Sleep enhances gamma oscillations in the seizure onset zone and broadband activity in the irritative zone of focal cortical dysplasia.

We aim to explore the microscopic neurophysiology of focal cortical dysplasia (FCD) induced epileptogenesis in specific macroscopic brain regions, therefore mapping a micro-macro neuronal network that potentially indicates the epileptogenic mechanism. Epileptic and relatively non-epileptic temporal neocortex specimens were resected from FCD and mesial temporal lobe epilepsy (mTLE) patients, respectively. Whole-cell patch-clamping was performed on cells from the seizure onset zone (SOZ) and non-SOZ inside the epileptogenic zone (EZ) of FCD patients, as well as the non-epileptic neocortex of mTLE patients. Microscopic data were recorded, including membrane characteristics, spontaneous synaptic activities, and evoked action potentials. Immunohistochemistry was also performed on parvalbumin-positive (PV+) interneurons. We found that SOZ interneurons exhibited abnormal neuronal expression and distribution as well as reduced overall function compared with non-SOZ and mTLE interneurons. The SOZ pyramidal cells experienced higher excitation but lower inhibition than the mTLE controls, whereas the non-SOZ pyramidal cells exhibited intermediate excitability. Action potential properties of both types of neurons also suggested more synchronized neuronal activity inside the EZ, particularly inside the SOZ. Together, our research provides evidence for a potential neurocircuit underlying SOZ epileptogenesis and non-SOZ seizure susceptibility. Further investigation of this microscopic network may promote understanding of the mechanism of FCD-induced epileptogenesis.

BackgroundEpilepsy surgery in patients with Focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural MRI so intracranial EEG (icEEG)...

Based on intracranial-video electroencephalography (EEG), histopathological features, and postoperative seizure outcome, we elucidated the epileptogenicity in patients with dysembryoplastic neuroepithelial tumor (DNT). Five patients (P1–P5) pathologically diagnosed with DNT underwent intracranial-video EEG to identify the ictal onset zone and irritative zone. We evaluated the correlations of ictal onset zone and irritative zone with the magnetic resonance imaging-visible lesion (MRI-lesion) and their histopatho-logical features. Intracranial-video EEG located the ictal onset zone adjacent to the MRI-lesion margin in four patients with complex/simple forms of DNT subcategory, and on the MRI-lesion in P3 with a nonspecific DNT form. The irritative zone extended to surrounding regions of the ictal onset zone in all patients. Histopathologically, MRI-lesions were characterized by specific glioneuronal elements, whereas the ictal onset zone and irritative zone were represented with dysplastic cortex accompanying oligodendroglia-like cells in four (P1, P2, P4, and P5) of five patients. Cortical dysplasia was identified with typical histopathologic features in the irritative zone remote from the MRI-lesion in P5. P3, with a nonspecific form, indicated prominent component of dysplastic cortex with oligodendroglia-like cells scattered in the MRI-lesion. Lesionectomy of MRI-lesion with additional cortical resections (including the ictal onset zone and irritative zone) yielded postoperative seizure freedom (Engel Class I) in P3, P4, and P5, while P1 and P2 (with only lesionectomy) experienced postoperative residual seizure (Class II and III in each patient). Our results suggest the intrinsic epileptogenicity of DNT. The topographical correlation indicated that the dysplastic cortex accompanying oligodendroglia-like cells was more epileptogenic than the specific glioneuronal elements itself. Meticulous intracranial-video EEG analysis delineating the MRI nonvisible ictal onset zone and the irritative zone may yield better seizure outcome.

Microscopic mild focal cortical dysplasia in temporal lobe dual pathology: An electrocorticography study

Ictal and interictal source imaging on intracranial EEG predicts epilepsy surgery outcome in children with focal cortical dysplasia

S.05.02 New developments in the pharmacotherapy of bipolar disorders

Occurrence of scalp-fast oscillations among patients with different spiking rate and their role as epileptogenicity marker

In focal ictogenesis, gamma oscillations (30–70 Hz) recorded by electroencephalography (EEG) are related to the epileptiform synchronization of interneurons that links the seizure onset zone (SOZ) to the surrounding epileptogenic zone. We hypothesized that the synchronization of interneurons could be detected as changes in the regularity of gamma oscillation rhythmicity. We used multiscale entropy (MSE) analysis, which can quantify the regularity of EEG rhythmicity, to investigate how the regularity of gamma oscillations changes over the course of a seizure event. We analyzed intracranial EEG data from 13 pediatric patients with focal cortical dysplasia. The MSE analysis revealed the following characteristic changes of MSE score (gamma oscillations): (1) during the interictal periods, the lowest MSE score (the most regular gamma oscillations) was always found in the SOZ; (2) during the preictal periods, the SOZ became more similar to the epileptogenic zone as the MSE score increased in the SOZ (gamma oscillations became less regular in the SOZ); and (3) during the ictal periods, a decreasing MSE score (highly regular gamma oscillations) propagated over the epileptogenic zone. These spatiotemporal changes in regularity of gamma oscillations constitute an important demonstration that focal ictogenesis is caused by dynamic changes in interneuron synchronization.

ObjectiveSurgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)-related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG-fMRI in patients with FCD-associated focal epilepsy by examining the relationship between IED-related hemodynamic changes, icEEG findings, and postoperative outcome.MethodsTwenty-three patients with FCD-associated focal epilepsy undergoing presurgical evaluation including icEEG underwent simultaneous EEG-fMRI at 3T. IED-related hemodynamic changes were modeled, and results were overlaid on coregistered T1-weighted MRI scans fused with computed tomography scans showing the intracranial electrodes. IED-related hemodynamic changes were compared with the SOZ on icEEG and postoperative outcome at 1 year.ResultsTwelve of 23 patients had IEDs during recording, and 11 of 12 had significant IED-related hemodynamic changes. The fMRI results were concordant with the SOZ in 5 of 11 patients, all of whom had a solitary SOZ on icEEG. Four of 5 had >50% reduction in seizure frequency following resective surgery. The remaining 6 of 11 patients had widespread or discordant regions of IED-related fMRI signal change. Five of 6 had either a poor surgical outcome (<50% reduction in seizure frequency) or widespread SOZ precluding surgery.InterpretationComparison of EEG-fMRI with icEEG suggests that EEG-fMRI may provide useful additional information about the SOZ in FCD. Widely distributed discordant regions of IED-related hemodynamic change appear to be associated with a widespread SOZ and poor postsurgical outcome. ANN NEUROL 2011

Interictal high-frequency oscillations indicate seizure onset zone in patients with focal cortical dysplasia

ObjectivesDebates over the relationship between hippocampal malrotation (HIMAL) and epilepsy continue without consensus. This study explores the role of HIMAL in a cohort of epilepsy caused by focal cortical dysplasia (FCD).MethodsIn this study, 90 patients with epilepsy caused by FCD type I and type II and 48 healthy adults underwent a 3 Tesla MRI following a dedicated epilepsy protocol for the analysis of the prevalence and morphologic features of HIMAL. In addition, numerous clinical characteristics and hippocampal volumes were evaluated.ResultsThe cohort included a total of 90 patients (32 were HIMAL, 58 were non-HIMAL). Among these patients, 32 (35.6%) had HIMAL (22 left, four right, and six bilateral), which did not differ from the 48 controls, where 16 (33.3%) had HIMAL (12 left, two right, and two bilateral). Neither the quantitative features of HIMAL (diameter ratio, dominant inferior temporal sulcus height ratio, medial distance ratio, dominant inferior temporal sulcus angle, and parahippocampal angle), nor the accompanying characteristics of HIMAL (vertical dominant inferior temporal sulcus, enlarged temporal horn, and a low position of ipsilateral fornix) showed differences between patients with FCD and controls. No statistical difference in the clinical characteristics between FCD patients with HIMAL and those without was found. Neither the side nor the existence of HIMAL was correlated with the lateralization and location of FCD. As to the hippocampal volume, there was no difference between FCD patients with HIMAL and those without.ConclusionHippocampal malrotation is a common morphologic variant in healthy controls as well as in patients with epilepsy caused by FCD type I and type II. Hippocampal malrotation could be less significant in epilepsy caused by FCD type I and type II.

Subdural EEG has a high sensitivity for detecting interictal spikes. The irritative zone is usually more extended than the seizure onset zone. Removal of the entire irritative zone improves outcome in extratemporal as well as neocortical and tumour-related temporal lobe epilepsy, but not in mesial TLE. Quantification of spike features like amplitude, frequency, or latency may help differentiate the localizing and prognostic value of different spike populations. Although EEG patterns are not aetiology, some pathologies such as focal cortical dysplasias are frequently associated with typical EEG patterns, in which case intraoperative electrocorticography should be applied to tailor resections. Presence of a focal seizure onset zone and slow propagation are associated with good surgical outcome. Definition of a sound hypothesis about location of the seizure onset zone from pre-invasive findings is a crucial prerequisite for the success of subdural recordings. Concordance of interictal and ictal recordings is highly predictive of outcomes.

BACKGROUND: Up to 30% of the patients with epilepsy are resistant to drug therapy. One of the leading causes of drug-resistant epilepsy in adults and children is the focal cortical dysplasia. The complete resection of the epileptogenic focus in 60–70% of the cases results in the complete resolving of epileptic seizures, however, its detection and determining its margins by using magnetic resonance imaging (MRI) could be a difficult task. Positron emission tomography combined with MRI (PET/MRI) is a new hybrid method of diagnostics, which can be used in case of negative and indefinite MRI results, as well as in case of non-compliance of the MRI findings to the data from videoelectroencephalography (video-EEG-monitoring). AIM: To evaluate the diagnostic possibilities of the hybrid brain PET/MRI method with the use of the radiopharmaceutical — Fluorodeoxyglucose (18F-FDG) in detecting the focal cortical dysplasia in patients with focal drug-resistant epilepsy and to analyze the metabolic patterns in cases of focal cortical dysplasia of various type and location. METHODS: The retrospective analysis of data from 23 patients included the comparison of data from the brain PET/MRI with 18F-FDG, from the MRI and from the video-EEG-monitoring, as well as the analysis of 18F-FDG hypometabolism patterns in cases of focal cortical dysplasia of various types and locations. RESULTS: Focal cortical dysplasia was found in 13 (56.5%) patients by means of MRI, in 22 (95.6%) — by means of PET/MRI with 18F-FDG; 6 (26.1%) were MRI-negative, while in 3 (13%) cases the signs of focal cortical dysplasia were found upon the retrospective targeted analysis of MRI images in the 18F-FDG hypometabolism zone. Small focal area of 18F-FDG hypometabolism in our research was found only when the epileptogenic focus was located in the frontal lobe, which was 75% of the cases of the frontal variant of FCD. In all the cases of the temporal location, the zone was spreading to two and more gyri. As of the moment of article publication, the absence of seizures acc. to the classification by J. Engel (Engel I) in the postoperative period was reported for 11 (84.6%) of 13 operated patients, the Engel II class outcome was registered in 1 (4.3%) patient. CONCLUSION: Brain PET/MRI with 18F-FDG in patients with focal drug-resistant epilepsy increases the detection rates of focal cortical dysplasia by 39% comparing to MRI, including the MRI-negative patients and the patients with minor structural changes. The analysis of PET/MRI images in patients with suspected presence of epileptogenic focus of frontal location requires special attention.

Cortical surface analysis for focal cortical dysplasia diagnosis by using PET images

Interictal fast oscillations between 100 and 500 Hz have been reported in signals recorded from implanted microelectrodes in epileptic patients and experimental rat models. Oscillations between 250 and 500 Hz, or fast ripples (FR), appeared related to the epileptic focus whereas ripples (80-200 Hz) were not. We report high-frequency oscillations recorded with intracranial macroelectrodes in seven patients with refractory focal epilepsy during slow-wave sleep. We characterize the relation of fast oscillations to the seizure focus and quantify their concordance with epileptiform transients, with which they are strongly associated. The patients were selected because interictal spikes were found within and outside the seizure onset zone. Visual inspection was used to identify and classify the ripples and FRs according to their relation to epileptiform spikes. Continuous-time wavelet analysis was used to compute their power. Ripples were present in all patients while FRs where found in five of the seven patients. Most ripples and FRs occurred at the same time as epileptiform transients. The rate of occurrence of ripples was higher within the seizure onset zone than outside in four of seven patients. The rate of FRs was much higher within the seizure onset zone than outside in four of the five patients with FRs (in these four patients, FRs were almost inexistent outside the seizure onset zone). The power of ripples and FRs tended to be higher in the electrodes where their rate was also higher. These results indicate that FRs were more restricted to the electrodes located within the seizure onset zone, especially to the hippocampus, than ripples. In only one patient, FRs were more frequent outside the seizure onset zone; this patient was the only one with cortical dysplasia and the electrode with a high rate of FRs was inside the lesion. This study demonstrates that interictal ripples and FRs can be recorded with depth macroelectrodes in patients. Most occur at the time of epileptiform spikes but some are isolated. Ripples do not show a clear differentiation between the seizure onset zone and remote areas, whereas FRs have a higher rate and higher power in the seizure onset zone. Our results also suggest a special capacity of the abnormal hippocampus to generate FRs, although they were also recorded in other structures.