Martin Tomášek

SISCOM and FDG-PET in patients with non-lesional extratemporal epilepsy: correlation with intracranial EEG, histology, and seizure outcome

AimsTo assess the practical localising value of subtraction ictal single-photon emission computed tomography (SISCOM) coregistered with MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with extratemporal epilepsy and normal MRI.MethodsWe retrospectively studied a group of 14 patients who received surgery due to intractable epilepsy and who were shown to have focal cortical dysplasia, undetected by MRI, based on histological investigation. We coregistered preoperative SISCOM and PET images with postoperative MRI and visually determined whether the SISCOM focus, PET hypometabolic area, and cerebral cortex, exhibiting prominent abnormalities on intracranial EEG, were removed completely, incompletely, or not at all. These results and histopathological findings were compared with postoperative seizure outcome.ResultsTwo patients underwent one-stage multimodal imageguided surgery and the remaining 12 underwent long-term invasive EEG. SISCOM findings were localised for all but 1 patient. FDG-PET was normal in 3 subjects, 2 of whom had favourable postsurgical outcome (Engel class I and II). Complete resection of the SISCOM focus (n=3), the area of PET hypometabolism (n=2), or the cortical regions with intracranial EEG abnormalities (n=7) were predictive of favourable postsurgical outcome. Favourable outcome was also encountered in: 4 of 8 patients with incomplete resection and 1 of 2 with no resection of the SISCOM focus; 4 of 7 patients with incomplete resection and 1 of 2 with no resection of the PET hypometabolic area; and 2 of 7 patients with incomplete resection of the area corresponding to intracranial EEG abnormality. Nocorrelation between histopathological FCD subtype and seizure outcome was observed.ConclusionComplete resection of the dysplastic cortex localised by SISCOM, FDG-PET or intracranial EEG is a reliable predictor of favourable postoperative seizure outcome in patients with non-lesional extratemporal epilepsy.

Clinical characteristics in patients with hippocampal sclerosis with or without cortical dysplasia.

BACKGROUND Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) constitutes a distinct clinical syndrome with variable pathogenesis. Extrahippocampal regions may be affected in MTLE/HS, association with cortical dysplasia is common and temporal polar cortex is frequently involved in seizure onset. Patients with dual pathology may have favourable outcome from the surgery provided that both pathologies are removed. The aim of the study was to review clinical variables of MTLE/HS patients in order to distinguish preoperatively patients with associated microscopic cortical dysplasia in the temporal pole. METHODS A series of 38 patients with the clinical diagnosis of MTLE and histopathologically proven HS were analysed. Patients were divided into two groups on the basis of histopathological finding in the temporal polar cortex: HS associated with malformation of cortical development (group HS+, n = 19) and a group with isolated HS (group HS, n = 19). Demographic, clinical, electrographic and seizure semiology variables were obtained and their prevalence compared between both groups. RESULTS At least one insult was identified in early childhood history of 18 patients in the HS group in comparison to 10 patients in the HS+ group (p < 0.01). Complicated febrile seizures were found in both groups with similar prevalence, the history of early childhood CNS infection prevailed in the HS group (p < 0.01). Absence of aura was reported in HS group only. Patients in the the HS+ group had earlier surgery (p < 0.05) but the seizure outcome was comparable between groups. CONCLUSIONS Microscopic dual pathology is common in MTLE/HS patients. This group of patients is difficult to distinguish preoperatively on the basis of noninvasive electrographic features or ictal clinical semiology. Detailed information regarding the possible precipitating insult in the history may be of critical importance.

Detection of Interictal Epileptiform Discharges Using Signal Envelope Distribution Modelling: Application to Epileptic and Non-Epileptic Intracranial Recordings

Interictal epileptiform discharges (spikes, IEDs) are electrographic markers of epileptic tissue and their quantification is utilized in planning of surgical resection. Visual analysis of long-term multi-channel intracranial recordings is extremely laborious and prone to bias. Development of new and reliable techniques of automatic spike detection represents a crucial step towards increasing the information yield of intracranial recordings and to improve surgical outcome. In this study, we designed a novel and robust detection algorithm that adaptively models statistical distributions of signal envelopes and enables discrimination of signals containing IEDs from signals with background activity. This detector demonstrates performance superior both to human readers and to an established detector. It is even capable of identifying low-amplitude IEDs which are often missed by experts and which may represent an important source of clinical information. Application of the detector to non-epileptic intracranial data from patients with intractable facial pain revealed the existence of sharp transients with waveforms reminiscent of interictal discharges that can represent biological sources of false positive detections. Identification of these transients enabled us to develop and propose secondary processing steps, which may exclude these transients, improving the detector’s specificity and having important implications for future development of spike detectors in general.

1H MR spectroscopy in histopathological subgroups of mesial temporal lobe epilepsy

The aim of the study was to analyze the lateralizing value of proton magnetic resonance spectroscopy (1H MRS) in histopathologically different subgroups of mesial temporal lobe epilepsies (MTLE) and to correlate results with clinical, MRI and seizure outcome data. A group of 35 patients who underwent resective epilepsy surgery was retrospectively studied. Hippocampal 1H MR spectra were evaluated. Metabolite concentrations were obtained using LCModel and NAA/Cr, NAA/Cho, NAA/(Cr+Cho), Cho/Cr ratios and coefficients of asymmetry were calculated. MRI correctly lateralized 89% of subjects and 1H MRS 83%. MRI together with 1H MRS correctly lateralized 100% of patients. Nineteen subjects had “classical” hippocampal sclerosis (HS), whereas the remaining 16 patients had “mild” HS. Nineteen patients had histopathologically proven malformation of cortical development (MCD) in the temporal pole; 16 subjects had only HS. No difference in 1H MRS findings was found between patients in different histopathological subgroups of MTLE. Our results support the hypothesis that 1H MRS abnormalities do not directly reflect histopathological changes in MTLE patients. Subjects with non-lateralized 1H MRS abnormalities did not have a worse postoperative seizure outcome. We found no significant impact of contralateral 1H MRS abnormality on post-surgical seizure outcome.

Predominance of Movement Speed Over Direction in Neuronal Population Signals of Motor Cortex: Intracranial EEG Data and A Simple Explanatory Model

How neuronal activity of motor cortex is related to movement is a central topic in motor neuroscience. Motor-cortical single neurons are more closely related to hand movement velocity than speed, that is, the magnitude of the (directional) velocity vector. Recently, there is also increasing interest in the representation of movement parameters in neuronal population activity, such as reflected in the intracranial EEG (iEEG). We show that in iEEG, contrasting to what has been previously found on the single neuron level, speed predominates over velocity. The predominant speed representation was present in nearly all iEEG signal features, up to the 600–1000 Hz range. Using a model of motor-cortical signals arising from neuronal populations with realistic single neuron tuning properties, we show how this reversal can be understood as a consequence of increasing population size. Our findings demonstrate that the information profile in large population signals may systematically differ from the single neuron level, a principle that may be helpful in the interpretation of neuronal population signals in general, including, for example, EEG and functional magnetic resonance imaging. Taking advantage of the robust speed population signal may help in developing brain–machine interfaces exploiting population signals.

Clinical impact of a high-frequency seizure onset zone in a case of bitemporal epilepsy

High-frequency activity has been described as having a role in the initiation of epileptic seizures. The case of a patient with refractory bitemporal epilepsy is presented. Extraoperative monitoring with depth and subdural electrodes revealed an ictal pattern with a build-up of high-frequency (> 80 Hz) activity originating in the cortex, with spread to both hippocampi. This observation was only revealed with the use of high-pass filtering, and represented crucial information that significantly influenced the decision about the side, localization and extent of resection. Removal of the cortex generating high-frequency activity, led to cessation of seizures in this patient. Current knowledge about the role of high-frequency activity and the case presented here support the importance of recording with equipment capable of detecting fast activity during the presurgical invasive monitoring. An active search for a high-frequency seizure onset zone in patients with structurally-unaffected hippocampi may improve the outcome beyond that possible with conventional bandwidth, invasive EEG recordings.

Familial temporal lobe epilepsy due to focal cortical dysplasia type IIIa

PURPOSE Focal cortical dysplasia (FCD) represents a common cause of refractory epilepsy. It is considered a sporadic disorder, but its occasional familial occurrence suggests the involvement of genetic mechanisms. METHODS Siblings with intractable epilepsy were referred for epilepsy surgery evaluation. Both patients were examined using video-EEG monitoring, MRI examination and PET imaging. They underwent left anteromedial temporal lobe resection. RESULTS Electroclinical features pointed to left temporal lobe epilepsy and MRI examination revealed typical signs of left-sided hippocampal sclerosis and increased white matter signal intensity in the left temporal pole. PET examination confirmed interictal hypometabolism in the left temporal lobe. Histopathological examination of resected tissue demonstrated the presence FCD type IIIa, i.e. hippocampal sclerosis and focal cortical dysplasia in the left temporal pole. CONCLUSION We present a unique case of refractory mesial temporal lobe epilepsy in siblings, characterized by an identical clinical profile and histopathology of FCD type IIIa, who were successfully treated by epilepsy surgery. The presence of such a high concordance between the clinical and morphological data, together with the occurrence of epilepsy and febrile seizures in three generations of the family pedigree points towards a possible genetic nature of the observed FCD type IIIa.

Ictal and postictal semiology in patients with bilateral temporal lobe epilepsy.

Bilateral temporal lobe epilepsy is characterized by evidence of seizure onset independently in both temporal lobes. The main aim of the present study was to determine whether patients with evidence of independent bilateral temporal lobe epilepsy (biTLE) can be identified noninvasively on the basis of seizure semiology analysis. Thirteen patients with biTLE, as defined by invasive EEG, were matched with 13 patients with unilateral temporal lobe epilepsy (uniTLE). In all 26 patients, the frequency of predefined clusters of ictal and periictal signs were evaluated: ictal motor signs (IMSs), periictal motor signs (PIMSs), periictal vegetative signs (PIVSs), the frequency of early oroalimentary automatisms (EOAs), and the duration of postictal unresponsiveness (PU). Some other noninvasive and clinical data were also evaluated. A lower frequency of IMSs was noted in the group with biTLE (patients = 46.2%, seizures = 20.7%) than in the group with uniTLE (patients = 92.3%, seizures = 61.0%) (p = 0.030; p < 0.001, respectively). The individual IMS average per seizure was significantly lower in the group with biTLE (0.14; range = 0-1.0) than in the group with uniTLE (0.80; range = 0-2.6) (p = 0.003). Postictal unresponsiveness was longer than 5 min in more patients (75.0%) and seizures (42.9%) in the group with biTLE than in the group with uniTLE (patients = 30.8%, seizures = 18.6%) (p = 0.047; p = 0.002). The frequency of EOAs, PIMSs, PIVSs, and other clinical data did not differ significantly. There is a lower frequency of ictal motor signs and longer duration of postictal unresponsiveness in patients with biTLE.

The dynamics of error processing in the human brain as reflected by high-gamma activity in noninvasive and intracranial EEG

&NA; Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high‐gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error‐related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error‐related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error‐related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error‐related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error‐related learning and behavioral adaptation. Our findings establish the basic spatio‐temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error‐related potential studies. Graphical abstract Figure. No caption available.

The Sub-Regional Functional Organization of Neocortical Irritative Epileptic Networks in Pediatric Epilepsy

Between seizures, irritative network generates frequent brief synchronous activity, which manifests on the EEG as interictal epileptiform discharges (IEDs). Recent insights into the mechanism of IEDs at the microscopic level have demonstrated a high variance in the recruitment of neuronal populations generating IEDs and a high variability in the trajectories through which IEDs propagate across the brain. These phenomena represent one of the major constraints for precise characterization of network organization and for the utilization of IEDs during presurgical evaluations. We have developed a new approach to dissect human neocortical irritative networks and quantify their properties. We have demonstrated that irritative network has modular nature and it is composed of multiple independent sub-regions, each with specific IED propagation trajectories and differing in the extent of IED activity generated. The global activity of the irritative network is determined by long-term and circadian fluctuations in sub-region spatiotemporal properties. Also, the most active sub-region co-localizes with the seizure onset zone in 12/14 cases. This study demonstrates that principles of recruitment variability and propagation are conserved at the macroscopic level and that they determine irritative network properties in humans. Functional stratification of the irritative network increases the diagnostic yield of intracranial investigations with the potential to improve the outcomes of surgical treatment of neocortical epilepsy.