Voxel-based morphometric comparison of hippocampal and extrahippocampal abnormalities in patients with left and right hippocampal atrophy

We used voxel-based morphometry (VBM), an automatic whole-brain MR image analysis technique, to investigate gray matter abnormalities in patients with temporal lobe epilepsy (TLE), in whom hippocampal atrophy (HA) was demonstrated by application of the Cavalieri method of modern design stereology. VBM results (P < 0.05, corrected) indicated preferential gray matter concentration (GMC) reduction in anterior hippocampus in patients with left HA and posterior hippocampus in patients with right HA. GMC reduction was also found in right dorsal prefrontal cortex in left and right HA patients. Prefrontal atrophy may be due to epileptiform excitotoxic discharges from the reciprocally connected pathological hippocampus, and may be the underlying biological cause for executive dysfunction in patients with TLE. GMC excess in ipsilateral parahippocampal, cerebellar, and pericallosal regions was common to both left and right HA groups relative to controls, and is hypothesized to reflect diminished gray-white matter demarcation, underlying white matter atrophy, or structural displacement due to cerebrospinal fluid expansion. However, bilateral temporal lobe GMC excess was observed in left HA patients, while ipsilateral temporal lobe GMC excess was observed in right HA patients. This work demonstrates methodological consistency between automated VBM and manual stereological analysis of the hippocampus in group comparisons, indicates widespread extrahippocampal gray matter abnormalities in unilateral HA, and suggests that there may be inherent differences in the effect of TLE on temporal lobe structures depending on the side of HA.     

Whole-brain voxel-based statistical analysis of gray matter and white matter in temporal lobe epilepsy

Volumetric MRI studies based on manual labeling of selected anatomical structures have provided in vivo evidence that brain abnormalities associated with temporal lobe epilepsy (TLE) extend beyond the hippocampus. Voxel-based morphometry (VBM) is a fully automated image analysis technique allowing identification of regional differences in gray matter (GM) and white matter (WM) between groups of subjects without a prior region of interest. The purpose of this study was to determine whole-brain GM and WM changes in TLE and to investigate the relationship between these abnormalities and clinical parameters. We studied 85 patients with pharmacologically intractable TLE and unilateral hippocampal atrophy and 47 age- and sex-matched healthy control subjects. The seizure focus was right sided in 40 patients and left sided in 45. Student's t test statistical maps of differences between patients' and controls' GM and WM concentrations were obtained using a general linear model. A further regression against duration of epilepsy, age of onset, presence of febrile convulsions, and secondary generalized seizures was performed with the TLE population. Voxel-based morphometry revealed that GM pathology in TLE extends beyond the hippocampus involving other limbic areas such as the cingulum and the thalamus, as well as extralimbic areas, particularly the frontal lobe. White matter reduction was found only ipsilateral to the seizure focus, including the temporopolar, entorhinal, and perirhinal areas. This pattern of structural changes is suggestive of disconnection involving preferentially frontolimbic pathways in patients with pharmacologically intractable TLE.     

Imaging the neocortex in epilepsy with double inversion recovery imaging

The neocortices of 10 patients with partial seizures and acquired lesions, 14 patients with malformations of cortical development (MCD) and 33 patients with partial seizures and normal conventional MRI were quantitatively evaluated using whole brain double inversion recovery imaging (DIR) and Statistical Parametric Mapping (SPM). Compared to a group of 30 control subjects, DIR and objective voxel-by-voxel statistical comparison identified regions of significantly abnormal DIR signal intensity (DSI) in 9 out of 10 patients with acquired nonprogressive cerebral lesions and partial seizures. In all 9 patients, the areas of abnormal DSI concurred with abnormalities identified on visual inspection of conventional MRI. In all 14 patients with MCD, SPM detected regions of significantly abnormal DSI; all of which corresponded to abnormalities identified on visual inspection of conventional MRI. In addition, in both groups, there were areas that were normal on conventional imaging, which demonstrated abnormal DSI. Voxel-by-voxel statistical analysis identified significantly abnormal DSI in 15 of the 33 patients with cryptogenic focal epilepsy. In 10 of these, the areas of abnormal DSI concurred with epileptic EEG abnormality and clinical seizure semiology. Group analysis of MRI-negative patients with electroclinical seizure onset localising to the left temporal and left and right frontal regions revealed significantly abnormal DSI within the white matter of each respective lobe. DIR analysed using SPM was sensitive in patients with MCDs and acquired cerebral damage. Significant abnormalities in DSI in individual and grouped MRI-negative patients suggest that occult epileptogenic cerebral lesions are associated with subtle structural abnormalities. DIR is, therefore, a useful quantitative MRI technique for characterising epileptic foci and may contribute to presurgical evaluation.     

MRI脑灰质形态学分析在双重病理所致颞叶癫痫的应用

目的应用基于体素形态学(VBM)及基于表面形态学(SBM)分析,探讨双重病理所致颞叶癫痫磁共振成像(MRI)脑灰质结构变化。方法收集病理确诊为海马硬化(HS)合并局灶性皮质发育不良(FCD)的双重病理颞叶癫痫患者36例(左侧癫痫组20例、右侧癫痫组16例)及健康对照组30例行MRI T_1WI 3D BRAVO序列扫描,使用SPM及Freesurfer软件分别进行灰质体积及皮层厚度、皮层表面积分析,并采用独立样本t检验获得有统计学差异脑区。结果左、右侧癫痫组与对照组比较,病侧大部分颞叶(含海马)灰质体积减小,左侧癫痫组同侧丘脑及杏仁核灰质体积减小,其差异均有显著统计学意义(FDR校正,P0.001,K≥20体素)。癫痫组均出现部分颞叶及颞叶以外脑区皮层增厚,但左、右侧癫痫组异常脑区存在不同;同时癫痫组病变侧颞叶脑区皮层表面积减小,上述差异均具有统计学意义(未校正,P0.01,顶点数≥100)。结论HS合并FCD致颞叶癫痫病变侧颞叶(含海马)灰质体积广泛缩小为主要形态学特征,皮层表面积减小对病变定侧也有一定作用,单纯通过皮层增厚观察双重病理中FCD存在一定局限性。     

颞叶癫痫儿童灰质异常脑区与神经心理学测验的关系及意义

[目的]评估儿童颞叶癫痫（ TLE）临床表现和神经心理学测验成绩与局部脑萎缩的相关性.[方法]症状性TLE患儿14例（海马萎缩所致中颞叶癫痫 9例,颞叶新皮质损伤所致TLE 5例）,健康对照儿童14名;中颞叶癫痫（ MTLE）成人及其对照各9例.所有入组对象进行脑MRI获取T1结构像,用像素为基础的形态测定法分析图像.所有儿童进行综合神经心理学测验.[结果]TLE患儿同侧海马和海马外周区灰质体积显著减小,灰质体积减小与神经心理学测验成绩显著相关（P〈0.05）.单侧海马萎缩的MTLE患儿中,癫痫发作区域同侧的海马灰质体积显著减小,同侧扣带和对侧额中回皮质萎缩,皮质萎缩程度及范围较同类成人患者小.[结论]与成人MTLE患者相似,儿童MTLE与海马和海马外周的细胞减少有关;儿童TLE灰质萎缩的程度和范围较成人患者小,仅限于额叶区;中颞叶和额叶区灰质体积的减小与神经心理学测验成绩显著相关;TLE患儿的认知或行为障碍是神经网络损伤的结果.     

Regional grey matter abnormalities in juvenile myoclonic epilepsy: a voxel-based morphometry study

Visual assessment of structural MRI is, by definition, normal in patients with juvenile myoclonic epilepsy (JME), a major subsyndrome of idiopathic generalized epilepsy (IGE). However, recent quantitative MRI studies have shown structural abnormalities in cortical and thalamic grey matter (GM) in JME. Voxel-based morphometry (VBM) is a fully automated, unbiased, operator-independent MRI analysis technique that detects regionally specific differences in brain tissue composition on a voxel-wise comparison between groups of subjects. Using VBM, we examined structural differences in cortical and subcortical GM volume (GMV) between 25 JME patients (15 women, mean age=22.7+/-5.1 years) and age- and sex-matched 44 control subjects (27 women, mean age=23.1+/-4.3 years). We also performed a correlation analysis to delineate a possible relationship between the GMV increases or reductions and the increasing duration of epilepsy. Group comparison showed GMV increases in the superior mesiofrontal region bilaterally and GMV reductions in the thalamus bilaterally in JME patients (P<0.05, corrected for multiple comparisons using false discovery rate). Correlation analysis revealed that bilateral thalamic GMV had negative correlations with the duration of epilepsy (P<0.05, corrected for multiple comparisons after small volume corrections; P<0.05, Pearson correlation test). Our findings of GMV increases in the superior mesiofrontal regions and progressive thalamic atrophy could further support the pathophysiological concept of the functional abnormalities in thalamocortical circuit in JME.     

儿童颞叶中内侧硬化所致颞叶癫痫的MRI研究

目的 对儿童颢叶癫痫进行前瞻性MRI研究分析。探讨儿童颢叶癫痫的MRI表现特征。方法 对127例临床和脑电图检查诊断为颢叶癫痫的儿童进行MRI多序列成像．分析研究颞叶的形态结构、信号并判断海马有无萎缩性改变。结果 127例颢叶癫痫患儿中，9例(7．1％)海马有萎缩性改变，且在T2加权成像和液体率减恢复(F1AIR)成像上呈高信号。9例中，6例伴有海马受累同侧颞叶信号异常；3例伴有同侧颞叶皮层结构不良；1例伴有同侧颞叶萎缩。结论 颞叶中内侧硬化是儿童颢叶癫痫的一个相对少见原因，受累侧海马MRI表现为萎缩和信号异常，同时常伴海马外颞叶结构受累。     

“Magnetic Resonance Imaging Negative Positron Emission Tomography Positive” Temporal Lobe Epilepsy: FDG-PET Pattern Differs from Mesial Temporal Lobe Epilepsy

Purpose Some patients with temporal lobe epilepsy (TLE) lack evidence of hippocampal sclerosis (HS) on MRI (HS-ve). We hypothesized that this group would have a different pattern of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET) hypometabolism than typical mesial TLE/HS patients with evidence of hippocampal atrophy on magnetic resonance imaging (MRI) (HS+ve), with a lateral temporal neocortical rather than mesial focus. Procedures Thirty consecutive HS-ve patients and 30 age- and sex-matched HS+ve patients with well-lateralized EEG were identified. FDG-PET was performed on 28 HS-ve patients and 24 HS+ve patients. Both groups were compared using statistical parametric mapping (SPM), directly and with FDG-PET from 20 healthy controls. Results Both groups showed lateralized temporal hypometabolism compared to controls. In HS+ve, this was antero–infero–mesial (T = 17.13); in HS-ve the main clustering was inferolateral (T = 17.63). When directly compared, HS+ve had greater hypometabolism inmesial temporal/hippocampal regions (T = 4.86); HS-ve had greater inferolateral temporal hypometabolism (T = 4.18). Conclusions These data support the hypothesis that focal hypometabolism involves primarily lateal neocortical rather than mesial temporal structures in ‘MRI-negative PET-positive TLE.’     

Voxel-based morphometry of unilateral temporal lobe epilepsy reveals abnormalities in cerebral white matter

Voxel-based morphometric (VBM) investigations of temporal lobe epilepsy have focused on the presence and distribution of gray matter abnormalities. VBM studies to date have identified the expected abnormalities in hippocampus and extrahippocampal temporal lobe, as well as more diffuse abnormalities in the thalamus, cerebellum, and extratemporal neocortical areas. To date, there has not been a comprehensive VBM investigation of cerebral white matter in nonlesional temporal lobe epilepsy. This study examined 25 lateralized temporal lobe epilepsy patients (13 left, 12 right) and 62 healthy controls in regard to both temporal and extratemporal lobe gray and white matter. Consistent with prior reports, gray matter abnormalities were evident in ipsilateral hippocampus and ipsilateral thalamus. Temporal and extratemporal white matter was affected ipsilateral to the side of seizure onset, in both left and right temporal lobe epilepsy groups. These findings indicate that chronic temporal lobe epilepsy is associated not only with abnormalities in gray matter, but also with concomitant abnormalities in cerebral white matter regions that may affect connectivity both within and between the cerebral hemispheres.     

Composite voxel-based analysis of volume and T2 relaxometry in temporal lobe epilepsy

Voxel-based analyses of tissue characteristics such as volume and T2 are usually carried out in isolation. However, as the images are analysed in a common voxel-based framework, it is possible to directly assess the spatial relationships of abnormalities detected by each technique. We utilize this approach in well-characterized patients with unilateral temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). TLE is associated with potentially widespread volume and T2 signal abnormalities in MRI images but the relationship between these two aspects of tissue abnormality is not well understood. Here we use a novel approach of combined univariate and multivariate voxel-wise analysis to investigate the spatial relationship of these abnormalities. We studied 19 TLE patients and compared them to 115 control subjects. Grey matter (GM) and white matter (WM) volume changes were assessed with voxel-based morphometry (VBM), and changes in T2 relaxation times were evaluated with voxel-based relaxometry (VBR). The volume and T2 changes obtained using the combined univariate approach were found in an extensive area, prominently in the ipsilateral hippocampus and amygdala (overlap of GM-VBM and VBR), and in the remaining temporal lobe (overlap of WM-VBR and VBR). Other cortical and subcortical areas showed isolated volume or T2 changes. The multivariate analysis based on the Hotelling T(2) statistic, indicated a similar pattern of distributed changes across the brain but with a greater degree of statistical significance in certain areas. The composite analyses appear to identify a network of affected areas not as easily appreciated by the individual analysis of volume or T2 changes.     

Voxel-based morphometry in patients with idiopathic generalized epilepsies

Idiopathic generalized epilepsies (IGE) are a group of frequent age-related epilepsy syndromes. IGE are clinically characterized by generalized tonic-clonic, myoclonic and absence seizures. According to predominant seizure type and age of onset, IGE are divided in subsyndromes: childhood absence and juvenile absence epilepsy (AE), juvenile myoclonic epilepsy (JME) and generalized tonic-clonic seizures on awakening (GTCS). The limits between these subsyndromes are not well defined, supporting the existence of only one major syndrome. Visual assessment of routine magnetic resonance imaging (MRI) in patients with IGE is normal. MRI voxel-based morphometry (VBM) uses automatically segmented gray and white matter for comparisons, eliminating the investigator bias. We used VBM to study 120 individuals (47 controls, 44 with JME, 24 with AE and 15 with GTCS) to investigate the presence of subtle structural abnormalities in IGE subsyndromes. VBM was performed searching for abnormalities on gray matter concentration (GMC) between patients groups and controls. Compared to controls, JME presented increased GMC in frontobasal region and AE showed increased GMC in the superior mesiofrontal region. The GTCS group did not differ from controls. There were no areas of reduced GMC with the statistical level selected. Region of interest analysis showed increased GMC in the anterior portion of the thalamus in patients with absence seizures. Our results support subtle GMC abnormalities in patients with JME and AE when compared to controls. These findings suggest the existence of different patterns of cortical abnormalities in IGE subsyndromes.     

Correlation of quantitative MRI and neuropathology in epilepsy surgical resection specimens--T2 correlates with neuronal tissue in gray matter

Newer MRI methods can detect cerebral abnormalities not identified on routine imaging in patients with focal epilepsy. Correlation of MRI with histopathology is necessary to understand the basis of MRI abnormalities and subsequently predict histopathology from in vivo MRI. The aim of this study was to determine if particular quantitative MR parameters were associated with particular histological features. Nine patients with temporal lobe epilepsy were imaged at 1.5 T using standard presurgical volumetric and quantifiable sequences: magnetization transfer and FFT2. The resected temporal lobe was registered with the volumetric MRI data according to our previously described method to permit correlation of the modalities. Stereologically measured neuronal densities and field fraction of GFAP, MAP2, synaptophysin and NeuN immunohistochemistry were obtained. Analyses were performed in the middle temporal gyrus and compared with quantitative MRI data from the equivalent regions. There was a significant Spearman Rho negative correlation between NeuN field fraction and the T2 value in gray matter (correlation coefficient -0.72, p=0.028). There were no significant correlations between any neuropathological and MR measures in white matter. These preliminary findings suggest that T2 in gray matter is sensitive to the proportion of neuronal tissue. Novel quantitative MRI measures acquired with higher field strength magnets, and so with superior signal to noise ratios, may generate data that correlate with histopathological measures. This will enable better identification and delineation of the structural causes of refractory focal epilepsy, and will be of particular benefit in patients in whom current optimal MRI does not identify a relevant abnormality.     

Quantitative MRI detects abnormalities in relatives of patients with epilepsy and malformations of cortical development

Malformations of cortical development (MCD) are a common etiology for epilepsy. Laminar heterotopia, bilateral subependymal heterotopia, and lissencephaly have a genetic basis. No gene mutations have yet been identified in patients with focal cortical dysplasias. The aim of this study was to use quantitative morphometric tools to determine if there were gray matter abnormalities in relatives of patients with MCD. We studied 19 relatives of 13 probands with MCD and 58 healthy controls with high-resolution MRI. The relatives and controls had no neocortical abnormalities on visual inspection. MRI data were analyzed with voxel-based morphometry and autoblock analysis. Voxel-based morphometry showed significant increases of gray matter in 9 of 10 probands, 5 of 19 relatives, and 5 of 58 controls. The autoblock analysis showed significant abnormalities in 7 of 8 probands, 8 of 19 relatives, and 2 of 57 controls. This finding suggests structural abnormality in the brains of a greater number of relatives of MCD patients than would be expected, and in the context, a reasonable inference is that this reflects subtle genetically determined cerebral abnormalities, although acquired pathologies are possible and are not excluded.     

Quality of life and burden in caregivers of patients with epilepsy.

The purpose of this study was to compare quality of life and burden in 100 caregivers of adolescent and adult patients with epilepsy that started in adolescence. We invited caregivers of 50 patients with temporal lobe epilepsy (TLE) related to mesial temporal sclerosis and caregivers of 50 patients with juvenile myoclonic epilepsy (JME) to participate. After the caregivers answered a sociodemographic questionnaire, they answered the Brazilian version of the Burden Interview (BI) Scale and we assessed their quality of life using the 36-Item Short-Form Health Survey (SF-36). The mean ages of patients were 25.4 and 36.4 years and epilepsy duration was 14 and 25.6 years in the JME and TLE groups, respectively. We found a mild to moderate burden on caregivers in both groups, with a BI average score of 25.5 for JME and 30.7 for TLE. Caregivers in the JME group had lower scores in all domains of the SF-36 and reported higher burden. Low scores were also seen in three domains for the TLE group. These results suggest that caregivers of patients with both epileptic syndromes experience interference in their lives. When we compared the two groups, we found no difference between caregiver data on SF-36 and BI. Quality of life was significantly compromised in caregivers of patients with JME and TLE, and the two groups were burdened to a similar degree (mild to moderate). Nurses can carry out psychoeducative programs with the objective of diagnosing the impact of epilepsy in the family, decreasing burden, and improving quality of life for caregivers.     

Tractography of the parahippocampal gyrus and material specific memory impairment in unilateral temporal lobe epilepsy

INTRODUCTION: Temporal lobe epilepsy (TLE) is associated with disrupted memory function. The structural changes underlying this memory impairment have not been demonstrated previously with tractography. METHODS: We performed a tractography analysis of diffusion magnetic resonance imaging scans in 18 patients with unilateral TLE undergoing presurgical evaluation, and in 10 healthy controls. A seed region in the anterior parahippocampal gyrus was selected from which to trace the white matter connections of the medial temporal lobe. A correlation analysis was carried out between volume and mean fractional anisotropy (FA) of the connections, and pre-operative material specific memory performance. RESULTS: There was no significant difference between the left and right sided connections in controls. In the left TLE patients, the connected regions ipsilateral to the epileptogenic region were found to be significantly reduced in volume and mean FA compared with the contralateral region, and left-sided connections in control subjects. Significant correlations were found in left TLE patients between left and right FA, and verbal and non-verbal memory respectively. CONCLUSION: Tractography demonstrated the alteration of white matter pathways that may underlie impaired memory function in TLE. A detailed knowledge of the integrity of these connections may be useful in predicting memory decline in chronic temporal lobe epilepsy.     

Quantitative analysis of temporal lobe white matter T2 relaxation time in temporal lobe epilepsy

The objective of this study was to assess temporal lobe white matter (WM) quantitatively using T2 relaxometry in patients with pharmacologically intractable temporal lobe epilepsy (TLE). T2 relaxometry was performed using a dual-echo sequence with 23 contiguous oblique coronal slices in 56 consecutive TLE patients and in 30 healthy subjects. Averages of six slices were chosen to calculate T2 relaxation time in the temporal lobe WM (WM-T2) and the hippocampus (Hippo-T2). Twenty-seven patients had unilateral hippocampal atrophy (HA), and twenty-nine patients had normal hippocampal volumes (NV) on volumetric MRI. Mean WM-T2 was increased ipsilateral to the seizure focus in TLE patients with HA and those with NV (P < 0.001). Contralateral mean WM-T2 was increased in left and right TLE with HA (P < 0.001) and in right TLE with NV (P = 0.001). There was a positive correlation between WM-T2 and Hippo-T2. Individual analysis showed a prolongation of WM-T2 in about 70% of TLE patients with HA and NV. In half of the patients, WM-T2 increase was bilateral and symmetric. However, in 33% of patients with NV and bilateral symmetric increase in Hippo-T2, WM-T2 provided a correct lateralization of the seizure focus. Regardless of the pattern of T2 abnormalities, that is, bilateral symmetric or ipsilateral, the majority of patients with HA became seizure-free after surgery, while those with NV did not have a favorable outcome. In patients with NV, WM-T2 measurement may provide additional lateralizing information compared to Hippo-T2.     

Abnormalities of language networks in temporal lobe epilepsy

Functional magnetic resonance imaging (fMRI) in patients with temporal lobe epilepsy (TLE) has demonstrated reorganisation of language functions with greater involvement of the non-dominant hemisphere. The structural brain connections supporting this atypical language dominance have not previously been identified. We performed fMRI of language functions and imaging of white matter connections using MR tractography in 14 patients with unilateral TLE and hippocampal sclerosis and 10 controls. Verb generation and reading comprehension paradigms were used to define functional regions which were used to generate starting regions for tractography. Controls and right TLE patients had a left-lateralised pattern of both language-related activations and the associated structural connections. Left TLE patients showed more symmetrical language activations, along with reduced left hemisphere and increased right hemisphere structural connections. Subjects with more lateralised functional activation had also more highly lateralised connecting pathways. We provide evidence for structural reorganisation of white matter tracts that reflects the altered functional language lateralisation in left TLE patients. The combination of fMRI and tractography offers a promising tool for studying the reorganisation of language functions in many neurological conditions and may prove useful in predicting language deficits following temporal lobe surgery.     

Automated MR image classification in temporal lobe epilepsy

In those with drug refractory focal epilepsy, MR imaging is important for identifying structural causes of seizures that may be amenable to surgical treatment. In up to 25% of potential surgical candidates, however, MRI is reported as unremarkable even when employing epilepsy specific sequences. Automated MRI classification is a desirable tool to augment the interpretation of images, especially when changes are subtle or distributed and may be missed on visual inspection. Support vector machines (SVM) have recently been described to be useful for voxel-based MR image classification. In the present study we sought to evaluate whether this method is feasible in temporal lobe epilepsy, with adequate accuracy.We studied 38 patients with hippocampal sclerosis and unilateral (mesial) temporal lobe epilepsy (mTLE) (20 left) undergoing presurgical evaluation and 22 neurologically normal control subjects. 3D T1-weighted images were acquired at 3T (GE Excite), segmented into tissue classes, normalized and smoothed with SPM8. Diffusion tensor imaging (DTI) and double echo images for T2 relaxometry were also acquired and processed. The SVM analysis was done with the libsvm software package in a leave-one-out cross-validation design and predictive accuracy was measured. Local weighting was applied by SPM F-contrast maps.Best accuracies were achieved using the gray matter based segmentation (90-100%) and mean diffusivity (95-97%). For the three-way classification, accuracies were 88 and 93% respectively. Local weighting generally improved the accuracies except in the FA-based processing for which no effect was noted. Removing the hippocampus from the analysis, on the other hand, reduced the obtainable diagnostic indices but these were still > 90% for DTI-based methods and lateralization based on gray matter maps. These findings show that automated SVM image classification can achieve high diagnostic accuracy in mTLE and that voxel-based MRI can be used at the individual subject level. This could be helpful for screening assessments of MRI scans in patients with epilepsy and when no lesion is detected on visual evaluation.     

Evidence that juvenile myoclonic epilepsy is a disorder of frontotemporal corticothalamic networks

The purpose of this study is to determine regions of cerebral cortex activated during the onset and propagation of dense array electroencephalographic (dEEG) epileptiform discharges in patients with juvenile myoclonic epilepsy (JME), through the use of 256 channel, dense array scalp EEG recordings. Ten patients (16–58 years old) with the clinical diagnosis of JME comprised the study group. In all cases the MRI and neurological exams were normal, while standard EEG recordings documented typical “generalized” 4–6 Hz epileptiform patterns. Outpatient dEEG recordings captured epileptiform discharges in each patient. Localization of onset and spread of discharges in relation to a standard MRI model was accomplished by applying dipole fits and a distributed linear inverse method of cortically constrained source analysis. All patients showed epileptiform discharges that localized to sources that included orbitofrontal/medial frontopolar cortex, while basal–medial temporal lobe sources were observed in 5/10 subjects. In many ways similar to discharges of typical absence, epileptiform patterns in JME are usually irregular and frequently include temporal lobe structures as the dominant contributors to the discharges. We find that epileptiform discharges in patients with JME are not “generalized” in the sense of bilaterally synchronous diffuse onset. Rather, discharges have both localized onsets and a restricted cortical network during propagation that includes regions of frontal and temporal cortex.