [18F]DPA-714 vs decrease in binding for [18F]FDG) were compared with clinical hypotheses concerning the localization of the EZ based on phase 1 presurgical assessment. The additional value of [18F]DPA-714 PET imaging to [18F]FDG for refining the localization of the EZ was assessed. To strengthen the visual analysis, [18F]DPA-714 PET imaging was also reviewed by 2 experienced clinicians blind to the EZ location. The study included 23 patients. Visual analysis of [18F]DPA-714 PET was significantly more accurate than [18F]FDG PET to both, show anomalies (95.7% vs 56.5%, p = 0.022), and provide additional information to refine the EZ localization (65.2% vs 17.4%, p = 0.019). All 10 patients with normal [18F]FDG PET had anomalies when using [18F]DPA-714 PET. The additional value of [18F]DPA-714 PET seemed to be greater in patients with normal brain MRI or with neocortical EZ (especially if insula is involved). Regional analysis of [18F]DPA-714 and [18F]FDG PET provided similar results. However, using voxel-wise analysis, [18F]DPA-714 was more effective than [18F]FDG for unveiling clusters whose localization was more often consistent with the EZ hypothesis (87.0% vs 39.1%, p = 0.019). Nonrelevant bindings were seen in 14 of 23 patients in visual analysis and 9 patients of 23 patients in voxel-wise analysis. [18F]DPA-714 PET imaging provides valuable information for presurgical assessments of patients with DRFE. TSPO PET could become an additional tool to help to the localization of the EZ, especially in patients with negative [18F]FDG PET. Eudract 2017-003381-27. Inclusion of the first patient: September 24, 2018. This study provides Class IV evidence on the utility of [18F]DPA-714 PET compared with [18F]FDG PET in identifying the epileptic zone in patients undergoing phase 1 presurgical evaluation for intractable epilepsy.

Basic Principles of Electroencephalogram

Electroencephalogram(EEG)signals are mainly generated by postsynaptic potentials(EPSP)in the apical dendrites of pyramidal cells in the cortex. The mechanism of generation of interictal epileptiform discharges(IED)is paroxysmal depolarization shift(PDS). IEDs are negative towards the cortical surface and positive towards the white matter. To interpret EEG, readers should know normal EEG waveforms of wakefulness and sleep, normal variants such as wicket spikes or small sharp spikes, and artifacts such as eye movements or electromyography. Overinterpretation of EEG is a major cause of misdiagnosis; therefore, the accurate identification of IED is essential. The International Federation of Clinical Neurophysiology has proposed a criteria for the identification of IED. Long-term video-EEG is useful for correct diagnosis and localization of the epileptogenic zone in the setting of presurgical evaluation of intractable epilepsy and is also useful for the differential diagnosis of epileptic seizures and non-epileptic events. Clinical history and symptomatology are of utmost importance for correct diagnosis. Diagnosis should not be made using only EEG findings.

BrainQuake: An Open-Source Python Toolbox for the Stereoelectroencephalography Spatiotemporal Analysis.

Intracranial stereoelectroencephalography (SEEG) is broadly used in the presurgical evaluation of intractable epilepsy, due to its high temporal resolution in neural activity recording and high spatial resolution within suspected epileptogenic zones. Neurosurgeons or technicians face the challenge of conducting a workflow of post-processing operations with the multimodal data (e.g., MRI, CT, and EEG) after the implantation surgery, such as brain surface reconstruction, electrode contact localization, and SEEG data analysis. Several software or toolboxes have been developed to take one or more steps in the workflow but without an end-to-end solution. In this study, we introduced BrainQuake, an open-source Python software for the SEEG spatiotemporal analysis, integrating modules and pipelines in surface reconstruction, electrode localization, seizure onset zone (SOZ) prediction based on ictal and interictal SEEG analysis, and final visualizations, each of which is highly automated with a user-friendly graphical user interface (GUI). BrainQuake also supports remote communications with a public server, which is facilitated with automated and standardized preprocessing pipelines, high-performance computing power, and data curation management to provide a time-saving and compatible platform for neurosurgeons and researchers.

Electrocorticography reveals spatiotemporal neuronal activation patterns of verbal fluency in patients with epilepsy

Verbal fluency is commonly used to evaluate cognitive dysfunction in a variety of neuropsychiatric diseases, yet the neurobiology underlying performance of this task is incompletely understood. Electrocorticography (ECoG) provides a unique opportunity to investigate temporal activation patterns during cognitive tasks with high spatial and temporal precision. We used ECoG to study high gamma activity (HGA) patterns in patients undergoing presurgical evaluation for intractable epilepsy as they completed an overt, free-recall verbal fluency task. We examined regions demonstrating changes in HGA during specific timeframes relative to speech onset. Early pre-speech high gamma activity was present in left frontal regions during letter fluency and in bifrontal regions during category fluency. During timeframes typically associated with word planning, a distributed network was engaged including left inferior frontal, orbitofrontal and posterior temporal regions. Peri-Rolandic activation was observed during speech onset, and there was post-speech activation in the bilateral posterior superior temporal regions. Based on these observations in the context of prior studies, we propose a model of neocortical activity patterns underlying verbal fluency.

Human posterior parietal cortex responds to visual stimuli as early as peristriate occipital cortex.

Much of what is known about the timing of visual processing in the brain is inferred from intracranial studies in monkeys, with human data limited to mainly noninvasive methods with lower spatial resolution. Here, we estimated visual onset latencies from electrocorticographic (ECoG) recordings in a patient who was implanted with 112 subdural electrodes, distributed across the posterior cortex of the right hemisphere, for presurgical evaluation of intractable epilepsy. Functional MRI prior to surgery was used to determine boundaries of visual areas. The patient was presented with images of objects from several categories. Event-related potentials (ERPs) were calculated across all categories excluding targets, and statistically reliable onset latencies were determined, using a bootstrapping procedure over the single trial baseline activity in individual electrodes. The distribution of onset latencies broadly reflected the known hierarchy of visual areas, with the earliest cortical responses in primary visual cortex, and higher areas showing later responses. A clear exception to this pattern was a robust, statistically reliable and spatially localized, very early response, on the bank of the posterior intraparietal sulcus (IPS). The response in the IPS started nearly simultaneously with responses detected in peristriate visual areas, around 60ms poststimulus onset. Our results support the notion of early visual processing in the posterior parietal lobe, not respecting traditional hierarchies, and give direct evidence for onset times of visual responses across the human cortex.

Seizure semiology and electroencephalography in young children with lesional temporal lobe epilepsy

PurposeThis study aimed to discuss the clinical features of seizure semiology and electroencephalography (EEG) in young children with lesional temporal lobe epilepsy (TLE). MethodChildren with lesional TLE received presurgical evaluation for intractable epilepsy. They were followed up for more than one year after temporal lobectomy. We reviewed the medical history and video-EEG monitoring of children with TLE to analyze the semiology of seizures and EEG findings and compared the semiology of seizures and EEG findings of childhood TLE and adult TLE. ResultsA total of 84 seizures were analyzed in 11 children (aged 23–108 months). The age of seizure onset was from 1 month to 26 months (a mean of 17.6 months). All of the patients exhibited prominent motor manifestations including epileptic spasm, tonic seizure, and unilateral clonic seizure. Seven children manifested behavioral arrest similar to an automotor seizure in adult TLE but with a shorter duration and higher frequency. The automatisms were typically orofacial, whereas manual automatisms were rarely observed. The EEG recordings revealed that diffuse discharge patterns were more common in younger children, whereas focal or unilateral patterns were more typical in older children. All of the patients were seizure-free after temporal lobectomy with more than one-year follow-up. All of the children had a mental development delay or regression; however, there was improvement after surgery, especially in those with surgery performed early. ConclusionIn contrast to TLE in adults, young children with lesional TLE probably represent a distinct nosological and probably less homogeneous syndrome. Although they had generalized clinical and electrographic features, resective epilepsy surgery should be considered as early as possible to obtain seizure control and improvement in mental development.

Neocortical pathological high-frequency oscillations are associated with frequency-dependent alterations in functional network topology

Synchronization of neural oscillations is thought to integrate distributed neural populations into functional cell assemblies. Epilepsy is widely regarded as a disorder of neural synchrony. Knowledge is scant, however, regarding whether ictal changes in synchrony involving epileptogenic cortex are expressed similarly across various frequency ranges. Cortical regions involved in epileptic networks also exhibit pathological high-frequency oscillations (pHFOs, >80 Hz), which are increasingly utilized as biomarkers of epileptogenic tissue. It is uncertain how pHFO amplitudes are related to epileptic network connectivity. By calculating phase-locking values among intracranial electrodes implanted in children with intractable epilepsy, we constructed ictal connectivity networks and performed graph theoretical analysis to characterize their network properties at distinct frequency bands. Ictal data from 17 children were analyzed with a hierarchical mixed-effects model adjusting for patient-level covariates. Epileptogenic cortex was defined in two ways: 1) a hypothesis-driven method using the visually defined seizure-onset zone and 2) a data-agnostic method using the high-frequency amplitude of each electrode. Epileptogenic cortex exhibited a logarithmic decrease in interregional functional connectivity at high frequencies (>30 Hz) during seizure initiation and propagation but not at termination. At slower frequencies, conversely, epileptogenic cortex expressed a relative increase in functional connectivity. Our findings suggest that pHFOs reflect epileptogenic network interactions, yielding theoretical support for their utility in the presurgical evaluation of intractable epilepsy. The view that abnormal network synchronization plays a critical role in ictogenesis and seizure dynamics is supported by the observation that functional isolation of epileptogenic cortex at high frequencies is absent at seizure termination.

Neurovascular coupling and functional neuroimaging in epilepsy

INTRODUCTION: The neural regulation of the microcirculation is done by the functional neurovascular unit that is composed of vascular, astroglial and neuronal cells. The neurovascular unit represents the interface between the Central Nervous System and the Vascular System. OBJECTIVE: This paper reviews the literature on functional neuroimaging with a particular focus on the mechanisms of the neurovascular coupling. CONCLUSIONS: Functional neuroimaging techniques as functional MRI, SPECT and PET distinguish metabolic and physiological processes underlying normal and abnormal events, based on neurovascular coupling. Although these techniques still have limitations in temporal and spatial resolution, they have considerably reduced the need for intracranial electrodes or invasive functional tests in the presurgical evaluation for intractable epilepsy. Recently, new techniques as optical approaches (measurement of intrinsic optical signals and near infrared spectroscopy) have increased both temporal and spatial resolutions. The use of such techniques in animal models has yielded experimental evidence for a neurovascular coupling in normal and epileptic conditions.

Unexpected right hemisphere language representation identified by the intracarotid amobarbital procedure in right-handed epilepsy surgery candidates

The intracarotid amobarbital procedure (IAP) is used for language lateralization in the presurgical evaluation for intractable epilepsy. Some epilepsy surgical centers forgo IAP for right temporal lobectomies in right-handed patients with no personal/family history of left-handedness, implying that right hemisphere language representation does not occur in these patients. To test this hypothesis, a retrospective analysis was performed on 156 consecutive epilepsy surgery candidates who underwent IAP. Of the 156 candidates, 122 were right-handed, and 55 of the 122 demonstrated right hemisphere seizure focus. Right hemisphere language representation was found in 22 of 55 patients, with two demonstrating significant right hemisphere language despite a right hemisphere seizure focus and no family history of left-handedness. Only 1 of 156 patients undergoing IAP experienced permanent neurological complications. Although relatively uncommon, right hemisphere language representation may occur more frequently than complications from cerebral angiography and, therefore, presurgical IAP is recommended for all epilepsy surgery candidates regardless of handedness to minimize the risk of severe language decline.

Long-term follow-up outcome after surgical treatment for lesional temporal lobe epilepsy

Objectives: Lateral or neocortical temporal lobe epilepsy (TLE) is regarded as a distinct clinical entity from medial TLE. Surgery for neocortical TLE can be considered as a viable treatment option; however, there is very limited information available on aspects such as long-term seizure outcome. Thus, we retrospectively reviewed our ten surgical cases of lateral TLE with a minimum 2 year follow-up outcome.Methods: The series comprised four male and six female patients, ranging in age from 3 to 46 years (mean: 28.8 years). Seven cases were found to be drug-resistant. Invasive pre-surgical evaluation for intractable epilepsy was performed in six patients.Results: The pathologic lesions were removed completely in nine cases. Lesionectomy alone was performed in four cases and total epileptogenic focus resection was confirmed in four cases. The epileptogenic regions within eloquent areas were preserved in two cases. The medial temporal structure was intact and preserved in all cases. Neuropathologic diagnoses were cavernoma in three cases, astrocytoma (grade 2) in two cases, arteriovenous malformation in two cases, gliosis in two cases and ganglioglioma in one case. The mean duration of follow-up was 6.5 years (range: 2.2–9.3 years). Outcomes categorized according to Engel classes were class I (E1) in six cases and class II (E2) in four cases. Patients who had post-operative seizures may also achieve long-term seizure decrease or freedom in three cases: case 5 (E4–E2), case 6 (E4–E2) and case 7 (E3–E1). Thus, worthwhile improvement was achieved in 100% of the cases in this series, with 60% of patients being seizure-free during the followed-up period.Conclusions: The controlled long-term follow-up results suggested that surgery for lesional TLE can be considered as a viable treatment option to control seizure with a low morbidity rate and good outcomes.

Neuroimaging and presurgical evaluation of symptomatic epilepsies.

The goal of presurgical evaluation of intractable epilepsy is to identify epileptogenic regions in the brain. From our experience of 38 cases of resective epilepsy surgery from the last 3 years, ictal SPECT was considered the most sensitive at detecting focal changes relating to seizures compared to other neuroimaging modalities, such as MRI, FDG-PET, SPECT and MEG. At interictal state, on the other hand, FDG-PET was most sensitive, especially in cases with focal cortical dysplasia, which is often MRI-invisible. In dysplastic tumors, MRI showed the highest concordance rate to clinically verified epileptogenic regions. Activation studies using functional neuroimaging such as PET and fMRI is useful to evaluate brain functions at epileptogenic regions presurgically. The role of functional brain imaging in epilepsy surgery is considered to be: (i). case selection for resective surgery, (ii). case selection for invasive EEG monitoring, and (iii). navigation of electrode placement and cortical resection.

Is Speech Arrest during Wada Testing a Valid Method for Determining Hemispheric Representation of Language?

Background and objective: The intracarotid amobarbital procedure, or Wada test, is the method of choice to determine hemispheric representation of language, and is routinely used in the presurgical evaluation for intractable epilepsy. Some investigators perform comprehensive language assessments, but others base language lateralization solely on speech arrest. This study sought to determine whether speech arrest alone during Wada testing provides valid data regarding language lateralization. Methods: The subjects (previously reported) were 21 patients evaluated for intractable epilepsy, who underwent language lateralization by Wada testing and functional MRI (FMRI). For each patient, language representation was determined by calculating: (1) a Wada laterality index based exclusively on speech arrest; (2) a Wada laterality index based on comprehensive language assessment; and (3) an FMRI laterality quotient. Correlation coefficients and categorical classifications were analyzed. Results: There was no significant correlation between the Wada laterality quotient derived from duration of speech arrest and either the comprehensive Wada language laterality score (r= .35,p= .12) or FMRI language laterality score (r= .32,p= .16). Categorical classification as left, right or bilateral language also showed marked discordance between speech arrest and the other two methods. Conclusion: Duration of speech arrest during Wada testing is not a valid measure of language dominance.

Epidural peg electrodes for the presurgical evaluation of intractable epilepsy

A new electrode design for the extradural recording of electrical brain activity is described. Epidural peg electrodes are implantable mushroom-shaped composites of Silastic elastomer and a stainless steel or platinum disc. These electrodes are useful for the preoperative mapping of seizure foci in some patients who have cranial defects or severe muscle artifacts on scalp recordings. They are also used for canvassing wide areas of cortex to determine whether a seizure is focal in origin, arises diffusely from a hemisphere, or has a bilateral origin. Advantages of epidural peg electrodes over screw and other types of epidural electrodes include low risk of infection or hemorrhage and improved patient comfort.