Search

Hemispherotomy is an effective surgery for treating refractory epilepsy from diffuse unihemispheric lesions. To date, postsurgery neuroplastic changes supporting behavioral recovery after left or right hemispherotomy remain unclear. In the present study, we systematically investigated changes in gray matter volume (GMV) before and after surgery and further analyzed their relationships with behavioral scores in two large groups of pediatric patients with left and right hemispherotomy (29 left and 28 right). To control for the dramatic developmental effect during this stage, age-adjusted GMV within unaffected brain regions was derived voxel by voxel using a normative modeling approach with an age-matched reference cohort of 2115 healthy children. Widespread GMV increases in the contralateral cerebrum and ipsilateral cerebellum and GMV decreases in the contralateral cerebellum were consistently observed in both patient groups, but only the left hemispherotomy patients showed GMV decreases in the contralateral cingulate gyrus. Intriguingly, the GMV decrease in the contralateral cerebellum was significantly correlated with improvement in behavioral scores in the right but not the left hemispherotomy patients. Importantly, the preoperative voxelwise GMV features can be used to significantly predict postoperative behavioral scores in both patient groups. These findings indicate an important role of the contralateral cerebellum in the behavioral recovery following right hemispherotomy and highlight the predictive potential of preoperative imaging features in postoperative behavioral performance., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

The ILAE Neuroimaging Task Force aims to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Previous quantitative MRI studies have established important imaging markers of epilepsy-related pathology, including features sensitive to hippocampal cell loss and reactive astrogliosis. Here, we review the case of a female with pediatric drug-resistant epilepsy. Throughout her course of treatment, she had seven MRI investigations at several centers; the first three did not follow optimized epilepsy imaging protocols whereas the remaining four adhered to HARNESS-MRI protocols ( har monized n euroimaging of e pilepsy s tructural s equences). Visual inspection of a set of HARNESS-MR images revealed conspicuous left hippocampal hyperintensity which may have been initially overlooked on non-optimized MR images. Quantitative analysis of these multimodal imaging data along hippocampal subfields provided clear evidence of hippocampal sclerosis, with increased atrophy, increased mean diffusivity, increased T2-FLAIR signal, and lower qT1 values observed in the anterior portions of the left, compared to the right hippocampus. The patient underwent a left anterior temporal lobectomy with amygdalohippocampectomy at age 16 years. Histopathology of the resected specimen also confirmed hippocampal sclerosis with widespread gliosis and focal neuronal loss in the hippocampal subfields overlapping with regions of multimodal quantitative alterations. The patient remains seizure-free one year after surgery. Collectively, this case highlights the need for optimized data acquisition protocols early in the treatment of epilepsy and supports quantitative analysis of MRI contrasts to enhance personalized diagnosis and prognosis of drug-resistant patients with epilepsy.

Multicompartment diffusion magnetic resonance imaging (MRI) approaches are increasingly being applied to estimate intra-axonal and extra-axonal diffusion characteristics in the human brain. Fiber ball imaging (FBI) and its extension fiber ball white matter modeling (FBWM) are such recently described multicompartment approaches. However, these particular approaches have yet to be applied in clinical cohorts. The modeling of several diffusion parameters with interpretable biological meaning may offer the development of new, noninvasive biomarkers of pharmacoresistance in epilepsy. In the present study, we used FBI and FBWM to evaluate intra-axonal and extra-axonal diffusion properties of white matter tracts in patients with longstanding focal epilepsy. FBI/FBWM diffusion parameters were calculated along the length of 50 white matter tract bundles and statistically compared between patients with refractory epilepsy, nonrefractory epilepsy and controls. We report that patients with chronic epilepsy had a widespread distribution of extra-axonal diffusivity relative to controls, particularly in circumscribed regions along white matter tracts projecting to cerebral cortex from thalamic, striatal, brainstem, and peduncular regions. Patients with refractory epilepsy had significantly greater markers of extra-axonal diffusivity compared to those with nonrefractory epilepsy. The extra-axonal diffusivity alterations in patients with epilepsy observed in the present study could be markers of neuroinflammatory processes or a reflection of reduced axonal density, both of which have been histologically demonstrated in focal epilepsy. FBI is a clinically feasible MRI approach that provides the basis for more interpretive conclusions about the microstructural environment of the brain and may represent a unique biomarker of pharmacoresistance in epilepsy., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

To investigate surgical prognostic factors in order to establish a surgical plan for children with drug-resistant epileptic spasms. We retrospectively analysed 64 children with drug-resistant spasms who were operated on in Beijing; the electroclinical features, surgical procedures, and surgical outcomes of these children were discussed in detail. We divided the seizure-free patients into several groups according to imaging, aetiology, and application of stereo-electroencephalography in order to investigate the extent of the various influencing factors. Fifty-three (82.8%) patients had favourable outcome, and 11 (17.2%) had unfavourable outcome. Based on the univariate analysis, the factors associated with favourable seizure outcome were interictal high γ frequency (χ 2 = 4.161; p = 0.041), concordance between MRI and interictal epileptic discharges (IEDs) (χ 2 = 6.148; p =0.013), and concordance between PET and IEDs (χ 2 = 4.281; p = 0.039). Concordance between MRI and IEDs (OR = 0.083, 95% CI = 0.014-0.483; p = 0.006) and continuous discharges on electrocorticography (OR = 0.109, 95% CI = 0.019-0.639; p = 0.014) were important factors associated with a favourable surgical outcome. Resective surgery is an effective treatment for drug-resistant ES in children. A deeper understanding of the predictors of seizure outcome is beneficial for establishing a standard, one-stage resection procedure for spasms in order to benefit more patients who have not previously considered surgery. We propose a workflow for presurgical evaluation in children with epileptic spasms.

The ILAE Neuroimaging Task Force aims to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. It is important to obtain MRI scans early in the clinical course of epilepsy, using an optimized protocol. Furthermore, it is critical that MRI scans are reviewed by experts who have been provided with all the clinical information and results from other investigations. We report a patient with a 21-year history of drug-resistant seizures who was admitted from another centre for presurgical evaluation. She had four previous MRI scans from this centre which were reported as unremarkable. However, a review of the MRI scan obtained on the day of admission, with the patient's ictal semiology in mind, resulted in identification of an epileptogenic lesion which was later confirmed by video-EEG monitoring and interictal PET. This lesion was present on all previous MRI scans and showed no change. The patient underwent lesionectomy, and histopathology of the resected specimen was consistent with a dysembryoplastic neuroepithelial tumour. The patient remains seizure-free, 2.5 years after surgery. This case highlights the importance of obtaining detailed descriptions of seizure semiology and considering them when reviewing MR images.

Temporal lobe epilepsy with amygdala enlargement (TLE-AE) has been considered a subtype of TLE. We evaluated the epileptogenic zone in patients with TLE-AE, who underwent intracranial video-EEG (ivEEG) and/or intraoperative electrocorticography (ioECoG) as well as epilepsy surgery. Eleven patients with TLE-AE were enrolled and investigated based on seizure profile, volumetric MRI, the Wechsler Memory Scale-Revised (WMS-R), the location of seizure onset zone (SOZ) and irritative zone (IZ) based on ivEEG (n=8), the location of interictal epileptiform discharges (IEDs) based on ioECoG (11), surgical procedure, and seizure outcome. The mean age at seizure onset was 34.9 years (range: 23-57). The mean duration of seizures was 5.0 years (range: 1-10). The number of AEDs was 2.3 (range: 1-5). The mean seizure frequency was nine per month (range: 1-30/month). All patients presented with focal impaired awareness seizures with (n=9) and without (2) secondary generalized convulsions. Volumetric MRI analysis showed unilateral enlarged amygdala with statistical significance (p<0.01). None of the patients' hippocampi had any abnormality based on MRI. Pre-operative mean verbal, visual, and delayed recall scores based on the WMS-R were over 100. The SOZ and IZ were identified in both the amygdala and hippocampus in seven patients and in only the amygdala in one patient based on ivEEG. IEDs were identified in the hippocampus in six patients and in both the amygdala and hippocampus in four patients based on ioECoG. All 11 patients underwent anterior temporal lobectomy, including amygdala resection, with multiple hippocampal transections (dominant hemisphere: seven patients) and resection (non-dominant hemisphere: three patients). Nine (81.8%) of 11 patients achieved seizure freedom with a mean follow-up of 26 months (range: 12-47). Post-operative WMS-R results did not show any significant deterioration, with a mean follow-up of 15 months (range: 12-24). The resected amygdala showed no histopathological abnormality. The epileptogenic zone of TLE-AE involves both the amygdala and hippocampus. ivEEG may be needed to explore the SOZ in normal hippocampus in addition to enlarged amygdala. Amygdala resection and multiple hippocampal transections may control the epileptogenic limbic system and save memory function in patients with TLE-AE.

Ulegyria refers to scarring of the cerebral cortex usually arising from perinatal ischaemia. The scarring has a specific configuration in which small atrophic circumvolutions at the bottom of a sulcus underlie an intact spared gyral apex. This disconnection of overlying cortex may allow an "epileptogenic" island of cortex to generate seizures. Ulegyria is often associated with epilepsy and developmental delay, however, the syndromic association of visual impairment with epilepsy due to occipital ulegyria may not be recognised as a specific entity. Here, we report a series of five patients with occipital ulegyria who presented with widely variable seizure semiology and an array of visual deficits. In some patients, the link between the epilepsy and the visual impairment was not appreciated until they attended an epilepsy clinic.

The pre-operative assessment and surgical management of patients with dual pathology is challenging. We describe a patient with drug-resistant focal epilepsy with hippocampal sclerosis and extensive periventricular nodular heterotopia in the same hemisphere. The semiology, scalp EEG, and imaging were divergent, but the presence of focal interictal and ictal epileptic discharges of the putative ictal onset zone resulted in successful localization of the epileptogenic zone. A less aggressive resection was performed based on intracranial EEG recording. The patient has been seizure-free for three years since resection. Electroclinical hypotheses and challenges in defining the epileptogenic network are discussed.

In-vivo measurements of human brain tissue conductivity at body temperature were conducted using focal electrical currents injected through intracerebral multicontact electrodes. A total of 1,421 measurements in 15 epileptic patients (age: 28 ± 10) using a radiofrequency generator (50 kHz current injection) were analyzed. Each contact pair was classified as being from healthy (gray matter, n = 696; white matter, n = 530) or pathological (epileptogenic zone, n = 195) tissue using neuroimaging analysis of the local tissue environment and intracerebral EEG recordings. Brain tissue conductivities were obtained using numerical simulations based on conductivity estimates that accounted for the current flow in the local brain volume around the contact pairs (a cube with a side length of 13 mm). Conductivity values were 0.26 S/m for gray matter and 0.17 S/m for white matter. Healthy gray and white matter had statistically different median impedances (P < 0.0001). White matter conductivity was found to be homogeneous as normality tests did not find evidence of multiple subgroups. Gray matter had lower conductivity in healthy tissue than in the epileptogenic zone (0.26 vs. 0.29 S/m; P = 0.012), even when the epileptogenic zone was not visible in the magnetic resonance image (MRI) (P = 0.005). The present in-vivo conductivity values could serve to create more accurate volume conduction models and could help to refine the identification of relevant intracerebral contacts, especially when located within the epileptogenic zone of an MRI-invisible lesion. Hum Brain Mapp 38:974-986, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: Focal epilepsies, such as temporal lobe epilepsy (TLE), are known to disrupt network activity in areas outside the epileptogenic zone [Tracy et al., 2015]. We devised a measure of temporal instability of resting state functional connectivity (FC), capturing temporal variations of BOLD correlations between brain regions that is less confounded than the "sliding window" approach common in the literature., Methods: We investigated healthy controls and unilateral TLE patients (right and left seizure focus groups), utilizing group ICA to identify the default mode network (DMN), a network associated with episodic memory, a key cognitive deficit in TLE. Our instability analyses focused on: (1) connectivity between DMN region pairs, both within and between TLE patients and matched controls, (2) whole brain group differences between region pairs ipsilateral or contralateral to the epileptogenic temporal lobe., Results: For both the whole brain and a more focused analysis of DMN region pairs, temporal stability appears to characterize the healthy brain. The TLE patients displayed more FC instability compared to controls, with this instability more pronounced for the right TLE patients., Significance: Our findings challenge the view that the resting state signal is stable over time, providing a measure of signal coherence change that may generate insights into the temporal components of network organization. The precuneus was the region within the DMN consistently expressing this instability, suggesting this region plays a key role in large scale temporal dynamics of the DMN, with such dynamics disrupted in TLE, putting key cognitive functions at risk. Hum Brain Mapp 38:528-540, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Detection of epileptic spikes in MagnetoEncephaloGraphy (MEG) requires synchronized neuronal activity over a minimum of 4cm2. We previously validated the Maximum Entropy on the Mean (MEM) as a source localization able to recover the spatial extent of the epileptic spike generators. The purpose of this study was to evaluate quantitatively, using intracranial EEG (iEEG), the spatial extent recovered from MEG sources by estimating iEEG potentials generated by these MEG sources. We evaluated five patients with focal epilepsy who had a pre-operative MEG acquisition and iEEG with MRI-compatible electrodes. Individual MEG epileptic spikes were localized along the cortical surface segmented from a pre-operative MRI, which was co-registered with the MRI obtained with iEEG electrodes in place for identification of iEEG contacts. An iEEG forward model estimated the influence of every dipolar source of the cortical surface on each iEEG contact. This iEEG forward model was applied to MEG sources to estimate iEEG potentials that would have been generated by these sources. MEG-estimated iEEG potentials were compared with measured iEEG potentials using four source localization methods: two variants of MEM and two standard methods equivalent to minimum norm and LORETA estimates. Our results demonstrated an excellent MEG/iEEG correspondence in the presumed focus for four out of five patients. In one patient, the deep generator identified in iEEG could not be localized in MEG. MEG-estimated iEEG potentials is a promising method to evaluate which MEG sources could be retrieved and validated with iEEG data, providing accurate results especially when applied to MEM localizations. Hum Brain Mapp 37:1661-1683, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objectives: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo., Experimental Design: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively assessed in CA1, CA2/3, and CA4/DG., Principal Observations: MRI volumes across all subfields were positively correlated with neuronal density and size. Higher T2 intensity related to increased GFAP fraction in CA1, while quantitative T1 and diffusion MRI parameters showed negative correlations with neuronal density in CA4 and DG. Multiple linear regression analysis revealed that in vivo multiparametric MRI can predict neuronal loss in all the analyzed subfields with up to 90% accuracy., Conclusion: Our results, based on an accurate co-registration pipeline and a subfield-specific analysis of MRI and histology, demonstrate the potential of MRI volumetry, diffusion, and quantitative T1 as accurate in vivo biomarkers of hippocampal pathology., (© 2015 Wiley Periodicals, Inc.)

Understanding the neurobiology and functional connectivity of hippocampal structures is essential for improving the treatment of mesial temporal lobe epilepsy. At the macroscale, in vivo MRI often reveals hippocampal atrophy and decreased fractional anisotropy, whereas at the microscopic scale, there frequently is evidence of neuronal loss and gliosis. Mossy fiber sprouting in the dentate gyrus (DG), with evidence of glutamatergic synapses in the stratum moleculare (SM) putatively originating from granule cell neurons, may also be observed. This aberrant connection between the DG and SM could produce a reverberant excitatory circuit. However, this hypothesis cannot easily be evaluated using macroscopic or microscopic techniques. We here demonstrate that the ex vivo mesoscopic MRI of surgically excised hippocampi can bridge the explanatory and analytical gap between the macro- and microscopic scale. Specifically, diffusion- and T2 -weighted MRI can be integrated to visualize a cytoarchitecture that is akin to immunohistochemistry. An appropriate spatial resolution to discern individual cell layers can then be established. Processing of diffusion tensor images using tractography detects extra- and intrahippocampal connections, hence providing a unique systems view of the hippocampus and its connected regions. Here, this approach suggests that there is indeed an aberrant connection between the DG and SM, supporting the sprouting hypothesis of a reverberant excitatory network. Mesoscopic ex vivo MR imaging hence provides an exciting new avenue to study hippocampi from treatment-resistant patients and allows exploration of existing hypotheses, as well as the development of new treatment strategies based on these novel insights. Hum Brain Mapp 37:780-795, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)