Frontal lobe connectivity and cognitive impairment in pediatric frontal lobe epilepsy

Purpose: Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its etiology is unknown. With functional magnetic resonance imaging (fMRI), we have explored the relationship between brain activation, functional connectivity, and cognitive functioning in a cohort of pediatric patients with FLE and healthy controls. Methods: Thirty‐two children aged 8–13 years with FLE of unknown cause and 41 healthy age‐matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls, and patients were grouped as cognitively impaired or unimpaired. Key Findings: Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, whereas brain activation patterns in children with FLE remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia. Significance: Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of impairment of functional integrity within the frontal lobe network, as well as its connections to distant areas, provides new insights in the etiology of the broad‐range cognitive impairments in children with FLE.     

MR spectroscopy, functional MRI, and diffusion-tensor imaging in the aging brain: a conceptual review

In vivo magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), and diffusion-tensor imaging (DTI) have recently opened new possibilities for noninvasively assessing the metabolic, functional, and connectivity correlates of aging in research and clinical settings. The purpose of this article is to provide a conceptual review intended for a multidisciplinary audience, covering physical principles and main findings related to normal aging and senile cognitive impairment. This article is divided into 3 sections, dedicated to MRS, to fMRI, and to DTI. The spectroscopy section surveys physiological function of the observable metabolites, concentration changes in normal aging and their interpretation, and correlation with cognitive performance. The functional MRI section surveys the hemispheric asymmetry reduction model from compensation and de-differentiation viewpoints, memory encoding, retrieval and consolidation, inhibitory control, perception and action, resting-state networks, and functional deactivations. The DTI section surveys age-related changes, correlation with behavioral scores, and transition to cognitive impairment.     

Hippocampal and thalamic diffusion abnormalities in children with temporal lobe epilepsy

PURPOSE: Previous studies using diffusion MRI in patients with temporal lobe epilepsy have shown abnormal water diffusion in the hippocampus. Because thalamus and lentiform nuclei are considered important for the regulation of cortical excitability and seizure propagation, we analyzed diffusion tensor imaging (DTI) abnormalities in these subcortical structures and in hippocampus of children with partial epilepsy with and without secondary generalization. METHODS: Fourteen children with partial epilepsy involving the temporal lobe underwent MRI including a DTI sequence. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained in the hippocampus, thalamus, and lentiform nucleus, and compared with DTI data of 14 control children with no epilepsy, as well as glucose positron emission tomography (PET) findings. RESULTS: Decreased FA (p < 0.001) and increased ADC (p = 0.003) values were found in the hippocampi ipsilateral to the seizure focus. Significant FA decreases (p = 0.002) also were seen in the contralateral hippocampi, despite unilateral seizure onset and excellent surgical outcome in patients who underwent surgery. ADC values showed a trend for increase in the thalami ipsilateral to the epileptic focus in the seven children with secondarily generalized seizures (p = 0.09). No group differences of ADC or FA were found in the lentiform nuclei. The DTI variables did not correlate with regional glucose metabolism in any of the structures analyzed. CONCLUSIONS: Increased ADC values in hippocampus can assist in lateralizing the seizure focus, but decreased FA in the contralateral hippocampus suggests that it too may be dysfunctional despite unilateral seizure onset. Less-robust thalamic abnormalities of water diffusion in patients with secondarily generalized seizures suggest secondary involvement of the thalamus, perhaps due to recruitment of this structure into the epileptic network; however, this must be confirmed in a larger population. DTI appears to be a sensitive method for detection abnormalities in children with partial epilepsy, even in structures without apparent changes on conventional MRI.     

Multimodal MR Imaging: Functional, Diffusion Tensor, and Chemical Shift Imaging in a Patient with Localization-Related Epilepsy

PURPOSE: To demonstrate the integration of complementary functional and structural data acquired with magnetic resonance imaging (MRI) in a patient with localization-related epilepsy. METHODS: We studied a patient with partial and secondarily generalized seizures and a hemiparesis due to a malformation of cortical development (MCD) in the right hemisphere by using EEG-triggered functional MRI (fMRI), diffusion tensor imaging (DTI), and chemical shift imaging (CSI). RESULTS: fMRI revealed significant changes in regional blood oxygenation associated with interictal epileptiform discharges within the MCD. DTI showed a heterogeneous microstructure of the MCD with reduced fractional anisotropy, a high mean diffusivity, and displacement of myelinated tracts. CSI demonstrated low N-acetyl aspartate (NAA) concentrations in parts of the MCD. CONCLUSIONS: The applied MR methods described functional, microstructural, and biochemical characteristics of the epileptogenic tissue that cannot be obtained with other noninvasive means and thus improve the understanding of the pathophysiology of epilepsy.     

Neuroimaging of Focal Cortical Dysplasia

Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy that is amenable to surgical resective treatment. The identification of structural FCD by magnetic resonance imaging (MRI) can contribute to the detection of the epileptogenic zone and improve the outcome of epilepsy surgery. MR epilepsy protocols that include specific T1 and T2 weighted, and fluid-attenuated inversion recovery (FLAIR) sequences give complementary information about the characteristic imaging features of FCD; focal cortical thickening, blurring of the gray-white junction, high FLAIR signal, and gyral anatomical abnormalities. Novel imaging techniques such as magnetic resonance spectroscopy (MRS), magnetization transfer imaging (MTI), and diffusion tensor imaging (DTI) can improve the sensitivity of MR to localize the anatomical lesion. Functional/metabolic techniques such as positron emission tomography (PET), ictal subtraction single photon emission computed tomography (SPECT), functional MRI (fMRI), and magnetic source imaging (MSI) have the potential to visualize the metabolic, vascular, and epileptogenic properties of the FCD lesion, respectively. Identification of eloquent areas of cortex, to assist in the surgical resection plan, can be obtained non-invasively through the use of fMRI and MSI. Although a significant number of FCD lesions remain unidentified using current neuroimaging techniques, future advances should result in the identification of an increasing number of these cortical malformations.     

New Techniques in Magnetic Resonance and Epilepsy

Summary: Developments in magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT) have opened new opportunities for noninvasive brain investigation. Functional imaging methods involving noninvasive MRI and minimally invasive PET and SPECT are available that allow investigation of brain abnormality in intractable epilepsy patients. Noninvasive techniques enable the investigation of many aspects of the underlying neuropathologic basis of intractable seizures and of the relationship of functional abnormalities both to structural abnormalities and to the seizure focus. New MRI techniques demonstrate the structure of the brain in fine detail (especially the hippocampus), provide information about the underlying metabolism of brain regions, and demonstrate functional activity of the brain with high spatial and temporal resolution. The clinical impact of this noninvasive information cannot be overstated and these techniques provide indispensable information to neurologists specializing in epi-leptology. The proper use and interpretation of the findings provided by these new technologies will be a major challenge to epilepsy programs in the next few years.     

功能性磁共振导航结合皮质电极描记切除功能区及其附近的癫痫灶

目的探讨利用fMRI导航结合皮质电极描记切除功能区及其附近癫痫灶的临床疗效。方法回顾性分析11例癫痫灶起源于功能区及其附近的癫痫病人的手术经验。病人术前发作频率（2．63±1．68）次／月。术前利用fMRI检查确定功能区位置并与导航图像进行融合,术中使用皮质电极描记标记出癫痫波的位置,通过导航系统了解功能区与癫痫波起源的关系。在保留功能区皮质的基础上,将病灶和癫痫波起源处皮质切除,而位于功能区皮质上的癫痫波起源处则给予小功率皮质热灼。结果皮质发育不全8例,灰质异位症2例,脑外伤后局部皮质软化1例。术后随访6～12个月,癫痫发作完全消失9例,术后3-6d内发作1次2例,随后未再出现癫痫发作。术后未出现明显的神经功能损害加重的情况。术后3个月复查脑电图显示基本正常。结论fMRI导航结合皮质电极描记切除起源于功能区及其附近的癫痫灶是一种微侵袭的手术方法,在切除癫痫灶的同时能最大限度地保留功能区的神经功能。     

Clinical Applications of Magnetic Resonance Spectroscopy

Summary: Magnetic resonance spectroscopy (MRS) is a new tool for evaluation of patients with epilepsy, demonstrating abnormalities of energy and lipid metabolism ictally and, more recently, interictally. These metabolic abnormalities include increased inorganic phosphate, pH, and decreased phosphomono-esters as determined by ³¹P MRS, as well as decreased N- acetylaspartate determined by ¹H MRS. Furthermore, increased lactic acid has been detected postictally. These metabolic changes appear to be confined to the region of seizure origination and can be detected interictally. Therefore, they can be used for lateralization of the epileptogenic focus. Ongoing research suggests that these abnormalities may also be useful in localization of the focus, demonstrating metabolic alterations in temporal lobe epilepsy (TLE) similar to those in neocortical epilepsy. However, further technical development will be required before the goal of using these techniques for localization of the epileptogenic focus can be realized. For TLE lobe epilepsy at least, the clinical utility of 'H MRS to lateralize the seizure focus has clearly been demonstrated by several centers. The consistent findings in TLE suggest that 'H MRS is ready to become part of the evaluation process of patients with medically refractory epilepsy being evaluated for seizure surgery.     

AEEG、MRI与MRS对非惊厥发作癫((癎))的诊断价值

目的探讨动态脑电图(AEEG)和头颅MRI与磁共振波谱分析(MRS)检查对临床非惊厥发作癫癎的诊断和和鉴别诊断意义。方法对76例临床拟诊非惊厥发作癫癎患者行AEEG、MRI与MRS检查,并将检查结果进行分析。结果确诊癫癎56例,其中MRI异常57.1%、~1HMRS异常76.8%。结论AEEG、头颅MRI与MRS对非惊厥发作癫癎的诊断和鉴别诊断有重要意义。     

Noninvasive dynamic imaging of seizures in epileptic patients

Epileptic seizures are due to abnormal synchronized neuronal discharges. Techniques measuring electrical changes are commonly used to analyze seizures. Neuronal activity can be also defined by concomitant hemodynamic and metabolic changes. Simultaneous electroencephalogram (EEG)‐functional MRI (fMRI) measures noninvasively with a high‐spatial resolution BOLD changes during seizures in the whole brain. Until now, only a static image representing the whole seizure was provided. We report in 10 focal epilepsy patients a new approach to dynamic imaging of seizures including the BOLD time course of seizures and the identification of brain structures involved in seizure onset and discharge propagation. The first activation was observed in agreement with the expected location of the focus based on clinical and EEG data (three intracranial recordings), thus providing validity to this approach. The BOLD signal preceded ictal EEG changes in two cases. EEG‐fMRI may detect changes in smaller and deeper structures than scalp EEG, which can only record activity form superficial cortical areas. This method allowed us to demonstrate that seizure onset zone was limited to one structure, thus supporting the concept of epileptic focus, but that a complex neuronal network was involved during propagation. Deactivations were also found during seizures, usually appearing after the first activation in areas close or distant to the activated regions. Deactivations may correspond to actively inhibited regions or to functional disconnection from normally active regions. This new noninvasive approach should open the study of seizure generation and propagation mechanisms in the whole brain to groups of patients with focal epilepsies. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

MRI-negative refractory partial epilepsy: role for diffusion tensor imaging in high field MRI

OBJECTIVE: Our aim is to use the high field MR scanner (3T) to verify whether diffusion tensor imaging (DTI) could help in locating the epileptogenic zone in patients with MRI-negative refractory partial epilepsy. METHOD: Fifteen patients with refractory partial epilepsy who had normal conventional MRI, and 40 healthy volunteers were recruited for the study. DTI was performed on a 3T MR scanner, individual maps of mean diffusivity (MD) and fractional anisotropy (FA) were calculated, and Voxel-Based Analysis (VBA) was performed for individual comparison between patients and controls. RESULT: Voxel-based analysis revealed significant MD increase in variant regions in 13 patients. The electroclinical seizure localization was concurred to seven patients. No patient exhibited regions of significant decreased MD. Regions of significant reduced FA were observed in five patients, with two of these concurring with electroclinical seizure localization. Two patients had regions of significant increase in FA, which were distinct from electroclinical seizure localization. CONCLUSION: Our study's results revealed that DTI is a responsive neuroradiologic technique that provides information about the epileptogenic areas in patients with MRI-negative refractory partial epilepsy. This technique may also helpful in pre-surgical evaluation.     

CPD - education and self-assessment: functional imaging in epilepsy.

Functional imaging plays a growing role in the clinical assessment and research investigation of patients with epilepsy. This article reviews the literature on functional MRI (fMRI) investigation of EEG activity, fMRI evaluation of cognitive and motor functions, magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT) and positron emission tomography (PET) in epilepsy. The place of these techniques in clinical evaluation and their contribution to a better neurobiological understanding of epilepsy are discussed.     

Functional imaging in the work-up of childhood epilepsy

In children with medically intractable lesional epilepsy, surgery is deemed successful if the epileptogenic focus can be removed while major neurological functions are spared. Current techniques rely on invasive intracranial recordings. The new developments in functional imaging offer the possibility of localizing the epileptogenic focus noninvasively (PET/SPECT) and mapping cognitive functions (fMRI). Ictal SPECT shows hyperperfusion in the focus and has proved to have better localizing value than interictal PET or SPECT, which show focal hypometabolism or hypoperfusion. Ictal SPECT is useful for deciding on the placement of intracranial electrodes in extratemporal epilepsies, particularly in young children. Functional MRI has proved highly accurate for localizing motor and language networks, thus offering the possibilities of replacing the Wada test (language hemispheric lateralization) and studying postlesional brain plasticity. Despite the difficulties of functional imaging in children owing to the limited cooperation that can be expected, ethical constraints, and poor normative data, SPECT/PET and fMRI provide clinically useful information for presurgical work-up of childhood epilepsies. Received: 30 March 2000     

Cerebrovascular diseases

Conventional neuroradiological techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), make a fundamental contribution in both the acute and chronic phases of stroke. Recent years have witnessed the development of new imaging modalities, which include diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), CT-angiography (CTA), MR-angiography (MRA), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and functional MRI (fMRI). While CTA, MRA, DWI and PWI are commonly used for clinical purposes, DTI, MRS and fMRI are becoming increasingly important in the field of experimental research of cerebrovascular diseases, but are still far from becoming of primary usefulness in the everyday clinical setting.     

癫(癎)患者认知功能障碍及其影响因素的分析

目的 探讨癫(癎)患者认知功能障碍及其影响因素.方法 采用韦氏儿童智力量表及成人智力量表对125例癫(癎)患者的认知功能进行测定,并分析年龄、发作类型、癫(癎)综合征类型、病因、发作频率、严重程度、脑电图改变、服用药物及家族史等因素对其的影响.结果 癫(癎)患者认知功能障碍发生率为18.4%,儿童(27.8%)高于成人(14.6%).癫(癎)组儿童和成人患者总智商(F7Q)、操作智商(PIQ)和言语智商(VIQ)、言语理解因子(VCF)、知觉组织因子(POF)和记忆/注意不分心因子(MF)显著低于相应的正常对照组(均P<0.01).多因素回归分析显示,发作程度越严重、服用药物的数量越多,智商越低,全面发作对智商的影响最明显.结论 癫(癎)患者存在明显的认知功能障碍,发作严重程度、服药数量,发作形式是影响其认知功能的独立危险因素.     

Imaging seizure activity: a combined EEG/EMG-fMRI study in reading epilepsy

Purpose:   To characterize the spatial relationship between activations related to language-induced seizure activity, language processing, and motor control in patients with reading epilepsy.
Methods:   We recorded and simultaneously monitored several physiological parameters [voice-recording, electromyography (EMG), electrocardiography (ECG), electroencephalography (EEG)] during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in nine patients with reading epilepsy. Individually tailored language paradigms were used to induce and record habitual seizures inside the MRI scanner. Voxel-based morphometry (VBM) was used for structural brain analysis. Reading-induced seizures occurred in six out of nine patients.
Results:   One patient experienced abundant orofacial reflex myocloni during silent reading in association with bilateral frontal or generalized epileptiform discharges. In a further five patients, symptoms were only elicited while reading aloud with self-indicated events. Consistent activation patterns in response to reading-induced myoclonic seizures were observed within left motor and premotor areas in five of these six patients, in the left striatum (n = 4), in mesiotemporal/limbic areas (n = 4), in Brodmann area 47 (n = 3), and thalamus (n = 2). These BOLD activations were overlapping or adjacent to areas physiologically activated during language and facial motor tasks. No subtle structural abnormalities common to all patients were identified using VBM, but one patient had a left temporal ischemic lesion.
Discussion:   Based on the findings, we hypothesize that reflex seizures occur in reading epilepsy when a critical mass of neurons are activated through a provoking stimulus within corticoreticular and corticocortical circuitry subserving normal functions.     

Minimally resective epilepsy surgery in MRI‐negative children

Aim. Performing epilepsy surgery on children with non‐lesional brain MRI often results in large lobar or multilobar resections. The aim of this study was to determine if smaller resections result in a comparable rate of seizure freedom. Methods. We reviewed 25 children who had undergone focal corticectomies restricted to one aspect of a single lobe or the insula at our institution within a 5.5‐year period. Data collected in the comprehensive non‐invasive pre‐surgical evaluation (including scalp video‐EEG, volumetric MRI, functional MRI, EEG source localization, and SPECT and PET), as well as from invasive recordings performed in each patient, was reviewed. Data from each functional modality was identified as convergent or divergent with the epileptogenic zone using image coregistration. Specific biomarkers (from extra‐operative and invasive testing) previously indicated to be indicative of focal epileptogenicity were used to further tailor each resection to an epileptogenic epicentre. Tissue pathology and postoperative outcomes were obtained from all 25 patients. Results. Two years postoperatively, 15/25 (60%) children were seizure‐free, three (12%) experienced >90% reduction in seizure frequency, two (8%) had a 50–90% reduction in seizure frequency, and the remaining five (20%) had no change in seizure burden. There was no significant difference in outcome based on numerous pre‐ and postoperative factors including location of resection, the number of preoperative functional tests providing convergent data, and tissue pathology. Conclusion. In MRI‐negative children with focal epilepsy, an epileptogenic epicentre within a larger epileptogenic zone can be identified when specific biomarkers are recognized on non‐invasive and invasive testing. When such children undergo resection of a small, well‐defined epileptogenic epicentre, favourable outcomes can be achieved.     

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.     

Electroencephalogram-triggered functional magnetic resonance imaging in focal epilepsy

The high spatial resolution and cost performance of functional magnetic resonance imaging (fMRI) is useful for estimating focus localization in epilepsy, but this is difficult in the case of ictal fMRI because this is susceptible to motion artifacts. Electroencephalogram (EEG)-triggered fMRI, which is interictal, can be performed without marked movement and is thought to be useful, but requires further investigation in order to establish a methodology. The authors studied EEG-triggered fMRI in partial epileptic patients. Six patients were examined using a Nihon Kohden digital EEG recorder and Signa Horizon High Speed LX 1.5 T MRI scanner. Six electrodes were attached in the vicinity of the focus detected by scalp EEG. The fMRI scans were recorded after the discharges (activation) and scans without spikes (baseline). Equal numbers of activation and baseline scans were collected and analyzed using SPM99. In three of the six patients, an activated area was observed near the focus, but no activated areas were found in the other three subjects who tended to have a low number of spikes and low spike amplitude. Although various approaches focusing on improvement of the activation/non-activation ratio are required, EEG-triggered fMRI is a promising technique for detecting focal epileptic brain activity.     

Evaluation of cognition, structural, and functional MRI in juvenile myoclonic epilepsy

Purpose:  Previous studies using advanced imaging techniques have suggested subtle structural and functional changes in patients with juvenile myoclonic epilepsy (JME), mainly associated with the frontal lobes. In addition, it has been reported that these patients show neuropsychological deficits, often summarized as frontal lobe dysfunction. The aim of this study was a comprehensive analysis of neuropsychological parameters, and functional and structural magnetic resonance imaging (MRI) in an independent cohort of patients with JME.
Methods:  We studied 19 JME patients and 20 age-, sex-, and education-matched controls using a battery of standardized neuropsychological tests, optimized voxel-based morphometry (VBM), and two domain-specific working-memory paradigms combined with functional MRI (fMRI).
Results:  Our investigations did not reveal statistically significant differences between the groups of JME patients and normal controls in either the VBM or the fMRI study of working memory. The neuropsychological examination showed a slightly worse performance for the JME patients across most tests used, reaching statistical significance for semantic and verbal fluency.
Conclusions:  In our cohort of JME patients, we could not reproduce the findings of frontal gray matter changes from previous studies, and we could not detect an fMRI correlate of previously reported differences in working memory in JME. The neuropsychological deficits may be attributed partially to antiepileptic medication. We conclude that structural and functional frontal lobe deficits in JME patients have to be interpreted with care. One reason for a variation between different cohorts may be the genetic heterogeneity of the disease.