Neuroimaging in epilepsy: diagnostic strategies in partial epilepsy

The diagnostic evaluation of the patient with partial or localization-related epilepsy is designed to identify treatment strategies that will permit the individual to be seizure-free. The use of magnetic resonance imaging (MRI) has been pivotal in elucidating the presence of an epileptogenic pathological alteration that may coexist with the site of seizure onset. There are compelling data that MRI is of significant diagnostic and prognostic importance in patients with partial epilepsy. Patients with MRI-negative partial epilepsy may be candidates for additional neuroimaging techniques including positron emission tomography, MR spectroscopy, and single photon emission tomography. Contemporary innovations with peri-ictal imaging may allow identification of the epileptogenic zone in patients with normal MRI scans. This discussion will focus on the management of the adult patient with seizures and epilepsy, emphasizing the neuroimaging evaluation and treatment of patients with medically refractory seizure disorders.     

Neuroimaging of epilepsy

It can sometimes be difficult, when examining surgical specimens, to detect underlying pathological abnormalities that may account for disordered electrical activity. For accurate diagnosis, neuropathologists and clinicians need to share common preoperative information about resected brain tissue. Our group has been able to use structural, functional, and electrophysiological neuroimaging techniques to visualize epileptogenic areas preoperatively. MRI is the most sensitive and useful examination to demonstrate structural abnormalities in patients with partial or localization‐related epilepsy. Temporal lobe epilepsy, neoplastic lesions, vascular lesions, and developmental anomaly can all be surgically corrected under favorable circumstances. Functional neuroimaging by positron emission tomography (PET) and single‐photon emission computed tomography (SPECT) are useful tools for detecting epileptic foci. PET and SPECT demonstrate subtle functional changes related to epilepsy that ultimately may enable the detection of epileptogenic areas invisible to MRI. PET/SPECT images coregistered to MRI and statistical parametric mappings are of more value for detecting than PET/SPECT images alone. Electrophysiological neuroimaging with analytical software is very useful for visually understanding epileptogenic phenomena. Computerized voltage topographic mappings overlapped on three‐dimensional MRI with multichannel electrodes visually demonstrate ictal onset areas and seizure propagation. A new method of multimodal image‐guided intervention enables the detection of epileptogenic areas by electrocorticography, PET images, and MRI during epilepsy surgery. Neuropathologists using this method can collect precise structural, functional, and electrophysiological findings on surgical specimens. Neuroimaging of epilepsy is useful for visually clarifying structural, functional, and electrophysiological information on epilepsy patients. This approach is key for diagnosing the background pathological abnormalities of resected tissue.     

Localizing value of alpha-methyl-L-tryptophan PET in intractable epilepsy of neocortical origin.

BACKGROUND: [(11)C] alpha-methyl-L-tryptophan (alpha-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that alpha-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of alpha-MTrp in 18 patients (11 men, mean +/- SD age 27.1 +/- 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data. METHOD: Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose ((18)FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity. RESULTS: In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of alpha-MTrp corresponding to the epileptogenic area. alpha-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05). CONCLUSIONS: alpha-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.     

Commentary: How Has Neuroimaging Improved Patient Care?

Summary: Neuroimaging has significantly altered the management of patients with partial epilepsy. Magnetic resonance imaging (MRI) has been demonstrated to be a reliable and accurate indicator of the common pathologic findings underlying a partial seizure disorder. Intracranial mass lesions have been shown to be highly coherent with the localization of the epileptogenic zone. An MRI-identified epileptogenic lesion affects the selection of patients for epilepsy surgery and alters the diagnostic evaluation and the operative strategy. The results of the MRI preoperatively have prognostic importance in patients undergoing surgical treatment for partial epilepsy. Patients with lesional epileptic syndromes are considered favorable candidates for surgical ablative treatment. Hippo-campal volume studies may predict the neurocognitive outcome in patients undergoing temporal lobe surgery. The use of MRI has resulted in a reduction in chronic intracranial EEG monitoring at most epilepsy centers, especially in patients with lesional pathology. MRI may be a reasonable initial "screening" procedure in selected patients with intractable partial epilepsy before consideration of a presurgical evaluation. A classification of partial epilepsy is proposed, based on the results of MRI, that may be useful for patients being considered for surgical treatment. Importantly, preoperative MRI must be correlated with the electrophysiologic studies and ictal semiology before decision-making regarding surgical therapy.     

Role of Neuroimaging in the Presurgical Evaluation of Epilepsy

A significant minority of patients with focal epilepsy are candidates for resective epilepsy surgery. Structural and functional neuroimaging plays an important role in the presurgical evaluation of theses patients. The most frequent etiologies of pharmacoresistant epilepsy in the adult population are mesial temporal sclerosis, malformations of cortical development, cavernous angiomas, and low-grade neoplasms. High-resolution multiplanar magnetic resonance imaging (MRI) with sequences providing T1 and T2 contrast is the initial imaging study of choice to detect these epileptogenic lesions. The epilepsy MRI protocol can be individually tailored when considering the patient''s clinical and electrophysiological data. Metabolic imaging techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) visualize metabolic alterations of the brain in the ictal and interictal states. These techniques may have localizing value in patients with a normal MRI scan. Functional MRI is helpful in non-invasively identifying areas of eloquent cortex.Developments in imaging technology and digital postprocessing may increase the yield for imaging studies to detect the epileptogenic lesion and to characterize its connectivity within the epileptic brain.     

MRI in the presurgical evaluation of patients with frontal lobe epilepsy and children with temporal lobe epilepsy: pathologic correlation and prognostic importance.

We performed magnetic resonance imaging (MRI) using a high-field strength magnet (1.5 T) in two series of 53 patients with intractable partial epilepsy of frontal lobe or temporal lobe origin who subsequently received ablative surgery for their seizure disorder. In the first series of patients the pathologic correlation and prognostic importance of an MRI-identified lesion in the frontal lobe were assessed. Twenty-five percent of the patients with negative MRI studies and 67% of patients with neuroimaging abnormalities restricted to the frontal lobe, were seizure-free at a minimum duration of follow-up of 1 year. None of the patients with a multilobar MRI-detected abnormality was seizure-free postoperatively. In the second study the sensitivity and specificity of MRI-based hippocampal volumetry was determined in pediatric patients with partial epilepsy of temporal lobe origin unrelated to foreign-tissue pathology. Hippocampal formation atrophy in the epileptic temporal lobe was identified in 63% of patients. The sensitivity and specificity of hippocampal volumetry was 100% in patients with mesial temporal sclerosis. The presence of an MRI-detected epileptogenic lesion in the frontal lobe and hippocampal formation atrophy in the temporal lobe may correlate with the underlying pathology and affect the identification of potential candidates for epilepsy surgery.     

Neuroimaging in Partial Epilepsy: Structural Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a noninvasive technique that has been shown to be the structural neuroimaging procedure of choice in evaluating patients with partial or localization-related epilepsy. The diagnostic yield of MRI has been confirmed in patients with partial epilepsy related to mesial temporal sclerosis (MTS) or foreign-tissue lesions. Magnetic resonance imaging may be used preoperatively to identify patients with intractable partial epilepsy who have surgically remediable epileptic syndromes. Preoperative MRI studies are predictive of long-term seizure outcome in patients receiving surgical treatment. Analysis of hippocampal formation size has also been shown to correlate with the neurocognitive outcome following temporal lobe surgery. A recent development involving subtraction ictal single photon emission computed tomography (SPECT) coregistered with structural MRI (SISCOM) has important clinical applications. SISCOM studies are more sensitive and specific than visual side-by-side interpretation of interictal and ictal SPECT scans. Also, SISCOM images have been shown to have prognostic importance in patients undergoing surgical treatment for epilepsy.     

Neuroimaging and neuropathology in epilepsy: With special reference to focal epileptogenic abnormalities

Modern diagnostic imaging techniques, such as computed tomography and magnetic resonance imaging (MRI) have had a profound impact on the management of patients with partial epileptic seizures. Among them, MRI has a prominent and often pivotal role in the evaluation of epilepsy because of its high sensitivity for detecting small or even subtle structural abnormalities. Current information on neuroimaging modalities with respect to neuropathologic features of well-defined and important epileptogenic lesions, such as hippocampal sclerosis, developmental and vascular abnormalities, and neoplasms, was reviewed. With modern neuroimaging modalities, these pathologic changes can now be identified with a high degree of confidence.     

Temporal Lobe Epilepsy: When Are Invasive Recordings Needed?

Temporal lobe epilepsy (TLE) is the most common type of medically intractable partial epilepsy amenable to surgery. In the majority of cases, the underlying pathology in temporal lobe epilepsy is mesial temporal sclerosis (MTS). Whereas historically invasive recordings were required for most epilepsy surgeries, indications have dramatically changed since the introduction of high-resolution MRI, which uncovers structural lesions in a high percentage of cases. No invasive recordings are required to perform a temporal lobectomy in patients with intractable epilepsy who have structural imaging suggesting unilateral MTS and concordant interictal and ictal surface EEG recordings, functional imaging, and clinical findings. Invasive testing is needed if there is evidence of bitemporal MTS on structural imaging and/or electrophysiologically, and additional information from functional imaging, neuropsychology, and the intracarotid amobarbital (Wada) test also does not help to lateralize the epileptogenic zone. Depth electrodes can be particularly helpful in this setting. However, no surgery is indicated, even without invasive recordings, if bitemporal-independent seizures are recorded by surface EEG and all additional testing is inconclusive. Other etiologies of TLE such as a tumor, vascular malformation, encephalomalacia, or congenital developmental abnormality account for about 30% of all patients who undergo epilepsy surgery. Epilepsy surgery is indicated after limited electrophysiologic investigations if neuroimaging and electrophysiology converge. However, approaches for resection in lesional temporal lobe epilepsy vary among centers. Completeness of resection is crucial and invasive recordings may be needed to guide the resection by mapping eloquent cortex and/or to determine the extent of the non-MRI-visible epileptogenic area. Specific approaches for the different pathologies are discussed because there is evidence that the relationship between the lesions visible on MRI and the epileptogenic zone varies among lesions of different pathologies, and therefore variable surgical strategies must be applied.     

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.     

脑裂畸形继发难治性癫的微创外科治疗

目的探讨脑裂畸形继发难治性癫的致灶定位以及微创外科治疗方法。方法回顾性分析11例脑裂畸形继发难治性癫病人的临床资料,术前通过多模态神经影像和长程视频脑电图进行解剖与功能定位。在神经导航引导下使用皮质电极描记了解脑裂畸形病灶与癫波的关系,显微镜下将脑裂畸形的致灶切除。其中位于功能区的脑裂畸形,可使用功能MRI(fMRI)导航并辅以小功率皮质热灼。结果随访11例,时间12个月。术后癫发作完全消失9例,好转2例。结论多模态神经影像和长程视频脑电图可以对脑裂畸形继发的难治性癫进行致灶的解剖与功能定位,在保护脑功能的基础上将脑裂畸形的致灶切除是手术关键。     

Delineating potential epileptogenic areas utilizing resting functional magnetic resonance imaging (fMRI) in epilepsy patients

ABSTRACT

Seizure localization includes neuroimaging like electroencephalogram, and magnetic resonance imaging (MRI) with limited ability to characterize the epileptogenic network. Temporal clustering analysis (TCA) characterizes epileptogenic network congruent with interictal epileptiform discharges by clustering together voxels with transient signals. We generated epileptogenic areas for 12 of 13 epilepsy patients with TCA, congruent with different areas of seizure onset. Resting functional MRI (fMRI) scans are noninvasive, and can be acquired quickly, in patients with different levels of severity and function. Analyzing resting fMRI data using TCA is quick and can complement clinical methods to characterize the epileptogenic network.     

Imaging Studies in Partial Epilepsy in Children and Adolescents

Summary: We reviewed the results of imaging studies on 111 children and adolescents with partial epilepsy to determine which imaging procedure had the greatest sensitivity and specificity for partial epilepsy in this age range. All cases were classified as idiopathic, lesional, and cryptogenic epilepsy based on the 1989 International League Against Epilepsy Classification. All patients had magnetic resonance imaging (MRI) and 98 also had computed tomography (CT). Thirty patients with negative CT had MRI lesions that were most likely the cause of the epilepsy, and the initial diagnosis of cryptogenic partial epilepsy was changed to lesional partial epilepsy. We concluded that CT use is unwarrantedly common. MRI should be considered the procedure of first choice. CT has a complementary role, and functional neuroimaging should be encouraged.     

联合应用电生理技术对癫痫灶精确定位的研究

目的:联合应用多种电生理技术(EEG)对痫灶进行定位。方法:运用多种EEG技术对50例癫痫患者行痫灶定位,并与各种神经影像学检查方法进行比较。定位明确患者行手术治疗,标本行光镜及透射电镜检查,治疗结果以Engel疗效分级评价。结果:使用EEG技术对痫灶定位,其准确率为83.3％,以EEG技术为基础,并与神经影像学方法联合应用,痫灶定位准确率则达到100％。具有EEG异常的癫痫患者,痫灶必然伴有相应病理性损害。结论:反复、多次视频脑电(VEEG)监测,是痫灶定位的首选方法。多种类型的EEG在不同的时段进行监测,是高效、经济、安全无创,可明显提高癫痫灶的检出率及定位的准确性,提高手术疗效。     

FDG-PET/MRI coregistration and diffusion-tensor imaging distinguish epileptogenic tubers and cortex in patients with tuberous sclerosis complex: a preliminary report

PURPOSE: Patients with tuberous sclerosis complex (TSC) are potential surgical candidates if the epileptogenic region(s) can be accurately identified. This retrospective study determined whether FDG-PET/MRI coregistration and diffusion-tensor imaging (DTI) showed better accuracy in the localization of epileptogenic cortex than structural MRI in TSC patients. METHODS: FDG-PET/MRI coregistration and/or DTI for apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were utilized in 15 TSC patients. Presurgery scalp EEG and postsurgery seizure control identified epileptogenic tubers (n = 27) and these were compared with nonepileptogenic tubers (n = 204) for MRI tuber volume, volume of FDG-PET hypometabolism on MRI coregistration, DTI, ADC, and FA values. RESULTS: Compared with nonepileptogenic tubers, epileptogenic regions had increased volume of FDG-PET hypometabolism (p < 0.0001), and increased ADC values in subtuber white matter (p < 0.0001). In contrast, the largest MRI identified tuber (p = 0.046) and decreased FA values (p = 0.58) were less accurate in identifying epileptogenic regions. Larger volumes of FDG-PET hypometabolism correlated positively with increased ADC values (p = 0.029), and localized to areas of cortical dysplasia adjacent to the tuber in four cases. CONCLUSIONS: Larger volumes of FDG-PET hypometabolism relative to MRI tuber size and higher ADC values identified epileptogenic tubers and adjoining cortex containing cortical dysplasia in TSC patients with improved accuracy compared with largest tuber by MRI or lowest FA values. Used in conjunction with ictal scalp EEG and interictal magnetoencephalography, these newer neuroimaging techniques should improve the noninvasive evaluation of TSC patients with intractable epilepsy in distinguishing epileptogenic sites for surgical resection.     

Chronic Intracranial EEG Monitoring for Localizing the Epileptogenic Zone: An Electroclinical Correlation

Summary: Purpose: To evaluate the diagnostic yield and identify predictive factors of the surgical outcome in patients with intractable partial epilepsy undergoing chronic intracranial EEG monitoring (CIEM).
Methods: The clinical, magnetic resonance imaging (MRI) and electrophysiologic data of 108 patients that underwent CIEM were retrospectively reviewed. The discharge pattern and spatial extent of the initial ictal discharge were determined by blinded visual inspection and computerized analysis.
Results: The main predictive indicator for epilepsy surgery outcome in patients that underwent CIEM was the presurgical MRI findings. Most patients with hippocampal atrophy or complete lesionectomy were rendered seizure free after epilepsy surgery (83 and 80%, respectively), whereas only a small minority of patients with partial lesipectomy or no detected MRI lesion had seizure–free operative outcomes (21 and 22%, respectively). Multifocal independent initiation of the initial ictal discharge was associated with a poor surgical outcome. In contrast, the pattern and local spatial extent of the initial ictal discharge observed with CIEM failed to predict the surgical outcome.
Conclusions: The main predictor of the surgical outcome in patients that underwent CIEM was the MRI findings, whereas CIEM had only limited use in localizing the epileptogenic zone in the absence of an MRI lesion. The reported findings indicate a low specificity of CIEM in defining the site of seizure onset, which in turn significantly impairs the reliability of CIEM in delineating the epileptogenic zone for epilepsy surgery. Further studies are required to define the indications and patient sub–populations who can benefit from CIEM before epilepsy surgery.     

额叶癫癎发作的癫癎灶定位

目的 通过分析40例额叶癫痫发作患者术前定位的临床资料，探讨额叶癫痫发作的癫痫灶综合定位方法。方法 应用临床发作症状评估、MRI／CT扫描、单光子发射计算机体层摄影术(SPECT)检查、长程视频脑电图监测以及颅内电极记录等方法综合定位额叶癫痫患者的癫痫灶。结果 应用非侵袭性检查可以为45．0％的患者进行额叶癫痫灶定位；结合颅内脑电图长程记录，癫痫灶定位率可达90．0％；当影像学检查阴性时，78．9％的患者可以定位癫痫灶。结论 应用临床发作症状学评估、影像学检查、长程视频脑电图监测以及颅内脑电图长程记录相结合的综合定位方法，可以显著提高额叶癫痫发作的癫痫灶定位效果。     

Pre-surgical evaluation and surgical treatment in children with extratemporal epilepsy

Introduction This review summarizes some patterns of pre-surgical evaluation and surgical treatment of extratemporal epilepsy in pediatric patients with medically refractory seizures, whose ictal behavior is variable. The most effective treatment for intractable partial epilepsy is a focal cortical resection with excision of the epileptogenic zone (the area of ictal onset and initial seizure propagation). This might be risky, though, in the case of a widespread lesion, sometimes encroaching one or more lobes, given the risk to the functional cerebral cortex. An anterior temporal lobectomy might prove more effective then in preventing seizures with fewer potential complications. If partial extratemporal epilepsy is associated with pharmaco-resistant seizures, the preoperative evaluation and operative strategy are determined according to the epileptogenic zone and to the relationship between a substrate-directed disorder and eloquent areas. The pediatric treatment of extratemporal epilepsy is aimed at controlling the seizures, avoiding morbidity, and improving the patient’s quality of life through psychosocial integration. Since the immature brain is more plastic than when mature, the recovery of functions after surgery is greater in children than in adults.Recommendation Early surgery is recommended for children with intractable epilepsy, and is now accepted as an important therapeutic modality also for children with chronic epilepsy.Conclusion Technological advances in the last two decades, mainly in neuroimaging, have led many medical centers to consider surgical treatment of epilepsy, accuracy being granted by MRI-based neuronavigation systems—an interface between the lesion seen in the preoperative magnetic resonance imaging (MRI) and the operative field, often invisible to the surgeon.     

Neuroimaging in identifying focal cortical dysplasia and prognostic factors in pediatric and adolescent epilepsy surgery

Purpose: The purpose of this study is to determine the sensibility of each imaging tool in identifying focal cortical dysplasia (FCD) in children and adolescents with epilepsy and to define the prognostic factors of pediatric and adolescent epilepsy surgery. Methods: We identified 48 children with FCD who underwent resective surgery and analyzed their preoperative data. The results of various anatomic and functional neuroimaging studies were compared for accuracy in locating the lesion. We also investigated clinical factors that affected the outcome of surgical treatment. Key Findings: Brain magnetic resonance imaging (MRI) was able to localize FCD in 30 patients and fluorodeoxyglucose positron emission tomography (FDG‐PET) and/or subtraction ictal single photon emission computed tomography (SPECT) coregistered with MRI provided additional information that helped to define the lesion in 13 patients. When comparing the pathologic results between a mild malformation of cortical development (MCD) and FCD type I and II, we noted a strong tendency for patients with FCD to have MRI abnormalities (p = 0.005). In addition, severe pathologic features (Palmini’s classification, FCD type II) (p = 0.025) showed significant correlation with a better surgical outcome. To define the primary epileptogenic area, various interictal epileptiform discharges and the results of multimodal neuroimaging studies were helpful, and younger age at the time of operation could aid in more favorable surgical outcomes (p = 0.048). Significance: Our study showed a significant relationship between pathologic grade and the detectability of FCD by brain MRI. In addition, early surgery can be justified by showing that advanced neuroimaging studies in children with FCD and even with extensive epileptiform discharges have a higher rate of success.